S-4/A

Large accelerated filer

Accelerated filer

Non-accelerated filer

☒ (Do not check if a smaller reporting company)

Smaller reporting company

Emerging growth company

(Address including zip code, and telephone number, including area code, of Registrant’s principal executive offices)

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Approximate date of commencement of proposed sale to the public: As soon as practicable after the effectiveness of this registration statement and the satisfaction or waiver of all other conditions under the Merger Agreement described herein.

If the securities being registered on this Form are being offered in connection with the formation of a holding company and there is compliance with General Instruction G, please check the following box. ☐

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☒

If applicable, place an X in the box to designate the appropriate rule provision relied upon in conducting this transaction:

The Registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment that specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

The information in this proxy statement/prospectus/information statement is not complete and may be changed. Nivalis may not sell its securities pursuant to the proposed transactions until the Registration Statement filed with the Securities and Exchange Commission is effective. This proxy statement/prospectus/information statement is not an offer to sell these securities and is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

To the Stockholders of Nivalis Therapeutics, Inc. and Alpine Immune Sciences, Inc.:

Nivalis Therapeutics, Inc. (“Nivalis”) and Alpine Immune Sciences, Inc. (“Alpine”) have entered into an Agreement and Plan of Merger and Reorganization (the “Merger Agreement”) pursuant to which a wholly owned subsidiary of Nivalis will merge with and into Alpine, with Alpine surviving as a wholly owned subsidiary of Nivalis (the “merger”). Alpine and Nivalis believe that the merger will result in a combined organization with a novel protein-based immunotherapy discovery platform focused on treating cancer and autoimmune /inflammatory disorders.

At the effective time of the merger, each share of (x) common stock of Alpine, $0.0001 par value (“Alpine common stock”), and (y) preferred stock of Alpine (“Alpine preferred stock” and, together with the Alpine common stock, “Alpine capital stock”) will be converted into the right to receive approximately 0.4969 shares of Nivalis’ common stock, assuming a 1:4 reverse stock split of Nivalis’ common stock to be implemented prior to the consummation of the merger as discussed in this proxy statement/prospectus/information statement. This exchange ratio is an estimate only and the final exchange ratio will be determined pursuant to a formula described in more detail in the Merger Agreement and in the attached proxy statement/prospectus/information statement. Nivalis will assume outstanding and unexercised warrants and options to purchase shares of Alpine capital stock, and they will be converted into warrants and options, as applicable, to purchase shares of Nivalis’ common stock. Nivalis’ stockholders will continue to own and hold their existing shares of Nivalis’ common stock, the vesting of all outstanding and unexercised options to purchase shares of Nivalis’ common stock will be accelerated in full as of immediately prior to the closing of the merger and all outstanding and unexercised warrants to purchase shares of Nivalis’ common stock will otherwise remain in effect pursuant to their terms. Immediately after the merger, current stockholders, warrantholders and optionholders of Alpine will own, or hold rights to acquire, approximately 74% of the fully-diluted common stock of Nivalis, which for these purposes is defined as the outstanding common stock of Nivalis, plus “in the money” options and warrants of Nivalis, assuming that all “in the money” options and warrants of Nivalis outstanding immediately prior to the merger are exercised on a cashless basis immediately prior to the closing of the merger (the “Fully-Diluted Common Stock of Nivalis”), with Nivalis’ current stockholders, optionholders and warrantholders owning, or holding rights to acquire, approximately 26% of the Fully-Diluted Common Stock of Nivalis.

Shares of Nivalis’ common stock are currently listed on The NASDAQ Global Market (“NASDAQ”) under the symbol “NVLS.” Prior to consummation of the merger, Nivalis intends to file an initial listing application with NASDAQ pursuant to NASDAQ’s “reverse merger” rules. After completion of the merger, Nivalis will be renamed “Alpine Immune Sciences, Inc.” and expects to trade on NASDAQ under the symbol “ALPN.” On May 18, 2017, the last trading day before the date of this proxy statement/prospectus/information statement, the closing sale price of Nivalis’ common stock on NASDAQ was $2.31 per share.

Nivalis is holding a special meeting of stockholders in order to obtain the stockholder approvals necessary to complete the merger and related matters. At the Nivalis special meeting, which will be held at 1:30 p.m., Mountain time, on July 19, 2017 at the offices of Ballard Spahr LLP, 5480 Valmont Road, Suite 200, Boulder, Colorado 80301, unless postponed or adjourned to a later date, Nivalis will ask its stockholders to, among other things, approve the Merger Agreement and thereby approve the transactions contemplated thereby, including the merger and the issuance of Nivalis’ common stock to Alpine’s stockholders, and approve an amendment to the Nivalis amended and restated certificate of incorporation effecting a reverse stock split of Nivalis’ common

stock, at a ratio of one new share for every four shares outstanding, and an amendment to Nivalis’ amended and restated certificate of incorporation changing the Nivalis corporate name to “Alpine Immune Sciences, Inc.”, each as described in the accompanying proxy statement/prospectus/information statement.

As described in the accompanying proxy statement/prospectus/information statement, certain of Alpine’s stockholders who in the aggregate own approximately 94% of the outstanding shares of Alpine capital stock on an as converted to common stock basis, and certain of Nivalis’ stockholders who in the aggregate own approximately 34% of the outstanding shares of Nivalis’ common stock, are parties to support agreements with Nivalis and Alpine, respectively, whereby such stockholders have agreed to vote their shares (under specified circumstances described in the support agreement, the aggregate number of shares of Alpine capital stock subject to the voting restrictions may be reduced from approximately 94% to 35% (the “Alpine Support Agreement Cutback”)), in favor of the adoption or approval, as applicable, of the Merger Agreement and the approval of the transactions contemplated therein, including the merger and the issuance of shares of Nivalis’ common stock to Alpine’s stockholders, subject to the terms of the support agreements. In addition, following the registration statement on Form S-4, of which this proxy statement/prospectus/information statement is a part, being declared effective by the U.S. Securities and Exchange Commission (the “SEC”) and pursuant to the conditions of the Merger Agreement and the support agreements, Alpine’s stockholders who are party to the support agreements will, subject to the Alpine Support Agreement Cutback, each execute an action by written consent of Alpine’s stockholders, referred to as the written consent, adopting the Merger Agreement, thereby approving the transactions contemplated therein, including the merger. Therefore, holders of a sufficient number of shares of Alpine capital stock required to adopt the Merger Agreement will, subject to the Alpine Support Agreement Cutback, adopt the Merger Agreement, and no meeting of Alpine’s stockholders to adopt the Merger Agreement and approve the merger and related transactions will be held. Nevertheless, all of Alpine’s stockholders will have the opportunity to elect to adopt the Merger Agreement, thereby approving the merger and related transactions, by signing and returning to Alpine a written consent.

After careful consideration, each of Nivalis’ and Alpine’s boards of directors have (i) determined that the transactions contemplated by the Merger Agreement are fair to, advisable and in the best interests of Nivalis or Alpine, as applicable, and their respective stockholders, (ii) approved and declared advisable the Merger Agreement and the transactions contemplated therein and (iii) determined to recommend, upon the terms and subject to the conditions set forth in the Merger Agreement, that its stockholders vote to adopt or approve, as applicable, the Merger Agreement and, therefore, approve the transactions contemplated therein. Nivalis’ board of directors recommends that Nivalis’ stockholders vote “FOR” the proposals described in the accompanying proxy statement/prospectus/information statement, and Alpine’s board of directors recommends that Alpine’s stockholders sign and return the written consent indicating their approval of the merger and adoption of the Merger Agreement and the transactions contemplated therein.

More information about Nivalis, Alpine and the proposed transaction is contained in this proxy statement/prospectus/information statement. Nivalis and Alpine urge you to read the accompanying proxy statement/prospectus/information statement carefully and in its entirety. IN PARTICULAR, YOU SHOULD CAREFULLY CONSIDER THE MATTERS DISCUSSED UNDER “RISK FACTORS” BEGINNING ON PAGE 25.

Nivalis and Alpine are excited about the opportunities the merger brings to both Nivalis’ and Alpine’s stockholders, and thank you for your consideration and continued support.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this proxy statement/prospectus/information statement. Any representation to the contrary is a criminal offense.

The accompanying proxy statement/prospectus/information statement is dated June 2, 2017, and is first being mailed to Nivalis’ and Alpine’s stockholders on or about [●], 2017.

On behalf of the board of directors of Nivalis Therapeutics, Inc., a Delaware corporation (“Nivalis”), we are pleased to deliver this proxy statement/prospectus/information statement for the proposed merger between Nivalis and Alpine Immune Sciences, Inc., a Delaware corporation (“Alpine”), pursuant to which Nautilus Merger Sub, Inc., a Delaware corporation and a wholly owned subsidiary of Nivalis (“Merger Sub”), will merge with and into Alpine, with Alpine surviving as a wholly owned subsidiary of Nivalis. The special meeting of stockholders of Nivalis will be held on July 19, 2017 at 1:30 p.m., Mountain time, at the offices of Ballard Spahr LLP, 5480 Valmont Road, Suite 200, Boulder, Colorado 80301, for the following purposes:

1. To consider and vote upon a proposal to approve the Agreement and Plan of Merger and Reorganization, dated as of April 18, 2017, by and among Nivalis, Merger Sub, and Alpine, a copy of which is attached as Annex A to this proxy statement/prospectus/information statement, and the transactions contemplated thereby, including the merger and the issuance of shares of Nivalis’ common stock to Alpine’s stockholders pursuant to the terms of the Merger Agreement.

2. To approve an amendment to the amended and restated certificate of incorporation of Nivalis to effect a reverse stock split of Nivalis’ common stock, at a ratio of one new share for every four shares outstanding, in the form attached as Annex D to this proxy statement/prospectus/information statement.

3. To approve an amendment to the amended and restated certificate of incorporation of Nivalis to change the corporate name of Nivalis from “Nivalis Therapeutics, Inc.” to “Alpine Immune Sciences, Inc.” in the form attached as Annex E to this proxy statement/prospectus/information statement.

4. To consider and vote upon an adjournment of the Nivalis special meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal Nos. 1 or 2.

5. To transact such other business as may properly come before the Nivalis special meeting or any adjournment or postponement thereof.

Nivalis’ board of directors has fixed May 26, 2017, as the record date for the determination of stockholders entitled to notice of, and to vote at, the Nivalis special meeting and any adjournment or postponement thereof. Only holders of record of shares of Nivalis’ common stock at the close of business on the record date are entitled to notice of, and to vote at, the Nivalis special meeting. At the close of business on the record date, Nivalis had 15,656,251 shares of common stock outstanding and entitled to vote.

Your vote is important. The affirmative vote of the holders of a majority of the shares of Nivalis’ common stock having voting power present in person or represented by proxy at the Nivalis special meeting is required for approval of Proposal Nos. 1 and 4. The affirmative vote of the holders of a majority of shares of Nivalis’ common stock having voting power outstanding on the record date for the Nivalis special meeting is required for approval of Proposal Nos. 2 and 3. Each of Proposal Nos. 1 and 2 are conditioned upon each other. Therefore, the merger cannot be consummated without the approval of Proposal Nos. 1 and 2.

Even if you plan to attend the Nivalis special meeting in person, Nivalis requests that you sign and return the enclosed proxy to ensure that your shares will be represented at the Nivalis special meeting if you are unable to attend.

NIVALIS’ BOARD OF DIRECTORS HAS DETERMINED AND BELIEVES THAT EACH OF THE PROPOSALS OUTLINED ABOVE IS ADVISABLE TO, AND IN THE BEST INTERESTS OF, NIVALIS AND ITS STOCKHOLDERS AND HAS APPROVED EACH SUCH PROPOSAL. NIVALIS’ BOARD OF DIRECTORS RECOMMENDS THAT NIVALIS’ STOCKHOLDERS VOTE “FOR” EACH SUCH PROPOSAL.

This proxy statement/prospectus/information statement incorporates important business and financial information about Nivalis that is not included in or delivered with this document. You may obtain this information without charge through the Securities and Exchange Commission, or the SEC, website (www.sec.gov) or upon your written or oral request by contacting the Chief Financial Officer of Nivalis Therapeutics, Inc., PO Box 18387, Boulder, Colorado 80308 or by calling (720) 600-4740.

To ensure timely delivery of these documents, any request should be made no later than July 12, 2017 to receive them before the special meeting.

For additional details about where you can find information about Nivalis, please see the section entitled “Where You Can Find More Information” in this proxy statement/prospectus/information statement.

Except where specifically noted, the following information and all other information contained in this proxy statement/prospectus/information statement does not give effect to the proposed 1:4 reverse stock split described in Proposal No. 2, beginning on page 154 in this proxy statement/prospectus/information statement (the “Nivalis Reverse Stock Split”).

The following section provides answers to frequently asked questions about the merger. This section, however, provides only summary information. For a more complete response to these questions and for additional information, please refer to the cross-referenced sections.

At the effective time of the merger (the “Effective Time”), each share of Alpine’s common stock and Alpine’s preferred stock outstanding immediately prior to the Effective Time (excluding certain shares to be canceled pursuant to the Merger Agreement, and shares held by stockholders who have exercised and perfected appraisal rights as more fully described in the section titled “The Merger—Appraisal Rights” below) will be converted into the right to receive approximately 1.9878 shares of Nivalis’ common stock, subject to adjustment to account for the Nivalis Reverse Stock Split. This exchange ratio is an estimate only and the final exchange ratio will be determined pursuant to a formula described in more detail in the Merger Agreement and in the attached proxy statement/prospectus/information statement. As a result of the merger, current holders of Alpine’s capital stock and options and warrants to purchase Alpine’s capital stock are expected to own, or hold rights to acquire, in the aggregate approximately 74% of the Fully-Diluted Common Stock of Nivalis and Nivalis’ current stockholders, optionholders and warrantholders are expected to own, or hold rights to acquire, in the aggregate approximately 26% of the Fully-Diluted Common Stock of Nivalis and, in each case, following the Effective Time. After the completion of the merger, Nivalis will change its corporate name to “Alpine Immune Sciences, Inc.” as required by the Merger Agreement (the “Nivalis Name Change”).

If Nivalis were to continue its business, it would need to hire scientific personnel necessary to resume research and development activities on its GSNOR inhibitor platform, or identify, acquire and develop other products or product candidates. In addition, as of May 1, 2017, the Nivalis workforce was comprised of five employees, all of whom are involved in either financial and administrative roles or in conducting limited activities related to maintenance of Nivalis’ patent portfolio. Nivalis has ceased all research activities and has no ongoing clinical trials. If Nivalis decides to reestablish a viable operating business and/or pursue development of other products or product candidates, Nivalis will need to rebuild its senior

management team and hire scientific managerial and other personnel to lead and staff all of its necessary functions, especially its research, development and commercialization areas, and raise substantial funds to support these activities.

The approval of the merger and the issuance of Nivalis’ common stock pursuant to the Merger Agreement by Nivalis’ stockholders requires the affirmative vote of the holders of a majority of the shares of Nivalis’ outstanding common stock having voting power present in person or represented by proxy at the Nivalis special meeting. The approval of the amendments to the amended and restated certificate of incorporation of Nivalis to effect the Nivalis Reverse Stock Split and the Nivalis Name Change requires the affirmative vote of the holders of a majority of the shares of Nivalis’ common stock having voting power outstanding on the record date for the Nivalis special meeting. The approval of the Nivalis Reverse Stock Split is required in order to authorize Nivalis’ issuance of the shares of its common stock pursuant to the Merger Agreement and avoid a delisting of Nivalis’ common stock from NASDAQ. Therefore, if the requisite stockholders of Nivalis approve the merger and the issuance of Nivalis’ common stock pursuant to the Merger Agreement but do not approve the Nivalis Reverse Stock Split, the merger will not be consummated.

The adoption of the Merger Agreement and the approval of the merger and related transactions by Alpine’s stockholders requires the affirmative vote (or written consent) of the holders of a majority of (a) the outstanding shares of Alpine’s common stock and preferred stock, voting together as one class and (b) the outstanding shares of Alpine’s preferred stock voting as a separate class.

Certain of Alpine’s stockholders who in the aggregate own approximately 94% of the outstanding shares of Alpine’s capital stock on an as converted to common stock basis (subject to the Alpine Support Agreement Cutback), and certain of Nivalis’ stockholders who in the aggregate own approximately 34% of the outstanding shares of Nivalis’ common stock, are parties to support agreements with Nivalis and Alpine, respectively, whereby such stockholders have agreed, subject to the terms of the support agreements, to vote their shares in favor of the adoption or approval, as applicable, of the Merger Agreement and the transactions contemplated therein, including the merger and the issuance of Nivalis’ common stock to Alpine’s stockholders pursuant to the Merger Agreement. In addition, following the registration statement on Form S-4, of which this proxy statement/prospectus/information statement is a part, being declared effective by the SEC and pursuant to the conditions of the Merger Agreement, Alpine’s stockholders who are party to the support agreements will, subject to the Alpine Support Agreement Cutback, each execute written consents approving the merger and related transactions. Therefore, holders of a sufficient number of shares of Alpine capital stock required to adopt the Merger Agreement, thereby approving the merger, have agreed, subject to the Alpine Support Agreement Cutback, to adopt the Merger Agreement via written consent. Stockholders of Alpine, including those who are parties to support agreements, are being requested to execute written consents providing such approvals.

In addition to the requirement of obtaining the stockholder approvals described above and appropriate regulatory approvals, each of the other closing conditions set forth in the Merger Agreement must be satisfied or waived. For a more complete description of the closing conditions under the Merger Agreement, we urge you to read the section entitled “The Merger Agreement—Conditions to the Completion of the Merger” in this proxy statement/prospectus/information statement.

For a more complete description of what Alpine’s stockholders, warrantholders and optionholders will receive in the merger, please see the sections entitled and “The Merger Agreement—Merger Consideration” in this proxy statement/prospectus/information statement.

If you are a stockholder of Nivalis, you may provide your proxy instructions in one of two different ways. First, you can mail your signed proxy card in the enclosed return envelope. You may also provide your proxy instructions via phone or via the Internet by following the instructions on your proxy card or voting instruction form. Please provide your proxy instructions only once, unless you are revoking a previously delivered proxy instruction, and as soon as possible so that your shares can be voted at the Nivalis special meeting.

If you are a stockholder of Alpine, you may execute and return your written consent to Alpine in accordance with the instructions provided by Alpine.

If you are a stockholder of Alpine, and would like additional copies, without charge, of this proxy statement/prospectus/information statement or if you have questions about the merger, including the procedures for voting your shares, you should contact:

Prospectus Summary

This summary highlights selected information from this proxy statement/prospectus/information statement and may not contain all of the information that is important to you. To better understand the merger, the proposals being considered at the Nivalis special meeting and Alpine’s stockholder actions that are the subject of the written consent, you should read this entire proxy statement/prospectus/information statement carefully, including the Merger Agreement attached as Annex A, the opinion of Ladenburg Thalmann & Co. Inc. attached as Annex B and the other annexes to which you are referred herein. For more information, please see the section entitled “Where You Can Find More Information” in this proxy statement/prospectus/information statement.

The Companies

Nivalis Therapeutics, Inc.

PO Box 18387

Boulder, Colorado 80308

(720) 600-4740

Nivalis is a pharmaceutical company that has historically been focused on the discovery and development of product candidates for patients with cystic fibrosis (“CF”). Nivalis’ GSNOR inhibitors selectively target an enzyme known as S-nitrosoglutathione reductase, which we refer to as GSNOR. GSNOR regulates levels of an endogenous protein known as S-nitrosoglutathione or GSNO. Depleted levels of GSNO have been associated with CF, asthma, inflammatory bowel diseases and certain cardiovascular diseases. Our lead product candidate, cavosonstat (N91115), is a small molecule inhibitor of GSNOR that was being evaluated in patients with CF. However, in light of recent negative results from two clinical trials of cavosonstat in CF patients, Nivalis determined to discontinue the development of this compound in CF and has shifted its strategic emphasis to focus on identifying and evaluating strategic alternatives not related to GSNOR inhibition or specific to CF. Nivalis currently does not have any drugs that are commercially available and none of its drug candidates have obtained the approval of the U.S. Food and Drug Administration (“FDA”) or any similar foreign regulatory authority.

Alpine Immune Sciences, Inc.

201 Elliott Avenue West, Suite 230

Seattle, Washington 98119

(206) 788-4545

Alpine is a development-stage specialty pharmaceutical company focused on discovering and developing protein-based immunotherapies targeting the immune synapse to treat cancer, inflammatory disorders, and other diseases. Alpine’s proprietary Variant Immunoglobulin Domain™ ( “vIgD™”) scientific platform uses a process known as directed evolution to create therapeutics potentially capable of modulating human immune system proteins. Alpine’s vIgD platform creates molecules which can be formatted in many different ways, including standard Fc fusion proteins, localized Fc fusion proteins, and monoclonal antibody fusion proteins as well as formulated as a Transmembrane Immunomodulatory Protein (“TIP™”) or as a Secreted Immunomodulatory Protein (“SIP™”). Alpine expects to request regulatory approval to begin human clinical trials of ALPN-101, Alpine’s dual ICOS/CD28 antagonist program, in the second half of 2018. Alpine expects the target indication for the ALPN-101 program will be inflammatory disorders. In October 2015, Alpine signed a research and license agreement with Kite Pharma, Inc. (“Kite”), granting Kite an exclusive license to two of Alpine’s TIP programs for use in Kite’s chimeric antigen receptor T cell (“CAR-T”) and T cell receptor (“TCR”) programs. Alpine received $5.5 million in up front cash and is eligible to receive up to $530 million in developmental, clinical, and regulatory milestone payments in addition to royalties on any products containing Alpine’s TIPs. Alpine currently does not have any drugs commercially available and none of its drug candidates have obtained approval of the FDA or any similar foreign regulatory authority.

Nautilus Merger Sub, Inc.

Merger Sub is a wholly owned subsidiary of Nivalis, and was formed solely for the purposes of carrying out the merger.

The Merger (see page 94)

If the merger is completed, Merger Sub will merge with and into Alpine, with Alpine surviving as a wholly owned subsidiary of Nivalis.

At the Effective Time, each share of Alpine capital stock outstanding immediately prior to the Effective Time (excluding certain shares to be canceled pursuant to the Merger Agreement, and shares held by stockholders who have exercised and perfected appraisal rights as more fully described in the section titled “The Merger—Appraisal Rights” below) will be converted into the right to receive approximately 1.9878 shares of Nivalis’ common stock, subject to adjustment to account for the Nivalis Reverse Stock Split. This exchange ratio is an estimate only and the final exchange ratio will be determined pursuant to a formula described in more detail in the Merger Agreement and in this proxy statement/prospectus/information statement. Immediately following the consummation of the merger, current stockholders, optionholders and warrantholders of Alpine will own, or hold rights to acquire, approximately 74% of the Fully-Diluted Common Stock of Nivalis, with current stockholders, optionholders and warrantholders of Nivalis owning, or holding rights to acquire, approximately 26% of the Fully-Diluted Common Stock of Nivalis. Nivalis will assume outstanding and unexercised options and warrants to purchase Alpine capital stock, and each such option or warrant will be converted into options or warrants, as applicable, to purchase Nivalis’ common stock.

For a more complete description of the merger exchange ratio please see the section entitled “The Merger Agreement” in this proxy statement/prospectus/information statement.

The closing of the merger will occur no later than the second business day after the last of the conditions to the merger has been satisfied or waived (other than those conditions that by their nature are to be satisfied at the closing, but subject to the satisfaction or waiver of each such conditions), or at such other time as Nivalis and Alpine agree. Nivalis and Alpine anticipate that the consummation of the merger will occur in the third quarter of the fiscal year. However, because the merger is subject to a number of conditions, neither Nivalis nor Alpine can predict exactly when the closing will occur or if it will occur at all. After completion of the merger, assuming that Nivalis receives the required stockholder approval of Proposal No. 3, Nivalis will be renamed “Alpine Immune Sciences, Inc.”

Reasons for the Merger (see page 108)

Following the merger, the combined organization will focus on the development and commercialization of Alpine’s innovative immunotherapies. Alpine is focused on discovering and developing modern, protein-based immunotherapies targeting the immune synapse to treat cancer, inflammation, and other diseases. Alpine’s proprietary variant immunoglobulin domain (“vIgD”) platform uses a process known as directed evolution to create therapeutics potentially capable of modulating human immune system proteins. In Alpine’s pre-clinical studies, the vIgD platform has identified novel proteins with the ability to either enhance or diminish an immune response. These proteins could be potentially applicable therapeutically to both oncology (cancer) and inflammatory diseases. Alpine has also developed its transmembrane immunomodulatory protein (“TIP”) technology, based on the vIgD platform, to potentially enhance engineered cellular therapies. Nivalis and Alpine believe that the combined organization will have the following potential advantages:

•

Emerging Development-Stage Company. Alpine is focused on discovering and developing, using its vIgD platform, modern, protein-based immunotherapies potentially capable of either enhancing or

diminishing an immune response and thereby potentially applicable therapeutically to both oncology and inflammatory diseases. Alpine expects to request regulatory approval to begin human clinical trials of ALPN-101, Alpine’s dual ICOS/CD28 antagonist program, in the second half of 2018.

•

Management Team. It is expected that the combined organization will be led by the experienced senior management from Alpine and a board of directors with representation from each of Nivalis and Alpine.

•

Cash Resources. The combined organization is expected to have approximately $90.0 million in cash and cash equivalents at the closing of the merger, which Nivalis and Alpine believe is sufficient to enable Alpine to implement its near-term business plans.

Each of Nivalis’ and Alpine’s respective board of directors also considered other reasons for the merger, as described herein. For example, Nivalis’ board of directors considered, among other things:

•

the strategic alternatives of Nivalis to the merger, including the discussions that Nivalis’ management and Nivalis’ board of directors previously conducted with other potential merger partners;

•

the failure of cavosonstat to show success in clinical trials and the unlikelihood that such circumstances would change for the benefit of Nivalis’ stockholders in the foreseeable future;

•

the risk associated with, and uncertain value and costs to stockholders of, liquidating Nivalis;

•

the risks of continuing to operate Nivalis on a stand-alone basis, including the early-stage nature of its GSNOR inhibitor portfolio and the need to raise additional funding and expend significant resources to advance this portfolio and to rebuild its infrastructure and management to continue its operations; and

•

the opportunity as a result of the merger for Nivalis’ stockholders to participate in the potential value of the Alpine product candidate portfolio.

In addition, Alpine’s board of directors approved the merger based on a number of factors, including the following:

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the potential increased access to sources of capital and a broader range of investors to support the clinical development of its products than it could otherwise obtain if it continued to operate as a privately held company;

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the potential to provide its current stockholders with greater liquidity by owning stock in a public company;

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Alpine’s board of directors’ belief that no alternatives to the merger were reasonably likely to create greater value for Alpine’s stockholders after reviewing the various strategic options to enhance stockholder value that were considered by Alpine’s board of directors;

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the cash resources of the combined organization expected to be available at the closing of the merger; and

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the expectation that the merger will be treated as a reorganization for U.S. federal income tax purposes.

Opinion of the Nivalis Financial Advisor (see page 113)

Ladenburg Thalmann & Co. Inc. (“Ladenburg”), the financial advisor of Nivalis, delivered to Nivalis’ board of directors a written opinion dated April 17, 2017, addressed to Nivalis’ board of directors, to the effect that, as of the date of the opinion and based on and subject to various assumptions, qualifications and limitations described in the opinion, the consideration to be paid by Nivalis in the proposed merger was fair, from a financial point of view, to Nivalis’ stockholders. The full text of this written opinion to Nivalis’ board of directors, which describes, among other things, the assumptions made, procedures followed, factors considered and limitations on the review undertaken, is attached as Annex B to this proxy statement/

prospectus/information statement and is incorporated by reference in its entirety into this proxy statement. Holders of Nivalis’ common stock are encouraged to read the opinion carefully in its entirety. The Ladenburg opinion was provided to Nivalis’ board of directors in connection with its evaluation of the consideration provided for in the merger. It does not address any other aspect of the proposed merger or any alternative to the merger and does not constitute a recommendation as to how Nivalis’ stockholders of Nivalis should vote or act in connection with the merger or otherwise.

Overview of the Merger Agreement

Merger Consideration (see page 128)

At the Effective Time, all outstanding shares of Alpine capital stock shall convert into the right to receive shares of Nivalis’ common stock as follows:

•

each share of Alpine’s capital stock outstanding immediately prior to the Effective Time (excluding shares of Alpine’s common stock held as treasury stock or held by Alpine, Merger Sub or any subsidiary of Alpine) will automatically be converted into the right to receive a number of shares of Nivalis’ common stock equal to approximately 1.9878 (subject to adjustment to account for the Nivalis Reverse Stock Split, if consummated, the “exchange ratio”). This exchange ratio is an estimate only and the final exchange ratio will be determined pursuant to a formula described in more detail in the Merger Agreement and in this proxy statement/prospectus/information statement.

Immediately after the merger, based on the exchange ratio, Alpine’s current stockholders, warrantholders and option holders will own, or hold rights to acquire, approximately 74% of the Fully-Diluted Common Stock of Nivalis with current stockholders, optionholders and warrantholders of Nivalis owning, or holding rights to acquire, approximately 26% of the Fully-Diluted Common Stock of Nivalis.

The Merger Agreement does not include a price-based termination right, and there will be no adjustment to the total number of shares of Nivalis’ common stock that Alpine’s stockholders will be entitled to receive for changes in the market price of Nivalis’ common stock after the date the Merger Agreement was signed. Accordingly, the market value of the shares of Nivalis’ common stock issued pursuant to the merger will depend on the market value of the shares of Nivalis’ common stock at the time the merger closes, and could vary significantly from the market value on the date of this proxy statement/prospectus/information statement.

Treatment of Nivalis’ Stock Options (see page 135)

Prior to the closing of the merger, Nivalis’ board of directors will adopt appropriate resolutions and take all other actions necessary and appropriate to provide that the vesting of each unexpired and unexercised option to purchase Nivalis’ common stock will be accelerated in full effective as of immediately prior to the Effective Time. The number of shares of common stock underlying such options and the exercise price for such options will be adjusted to account for the Reverse Stock Split. The terms governing options to purchase Nivalis’ common stock will otherwise remain in full force and effect following the closing of the merger.

Treatment of Alpine’s Stock Options and Warrants (see page 135)

Pursuant to the Merger Agreement, at the Effective Time:

•

each option to purchase shares of Alpine’s capital stock that is outstanding and unexercised immediately prior to the Effective Time granted under the Alpine Amended and Restated 2015 Stock Plan, whether or not vested, will be assumed by Nivalis and will become an option to purchase that number of shares of Nivalis’ common stock equal to the product obtained by multiplying (i) the number of shares of Alpine’s common stock that were subject to such option immediately prior to the

Effective Time by (ii) the exchange ratio. The per share exercise price for shares of Nivalis’ common stock issuable upon exercise of each Alpine option assumed by Nivalis shall be determined by dividing (a) the per share exercise price of Alpine’s common stock subject to such Alpine option, as in effect immediately prior to the Effective Time, by (b) the exchange ratio. Any restriction on the exercise of any Alpine option assumed by Nivalis will continue in full force and effect and the term, exercisability, vesting schedule and other provisions of such Alpine option shall otherwise remain unchanged; and

•

each warrant to purchase shares of Alpine capital stock outstanding and unexercised immediately prior to the Effective Time will be assumed by Nivalis and will become a warrant to purchase that number of shares of Nivalis’ common stock equal to the product obtained by multiplying (i) the number of shares of Alpine’s common stock, or the number of shares of Alpine’s common stock issuable upon conversion of the shares of Alpine’s preferred stock issuable upon exercise of the Alpine warrant, as applicable, that were subject to such warrant immediately prior to the Effective Time by (ii) the exchange ratio. The per share exercise price for shares of Nivalis’ common stock issuable upon exercise of each Alpine warrant assumed by Nivalis shall be determined by dividing (a) the per share exercise price of Alpine’s common stock or preferred stock subject to such Alpine warrant, as in effect immediately prior to the Effective Time, by (b) the exchange ratio. Any restriction on any Alpine warrant assumed by Nivalis shall continue in full force and effect and the terms and other provisions of such Alpine warrant shall otherwise remain unchanged.

Conditions to the Completion of the Merger (see page 135)

To consummate the merger, Nivalis’ stockholders must approve (a) the Merger Agreement and the transactions contemplated thereby, including the merger and the issuance of shares of Nivalis’ common stock in the merger, and (b) an amendment to the amended and restated certificate of incorporation of Nivalis effecting the Nivalis Reverse Stock Split. Additionally, Alpine’s stockholders must adopt the Merger Agreement thereby approving the merger and the other transactions contemplated by the Merger Agreement. In addition to obtaining such stockholder approvals and appropriate regulatory approvals, each of the other closing conditions set forth in the Merger Agreement must be satisfied or waived.

No Solicitation (see page 140)

Each of Nivalis and Alpine agreed that, except as described below, from the date of the Merger Agreement until the earlier of the consummation of the merger or the termination of the Merger Agreement in accordance with its terms, Nivalis and Alpine and any of their respective subsidiaries will not, nor will either party or any of its subsidiaries authorize any of the directors, officers, employees, agents, attorneys, accountants, investment bankers, advisors or representatives retained by it or any of its subsidiaries to, directly or indirectly:

•

solicit, initiate or knowingly encourage, induce or facilitate the communication, making, submission or announcement of, any “acquisition proposal” (as defined in the section titled “The Merger Agreement—No Solicitation” below), or “acquisition inquiry” (as defined in the section titled “The Merger Agreement—No Solicitation” below);

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furnish any non-public information with respect to it to any person in connection with or in response to an acquisition proposal or acquisition inquiry;

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engage in discussions or negotiations with any person with respect to any acquisition proposal or acquisition inquiry;

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approve, endorse or recommend an acquisition proposal;

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execute or enter into any letter of intent or similar document or any contract contemplating or otherwise relating to an acquisition transaction (as defined in the section titled “The Merger Agreement—No Solicitation” below); or

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publicly propose to do any of the above.

Termination of the Merger Agreement (see page 145)

Either Nivalis or Alpine can terminate the Merger Agreement under certain circumstances, which would prevent the merger from being consummated.

Termination Fee (see page 147)

If the Merger Agreement is terminated under certain circumstances, Nivalis or Alpine will be required to pay the other party a termination fee of $2.5 million or, in some circumstances, reimburse the other party for expenses incurred in connection with the merger, up to a maximum of $1.0 million.

Subscription Agreement (see page 149)

On April 18, 2017, in conjunction with the execution and delivery of the Merger Agreement, Alpine entered into the subscription agreement (the “Subscription Agreement”) with certain current stockholders of Alpine pursuant to which Alpine agreed to sell, and the purchasers listed therein agreed to purchase, shares of Alpine’s capital stock for an aggregate purchase price of approximately $17.0 million. The merger is conditioned upon the closing of the Pre-Closing Financing (as defined in the section titled “The Merger—Background of the Merger—Historical Background for Alpine” below), to occur immediately prior to the closing of the merger.

The consummation of the Pre-Closing Financing is subject to certain conditions, including the satisfaction or waiver of each of the conditions to the consummation of the merger set forth in the Merger Agreement (other than those conditions that are to be satisfied or waived at the closing of the merger or the Pre-Closing Financing, but subject to the satisfaction or waiver of such conditions) and the parties to the Merger Agreement being ready, willing and able to consummate the merger immediately after the closing of the Pre-Closing Financing, the SEC having declared effective the registration statement of which this proxy statement/prospectus/information statement is a part and no stop order suspending the effectiveness of the registration statement of which this proxy statement/prospectus/information statement is a part having been issued and remain pending, and the adoption of the Merger Agreement and the approval of the merger by Alpine’s stockholders.

Nivalis has certain termination and amendment consent rights under the Subscription Agreement and is also an express third-party beneficiary of the Subscription Agreement, with the right to specifically enforce its terms, including the obligations of the parties to consummate the Pre-Closing Financing if the conditions to consummation have been satisfied.

Support Agreements (see page 151)

Certain stockholders of Alpine are each party to a support agreement with Nivalis pursuant to which, among other things, each of these stockholders agreed, solely in his, her or its capacity as a stockholder of Alpine, to vote all of his, her or its shares of Alpine’s capital stock in favor of the adoption of the Merger Agreement and the approval of any other matter necessary to consummate the transactions contemplated by the Merger Agreement that are considered and voted upon by Alpine’s stockholders and against any acquisition proposal. The parties to the support agreements with Nivalis are as follows:

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Alpine Immunosciences, L.P.

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OrbiMed Private Investments VI, LP

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Frazier Life Sciences VIII, L.P.

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Mitchell H. Gold, M.D.

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Jay Venkatesan, M.D.

The stockholders of Alpine that are party to a support agreement with Nivalis owned an aggregate of 315,625 shares of Alpine’s common stock and 16,032,028 shares of Alpine’s preferred stock, representing approximately 94% of the outstanding shares of Alpine’s capital stock on an as converted to common stock basis, in each case as of April 18, 2017. These stockholders include only executive officers and directors of Alpine and any stockholder owning more than 5% of Alpine’s outstanding stock. Following the effectiveness of the registration statement of which this proxy statement/prospectus/information statement is a part, stockholders of Alpine holding a sufficient number of shares to adopt the Merger Agreement and thereby approve the merger will execute written consents (subject to the Alpine Support Agreement Cutback) providing for such adoption and approval.

Certain of Nivalis’ stockholders are each party to a support agreement with Alpine pursuant to which, among other things, each of these stockholders agreed, solely in his, her or its capacity as a stockholder, to vote all of his, her or its shares of Nivalis’ common stock in favor of approval of (i) the Merger Agreement and the transactions contemplated thereby, including the merger and the issuance of Nivalis’ common stock to Alpine’s stockholders, (ii) an amendment to the amended and restated certificate of incorporation of Nivalis to effect the Nivalis Reverse Stock Split, (iii) an amendment to the amended and restated certificate of incorporation of Nivalis to effect the Nivalis Name Change, (iv) any proposal to adjourn or postpone the meeting to a later date, if there are not sufficient votes for the approval of the other matters to be approved on date of the Nivalis special meeting, and (v) any other matter necessary to consummate the transactions contemplated by the Merger Agreement that are considered and voted upon by Nivalis’ stockholders at the Nivalis special meeting and against any acquisition proposal.

The stockholders of Nivalis that are party to a support agreement with Alpine owned an aggregate of 5,367,209 shares of Nivalis’ common stock, representing approximately 34% of the outstanding common stock of Nivalis as of April 18, 2017. These stockholders include executive officers and directors of Nivalis and certain stockholders owning more than 5% of Nivalis’ outstanding stock. The parties to the support agreements with Alpine are as follows:

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The Estate of Arnold S. Snider, III

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Deerfield Special Situations Fund, L.P.

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Deerfield Private Design Fund, L.P.

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Deerfield Private Design International, L.P.

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Deerfield Private Design Fund II., L.P.

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Deerfield Private Design International II, L.P.

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R. Michael Carruthers

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Robert Conway

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Howard Furst, M.D.

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Evan Loh, M.D.

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John Moore

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Paul Sekhri

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Cynthia Smith

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Janice Troha

The support agreements are discussed in greater detail in the section entitled “Agreements Related to the Merger—Support Agreements and Written Consent” in this proxy statement/prospectus/information statement.

Lock-up Agreements (see page 153)

As a condition to the closing of the merger, certain of Nivalis’ stockholders and Alpine’s stockholders have entered into lock-up agreements, pursuant to which such parties have agreed not to, except in limited circumstances, sell or transfer, or engage in swap or similar transactions with respect to, shares of Nivalis’ common stock, including, as applicable, shares received in the merger and issuable upon exercise of certain warrants and options, from the closing of the merger until 180 days from the closing date of the merger.

As of April 18, 2017, Nivalis’ stockholders who have committed to execute lock-up agreements beneficially owned in the aggregate approximately 24% of the outstanding shares of Nivalis’ common stock.

Alpine’s stockholders who have committed to execute lock-up agreements as of April 18, 2017 owned in the aggregate approximately 94% of the outstanding shares of Alpine’s capital stock on an as if converted into common stock basis.

Management Following the Merger (see page 237)

Effective as of the closing of the merger, Nivalis’ executive officers are expected to include:


Name		Title
Mitchell H. Gold, M.D. Jay Venkatesan, M.D.		Chief Executive Officer President
Stanford Peng, M.D. Ph.D.		Executive Vice President of Research and Development and Chief Medical Officer
Paul Rickey		Senior Vice President and Chief Financial Officer

Interests of Certain Directors, Officers and Affiliates of Nivalis and Alpine (see pages 120 and 124)

In considering the recommendation of Nivalis’ board of directors with respect to the issuance of Nivalis’ common stock pursuant to the Merger Agreement and the other matters to be acted upon by Nivalis’ stockholders at the Nivalis special meeting, Nivalis’ stockholders should be aware that certain members of Nivalis’ board of directors and executive officers of Nivalis have interests in the merger that may be different from, or in addition to, interests they have as Nivalis’ stockholders. For example, Nivalis has entered into certain employment and retention agreements with each of its remaining executive officers that may result in the receipt by such executive officers of cash severance payments and other benefits with a total value of approximately $940,835 (collectively, not individually, and excluding the value of any accelerated vesting of stock options) and the acceleration of options to purchase shares of Nivalis’ common stock, held by those officers, based on data available as of April 25, 2017 and assuming a covered termination of employment of each executive officer’s employment as of such date.

As of May 30, 2017, Nivalis’ directors and executive officers beneficially owned, in the aggregate approximately 3.5% of the outstanding shares of Nivalis’ common stock. Additionally, approximately 24%

of the outstanding shares of Nivalis’ common stock are beneficially owned by funds affiliated with Deerfield Management Company, L.P., an investment firm with which one of Nivalis’ directors is affiliated. Certain of Nivalis’ officers and directors, and their affiliates, have also entered into support agreements in connection with the merger. The support agreements are discussed in greater detail in the section entitled “Agreements Related to the Merger—Support Agreements and Written Consent” in this proxy statement/prospectus/information statement.

In considering the recommendation of Alpine’s board of directors with respect to approving the merger and related transactions by written consent, Alpine’s stockholders should be aware that certain members of Alpine’s board of directors and certain of Alpine’s executive officers have interests in the merger that may be different from, or in addition to, interests they have as Alpine’s stockholders. For example, certain of Alpine’s directors and executive officers have options, subject to vesting, to purchase shares of Alpine’s common stock which, at the closing of the merger, shall be converted into and become options to purchase shares of Nivalis’ common stock, certain of Alpine’s directors and executive officers are expected to become directors and executive officers of Nivalis upon the closing of the merger, and all of Alpine’s directors and executive officers are entitled to certain indemnification and liability insurance coverage pursuant to the terms of the Merger Agreement.

As of May 30, 2017, all of Alpine’s directors and executive officers, together with their affiliates, owned approximately 94% of the outstanding shares of Alpine capital stock, on an as converted to common stock basis. Certain of Alpine’s officers and directors, and their affiliates, have also entered into support agreements in connection with the merger. The support agreements are discussed in greater detail in the section entitled “Agreements Related to the Merger—Support Agreements and Written Consent” in this proxy statement/prospectus/information statement.

Risk Factors (see page 25)

Both Nivalis and Alpine are subject to various risks associated with their businesses and their industries. In addition, the merger poses a number of risks to each company and its respective stockholders, including the possibility that the merger may not be completed and the following risks:

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The exchange ratio is not adjustable based on the market price of Nivalis’ common stock, so the merger consideration at the closing may have a greater or lesser value than at the time the Merger Agreement was signed;

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The exchange ratio is not adjustable based on the net cash of either Nivalis or Alpine at the Effective Time, so the relative ownership of the combined organization as between current stockholders of Alpine and current stockholders of Nivalis may not reflect the ratio of net cash of Nivalis and Alpine, respectively, at the closing of the merger;

•

Failure to complete the merger may result in Nivalis and Alpine paying a termination fee or expenses to the other and could harm the price of Nivalis’ common stock and the future business and operations of each company;

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The merger may be completed even though material adverse changes may result solely from the announcement of the merger, changes in the industry in which Nivalis and Alpine operate that apply to all companies generally and other causes;

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Some of Nivalis’ and Alpine’s respective officers and directors have interests that are different from or in addition to those considered by other stockholders of Alpine and Nivalis and which may influence them to support or approve the merger;

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The market price of the combined organization’s common stock may decline as a result of the merger;

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Nivalis’ and Alpine’s stockholders may not realize a benefit from the merger commensurate with the ownership dilution they will experience in connection with the merger;

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During the pendency of the merger, Nivalis and Alpine may not be able to enter into a business combination with another party under certain circumstances because of restrictions in the Merger Agreement, which could adversely affect their respective businesses;

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Certain provisions of the Merger Agreement may discourage third parties from submitting alternative takeover proposals, including proposals that may be superior to the arrangements contemplated by the Merger Agreement;

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Because the lack of a public market for shares of Alpine’s capital stock makes it difficult to evaluate the fairness of the merger, Alpine’s stockholders may receive consideration in the merger that is less than the fair market value of the shares of Alpine’s capital stock and/or Nivalis may pay more than the fair market value of the shares of Alpine’s capital stock; and

•

If the conditions to the merger are not met, the merger will not occur.

These risks and other risks are discussed in greater detail under the section entitled “Risk Factors” in this proxy statement/prospectus/information statement. Nivalis and Alpine both encourage you to read and consider all of these risks carefully.

Regulatory Approvals (see page 129)

In the United States, Nivalis must comply with applicable federal and state securities laws and the rules and regulations of The NASDAQ Global Market (“NASDAQ”) in connection with the issuance of shares of Nivalis’ common stock and the filing of this proxy statement/prospectus/information statement with the SEC. As of the date hereof, the registration statement of which this proxy statement/prospectus/information statement is a part has not become effective.

NASDAQ Stock Market Listing (see page 129)

Prior to consummation of the merger, Nivalis intends to file an initial listing application with NASDAQ pursuant to NASDAQ Stock Market LLC “reverse merger” rules. If such application is accepted, Nivalis anticipates that Nivalis’ common stock will be listed on The NASDAQ Global Market following the closing of the merger under the trading symbol “ALPN”.

Anticipated Accounting Treatment (see page 130)

The merger will be treated by Nivalis as a reverse merger under the acquisition method of accounting in accordance with accounting principles generally accepted in the United States. For accounting purposes, Alpine is considered to be acquiring Nivalis in the merger.

Appraisal Rights (see page 130)

Holders of Nivalis’ common stock are not entitled to appraisal rights in connection with the merger. Alpine’s stockholders are entitled to appraisal rights in connection with the merger under Delaware law. For more information about such rights, see the provisions of Section 262 of the General Corporation Law of the State of Delaware (“DGCL”) attached hereto as Annex C, and the section entitled “The Merger—Appraisal Rights” in this proxy statement/prospectus/information statement.

Comparison of Stockholder Rights (see page 273)

Both Nivalis and Alpine are incorporated under the laws of the State of Delaware and, accordingly, the rights of the stockholders of each are currently, and will continue to be, governed by the DGCL. If the merger is completed, Alpine’s stockholders will become stockholders of Nivalis, and their rights will be governed by the DGCL, Nivalis’ amended and restated bylaws and, Nivalis’ amended and restated certificate of incorporation, as amended by the amendments set forth in Annex D and Annex E, assuming Proposal Nos. 2 and 3 are approved. The rights of Nivalis’ stockholders contained in Nivalis’ amended and restated certificate of incorporation and Nivalis’ amended and restated bylaws differ from the rights of Alpine’s stockholders under Alpine’s amended and restated certificate of incorporation and Alpine’s bylaws, as more fully described under the section entitled “Comparison of Rights of Holders of Nivalis Stock and Alpine Stock” in this proxy statement/prospectus/information statement.

The following tables present summary historical financial data for Nivalis and Alpine, summary unaudited pro forma condensed financial data for Nivalis and Alpine, and comparative historical and unaudited pro forma per share data for Nivalis and Alpine.

The selected financial data as of December 31, 2016 and 2015 and for the years ended December 31, 2016, 2015 and 2014 are derived from the Nivalis audited financial statements prepared using accounting principles generally accepted in the United States, which are included in this proxy statement/prospectus/information statement. The selected financial data as of December 31, 2014, 2013, and 2012 and for the years ended December 31, 2013 and 2012 are derived from the Nivalis audited financial statements, which are not included in this proxy statement/prospectus/information statement. The statement of operations data for the three months ended March 31, 2017 and 2016, as well as the balance sheet data as of March 31, 2017, are derived from the Nivalis unaudited condensed financial statements included in this proxy statement/prospectus/information statement. The financial data should be read in conjunction with “Nivalis Management’s Discussion and Analysis of Financial Condition and Results of Operations” and Nivalis’ financial statements and related notes appearing elsewhere in this proxy statement/prospectus/information statement. These historical results are not necessarily indicative of results to be expected in any future period.

The selected financial data as of December 31, 2016 and 2015 and for the years ended December 31, 2016 and 2015 are derived from Alpine’s audited financial statements prepared using accounting principles generally accepted in the United States, which are included in this proxy statement/prospectus/information statement. The statement of operations data for the three months ended March 31, 2017 and 2016, as well as the balance sheet data as of March 31, 2017, are derived from the Alpine unaudited condensed financial statements included in this proxy statement/prospectus/information statement. In the opinion of management, the unaudited financial statements reflect all adjustments, which include normal recurring adjustments, necessary to state fairly Alpine’s results of operations and financial position. These historical results are not necessarily indicative of results to be expected in any future period. The selected financial data should be read in conjunction with Alpine’s financial statements and the related notes to those statements included in this proxy statement/prospectus/information statement and “Alpine Management’s Discussion and Analysis of Financial Condition and Results of Operations”.

Selected Unaudited Pro Forma Condensed Combined Financial Data of Nivalis and Alpine

The following information does not give effect to the proposed one-for-four Reverse Stock Split of Nivalis common stock described in Nivalis’ Proposal No. 2.

The following selected unaudited pro forma condensed combined financial data was prepared using the acquisition method of accounting under U.S. GAAP. For accounting purposes, Alpine is considered to be acquiring Nivalis in the merger. The Nivalis and Alpine unaudited pro forma combined balance sheet data assume that the merger took place on March 31, 2017, and combines the Nivalis and Alpine historical balance sheets at March 31, 2017. The Nivalis and Alpine unaudited pro forma condensed combined statements of operations data assume that the merger took place as of January 1, 2016, and combines the historical results of Nivalis and Alpine for the three months ended March 31, 2017 and the year ended December 31, 2016.

The selected unaudited pro forma condensed combined financial data are presented for illustrative purposes only and are not necessarily indicative of the combined financial position or results of operations of future periods or the results that actually would have been realized had the entities been a single entity during these periods. The selected unaudited pro forma condensed combined financial data as of and for the three months ended March 31, 2017, and for the year ended December 31, 2016 are derived from the unaudited pro forma condensed combined financial information and should be read in conjunction with that information. For more information, please see the section entitled “Unaudited Pro Forma Condensed Combined Financial Information” in this proxy statement/prospectus/information statement.

The unaudited pro forma condensed combined financial information assumes that, at the Effective Time, each share of Alpine’s capital stock will be converted into the right to receive shares of Nivalis common stock such that, immediately following the Effective Time, Nivalis’ current stockholders, optionholders, and warrantholders are expected to own, or hold rights to acquire, approximately 26% of the Fully-Diluted Common Stock of Nivalis, and Alpine’s current stockholders, optionholders and warrantholders are expected to own, or hold rights to acquire, approximately 74% of the Fully-Diluted Common Stock of Nivalis, and is subject to adjustment to account for the occurrence of certain events discussed elsewhere in this proxy statement/prospectus/information statement, including the additional investments in Alpine of $16.7 million in April 2017 and approximately $17.0 million immediately prior to the consummation of the merger, as contemplated by the Subscription Agreement.

The information below reflects the historical net loss and book value per share of Nivalis common stock and the historical net loss and book value per share of Alpine common stock in comparison with the unaudited pro forma net loss and book value per share after giving effect to the proposed merger of Nivalis with Alpine on a pro forma basis. The unaudited pro forma net loss and book value per share does not give effect to the proposed one-for-four reverse stock split of Nivalis common stock.

You should read the tables below in conjunction with the audited financial statements of Nivalis included in this proxy statement/prospectus/information statement and the audited financial statements of Alpine included in this proxy statement/prospectus/information statement and the related notes and the unaudited pro forma condensed combined financial information and notes related to such financial statements included elsewhere in this proxy statement/prospectus/information statement.

The combined organization will be faced with a market environment that cannot be predicted and that involves significant risks, many of which will be beyond its control. In addition to the other information contained in this proxy statement/prospectus/information statement, you should carefully consider the material risks described below before deciding how to vote your shares of stock. In addition, you should read and consider the risks associated with Nivalis’ business because these risks may also affect the combined organization — these risks can be found under the heading “Risk Factors — Risks Related to Nivalis” in this proxy statement/prospectus/information statement and in Nivalis’ Annual Report on Form 10-K, as updated by subsequent Quarterly Reports on Form 10-Q, and other documents Nivalis has filed with the SEC and incorporated by reference into this proxy statement/prospectus/information statement. You should also read and consider the other information in this proxy statement/prospectus/information statement and the other documents incorporated by reference into this proxy statement/prospectus/information statement. Please see the section entitled “Where You Can Find More Information” in this proxy statement/prospectus/information statement.

The exchange ratio is not adjustable based on the market price of Nivalis common stock, so the merger consideration at the closing may have a greater or lesser value than at the time the Merger Agreement was signed.

The Merger Agreement has set the exchange ratio for the Alpine capital stock, and the exchange ratio is based on the outstanding capital stock of Alpine and the outstanding common stock of Nivalis, in each case immediately prior to the closing of the merger as described under the heading “The Merger—Merger Consideration.” Any changes in the market price of Nivalis common stock before the completion of the merger will not affect the number of shares of Nivalis’ common stock issuable to Alpine’s stockholders pursuant to the Merger Agreement. Therefore, if before the completion of the merger the market price of Nivalis’ common stock declines from the market price on the date of the Merger Agreement, then Alpine’s stockholders could receive merger consideration with substantially lower value than the value of such merger consideration on the date of the Merger Agreement. Similarly, if before the completion of the merger the market price of Nivalis’ common stock increases from the market price of Nivalis’ common stock on the date of the Merger Agreement, then Alpine’s stockholders could receive merger consideration with substantially greater value than the value of such merger consideration on the date of the Merger Agreement. The Merger Agreement does not include a price-based termination right. Because the exchange ratio does not adjust as a result of changes in the market price of Nivalis’ common stock, for each one percentage point change in the market price of Nivalis’ common stock, there is a corresponding one percentage point rise or decline, respectively, in the value of the total merger consideration payable to Alpine’s stockholders pursuant to the Merger Agreement.

Failure to complete the merger may result in Nivalis and Alpine paying a termination fee or expenses to the other party and could significantly harm the market price of Nivalis’ common stock and negatively affect the future business and operations of each company.

If the merger is not completed and the Merger Agreement is terminated under certain circumstances, Nivalis or Alpine may be required to pay the other party a termination fee of $2.5 million or reimburse the transaction expenses of the other party, up to a maximum of $1.0 million. Even if a termination fee is not payable or transaction expenses are not reimbursable in connection with a termination of the Merger Agreement, each of Nivalis and Alpine will have incurred significant fees and expenses, such as legal and accounting fees which Nivalis and Alpine estimate will total approximately $1.3 million and $1.4 million, respectively, which must be paid whether or not the merger is completed. Further, if the merger is not completed, it could significantly harm the market price of Nivalis’ common stock.

In addition, if the Merger Agreement is terminated and the board of directors of Nivalis or Alpine determines to seek another business combination, there can be no assurance that either Nivalis or Alpine will be able to find a partner and close an alternative transaction on terms that are as favorable or more favorable than the terms set forth in the Merger Agreement.

The merger may be completed even though certain events occur prior to the closing that materially and adversely affect Nivalis or Alpine.

The Merger Agreement provides that either Nivalis or Alpine can refuse to complete the merger if there is a material adverse change affecting the other party between April 18, 2017, the date of the Merger Agreement, and the closing of the merger. However, certain types of changes do not permit either party to refuse to complete the merger, even if such change could be said to have a material adverse effect on Nivalis or Alpine, including:

If adverse changes occur and Nivalis and Alpine still complete the merger, the market price of the combined organization’s common stock may suffer. This in turn may reduce the value of the merger to the stockholders of Nivalis, Alpine or both.

Some Nivalis and Alpine officers and directors have interests in the merger that are different from yours and that may influence them to support or approve the merger without regard to your interests.

Certain officers and directors of Nivalis and Alpine participate in arrangements that provide them with interests in the merger that are different from yours, including, among others, the continued service as an officer or director of the combined organization, severance benefits, the acceleration of stock option vesting, continued indemnification and the potential ability to sell an increased number of shares of common stock of the combined organization in accordance with Rule 144 under the Securities Act of 1933, as amended (“Securities Act”).

For example, Nivalis has entered into certain employment and severance benefits agreements with certain of its executive officers that may result in the receipt by such executive officers of cash severance payments and other benefits in the event of a covered termination of employment of each executive officer’s employment. The

closing of the merger will also result in the acceleration of vesting of options to purchase shares of Nivalis’ common stock held by Nivalis’ executive officers and directors, whether or not there is a covered termination of such officer’s employment. For more information concerning the treatment of Nivalis’ stock options in connection with the merger, see the section entitled “The Merger Agreement—Treatment of Nivalis Stock Options” in this proxy statement/prospectus/information statement. In addition, and for example, certain of Alpine’s directors and executive officers have options, subject to vesting, to purchase shares of Alpine’s common stock which, at the closing of the merger, shall be converted into and become options to purchase shares of Nivalis’ common stock, certain of Alpine’s directors and executive officers are expected to become directors and executive officers of Nivalis upon the closing of the merger, and all of Alpine’s directors and executive officers are entitled to certain indemnification and liability insurance coverage pursuant to the terms of the Merger Agreement. These interests, among others, may influence the officers and directors of Nivalis and Alpine to support or approve the merger. For more information concerning the interests of Nivalis’ and Alpine’s executive officers and directors, see the sections entitled “The Merger—Interests of Nivalis Directors and Executive Officers in the Merger” and “The Merger—Interests of Alpine Directors and Executive Officers in the Merger” in this proxy statement/prospectus/information statement.

The market price of Nivalis’ common stock following the merger may decline as a result of the merger.

The market price of Nivalis’ common stock may decline as a result of the merger for a number of reasons including if:

Nivalis and Alpine stockholders may not realize a benefit from the merger commensurate with the ownership dilution they will experience in connection with the merger.

If the combined organization is unable to realize the strategic and financial benefits currently anticipated from the merger, Nivalis’ and Alpine’s stockholders will have experienced substantial dilution of their ownership interests in their respective companies without receiving the expected commensurate benefit, or only receiving part of the commensurate benefit to the extent the combined organization is able to realize only part of the expected strategic and financial benefits currently anticipated from the merger.

During the pendency of the merger, Nivalis and Alpine may not be able to enter into a business combination with another party at a favorable price because of restrictions in the Merger Agreement, which could adversely affect their respective businesses.

Covenants in the Merger Agreement impede the ability of Nivalis and Alpine to make acquisitions, subject to certain exceptions relating to fiduciary duties, as set forth below, or to complete other transactions that are not in the ordinary course of business pending completion of the merger. As a result, if the merger is not completed, the parties may be at a disadvantage to their competitors during such period. In addition, while the Merger Agreement is in effect, each party is generally prohibited from soliciting, initiating, encouraging or entering into certain extraordinary transactions, such as a merger, sale of assets, or other business combination outside the ordinary course of business with any third party, subject to certain exceptions relating to fiduciary duties, as set forth below. Any such transactions could be favorable to such party’s stockholders.

The terms of the Merger Agreement prohibit each of Nivalis and Alpine from soliciting alternative takeover proposals or cooperating with persons making unsolicited takeover proposals, except in limited circumstances when such party’s board of directors determines in good faith that an unsolicited alternative takeover proposal is or is reasonably likely to lead to a superior takeover proposal and that failure to cooperate with the proponent of the proposal would be reasonably likely to be inconsistent with the board’s fiduciary duties. Moreover, even if a party receives what the party’s board of directors determines is a superior proposal, the Merger Agreement does not permit either party to terminate the Merger Agreement to enter into a superior proposal.

Because the lack of a public market for Alpine’s capital stock makes it difficult to evaluate the value of Alpine’s capital stock, the stockholders of Alpine may receive shares of Nivalis’ common stock in the merger that have a value that is less than, or greater than, the fair market value of Alpine’s capital stock.

The outstanding capital stock of Alpine is privately held and is not traded in any public market. The lack of a public market makes it extremely difficult to determine the fair market value of Alpine. Because the percentage of Nivalis’ common stock to be issued to Alpine’s stockholders was determined based on negotiations between the parties, it is possible that the value of Nivalis’ common stock to be received by Alpine’s stockholders will be less than the fair market value of Alpine, or Nivalis may pay more than the aggregate fair market value for Alpine.

Even if the merger is approved by the stockholders of Nivalis and Alpine, specified conditions must be satisfied or waived to complete the merger. These conditions are set forth in the Merger Agreement and described in the section entitled “The Merger Agreement—Conditions to the Completion of the Merger” in this proxy statement/prospectus/information statement. Nivalis and Alpine cannot assure you that all of the conditions will be satisfied or waived. If the conditions are not satisfied or waived, the merger will not occur or will be delayed, and Nivalis and Alpine each may lose some or all of the intended benefits of the merger.

Nivalis is a clinical-stage company with no drug products approved for commercial sale, Nivalis has incurred net losses since Nivalis’ inception, Nivalis anticipates that it will continue to incur significant losses for the foreseeable future, and Nivalis has had a limited operating history that may make it difficult for investors to evaluate the potential success of its business.

Nivalis is a clinical-stage pharmaceutical company and has not generated sustainable revenue from operations or been profitable since its inception in 2007, and it may never achieve profitability. Nivalis has devoted its resources to discovering and developing proprietary product candidates, but such product candidates cannot be marketed until clinical development and governmental approvals have been obtained. None of its product candidates have been approved for sale by any regulatory agency or are available for commercial sale and each will require significant additional capital to advance their development toward regulatory approval for commercial sale.

Nivalis has incurred significant net losses in each year since its inception, including net losses of $8.9 million for the three months ended March 31, 2017 and $31.5 million, $22.8 million, and $15.0 million for the years ended December 31, 2016, 2015, and 2014, respectively. As of March 31, 2017, Nivalis had an accumulated deficit of $189.2 million. Nivalis expects to continue to incur operating expenses and anticipates that it will continue to have losses in the foreseeable future.

Nivalis’ future funding requirements, both near- and long-term, will depend on many factors, including, but not limited to:

Nivalis’ losses and expected future losses have had and will continue to have an adverse effect on its stockholders’ equity and working capital. Further, because of uncertainties relating to the outcome of the merger and the risks and uncertainties inherent in the biotechnology industry, Nivalis is unable to predict the extent of any future losses or whether it will become profitable.

There is no assurance that the proposed merger between Nivalis and Alpine will be completed in a timely manner or at all. If the merger with Alpine is not consummated, Nivalis’ business could suffer materially and its stock price could decline.

The consummation of the proposed merger between Nivalis and Alpine is subject to a number of closing conditions, including approval by Nivalis’ and Alpine’s stockholders and other customary closing conditions. The parties are targeting a closing of the transaction in the third quarter of 2017, however, there can be no assurance that the proposed merger will be consummated within their desired timeframe, or at all.

If the proposed merger between Nivalis and Alpine is not consummated, Nivalis may be subject to a number of material risks, and its business and stock price could be adversely affected, as follows:

If the merger is not completed, Nivalis may be unsuccessful in completing an alternative transaction on terms that are as favorable as the terms of the proposed transaction with Alpine, or at all, and Nivalis may be unable to reestablish a viable operating business.

To date, Nivalis has not generated any revenue from product sales, and its assets currently consist primarily of cash, cash equivalents and marketable securities, its patent portfolio, Nivalis’ listing on NASDAQ and the

Merger Agreement with Alpine. While Nivalis has entered into the Merger Agreement with Alpine, the consummation of the merger with Alpine may be delayed or may not occur at all. If the merger is not completed, Nivalis’ board of directors may elect to pursue an alternative strategic transaction similar to the proposed merger with Alpine. Attempting to complete an alternative transaction will be costly and time consuming. If the merger with Alpine is not completed and Nivalis’ board of directors determines to pursue an alternative transaction, the terms of any such alternative transaction may not be as favorable to Nivalis and its stockholders as the terms of the proposed merger with Alpine, and Nivalis can make no assurances that such an alternative transaction would occur at all. Further, if the merger with Alpine is not completed, given the failure of the two Phase 2 trials of cavosonstat to achieve their primary endpoints, the discontinuation of Nivalis’ research and development efforts commencing in January 2017 and the cost to engage in further development activities, it is unlikely that Nivalis would be able to obtain the funding required to recommence its drug development activities.

If the merger is not completed, Nivalis’ board of directors may decide to pursue a dissolution and liquidation of Nivalis. In such an event, the amount of cash available for distribution to its stockholders will depend heavily on the timing of such liquidation as well as the amount of cash that will need to be reserved for commitments and contingent liabilities.

There can be no assurance that the merger will be completed. If the merger is not completed, Nivalis’ board of directors may decide to pursue a dissolution and liquidation of Nivalis. In such an event, the amount of cash available for distribution to its stockholders will depend heavily on the timing of such decision, as with the passage of time the amount of cash available for distribution will be reduced as Nivalis continues to fund its operations. In addition, if Nivalis’ board of directors were to approve and recommend, and its stockholders were to approve, a dissolution and liquidation of Nivalis, Nivalis would be required under Delaware corporate law to pay its outstanding obligations, as well as to make reasonable provision for contingent and unknown obligations, prior to making any distributions in liquidation to its stockholders. As a result of this requirement, a portion of Nivalis’ assets may need to be reserved pending the resolution of such obligations. In addition, Nivalis may be subject to litigation or other claims related to a dissolution and liquidation of Nivalis. If a dissolution and liquidation were pursued, Nivalis’ board of directors, in consultation with its advisors, would need to evaluate these matters and make a determination about a reasonable amount to reserve. Accordingly, holders of Nivalis’ common stock could lose all or a significant portion of their investment in the event of Nivalis’ liquidation, dissolution or winding up.

There is substantial doubt as to Nivalis’ ability to continue as a going concern if the merger is not completed.

Nivalis has had recurring losses from operations since inception and will likely not generate revenue for the foreseeable future. Nivalis believes that its existing cash, cash equivalents and marketable securities and interest thereon will be sufficient to fund its projected operating requirements under its current operating plan. However, if the merger is not completed and Nivalis’ operating plans change and its projected operating requirements increase, Nivalis may be unable to continue as a going concern. In this event, the perception that Nivalis may not be able to continue as a going concern may have an adverse impact on its business due to concerns about its ability to meet its future contractual obligations. Further, if Nivalis is unable to continue as a going concern, Nivalis may have to liquidate its assets, and the values it receives for its assets in liquidation and dissolution could be significantly lower than the values reflected in its financial statements and an investor could lose all or part of its investment in Nivalis.

Although Nivalis has ceased all further development of cavosonstat and its other potential product candidates, if it were to resume research and development activities, it would require substantial additional funding. Raising additional capital may cause dilution to its existing stockholders, restrict its operations or require it to relinquish rights to its technologies or to a product candidate.

Nivalis currently does not have any committed external source of funds and does not expect to generate any revenue in the foreseeable future. Nivalis believes that its existing cash, cash equivalents and marketable

securities and interest thereon will be sufficient to fund its projected operating requirements under its current operating plan. Nivalis has based its estimates on assumptions that may prove to be wrong, and it may use its available capital resources sooner than it currently expects if its operating plans change. If the merger is not completed and Nivalis’ current operating plans change and it determines to pursue further research and development activities, it will require substantial additional funding to operate, and would expect to finance these cash needs through a combination of equity offerings, debt financings, government or other third-party funding and licensing or collaboration arrangements.

To the extent that Nivalis raises additional capital through the sale of equity or convertible debt, the ownership interests of its stockholders will be diluted. In addition, the terms of any equity or convertible debt it agrees to issue may include liquidation or other preferences that adversely affect the rights of Nivalis’ stockholders. Convertible debt financing, if available, may involve agreements that include covenants limiting or restricting Nivalis’ ability to take specific actions, such as incurring additional debt, making capital expenditures, and declaring dividends, and may impose limitations on its ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact its ability to conduct its business.

Additional funds may not be available when Nivalis needs them on terms that are acceptable to Nivalis, or at all. If adequate funds are not available to Nivalis on a timely basis, it may be required to curtail or cease its operations or it may have to relinquish rights to its technologies, future revenue streams, research programs or product candidates, or grant licenses on terms that may not be favorable to Nivalis.

If the merger is not completed, raising additional funding through debt or equity financing is likely to be difficult, could be dilutive and may cause the market price of Nivalis’ common stock to decline further.

To the extent that Nivalis raises additional capital through the sale of equity or convertible debt securities, the issuance of those securities could result in substantial dilution for Nivalis’ current stockholders and the terms may include liquidation or other preferences that adversely affect the rights of its current stockholders. Furthermore, the issuance of additional securities, whether equity or debt, by Nivalis, or the possibility of such issuance, may cause the market price of its common stock to decline further and existing stockholders may not agree with its financing plans or the terms of such financings.

The issuance of shares of Nivalis’ common stock to Alpine’s stockholders in the pending merger will dilute substantially the voting power of Nivalis’ current stockholders.

If the pending merger is completed, each outstanding share of Alpine capital stock will be converted into the right to receive approximately 1.9878 shares of Nivalis’ common stock, subject to adjustment to account for the Nivalis Reverse Stock Split. Immediately following the merger, Nivalis’ stockholders, optionholders and warrantholders are expected to own, or hold rights to acquire, approximately 26% of the Fully-Diluted Common Stock of Nivalis, and Alpine’s stockholders, optionholders and warrantholders are expected to own, or hold rights to acquire, approximately 74% of the Fully-Diluted Common Stock of Nivalis. Accordingly, the issuance of shares of Nivalis’ common stock to Alpine’s stockholders in the merger will reduce significantly the relative voting power of each share of Nivalis’ common stock held by its current stockholders. Consequently, Nivalis’ stockholders as a group will have significantly less influence over the management and polices of the combined organization after the merger than prior to the merger.

Nivalis has incurred and will continue to incur significant transaction costs in connection with the merger.

Nivalis has incurred and will continue to incur significant transaction costs in connection with the merger. Nivalis estimates that it will incur aggregate direct transaction costs of approximately $2.9 million associated with the merger and approximately $100,000 for its portion of shared transaction expenses, as well as additional costs associated with the commencement of the combined organization’s operation as a public company, which cannot be estimated accurately at this time.

If Nivalis fails to continue to meet all applicable NASDAQ requirements and NASDAQ determines to delist Nivalis’ common stock, the delisting could adversely affect the value of the merger, market liquidity of Nivalis’ common stock and the market price of its common stock could decrease.

Nivalis’ common stock is listed on NASDAQ. In order to maintain the listing, Nivalis must meet minimum financial and other requirements, including requirements for a minimum amount of capital, a minimum price per share and continued business operations so that it is not characterized as a “public shell company.” If Nivalis is unable to comply with NASDAQ’s listing standards, NASDAQ may determine to delist its common stock from NASDAQ. If its common stock is delisted for any reason, it could reduce the value of its common stock and its liquidity. Delisting would prevent Nivalis from satisfying a closing condition for the merger, and, in such event, Alpine may elect not to consummate the merger. If the merger is not completed and Nivalis chooses to reestablish a viable operating business, delisting could adversely affect Nivalis’ ability to obtain financing for the continuation of Nivalis’ operations or use its common stock in another strategic transaction. In addition, the combined organization must submit a new application for listing on NASDAQ pursuant to the reverse merger rules, and the combined organization will need to meet NASDAQ’s minimum listing requirements conditions.

Nivalis’ inability to utilize its net operating loss carryforwards before they expire may adversely affect its results of operations and financial condition.

In general, a corporation that undergoes an “ownership change” is subject to limitations on its ability to utilize its pre-change net operating loss carryforwards (“NOLs”), to offset future taxable income. In general, an ownership change occurs if the aggregate stock ownership of certain stockholders, generally stockholders beneficially owning five percent or more of Nivalis’ common stock, applying certain look-through and aggregation rules, increases by more than 50 percentage points over such stockholders’ lowest percentage ownership during the testing period, generally three years. Nivalis may have experienced ownership changes in the past and may experience ownership changes in the future. In addition, the closing of the merger may result in an ownership change. Limitations imposed on Nivalis’ ability to utilize NOLs as a result of ownership changes could cause it to pay U.S. federal and state income taxes earlier than it would otherwise be required if such limitations were not in effect and could cause such NOLs to expire unused.

Cavosonstat did not achieve its primary endpoint in two Phase 2 trials with CF patients, and Nivalis’ previous findings from preclinical studies in other potential disease areas may not be predictive of a benefit for cavosonstat or any other of Nivalis’ GSNOR inhibitors.

Nivalis has ceased all research and development activities for cavosonstat and all of its GSNOR inhibitors and it currently has no plans to pursue such development itself as it pursues closing of the merger. If, however, Nivalis’ operating plans change, and, whether or not it is successful in completing the merger, it resumes further development of cavosonstat or Nivalis’ other GSNOR inhibitors, these development activities may not result in drugs that are approved by regulatory authorities. Regulatory agencies, including the FDA, ultimately must approve any product candidate before it can be promoted, marketed or commercially distributed. Cavosonstat and any other potential product candidate Nivalis may develop will be subject to extensive and rigorous review and regulation by governmental authorities. Nivalis has never obtained approval for or commercialized a product candidate, and its portfolio of GSNOR inhibitors outside of CF is at an early stage of development and unproven. The timing of the drug development process is lengthy and can be unpredictable and may include post-marketing studies and surveillance. Any such development of Nivalis’ GSNOR inhibitors would require the expenditure of additional resources beyond Nivalis’ existing cash, cash equivalents or marketable securities. Of the large number of drugs in development for approval in the U.S., only a small percentage successfully complete the regulatory approval process and are commercialized. The success of any of Nivalis’ potential product candidates depends on, among other things:

If Nivalis were to resume development of one or more of its drug product candidates and is not successful with respect to one or more of these factors either in a timely manner or at all, significant delays in obtaining regulatory approval, including, but not limited to, denial of a new drug application (“NDA”), could result. Nivalis has never applied for, and has never received, regulatory approval for a drug. If Nivalis were to resume development of one or more of its drug product candidates and is unable to successfully complete the clinical development of a product candidate and meet other related regulatory requirements, it will be unable to obtain approval of an NDA from the FDA. It is possible that, even if Nivalis successfully completes clinical development, the FDA may refuse to accept Nivalis’ NDA for substantive review or may conclude after review of Nivalis’ data that Nivalis’ application is insufficient. If the FDA does not accept or approve Nivalis’ NDA, it may require that Nivalis conducts additional clinical, nonclinical or manufacturing studies or analyses and submit that data to it before it will reconsider Nivalis’ application. Depending on the extent of these or any other FDA requirements, approval of any NDA or application that Nivalis submits may be delayed by several years, or may require Nivalis to expend more resources than Nivalis has available. It is also possible that additional studies, if performed and completed, may not be considered sufficient by the FDA to approve Nivalis’ NDA.

In addition, the regulatory agencies may not complete their review processes in a timely manner, or additional delays may result if a potential drug candidate is brought before an FDA advisory committee, which could recommend restrictions on approval or recommend non-approval of the product candidate. In addition, delays or rejections could result based upon additional government regulation from future legislation or administrative action, or changes in regulatory agency policy during the period of product development, clinical studies and the review process. As a result, Nivalis cannot predict when, if at all, it will receive regulatory approval of any product candidate if Nivalis were to resume development of one or more of its drug product candidates.

Any delay in obtaining, or an inability to obtain, regulatory approvals would prevent Nivalis from commercializing a product candidate, generating revenue and achieving and sustaining profitability. If any of these outcomes occur, it could have a material adverse effect on Nivalis’ business and could potentially cause it to cease operations. These factors could materially harm Nivalis’ business, and the value of its common stock would likely decline.

The regulatory approval processes of the FDA, the European Medicines Agency (“EMA”), and comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable.

Nivalis is not permitted to market any of its potential product candidates in the U.S. or outside the U.S. until it receives approval of an NDA from the FDA or approval of a marketing application from the comparable regulatory authority in other countries. Should Nivalis determine to resume development of any of its GSNOR inhibitors, prior to submitting an NDA to the FDA for approval, Nivalis will need to complete its preclinical studies in the applicable indication, as well as all necessary clinical trials. Successfully initiating and completing clinical programs and obtaining approval of an NDA is a complex, lengthy, expensive and uncertain process, and FDA and other comparable foreign regulatory authorities may delay, limit or deny approval of a potential product candidate for many reasons, including, among others:

Any of these factors, many of which are beyond Nivalis’ control, could jeopardize Nivalis’ ability to obtain regulatory approval for and successfully market any of its potential product candidates, which would have a material adverse effect on Nivalis’ business and prospects.

If Nivalis were to resume research and development activities on its potential product candidates, Nivalis would depend on the successful completion of clinical trials for any potential product candidate. The positive clinical results, if any, obtained by Nivalis in future clinical trials may not be repeated in later-stage clinical trials.

Before obtaining regulatory approval for the sale of a potential product candidate, extensive clinical trials are required to demonstrate safety and efficacy in humans. Nivalis has not completed the clinical trials necessary to support an application for approval to market cavosonstat or any other potential product candidate. Successful completion of such clinical trials is a prerequisite to submitting an NDA to the FDA and, consequently, the ultimate approval and commercial marketing of any of Nivalis’ potential product candidates. A failure of one or more clinical trials can occur at any stage of testing. Further, the outcome of preclinical testing and early clinical trials may not be predictive of the success of later preclinical testing or clinical trials, and interim results of a clinical trial do not necessarily predict final results. For example, despite positive preclinical and early stage clinical results, cavosonstat did not achieve the primary endpoint in two recently completed Phase 2 clinical trials in CF that were announced in November 2016 and February 2017, respectively. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed

their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval for their products.

Should Nivalis choose to resume development of any of its potential candidates, Nivalis may experience a number of unforeseen events during, or as a result of, any future clinical trials that may be conducted on any of its potential product candidates that could adversely affect the completion of those clinical trials, including:

Negative or inconclusive results of any future clinical trials of Nivalis’ potential product candidates could mandate repeated or additional clinical studies. Despite the safety results reported in earlier clinical trials for cavosonstat, Nivalis does not know whether any other clinical trials it may conduct will demonstrate adequate efficacy and safety to result in regulatory approval to market cavosonstat in any other indications or any other potential product candidate. If later stage clinical trials do not produce favorable results, Nivalis’ ability to obtain regulatory approval for a potential product candidate may be adversely impacted.

Should Nivalis resume research and development activities, delays in clinical trials are common and have many causes, and any delay could have a material adverse effect on Nivalis’ business, such as increased costs and delays in Nivalis’ ability to obtain regulatory approval and commence product sales. In this event, Nivalis may be required to suspend, repeat or terminate its clinical trials if they are not conducted in accordance with regulatory requirements, the results are negative or inconclusive or the trials are not well designed.

Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. Clinical trials must be conducted in accordance with FDA regulations or other applicable foreign government regulations, and are subject to oversight by the FDA or other foreign regulatory authorities and institutional review boards at the medical institutions where the clinical trials are conducted. In addition, clinical trials must be conducted with product candidates produced under cGMP and may require large numbers of test subjects.

If Nivalis resumes research and development activities relating to its GSNOR inhibitors, Nivalis may experience delays in clinical trials at any stage of development and testing of any such potential product

candidate. Events which may result in a delay or unsuccessful completion of clinical trials for any of Nivalis’ GSNOR inhibitors include:

If initiation or completion of any of Nivalis’ clinical trials are delayed for any of the above reasons, Nivalis’ development may be arrested, development costs may increase, the approval process could be delayed, any periods during which Nivalis may have the exclusive right to commercialize a potential product candidate may be reduced and Nivalis’ competitors may have more time to bring products to market before Nivalis does or otherwise delay Nivalis. Any of these events could impair Nivalis’ ability to generate revenue from product sales and impair its ability to generate regulatory and commercialization milestones and royalties, all of which could have a material adverse effect on Nivalis’ business.

Nivalis’ potential product candidates may cause adverse events or have other properties that could delay or prevent their regulatory approval or limit the scope of any approved label or market acceptance.

If Nivalis were to resume research and development activities relating to its GSNOR inhibitors, undesirable adverse events caused by the potential product candidates could cause Nivalis or regulatory authorities to interrupt, delay, halt or terminate clinical trials and could result in the denial of regulatory approval by the FDA or other comparable foreign regulatory authorities for any or all targeted indications. It is possible that during the course of the clinical development of a potential product candidate, results of Nivalis’ clinical trials could reveal an unacceptable severity and prevalence of adverse events. In addition, Nivalis’ remaining preclinical testing may produce inconclusive or negative safety results, which may require it to conduct additional preclinical testing or to abandon a potential product candidate. Also, a potential product candidate may have unfavorable pharmacology or toxicity characteristics, or cause undesirable side effects.

Undesirable adverse events caused by a potential product candidate could affect patient recruitment or the ability of enrolled patients to complete a clinical trial or result in potential product liability claims. In addition, adverse events that occur in Nivalis’ trials as a consequence of the serious disease that is being studied may negatively affect the profile of the potential product candidate. The FDA or other regulatory authorities may determine that additional safety testing is required for a potential product candidate, which would cause a delay in Nivalis’ clinical development of such product candidate.

Additionally, if any potential product candidate receives marketing approval, and Nivalis or others later identify undesirable adverse events caused by such products, a number of potentially significant negative consequences could result, including:

Any of these events could prevent Nivalis from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm Nivalis’ business, results of operations and prospects. Any such events would increase Nivalis’ costs and could delay or prevent Nivalis’ ability to commercialize its product candidates should Nivalis resume development activities, which could adversely impact Nivalis’ business, financial condition and results of operations.

Cavosonstat and any other potential product candidate based on Nivalis’ GSNOR inhibitor portfolio are based on a novel technology, which may raise development issues Nivalis may not anticipate or be able to resolve, and regulatory issues that could delay or prevent approval.

Cavosonstat and any other potential product candidate based on Nivalis’ GSNOR inhibitor technology platform are based on a novel technology, and there can be no assurance that unforeseen development problems related to the novel technology will not arise in the future and cause significant delays should Nivalis determine to resume research and development activities relating to its GSNOR inhibitors. In this event, Nivalis may be unable to resolve any such unforeseen problems.

Regulatory approval of novel product candidates can be more expensive and take longer than other, more well-known or extensively studied pharmaceutical product candidates due to Nivalis’ and regulatory agencies’ lack of experience with them. There are no GSNOR inhibitors that Nivalis knows of in clinical development and none have been approved to date. Should Nivalis resume research and development activities relating to its GSNOR inhibitors, the novelty of Nivalis’ platform may lengthen the regulatory review process, require Nivalis to conduct additional studies or clinical trials, increase Nivalis’ development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of cavosonstat or any other potential product candidate based on its GSNOR inhibitor technology platform or lead to significant post-approval limitations or restrictions. For example, the FDA could require additional studies or characterization that may be difficult or impossible to perform.

Even if Nivalis obtains regulatory approval for a potential product candidate, Nivalis will still face extensive ongoing regulatory requirements.

If Nivalis were to resume research and development activities relating to its GSNOR inhibitors, even if Nivalis obtains regulatory approval in the U.S., the FDA may still impose significant future restrictions on the

indicated uses or marketing of a potential product candidate, or impose ongoing requirements for potentially costly post-approval studies or post-market surveillance, including Phase 4 clinical trials. Should Nivalis obtain regulatory approval, it will be subject to ongoing FDA requirements governing the labeling, manufacturing, packaging, storage, distribution, safety surveillance, advertising, promotion, record-keeping and reporting of safety and other post-market information. The holder of an approved NDA is obligated to monitor and report adverse events and any failure of a product to meet the specifications in the NDA. The holder of an approved NDA must also submit new or supplemental applications and obtain FDA approval for certain changes to the approved product, product labeling or manufacturing process. Advertising and promotional materials must comply with FDA rules and are subject to FDA review, in addition to other potentially applicable federal and state laws.

In addition, manufacturers of drug products and their facilities are subject to payment of user fees and continual review and periodic inspections by the FDA and other regulatory authorities for compliance with cGMPs, and adherence to commitments made in the NDA. If Nivalis or a regulatory agency discover previously unknown problems with a product, such as quality issues or adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose restrictions relative to that product or the manufacturing facility, including necessitating recall or withdrawal of the product from the market or suspension of manufacturing.

If Nivalis fails to comply with applicable ongoing regulatory requirements following approval of a product candidate, a regulatory agency may:

Any government investigation of alleged violations of law could require Nivalis to expend significant time and resources in response and could generate negative publicity. The occurrence of any event or penalty described above may inhibit the commercialization of any potential product candidate and inhibit Nivalis’ ability to generate revenue.

The approval of a potential product candidate in any given market does not ensure approval in any other market.

If Nivalis were to resume research and development activities relating to its GSNOR inhibitors, in order to market any product candidate, Nivalis must establish and comply with numerous and varying regulatory requirements on a country-by-country basis regarding safety and efficacy. Approval in the U.S. by the FDA or by a regulatory agency in another country does not ensure approval by the regulatory authorities in other countries or jurisdictions or ensure approval for the same conditions of use. In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country. Approval processes vary among countries and can involve additional product testing and validation and additional administrative review periods. Seeking foreign regulatory approval could result in difficulties and costs for Nivalis and require additional preclinical studies or clinical trials which could be costly and time-consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of Nivalis’ product candidates in those countries. Nivalis does not have any product candidates approved for sale in any jurisdiction, including international markets, and Nivalis does not have experience in obtaining regulatory approval in international markets. If Nivalis fails to

comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed, Nivalis’ target market will be reduced and its ability to realize the full market potential of its product candidates will be unrealized.

If Nivalis attempts to form strategic alliances or collaborations in the future with third parties for the development and commercialization of any of its product candidates, Nivalis may not be successful in establishing these alliances or collaborations.

Nivalis may seek to form strategic alliances or collaborations for the development and potential commercialization of its product candidates. Nivalis may not be successful in entering into any such transaction on favorable terms or at all. Nivalis’ potential product candidates may be considered to be too early in development for a collaborative effort or may be perceived as being too risky or without sufficient market potential or otherwise as insufficient for clinical, market or other reasons. If Nivalis were successful in entering into a strategic alliance or collaboration, its ability to generate revenue from the alliance or collaboration will depend on its collaborators’ abilities to establish the safety and efficacy of its product candidates, to obtain regulatory approvals and to achieve market acceptance. Strategic alliances and collaborations involving Nivalis product candidates pose many risks to Nivalis, including:

Nivalis employees, consultants or CROs may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on Nivalis’ business.

Nivalis is exposed to the risk of fraud or other misconduct by its employees, consultants and other third parties, such as principal investigators, CROs and vendors, if any. Misconduct by these parties could include intentional, reckless or negligent conduct, and/or failures to comply with FDA regulations, provide accurate information to the FDA, comply with manufacturing standards Nivalis has established, comply with federal and state healthcare fraud and abuse laws and regulations, report financial information or data accurately or disclose unauthorized activities to Nivalis. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Misconduct by these parties could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to Nivalis’ reputation. Nivalis has adopted a Code of Business Conduct and Ethics, but it is not always possible to identify and deter misconduct, and the precautions Nivalis takes to detect and prevent misconduct may not be effective in controlling unknown or unmanaged risks or losses or in protecting Nivalis from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. If any such actions are instituted against Nivalis, and Nivalis is not successful in defending itself or asserting its rights, those actions could have a significant impact on Nivalis’ business and results of operations, including the imposition of significant fines or other sanctions.

It is difficult and expensive to protect Nivalis’ intellectual property rights and Nivalis cannot ensure that the protections used will prevent third parties from competing against Nivalis.

If Nivalis were to resume research and development activities relating to its GSNOR inhibitors, Nivalis’ success will depend, in part, on its ability to obtain and maintain intellectual property rights, both in the U.S. and other countries, successfully defend this intellectual property against third-party challenges and successfully enforce this intellectual property to prevent third-party infringement. Nivalis relies upon a combination of patents, trade secret protection and confidentiality agreements.

Nivalis’ ability to protect any of its product candidates and technologies from unauthorized or infringing use by third parties depends in substantial part on its ability to obtain and maintain valid and enforceable patents in both the U.S. and other countries. Patent matters in the biotechnology and pharmaceutical industries can be highly uncertain and involve complex legal and factual questions. Changes in either the patent laws, implementing regulations or in interpretations of patent laws may diminish the value of Nivalis patent rights.

There can be no assurance that Nivalis will discover or develop patentable products or processes or that patents will issue from any pending patent applications owned or licensed by Nivalis or any patent applications Nivalis may own or license in the future, or if issued, that the breadth of such patent coverage will be sufficient. Nivalis cannot guarantee that claims of issued patents owned or licensed to Nivalis, either now or in the future, are or will be held valid or enforceable by the courts or, even if unchallenged, will provide Nivalis with exclusivity or commercial value for its product candidates or technology or any significant protection against competitive products or prevent others from designing around Nivalis’ claims. Further, if Nivalis encounters delays in regulatory approvals, the period of time during which Nivalis could market its product candidates under patent protection could be reduced. Nivalis’ patent rights also depend on Nivalis’ compliance with technology and patent licenses upon which Nivalis’ patent rights are based and upon the validity of assignments of patent rights from consultants and other inventors that were, or are, not employed by Nivalis.

Patent applications are generally maintained in confidence until publication. In the U.S., for example, patent applications are maintained in secrecy for up to 18 months after their filing. Similarly, publication of discoveries

in scientific or patent literature often lag behind actual discoveries. Consequently, Nivalis cannot be certain that it was the first to invent, or the first to file patent applications on its product candidates. There is also no assurance that all of the potentially relevant prior art relating to Nivalis’ patents and patent applications has been found, which could be used by a third party to challenge the validity of Nivalis’ patents or prevent a patent from issuing from a pending patent application.

In addition, even if patents do successfully issue, third parties may challenge any patent Nivalis owns or licenses through adversarial proceedings in the issuing offices, which could result in the invalidation or unenforceability of some or all of the relevant patent claims. If a third party asserts a substantial new question of patentability against any claim of a U.S. patent Nivalis owns or licenses, the USPTO may grant a request for reexamination, which may result in a loss of scope of some claims or a loss of the entire patent. The adoption of the Leahy-Smith America Invents Act (the “Leahy-Smith Act”) has established additional opportunities for third parties to invalidate U.S. patent claims, including inter partes review and post-grant review, on the basis of a lower legal standards than reexamination and additional grounds.

Nivalis will incur significant ongoing expenses in maintaining its patent portfolio. Should Nivalis lack the funds to maintain its patent portfolio or to enforce its rights against infringers, Nivalis could be adversely impacted. Even if claims of infringement are without merit, any such action could divert the time and attention of management and impair Nivalis’ ability to access additional capital and/or cost Nivalis significant funds to defend.

Nivalis may not be able to protect its intellectual property rights throughout the world.

Filing, prosecuting and defending patents on all of Nivalis’ product candidates throughout the world would be prohibitively expensive. Competitors may manufacture and sell Nivalis’ potential products in those foreign countries where Nivalis has not filed for patent protection or where patent protection may be unavailable, not obtainable or ultimately not enforceable. Nivalis’ competitors might conduct research and development activities in countries where Nivalis does not have patent rights and then use the information learned from such activities to develop competitive products for sale in Nivalis’ major commercial markets and, further, may be able to export otherwise infringing products to territories where Nivalis has patent protection but where enforcement is not as strong as that in the U.S. These products may compete with Nivalis’ products in jurisdictions where Nivalis does not have any issued patents and Nivalis’ patent claims or other intellectual property rights may not be effective or sufficient to prevent them from so competing.

Nivalis’ patent portfolio includes patents and patent applications in countries outside of the U.S., including Europe, Canada, Japan and Australia. The scope of coverage provided by these patents varies from country to country. Moreover, the laws of some foreign jurisdictions do not provide intellectual property rights to the same extent as in the U.S. and many companies have encountered significant difficulties in obtaining such rights in foreign jurisdictions. Outside of the U.S., patents Nivalis owns or licenses may become subject to patent opposition in the European Patent Office or similar proceedings, which may result in loss of scope of some claims or loss of the entire patent. Participation in adversarial proceedings is very complex, expensive, and may divert Nivalis’ management’s attention from the core business and may result in unfavorable outcomes that could adversely affect Nivalis’ ability to prevent third parties from competing with Nivalis.

Many companies have also encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to pharmaceuticals, which could make it difficult for Nivalis to stop the infringement of its patents or marketing of competing products in violation of Nivalis’ proprietary rights generally. For example, an April 2014 report from the Office of the United States Trade Representative identified a number of countries, including India and China, where challenges to the procurement and enforcement of patent rights have been reported. Several countries, including India and China, have been listed in the report every year since 1989.

If Nivalis encounters difficulties in protecting Nivalis’ intellectual property rights in foreign jurisdictions, the value of Nivalis’ proprietary technology could be substantially harmed. Proceedings to enforce Nivalis’ patent rights in certain foreign jurisdictions could result in substantial cost and divert Nivalis’ efforts and attention from other aspects of Nivalis’ business.

Intellectual property rights do not necessarily address all potential threats to Nivalis’ competitive advantage.

The degree of future protection afforded by Nivalis’ intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect Nivalis’ business, or permit Nivalis to maintain its competitive advantage. The following examples are illustrative:

Should any of these events occur, they could significantly harm Nivalis’ business, results of operations and prospects.

Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of Nivalis’ patent applications and the enforcement or defense of Nivalis’ issued patents.

On September 16, 2011, the Leahy-Smith Act was signed into law. The Leahy-Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications will be prosecuted and may also affect patent litigation. Accordingly, it is not clear what, if any, impact the Leahy-Smith Act will have on the operation of Nivalis’ business, its current and pending patent portfolio and future intellectual property strategy. However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of Nivalis’ patent applications and the enforcement or defense of Nivalis’ issued patents, all of which could have a material adverse effect on Nivalis’ business and financial condition.

Obtaining and maintaining Nivalis’ patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and Nivalis’ patent protection could be reduced or eliminated for non-compliance with these requirements.

Periodic maintenance fees on any issued patent are due to be paid to the U.S. Patent and Trademark Office (“USPTO”), the European Patent Office (“EPO”), and other foreign patent agencies in several stages over the

lifetime of the patent. The USPTO and various foreign national or international patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of patent rights include, but are not limited to, failure to timely file national and regional stage patent applications based on Nivalis’ international patent application, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. If Nivalis or its licensors fail to maintain the patents and patent applications covering Nivalis’ product candidates, Nivalis’ competitors might be able to enter the market, which would have a material adverse effect on Nivalis’ business.

Some of Nivalis’ intellectual property is licensed to it by a third party. If Nivalis fails to comply with its obligations in the agreement under which it licenses intellectual property rights from that third party, or otherwise experience disruptions to Nivalis’ business relationships with its licensor, Nivalis could lose license rights that are important to its business.

Nivalis has a license under certain patents and/or know-how to develop and commercialize certain of its potential product candidates. Nivalis’ existing license agreements impose, and Nivalis expects that any future license agreements will impose on Nivalis, various obligations. If Nivalis fails to comply with its obligations under these agreements, the licensor may have the right to terminate the license. If any of Nivalis’ licenses are terminated and Nivalis is not able to negotiate other agreements for use of the intellectual property protections underlying these product candidates, Nivalis would not be able to manufacture and market these potential products, which would adversely affect its business prospects and financial condition.

The patent protection and patent prosecution for some of Nivalis’ potential product candidates is dependent or may be dependent in the future on third parties.

While Nivalis normally seeks and gains the right to fully prosecute the patents relating to its potential product candidates, there may be times when platform technology patents or product-specific patents that relate to its potential product candidates are controlled by Nivalis’ licensors. In addition, Nivalis’ licensors and/or licensees may have back-up rights to prosecute patent applications in the event that Nivalis does not do so or chooses not to do so, and Nivalis’ licensees may have the right to assume patent prosecution rights after certain milestones are reached. If any of Nivalis’ licensing partners fail to appropriately prosecute and maintain patent protection for patents covering any of Nivalis’ potential product candidates, Nivalis’ ability to develop and commercialize those potential product candidates may be adversely affected and Nivalis may not be able to prevent competitors from making, using and selling competing products.

Nivalis may be subject to litigation alleging that Nivalis is infringing the intellectual property rights of third parties or litigation or other adversarial proceedings seeking to invalidate its patents or other proprietary rights, and Nivalis may need to resort to litigation to protect or enforce its patents or other proprietary rights, all of which will be costly to defend or pursue and uncertain in outcome and may prevent or delay any future development and commercialization efforts or otherwise affect its business.

Nivalis’ success also will depend, in part, on refraining from infringing patents or otherwise violating intellectual property owned or controlled by others. Numerous patents and pending applications are owned by third parties in the fields in which Nivalis may develop product candidates, both in the U.S. and elsewhere. It is difficult for industry participants, including Nivalis, to identify all third-party patent rights that may be relevant to any of its potential product candidates because patent searching is imperfect due to differences in terminology among patents, incomplete databases and the difficulty in assessing the meaning of patent claims. Moreover, because some patent applications are maintained in secrecy until the patents publish, Nivalis cannot be certain that third parties have not filed patent applications that cover Nivalis’ potential product candidates and

technologies. Pharmaceutical companies, biotechnology companies, universities, research institutions and others may have filed patent applications or have received, or may obtain, issued patents in the U.S. or elsewhere relating to aspects of Nivalis’ technology, including its potential product candidates, processes for manufacture or methods of use, including combination therapy. It is uncertain whether the issuance of any third-party patents will require Nivalis to alter its potential product candidates or processes, obtain licenses, or cease certain activities.

If patents issued to third parties contain blocking, dominating or conflicting claims and such claims are ultimately determined to be valid, Nivalis may be required to obtain licenses to these patents or to develop or obtain alternative non-infringing technology and cease practicing those activities, including potentially manufacturing or selling any products deemed to infringe those patents. If any licenses are required, there can be no assurance that Nivalis will be able to obtain any such licenses on commercially favorable terms, if at all, and if these licenses are not obtained, Nivalis might be prevented from pursuing the development and commercialization of certain of its potential product candidates. Even if a license can be obtained on acceptable terms, the rights may be non-exclusive, which could give Nivalis’ competitors access to the same technology or intellectual property rights licensed to Nivalis. Nivalis’ failure to obtain a license to any technology that it may require to commercialize its potential product candidates on favorable terms may have a material adverse impact on its business, financial condition and results of operations.

Nivalis may be exposed to, or threatened with, future litigation by third parties having patent or other intellectual property rights alleging that Nivalis’ technologies, including its potential product candidates, processes for manufacture or methods of use, including combination therapy, or other proprietary technologies infringe their intellectual property rights. Parties making claims against Nivalis may obtain injunctive or other equitable relief, which could effectively block Nivalis’ ability to further develop and commercialize one or more of its potential product candidates. Defense of these claims, regardless of their merit, would involve substantial litigation expense and would be a substantial diversion of employee resources from the business. In the event of a successful infringement or other intellectual property claim against Nivalis, it may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, obtain one or more licenses from third parties, pay royalties or redesign Nivalis’ affected products, which may be impossible or require substantial time and monetary expenditure. Nivalis cannot predict whether any such license would be available at all or whether it would be available on commercially reasonable terms. Parties making successful claims against Nivalis may obtain injunctive or other equitable relief, which could effectively block Nivalis’ ability to further develop and commercialize one or more of its potential product candidates. Nivalis cannot provide any assurances that third-party patents do not exist which might be enforced against Nivalis’ products or potential product candidates, resulting in either an injunction prohibiting Nivalis’ sales, or, with respect to Nivalis’ sales, an obligation on Nivalis’ part to pay royalties and/or other forms of compensation to third parties.

Litigation, which could result in substantial costs to Nivalis (even if determined in Nivalis’ favor), may also be necessary to enforce any patents issued or licensed to Nivalis. The cost to Nivalis in initiating any litigation or other proceeding relating to patent or other proprietary rights, even if resolved in Nivalis’ favor, could be substantial, and litigation would divert management’s attention. Some of Nivalis’ competitors may be able to sustain the costs of complex patent litigation more effectively than Nivalis can because they have substantially greater resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could delay Nivalis’ research and development efforts and limit its ability to continue its operations.

If Nivalis were to initiate legal proceedings against a third party to enforce a patent covering one of its potential product candidates or its technology, the defendant could counterclaim that its patent is invalid or unenforceable. In patent litigation in the U.S. and in most European countries, defendant counterclaims alleging invalidity or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, for example, lack of novelty, obviousness or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. The

outcome following legal assertions of invalidity and unenforceability during patent litigation is unpredictable. With respect to the validity question, for example, Nivalis cannot be certain that there is no invalidating prior art, of which Nivalis and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, Nivalis would lose at least part, and perhaps all, of the patent protection on one or more of its products or certain aspects of its platform technology. Such a loss of patent protection could have a material adverse impact on Nivalis’ business. Patents and other intellectual property rights also will not protect Nivalis’ technology if competitors design around its protected technology without legally infringing its patents or other intellectual property rights.

In addition, if a third party has filed patent applications in the U.S. prior to March 16, 2013 that claim technology also claimed by Nivalis, Nivalis may have to participate in interference proceedings in the USPTO to determine priority of invention. Such proceedings can be lengthy, are costly to defend and involve complex questions of law and fact the outcomes of which are difficult to predict. Moreover, Nivalis may have to participate in adversarial proceedings in the USPTO or foreign patent offices. An adverse decision relating to Nivalis’ patent rights could require it to cease using such technology, any of which could have a material adverse effect on its business, financial condition and results of operations. If initiated, adversarial proceedings could result in substantial costs to Nivalis, even if the eventual outcome is favorable to Nivalis.

If Nivalis is not able to adequately prevent disclosure of trade secrets and other proprietary information, the value of its technology and products could be significantly diminished.

Nivalis also relies on trade secrets to protect technology, especially where patent protection is not believed to be appropriate or obtainable or where patents have not issued. Nivalis attempts to protect its proprietary technology and processes, in part, with confidentiality agreements and assignment of invention agreements with its employees and confidentiality agreements with its consultants and certain contractors. There can be no assurance that these agreements will not be breached, that Nivalis would have adequate remedies for any breach, or that its trade secrets will not otherwise become known or be independently discovered by competitors. Nivalis may fail in certain circumstances to obtain the necessary confidentiality agreements, or their scope or term may not be sufficiently broad to protect Nivalis’ interests.

If Nivalis’ trade secrets or other intellectual property become known to its competitors, it could result in a material adverse effect on the business, financial condition and results of operations. To the extent that Nivalis or its consultants or research collaborators use intellectual property owned by others in work for Nivalis, disputes may also arise as to the rights to related or resulting know-how and inventions.

Nivalis may be subject to claims that it or its employees or consultants have wrongfully used or disclosed alleged trade secrets of its employees’ or consultants’ former employers or their clients. These claims may be costly to defend and if Nivalis does not successfully do so, Nivalis may be required to pay monetary damages and may lose valuable intellectual property rights or personnel.

Many of Nivalis’ current or former employees were previously employed at universities or biotechnology or pharmaceutical companies, including Nivalis’ competitors or potential competitors. Although no claims against Nivalis are currently pending, Nivalis may be subject to claims that these employees or Nivalis have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers. Litigation may be necessary to defend against these claims. If Nivalis fails in defending such claims, in addition to paying monetary damages, it may lose valuable intellectual property rights or personnel. A loss of key research personnel or their work product could compromise Nivalis’ ability to commercialize, or prevent it from commercializing, its product candidates, which could severely harm the business. Even if Nivalis is successful in defending against these claims, litigation could result in substantial costs and be a distraction to management.

Following its recent workforce reduction, Nivalis will not have resources or the required expertise to develop any of its potential product candidates, which may impair their value.

Because of the specialized scientific nature of the business and the unique properties of the GSNOR inhibitor platform, Nivalis’ ability to develop and commercialize any of its potential product candidates is highly dependent upon Nivalis’ ability to attract and retain qualified scientific and technical personnel, consultants and advisors. Nivalis’ recent workforce reduction resulted in the departure of Mr. Jon Congleton, the CEO, Dr. David Rodman, the CMO, Dr. Steven Shoemaker, the Vice President of Clinical Research and Development, and Dr. Sherif Gabriel, the Vice President of Research and Discovery. Additionally, the workforce reduction resulted in the elimination of all of Nivalis’ research and development staff. The loss of their services will significantly delay or prevent any resumption of the research and development of the GSNOR inhibitors should Nivalis choose to resume those activities in the future.

Should Nivalis need to recruit additional personnel in order to resume research and development activities, it will need to hire additional qualified scientific personnel to perform research and development, as well as personnel with expertise in clinical testing, government regulation, manufacturing, marketing and sales, which may strain Nivalis’ existing managerial, operational, regulatory compliance, financial and other resources. Nivalis also relies on consultants and advisors to assist in formulating its research and development strategy and adhering to complex regulatory requirements. Nivalis faces competition for qualified individuals from numerous pharmaceutical and biotechnology companies, universities and other research institutions. There can be no assurance that Nivalis will be able to attract and retain such individuals in the future, on acceptable terms, if at all. Additionally, Nivalis’ operations are in Colorado, which may make attracting and retaining qualified scientific and technical personnel from outside of Colorado difficult. The failure to attract and retain qualified personnel, consultants and advisors could delay or prevent Nivalis’ ability to commercialize any of its potential product candidates based on the GSNOR inhibitor portfolio, which could have a material adverse effect on the business, financial condition and results of operations.

If research and development activities resume, Nivalis is exposed to potential product liability or similar claims, and insurance against these claims may not be available at a reasonable rate in the future or at all.

Drug development involves potential liability risks that are inherent in the testing, manufacturing and marketing of human therapeutic products. Clinical trials involve the testing of product candidates on human subjects or volunteers under a research plan, and carry a risk of liability for personal injury or death to patients due to unforeseen adverse side effects, improper administration of the product candidate, or other factors. Many of these patients are already seriously ill and are therefore particularly vulnerable to further illness or death.

Nivalis currently carries clinical trial liability insurance in the amount of $10.0 million in the aggregate, but there can be no assurance that it will be able to maintain such insurance if it were to resume drug development activities or that the amount of such insurance will be adequate to cover claims. Nivalis could be materially and adversely affected if it were required to pay damages or incur defense costs in connection with a claim outside the scope of indemnity or insurance coverage, if the indemnity is not performed or enforced in accordance with its terms, or if its liability exceeds the amount of applicable insurance. In addition, there can be no assurance that insurance will continue to be available on terms acceptable to Nivalis, if at all, or that if obtained, the insurance coverage will be sufficient to cover any potential claims or liabilities. Similar risks would exist upon the commercialization or marketing of any products by Nivalis or its collaborators.

Regardless of their merit or eventual outcome, product liability claims may result in:

Should any of these events occur, it could have a material adverse effect on Nivalis’ business and financial condition.

Nivalis may become involved in securities class action litigation that could divert management’s attention and adversely affect the business and could subject Nivalis to significant liabilities.

The stock markets have from time to time experienced significant price and volume fluctuations that have affected the market prices for the common stock of pharmaceutical companies. These broad market fluctuations as well a broad range of other factors, including the realization of any of the risks described in this “Risk Factors” section of this proxy statement/prospectus/information statement and the consummation of any transaction resulting from Nivalis’ review of various strategic alternatives, may cause the market price of Nivalis’ common stock to decline. In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for Nivalis because biotechnology and pharmaceutical companies generally experience significant stock price volatility. Nivalis may become involved in this type of litigation in the future. Litigation typically is expensive and diverts management’s attention and resources, which could adversely affect the business. Any adverse determination in any such litigation or any amounts paid to settle any such actual or threatened litigation could require that Nivalis make significant payments.

Nivalis’ stock price is likely to be volatile and an active, liquid and orderly trading market may not develop for its common stock. As a result, stockholders may not be able to resell shares at or above their purchase price.

Prior to its initial public offering, which was completed in June 2015, there was no public market for shares of Nivalis’ common stock. Although Nivalis’ common stock is listed on NASDAQ, an active trading market for its common stock may not develop or, if it develops, may not be sustained. The lack of an active market may impair the ability of its stockholders to sell their shares at the time they wish to sell them or at a price that they consider reasonable, which may reduce the fair market value of their shares. Further, an inactive market may also impair Nivalis’ ability to raise capital by selling its common stock should it determine additional funding is required.

The market price of Nivalis’ common stock may fluctuate substantially as a result of many factors, some of which are beyond its control. For example, shares of Nivalis’ common stock have traded as high as $20.43 and as low as $2.00 in the twenty-three month period following the effective date of Nivalis’ IPO. These fluctuations could cause an investor to lose all or part of the value of his, her or its investment in Nivalis’ common stock. Factors that could cause fluctuations in the market price of Nivalis’ common stock include the following:

In addition, the stock market in general has experienced significant price and volume fluctuations that have often been unrelated or disproportionate to operating performance of individual companies. These broad market factors may adversely affect the market price of Nivalis’ common stock, regardless of Nivalis’ operating performance. In the past, following periods of volatility in the market price of a company’s securities, securities class action litigation has often been instituted. A securities class action suit against Nivalis could result in significant liabilities and, regardless of the outcome, could result in substantial costs and the diversion of management’s attention and resources.

Nivalis’ common stock may be delisted from NASDAQ if Nivalis is unable to maintain compliance with NASDAQ’s continued listing standards.

NASDAQ imposes, among other requirements, continued listing standards including minimum bid and public float requirements. The price of Nivalis’ common stock must trade at or above $1.00 to comply with NASDAQ’s minimum bid requirement for continued listing on NASDAQ. If Nivalis’ common stock trades at bid prices of less than $1.00 for a period in excess of 30 consecutive business days, NASDAQ could send a deficiency notice to Nivalis for not remaining in compliance with the minimum bid listing standards. Nivalis’ common stock has never traded below $1.00. However, if the closing bid price of Nivalis’ common stock fails to meet NASDAQ’s minimum closing bid price requirement, or if Nivalis otherwise fails to meet any other applicable requirements of NASDAQ and Nivalis is unable to regain compliance, NASDAQ may make a determination to delist Nivalis’ common stock. Any delisting of Nivalis’ common stock could adversely affect the market liquidity of Nivalis’ common stock and the market price of Nivalis’ common stock could decrease. Furthermore, if Nivalis’ common stock were delisted it could adversely affect Nivalis’ ability to obtain financing for the continuation of its operations and/or result in the loss of confidence by investors, customers, suppliers and employees.

Nivalis’ principal stockholders have a controlling influence over Nivalis’ business affairs and may make business decisions with which stockholders disagree and which may adversely affect the value of their investment.

Nivalis’ principal stockholders, which consist of entities affiliated with Deerfield Management Company, L.P., the Estate of Arnold H. Snider, III, and BVF Partners L.P., and certain of their affiliates, beneficially own or control, directly or indirectly, approximately 46% of the outstanding shares of Nivalis’ common stock. As a result, if some of these persons or entities act together, they will have the ability to exercise significant influence over matters submitted to the stockholders for approval, including the election and removal of directors, amendments to the certificate of incorporation and bylaws and the approval of any strategic transaction requiring the approval of the stockholders, including the approval of the Merger Agreement and the transactions contemplated by the Merger Agreement, including the merger and the issuance of shares of Nivalis’ common stock to Alpine’s stockholders in the merger. These actions may be taken even if they are opposed by other stockholders. This concentration of ownership may also have the effect of delaying or preventing a change of control of Nivalis or discouraging others from making tender offers for Nivalis shares, which could prevent Nivalis’ stockholders from receiving a premium for their shares. Some of these persons or entities who make up Nivalis’ principal stockholders may have interests different from other stockholders.

Future sales, or the perception of future sales, of a substantial amount of Nivalis’ common stock could depress the trading price of Nivalis’ common stock.

As of May 30, 2017, Nivalis has 200,000,000 shares of common stock authorized and 15,656,251 shares of common stock outstanding. Of these shares, the 6,325,000 shares sold during Nivalis’ IPO are freely tradable and, without giving effect to the purchase of shares by entities affiliated with certain of Nivalis’ existing stockholders, approximately 5.6 million shares are freely tradable under Rule 144 under the Securities Act by non-affiliates, and approximately 3.6 million shares are eligible for resale pursuant to Rule 144 under the Securities Act, subject to the volume, manner of sale, holding period and other limitations of Rule 144. In addition, Nivalis has registered on a registration statement on Form S-3 that has been declared effective, (i) the sale of up to $125,000,000 in the aggregate of an indeterminate number of shares of common stock and preferred stock, an indeterminate principal amount of debt securities and an indeterminate number of warrants and (ii) the resale of up to 3,732,412 shares of common stock that are freely tradable by selling stockholders pursuant to a base prospectus that forms a part of the registration statement. The registration statement also registers the offering, issuance and sale of common stock having up to a maximum aggregate offering price of $20,000,000 that Nivalis may issue and sell in an at-the-market offering under a sales agreement Nivalis entered into with Cowen and Company, LLC on July 5, 2016 pursuant to a sales agreement prospectus that forms a part of the registration statement. As of March 31, 2017, approximately $19.8 million in shares of common stock remain for sale under the sales agreement.

If Nivalis or Nivalis’ stockholders sell substantial amounts of shares of Nivalis’ common stock in the public market or if the market perceives that these sales could occur, the market price of shares of Nivalis’ common stock could decline. These sales may make it more difficult for Nivalis to sell equity or equity-related securities in the future at a time and price that Nivalis deems appropriate, or to use equity as consideration for future acquisitions.

The JOBS Act allows Nivalis to postpone the date by which it must comply with certain laws and regulations intended to protect investors and to reduce the amount of information it provides in Nivalis’ reports filed with the SEC. Nivalis cannot be certain if this reduced disclosure will make Nivalis’ common stock less attractive to investors.

The JOBS Act is intended to reduce the regulatory burden on “emerging growth companies.” As defined in the JOBS Act, Nivalis qualifies as an “emerging growth company” and could remain an “emerging growth company” until as late as December 31, 2020. For so long as Nivalis is an “emerging growth company,” it will, among other things:

Nivalis has irrevocably elected not to avail itself of an extended transition period under the JOBS Act that permits an emerging growth company to delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. As a result, Nivalis will adopt new or revised accounting standards on the relevant dates on which adoption of such standards is required for other companies.

Furthermore, if Nivalis takes advantage of some or all of the reduced disclosure requirements above, investors may find Nivalis’ common stock less attractive, which may result in a less active trading market for Nivalis’ common stock and greater stock price volatility.

Nivalis first became subject to rules and regulations established by the SEC and the Public Company Accounting Oversight Board (“PCAOB”) regarding Nivalis’ internal control over financial reporting in the fiscal year ended December 31, 2016. If Nivalis’ internal controls are not determined to be effective, it may adversely affect investor confidence in Nivalis and, as a result, the market price of Nivalis’ common stock and a stockholder’s investment in Nivalis’ common stock.

As a public reporting company, Nivalis is subject to the rules and regulations established from time to time by the SEC and the PCAOB. These rules and regulations require, among other things, that Nivalis establish and periodically evaluate procedures with respect to its internal controls over financial reporting. Reporting obligations as a public company place a considerable strain on Nivalis’ financial and management systems, processes and controls, as well as on Nivalis’ personnel, particularly following Nivalis’ reduction in force, which resulted in approximately five employees remaining with Nivalis after March 31, 2017.

In addition, as a public company Nivalis is required to document and test its internal control over financial reporting pursuant to Section 404 of Sarbanes-Oxley so that its management can certify as to the effectiveness of its internal control over financial reporting. Maintaining and monitoring these internal controls may be more difficult with fewer resources available to perform the necessary documentation and testing, and Nivalis’ internal controls may be found to be deficient. Likewise, Nivalis’ independent registered public accounting firm will be required to provide an attestation report on the effectiveness of Nivalis’ internal control over financial reporting at such time as Nivalis ceases to be an “emerging growth company,” as defined in the JOBS Act, although, as described in the preceding risk factor, Nivalis could potentially qualify as an “emerging growth company” until December 31, 2020. At such time, Nivalis’ independent registered public accounting firm may issue a report that is adverse in the event it is not satisfied with the level at which Nivalis’ controls are documented, designed or operating.

If Nivalis senior management is unable to conclude that it has effective internal control over financial reporting, or to certify the effectiveness of such controls, or if Nivalis’ independent registered public accounting firm cannot render an unqualified opinion on management’s assessment and the effectiveness of Nivalis’ internal control over financial reporting, or if material weaknesses in Nivalis’ internal controls are identified, Nivalis could be subject to regulatory scrutiny and a loss of public confidence, which could have a material adverse effect on the business and stock price. In addition, if Nivalis does not maintain adequate financial and management personnel, processes and controls, Nivalis may not be able to manage its business effectively or accurately report its financial performance on a timely basis, which could cause a decline in Nivalis’ common stock price and adversely affect the results of operations and financial condition.

Nivalis’ disclosure controls and procedures may not prevent or detect all errors or acts of fraud.

Nivalis’ disclosure controls and procedures are designed to reasonably ensure that information required to be disclosed by Nivalis in reports it files or submits under the Exchange Act is accumulated and communicated to management and recorded, processed, summarized and reported within the time periods specified in the rules and forms of the SEC. Nivalis believes that any disclosure controls and procedures as well as internal controls and procedures, no matter how well-conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are and will be met. These inherent limitations include the realities that judgments in decision-making can be faulty and that breakdowns can occur because of simple error or mistake. Additionally, controls can be circumvented by the individual acts of some persons, by collusion of two or more people or by an unauthorized override of the controls. Accordingly, because of the inherent limitations in Nivalis’ control system, misstatements due to error or fraud may occur and not be detected.

Nivalis expects to continue to incur significant costs as a result of operating as a public company, and the remaining management team will be required to devote substantial time to compliance efforts.

Nivalis will continue to incur significant legal, accounting, insurance and other expenses as a result of being a public company. The Dodd-Frank Act and Sarbanes-Oxley as well as related rules implemented by the SEC and The NASDAQ Global Market, have imposed corporate governance requirements on public companies. In addition, rules that the SEC is implementing or is required to implement pursuant to the Dodd-Frank Act are expected to require additional changes. Nivalis expects that compliance with these and other similar laws, rules and regulations, including compliance with Section 404 of Sarbanes-Oxley, will substantially increase Nivalis’ expenses, including its legal and accounting costs, and make some activities more time-consuming and costly. Although the JOBS Act may for a limited period of time somewhat lessen the cost of complying with these additional regulatory and other requirements, Nivalis nonetheless expects to incur significant legal, accounting, insurance and certain other expenses in the future, which will negatively impact the business, results of operations and financial condition.

Anti-takeover provisions in Nivalis’ charter documents could discourage, delay or prevent a change in control of Nivalis and may affect the trading price of Nivalis’ common stock.

Nivalis’ corporate documents and the General Corporation Law of the State of Delaware (“DGCL”) contain provisions that may enable Nivalis’ board of directors to resist a change in control of Nivalis even if a change in control were to be considered favorable by Nivalis’ stockholders. These provisions:

These provisions could discourage, delay or prevent a transaction involving a change in control of Nivalis. These provisions could also discourage proxy contests and make it more difficult for stockholders to elect directors of their choosing and cause Nivalis to take other corporate actions Nivalis’ stockholders desire.

Claims for indemnification by Nivalis’ directors and officers may reduce Nivalis’ available funds to satisfy successful third-party claims against Nivalis and may reduce the amount of available cash.

Nivalis’ amended and restated certificate of incorporation provides that Nivalis will indemnify its directors to the fullest extent permitted by Delaware law.

In addition, as permitted by Section 145 of the DGCL, Nivalis’ amended and restated bylaws and Nivalis’ indemnification agreements that it has entered into with its directors and officers provide that:

As a result, if Nivalis is required to indemnify one or more of its directors or officers, it may reduce its available funds to satisfy successful third-party claims against it, may reduce the amount of available cash and may have a material adverse effect on the business and financial condition.

Nivalis’ amended and restated certificate of incorporation designates the Court of Chancery of the State of Delaware as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by Nivalis’ stockholders, which could limit Nivalis’ stockholders’ ability to obtain a favorable judicial forum for disputes with Nivalis or Nivalis’ directors, officers, employees or agents.

Nivalis’ amended and restated certificate of incorporation provides that, unless Nivalis consents in writing to an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for any derivative action or proceeding brought on Nivalis’ behalf, any action asserting a claim of breach of a fiduciary duty owed by any of Nivalis’ directors, officers, employees or agents to Nivalis or Nivalis’ stockholders, any action asserting a claim arising pursuant to any provision of the DGCL, Nivalis’ amended and restated certificate of incorporation or Nivalis’ amended and restated bylaws or any action asserting a claim that is governed by the internal affairs doctrine, in each case subject to the Court of Chancery having personal jurisdiction over the indispensable parties named as defendants therein and the claim not being one which is vested in the exclusive jurisdiction of a court or forum other than the Court of Chancery or for which the Court of Chancery does not have subject matter jurisdiction. Any person purchasing or otherwise acquiring any interest in any shares of Nivalis’ common stock shall be deemed to have notice of and to have consented to this provision of Nivalis’ amended and restated certificate of incorporation. This choice of forum provision may limit Nivalis’ stockholders’ ability to bring a claim in a judicial forum that it finds favorable for disputes with Nivalis or Nivalis’ directors, officers, employees or agents, which may discourage such lawsuits against Nivalis and Nivalis’ directors, officers, employees and agents even though an action, if successful, might benefit Nivalis’ stockholders. Stockholders who do bring a claim in the Court of Chancery could face additional litigation costs in pursuing any such claim, particularly if they do not reside in or near Delaware. The Court of Chancery may also reach different judgments or results than would other courts, including courts where a stockholder considering an action may be located or would otherwise choose to bring the action, and such judgments or results may be more favorable to Nivalis than to Nivalis’ stockholders. Alternatively, if a court were to find this provision of Nivalis’ amended and restated certificate of incorporation inapplicable to, or unenforceable in respect of, one or more of

the specified types of actions or proceedings, Nivalis may incur additional costs associated with resolving such matters in other jurisdictions, which could have a material adverse effect on Nivalis’ business, financial condition or results of operations.

Nivalis does not expect to pay any dividends on its common stock for the foreseeable future.

Nivalis currently expects to retain all future earnings, if any, for future operations and expansion, and has no current plans to pay any cash dividends to holders of Nivalis’ common stock for the foreseeable future. Any decision to declare and pay dividends in the future will be made at the discretion of Nivalis’ board of directors and will depend on, among other things, Nivalis’ results of operations, financial condition, cash requirements, contractual restrictions and other factors that Nivalis’ board of directors may deem relevant. As a result, stockholders may not receive any return on an investment in Nivalis’ common stock unless stockholders sell Nivalis’ common stock for a price greater than that which they paid for it.

Alpine will need to raise substantial additional funds to advance development of its therapeutic candidates, and it cannot guarantee it will have sufficient funds available in the future to develop and commercialize its current or future therapeutic candidates.

Alpine will need to raise substantial additional funds to expand Alpine’s development, regulatory, manufacturing, marketing, and sales capabilities or contract with other organizations to provide these capabilities to Alpine. Alpine has used substantial funds to develop its therapeutic candidates and will require significant funds to conduct further research and development, preclinical testing, and clinical trials of its therapeutic candidates, to seek regulatory approvals for its therapeutic candidates, and to manufacture and market products, if any are approved for commercial sale. As of March 31, 2017, Alpine had $13.6 million in cash and cash equivalents. Based on Alpine’s current operating plan, and assuming consummation of the merger, Alpine believes its available cash and cash equivalents, will be sufficient to fund its planned level of operations for at least the next 12 months. Alpine’s future capital requirements and the period for which it expects its existing resources to support its operations may vary significantly from what it expects. Alpine’s monthly spending levels vary based on new and ongoing development and corporate activities. Because the length of time and activities associated with successful development of Alpine’s therapeutic candidates are highly uncertain, Alpine is unable to estimate the actual funds it will require for development and any approved marketing and commercialization activities. To execute Alpine’s business plan, Alpine will need, among other things:

If Alpine is unable to obtain necessary funding on a timely basis or on acceptable terms, Alpine may have to delay, reduce, or terminate its research and development programs, preclinical studies, or clinical trials, if any,

limit strategic opportunities, or undergo reductions in Alpine’s workforce or other corporate restructuring activities. Alpine also could be required to seek funds through arrangements with collaborators or others requiring Alpine to relinquish rights to some of its technologies or therapeutic candidates Alpine would otherwise pursue on its own. Alpine does not expect to realize revenue from product sales, milestone payments, or royalties in the foreseeable future, if at all. Alpine’s revenue sources are, and will remain, extremely limited unless and until Alpine’s therapeutic candidates are clinically tested, approved for commercialization, and successfully marketed.

To date, Alpine has financed its operations primarily through the sale of equity securities and payments received under Alpine’s license and research agreement with Kite. Alpine will be required to seek additional funding in the future and intends to do so through a combination of public or private equity offerings, debt financings, credit and loan facilities, research collaborations, and license agreements. Alpine’s ability to raise additional funds from these or other sources will depend on financial, economic, and other factors, many of which are beyond its control. Additional funds may not be available to Alpine on acceptable terms or at all.

If Alpine raises additional funds by issuing equity securities, its stockholders will suffer dilution, and the terms of any financing may adversely affect the rights of its stockholders. In addition, as a condition to providing additional funds to Alpine, future investors may demand, and may be granted, rights superior to those of existing stockholders. Debt financing, if available, may involve restrictive covenants limiting Alpine’s flexibility in conducting future business activities, and, in the event of a liquidation or insolvency, debt holders would be repaid before holders of equity securities receive any distribution of corporate assets. Alpine’s failure to raise capital or enter into such other arrangements within a reasonable timeframe would have a negative impact on its financial condition, and Alpine may have to delay, reduce, or terminate its research and development programs, preclinical or clinical trials, or undergo reductions in its workforce or other corporate restructuring activities.

Alpine is a biopharmaceutical company with a history of losses, expects to continue to incur significant losses for the foreseeable future, and may never achieve or maintain profitability.

Alpine is a biopharmaceutical company with a limited operating history, focused on the discovery and development of treatments based on protein-based immunotherapies. Since Alpine’s inception in 2014, Alpine has devoted its resources to developing novel protein-based immunotherapies using Alpine’s proprietary vIgD platform technology. Alpine has had significant operating losses since inception. As of March 31, 2017, Alpine had an accumulated deficit of $3.6 million. For the three months ended March 31, 2017 and for the years ended December 31, 2016 and 2015, Alpine’s net loss was $2.0 million, $1.2 million, and $0.4 million, respectively. Substantially all of Alpine’s losses have resulted from expenses incurred in connection with Alpine’s research programs and from general and administrative costs associated with Alpine’s operations. Alpine’s technologies and therapeutic candidates are in early stages of development, and Alpine is subject to the risks of failure inherent in the development of therapeutic candidates based on novel technologies.

To date, Alpine has generated revenue primarily from the receipt of research funding and upfront payments under Alpine’s license and research agreement with Kite. Alpine has not generated, and does not expect to generate, any revenue from product sales for the foreseeable future, and Alpine expects to continue to incur significant operating losses for the foreseeable future due to the cost of research and development, preclinical studies, clinical trials, and the regulatory approval process for therapeutic candidates. The amount of future losses is uncertain. Alpine’s ability to achieve profitability, if ever, will depend on, among other things, Alpine’s or Alpine’s existing collaborators, or any future collaborators, successfully developing therapeutic candidates, obtaining regulatory approvals to market and commercialize therapeutic candidates, manufacturing any approved products on commercially reasonable terms, establishing a sales and marketing organization or suitable third party alternatives for any approved product, and raising sufficient funds to finance business activities. If Alpine or Alpine’s existing collaborators, or any future collaborators, are unable to develop and commercialize one or more of Alpine’s therapeutic candidates or if sales revenue from any therapeutic candidate receiving approval is insufficient, Alpine will not achieve profitability, which could have a material adverse effect on Alpine’s business, financial condition, results of operations, and prospects.

Alpine’s approach to the discovery and development of innovative therapeutic treatments based on Alpine’s technology is unproven and may not result in marketable products.

Alpine plans to develop novel protein-based immunotherapies using its proprietary vIgD platform technology for the treatment of cancer and inflammatory diseases. The potential to create therapies capable of working within an immune synapse, forcing a synapse to occur, or preventing a synapse from occurring is an important, novel attribute of Alpine’s vIgD platform. However, the scientific research forming the basis of Alpine’s efforts to develop therapeutic candidates based on Alpine’s vIgD platform is relatively new. Further, the scientific evidence to support the feasibility of developing therapeutic treatments based on Alpine’s vIgD platform is both preliminary and limited.

Relatively few therapeutic candidates based on immunoglobulin superfamily (“IgSF”) domains have been tested in animals or humans, and a number of clinical trials conducted by other companies using IgSF domains technologies have not been successful. Alpine may discover the therapeutic candidates Alpine develops using its vIgD platform do not possess certain properties required for the therapeutic to be effective, such as the ability to remain stable in the human body for the period of time required for the therapeutic to reach the target tissue or the ability to cross the cell wall and enter into cells within the target tissue for effective delivery. Alpine currently has only limited data, and no conclusive evidence, to suggest it can introduce these necessary therapeutic properties into vIgDs. Alpine may spend substantial funds attempting to introduce these properties and may never succeed in doing so. In addition, vIgDs may demonstrate different chemical and pharmacological properties in patients than they do in laboratory studies. Even if Alpine’s programs, such as the ALPN-101 program, have successful results in animal studies, they may not demonstrate the same chemical and pharmacological properties in humans and may interact with human biological systems in unforeseen, ineffective, or harmful ways. For example, in the context of immunotherapies, in a Phase I clinical trial of TeGenero AG’s product candidate TGN1412, healthy volunteer subjects receiving the product candidate experienced cytokine release syndrome resulting in acute renal failure and acute respiratory distress syndrome requiring interventions such as dialysis and critical care support. Following this experience, regulatory agencies now ask for evaluation of immunomodulatory antibodies with a number of in vitro assays with human cells. While Alpine is currently performing in vitro proof of concept studies for several of its vIgDs, the risk profile in humans has yet to be assessed. As a result of all this, Alpine may never succeed in developing a marketable therapeutic, Alpine may not become profitable and the value of Alpine will decline.

Further, the FDA has relatively limited experience with vIgDs. No regulatory authority has granted approval to any person or entity, including Alpine, to market and commercialize therapeutics using vIgDs, which may increase the complexity, uncertainty, and length of the regulatory approval process for Alpine’s therapeutic candidates. Alpine and its current collaborators, or any future collaborators, may never receive approval to market and commercialize any therapeutic candidate. Even if Alpine or a collaborator obtains regulatory approval, the approval may be for disease indications or patient populations not as broad as Alpine intended or desired or may require labeling, including significant use or distribution restrictions or safety warnings. Alpine or a collaborator may be required to perform additional or unanticipated clinical trials to obtain approval or be subject to post-marketing testing requirements to maintain regulatory approval. If therapeutic candidates Alpine develops using Alpine’s vIgD platform prove to be ineffective, unsafe or commercially unviable, Alpine’s entire platform and pipeline would have little, if any, value, which could have a material adverse effect on Alpine’s business, financial condition, results of operations, and prospects.

The market may not be receptive to Alpine’s therapeutic products based on a novel therapeutic modality, and Alpine may not generate any future revenue from the sale or licensing of therapeutic products.

Even if approval is obtained for a therapeutic candidate, Alpine may not generate or sustain revenue from sales of the therapeutic product due to factors such as whether the therapeutic product can be sold at a competitive price and otherwise accepted in the market, and therefore any revenue from sales of the therapeutic product may not offset the cost of development. The therapeutic candidates Alpine is developing are based on

new technologies and therapeutic approaches. Market participants with significant influence over acceptance of new treatments, such as physicians and third-party payors, may not adopt a treatment based on Alpine’s vIgDs, and Alpine may not be able to convince the medical community and third-party payors to accept and use, or to provide favorable coverage or reimbursement for, any therapeutic products developed by Alpine or Alpine’s existing collaborator or any future collaborators. Market acceptance of Alpine’s therapeutic products will depend on, among other factors:

With Alpine’s focus on protein engineering wild-type IgSFs, these risks may increase to the extent this field becomes more competitive or less favored in the commercial marketplace. Additional risks apply in relation to any disease indications Alpine pursues which are classified as rare diseases and allow for orphan drug designation by regulatory agencies in major commercial markets, such as the U.S., EU and Japan. Because of the small patient population for a rare disease, if pricing is not approved or accepted in the market at an appropriate level for an approved therapeutic product with orphan drug designation, such drug may not generate enough revenue to offset costs of development, manufacturing, marketing, and commercialization despite any benefits received from the orphan drug designation, such as market exclusivity, assistance in clinical trial design, or a reduction in user fees or tax credits related to development expense. Market size is also a variable in disease indications not classified as rare. Alpine’s estimates regarding potential market size for any rare indication may be materially different from what Alpine discovers to exist at the time Alpine commences commercialization, if any, for a therapeutic product, which could result in significant changes in Alpine’s business plan and have a material adverse effect on Alpine’s business, financial condition, results of operations, and prospects.

If a therapeutic product with orphan drug designation subsequently receives the first FDA approval for the indication for which it has such designation, the therapeutic product is entitled to orphan product exclusivity, which means the FDA may not approve any other applications to market the same therapeutic product for the same indication, except in very limited circumstances, for seven years. Orphan drug exclusivity, however, could also block the approval of one of Alpine’s therapeutic products for seven years if a competitor obtains approval of the same therapeutic product as defined by the FDA or if Alpine’s therapeutic product is determined to be within the same class as the competitor’s therapeutic product for the same indication or disease.

As in the U.S., Alpine may apply for designation of a therapeutic product as an orphan drug for the treatment of a specific indication in the EU before the application for marketing authorization is made. Sponsors of orphan drugs in the EU can enjoy economic and marketing benefits, including up to ten years of market exclusivity for the approved indication unless another applicant can show its therapeutic product is safer, more

effective, or otherwise clinically superior to the orphan-designated therapeutic product. The respective orphan designation and exclusivity frameworks in the U.S. and in the EU are subject to change, and any such changes may affect Alpine’s ability to obtain EU or U.S. orphan designations in the future.

Alpine’s therapeutic candidates are in early stages of development and may fail in development or suffer delays that materially and adversely affect their commercial viability.

Alpine has no products on the market and all of Alpine’s therapeutic candidates are in early stages of development. Alpine’s ability to achieve and sustain profitability depends on obtaining regulatory approvals, Institutional Review Board (“IRB”) approval to conduct clinical trials at particular sites, and successfully commercializing Alpine’s therapeutic candidates, either alone or with third parties, such as its collaborator Kite. Before obtaining regulatory approval for the commercial distribution of Alpine’s therapeutic candidates, Alpine or a collaborator must conduct extensive preclinical tests and clinical trials to demonstrate the safety and efficacy in humans of Alpine’s therapeutic candidates. Preclinical testing and clinical trials are expensive, difficult to design and implement, can take many years to complete, and are uncertain as to outcome. The start or end of a clinical study is often delayed or halted due to changing regulatory requirements, manufacturing challenges, required clinical trial administrative actions, slower than anticipated patient enrollment, changing standards of care, availability or prevalence of use of a comparative therapeutic or required prior therapy, clinical outcomes, or financial constraints. For instance, delays or difficulties in patient enrollment or difficulties in retaining trial participants can result in increased costs, longer development times, or termination of a clinical trial. Clinical trials of a new therapeutic candidate require the enrollment of a sufficient number of patients, including patients who are suffering from the disease the therapeutic candidate is intended to treat and who meet other eligibility criteria. Rates of patient enrollment are affected by many factors, including the size of the patient population, the eligibility criteria for the clinical trial, the age and condition of the patients, the stage and severity of disease, the nature of the protocol, the proximity of patients to clinical sites, and the availability of effective treatments for the relevant disease.

A therapeutic candidate can unexpectedly fail at any stage of preclinical and clinical development. The historical failure rate for therapeutic candidates is high due to scientific feasibility, safety, efficacy, changing standards of medical care, and other variables. The novelty of Alpine’s platform may mean that Alpine’s failure rates are higher than historical norms. The results from preclinical testing or early clinical trials of a therapeutic candidate may not predict the outcome of later phase clinical trials of the therapeutic candidate, particularly in immuno-oncology and inflammatory disorders. Alpine, the FDA, an IRB, an independent ethics committee, or other applicable regulatory authorities may suspend clinical trials of a therapeutic candidate at any time for various reasons, including a belief that subjects participating in such trials are being exposed to unacceptable health risks or adverse side effects. Similarly, an IRB or ethics committee may suspend a clinical trial at a particular trial site. Alpine may not have the financial resources to continue development of, or to enter into collaborations for, a therapeutic candidate if Alpine experiences any problems or other unforeseen events delaying or preventing regulatory approval of, or Alpine’s ability to commercialize, therapeutic candidates, including:

Product development involves a lengthy and expensive process with an uncertain outcome, and results of earlier pre-clinical and clinical trials may not be predictive of future clinical trial results.

Clinical testing is expensive and generally takes many years to complete, and the outcome is inherently uncertain. Failure can occur at any time during the clinical trial process. The results of pre-clinical trials and early clinical trials of Alpine’s product candidates may not be predictive of the results of larger, later-stage controlled clinical trials. Product candidates that have shown promising results in early-stage clinical trials may still suffer significant setbacks in subsequent clinical trials. Alpine has conducted no clinical trials to date. Alpine will have to conduct trials in its proposed indications to verify the results obtained to date and to support any regulatory submissions for further clinical development. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles despite promising results in earlier, smaller clinical trials. Moreover, clinical data are often susceptible to varying interpretations and analyses. Alpine does not know whether Phase 1, Phase 2, Phase 3, or other clinical trials Alpine may conduct will demonstrate consistent or adequate efficacy and safety with respect to the proposed indication for use sufficient to receive regulatory approval or market its therapeutic candidates.

To date, Alpine’s revenue has been primarily derived from Alpine’s license and research agreement with Kite, and Alpine is dependent on Kite for the successful development of therapeutic candidates in the collaboration.

In October 2015, Alpine entered into an exclusive, worldwide license and research agreement with Kite to research, develop, and commercialize engineered autologous T cell therapies incorporating two programs from Alpine’s technology. Under the terms of the license and research agreement, Alpine will conduct initial research to deliver two program TIPs with certain pre-defined characteristics. Kite will then conduct further research on the program TIPs with the goal of demonstrating proof-of-concept. If successful, Kite would further engineer the program TIPs into certain CAR-T and TCR product candidates potentially enhancing anti-tumor response. Pursuant to the license and research agreement, Kite paid Alpine a $5.0 million upfront payment. Kite also paid $0.5 million in additional payments to support Alpine’s research. Alpine will be potentially eligible to receive up to $530.0 million in total milestone payments upon the successful completion of research, clinical, and regulatory milestones relating to both program TIPs. At Kite’s option, a portion of the milestone payments may be paid in shares of Kite’s common stock. Alpine will also potentially be eligible to receive a low single digit royalty for

sales on a licensed product-by-licensed product and country-by-country basis, until the later of (i) the date on which the licensed product is no longer covered by certain intellectual property rights, and (ii) the expiration of a defined term beginning on the first commercial sale of the licensed product.

Continued success of Alpine’s collaboration with Kite, and its realization of the milestone and royalty payments under the agreement, depends entirely upon the efforts of Kite. Kite has sole discretion in determining and directing the efforts and resources, including the ability to discontinue all efforts and resources, it applies to the development and, if approval is obtained, commercialization and marketing of the therapeutic candidates covered by the collaboration. Kite may not be effective in obtaining approvals for the therapeutic candidates developed under the collaboration arrangement or marketing or arranging for necessary supply, manufacturing, or distribution relationships for any approved products. Kite may change its strategic focus or pursue alternative technologies in a manner resulting in reduced, delayed, or no revenue to Alpine. Kite has a variety of marketed products and its own corporate objectives and strategies may not be consistent with Alpine’s best interests. If Kite fails to develop, obtain regulatory approval for, or ultimately commercialize any therapeutic candidate under the Alpine collaboration or if Kite terminates the Alpine collaboration, Alpine’s business, financial condition, results of operations, and prospects could be materially and adversely affected. In addition, any dispute or litigation proceedings Alpine may have with Kite in the future could delay development programs, create uncertainty as to ownership of intellectual property rights, distract management from other business activities and generate substantial expense.

If Alpine is unable to secure intellectual property rights to programs covered under the license and research agreement, Kite may terminate the agreement and Alpine’s business, financial condition, results of operations, and prospects could be materially and adversely affected. In addition, any dispute or litigation proceedings Alpine may have with Kite related to intellectual property rights or other aspects of the agreement or the relationship could delay development programs, create uncertainty as to ownership of intellectual property rights, may distract management from other business activities and generate substantial expense.

If third parties on which Alpine depends to conduct its preclinical studies, or any future clinical trials, do not perform as expected, fail to satisfy regulatory or legal requirements, or miss expected deadlines, Alpine’s development program could be delayed, which may result in materially adverse effects on Alpine’s business, financial condition, results of operations and prospects.

Alpine relies in part on third party clinical investigators, contract research organizations (“CROs”), clinical data management organizations, and consultants to design, conduct, supervise, and monitor preclinical studies of Alpine’s therapeutic candidates and may do the same for any clinical trials. Because Alpine relies on third parties to conduct preclinical studies or clinical trials, Alpine has less control over the timing, quality, compliance, and other aspects of preclinical studies and clinical trials than Alpine would if Alpine conducted all preclinical studies and clinical trials on its own. These investigators, CROs and consultants are not Alpine’s employees and Alpine has limited control over the amount of time and resources they dedicate to Alpine’s programs. These third parties may have contractual relationships with other entities, some of which may be Alpine’s competitors, which may draw time and resources from Alpine’s programs. The third parties with which Alpine contracts might not be diligent, careful, compliant, or timely in conducting Alpine’s preclinical studies or clinical trials, resulting in the preclinical studies or clinical trials being delayed or unsuccessful.

If Alpine cannot contract with acceptable third parties on commercially reasonable terms, or at all, or if these third parties do not carry out their expected duties, satisfy legal and regulatory requirements for the conduct of preclinical studies or clinical trials, or meet expected deadlines, Alpine’s clinical development programs could be delayed and otherwise adversely affected. In all events, Alpine is responsible for ensuring each of its preclinical studies and clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. The FDA and certain foreign regulatory authorities, such as the EMA, require preclinical studies to be conducted in accordance with applicable Good Laboratory Practices (“GLPs”) and clinical trials to be conducted in accordance with applicable FDA regulations and Good Clinical Practices (“GCPs”), including requirements for conducting, recording, and reporting the results of preclinical studies and clinical trials to assure

data and reported results are credible and accurate and the rights, integrity, and confidentiality of clinical trial participants are protected. Alpine’s reliance on third parties Alpine does not control and does not relieve Alpine of these responsibilities and requirements. Any such event could have a material adverse effect on Alpine’s business, financial condition, results of operations, and prospects.

Because Alpine relies on third party manufacturing and supply partners, Alpine’s supply of clinical trial materials may become limited or interrupted or may not be of satisfactory quantity or quality.

Alpine has established in-house recombinant protein generation capabilities for producing sufficient protein materials to enable a portion of its current preclinical studies. Alpine relies on third party supply and manufacturing partners to supply the materials, components, and manufacturing services for a portion of preclinical studies and its clinical trial drug supplies. Alpine does not own manufacturing facilities or supply sources for such components and materials for clinical trial supplies and its current manufacturing facilities are insufficient to supply sources for such components and materials for all of its preclinical studies. Certain raw materials necessary for the manufacture of Alpine’s therapeutic products, such as cell lines, are available from a single or limited number of source suppliers on a purchase order basis. There can be no assurance that Alpine’s supply of research and development, preclinical study, and clinical trial drugs and other materials will not be limited, interrupted, restricted in certain geographic regions, or of satisfactory quality or quantity, or continue to be available at acceptable prices. In particular, any replacement of Alpine’s therapeutic substance manufacturer could require significant effort and expertise and could result in significant delay of Alpine’s preclinical or clinical activities because there may be a limited number of qualified replacements.

The manufacturing process for a therapeutic candidate is subject to FDA and foreign regulatory authority review. Suppliers and manufacturers must meet applicable manufacturing requirements and undergo rigorous facility and process validation tests required by regulatory authorities in order to comply with regulatory standards, such as cGMPs. In the event any of Alpine’s suppliers or manufacturers fails to comply with such requirements or to perform its obligations to Alpine in relation to quality, timing, or otherwise, or if Alpine’s supply of components or other materials becomes limited or interrupted for other reasons, Alpine may experience shortages resulting in delayed shipments, supply constraints, and/or stock-outs of Alpine’s products, be forced to manufacture the materials itself, for which Alpine currently does not have the capabilities or resources, or enter into an agreement with another third party, which Alpine may not be able to do on reasonable terms, if at all. In some cases, the technical skills or technology required to manufacture Alpine’s therapeutic candidates may be unique or proprietary to the original manufacturer and Alpine may have difficulty, or there may be contractual and intellectual property restrictions prohibiting Alpine from, transferring such skills or technology to another third party and a feasible alternative may not exist. These factors may increase Alpine’s reliance on such manufacturer or require Alpine to obtain a license from such manufacturer in order to have another third party manufacture Alpine’s therapeutic candidates. If Alpine is required to change manufacturers for any reason, Alpine will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations. The delays associated with the verification of a new manufacturer could negatively affect Alpine’s ability to develop therapeutic candidates in a timely manner or within budget or at all.

Alpine expects to continue to rely on third party manufacturers if Alpine receives regulatory approval for any therapeutic candidate. To the extent Alpine has existing, or enters into future, manufacturing arrangements with third parties, Alpine will depend on these third parties to perform their obligations in a timely manner consistent with contractual and regulatory requirements, including those related to quality control and assurance. If Alpine is unable to obtain or maintain third-party manufacturing for therapeutic candidates, or to do so on commercially reasonable terms, Alpine may not be able to develop and commercialize Alpine’s therapeutic candidates successfully. Alpine’s or a third party’s failure to execute on Alpine’s manufacturing requirements could adversely affect Alpine’s business in a number of ways, including as a result of:

Alpine may not successfully engage in strategic transactions, including any additional collaborations Alpine seeks, which could adversely affect Alpine’s ability to develop and commercialize therapeutic candidates, impact Alpine’s cash position, increase Alpine’s expenses, and present significant distractions to Alpine’s management.

From time to time, Alpine may consider strategic transactions, such as collaborations, acquisitions of companies, asset purchases, and out- or in-licensing of therapeutic candidates or technologies. In particular, in addition to Alpine’s current arrangements with Kite, Alpine intends to evaluate and, if strategically attractive, seek to enter into additional collaborations, including with major biotechnology or pharmaceutical companies. The competition for collaborative partners is intense, and the negotiation process is time-consuming and complex. Any new collaboration may be on suboptimal terms for Alpine, and Alpine may be unable to maintain any new or existing collaboration if, for example, development or approval of a therapeutic candidate is delayed, sales of an approved therapeutic candidate do not meet expectations, or the collaborator terminates the collaboration. Any such collaboration, or other strategic transaction, may require Alpine to incur non-recurring or other charges, increase Alpine’s near- and long-term expenditures and pose significant integration or implementation challenges or disrupt Alpine’s management or business.

These transactions would entail numerous operational and financial risks, including:

Accordingly, although there can be no assurance Alpine will undertake or successfully complete any transactions of the nature described above, any transactions Alpine does complete may be subject to the foregoing or other risks and have a material adverse effect on Alpine’s business, results of operations, financial condition, and prospects. Conversely, any failure to enter any collaboration or other strategic transaction that would be beneficial to Alpine could delay the development and potential commercialization of Alpine’s therapeutic candidates and have a negative impact on the competitiveness of any therapeutic candidate reaching market.

Alpine faces competition from entities that have developed or may develop therapeutic candidates for Alpine’s target disease indications, including companies developing novel treatments and technology platforms based on modalities and technology similar to Alpine. If these companies develop technologies or therapeutic candidates more rapidly than Alpine does, or their technologies, including delivery technologies, are more effective, Alpine’s ability to develop and successfully commercialize therapeutic candidates may be adversely affected.

The development and commercialization of therapeutic candidates is highly competitive. Alpine believes a significant number of products are currently under development, and may become commercially available in the future, for the treatment of conditions for which Alpine may try to develop therapeutic candidates. There are also competitors to Alpine’s proprietary therapeutic candidates currently in development, some of which may become commercially available before Alpine’s therapeutic candidates.

Alpine competes with a variety of multinational pharmaceutical companies and specialized biotechnology companies, as well as with technologies being developed at universities and other research institutions. Alpine’s competitors have developed, are developing or may develop therapeutic candidates and processes competitive with Alpine’s therapeutic candidates. Competitive therapeutic treatments include those already approved and accepted by the medical community and any new treatments entering or about to enter the market. Alpine is aware of multiple companies developing therapies with the same target as Alpine’s lead program (ICOSL/CD28) as well as companies building novel platforms to generate multi-specific antibody or non-antibody-based targeting proteins. While it is still premature for Alpine to determine which indications may be targeted by its lead program, potential competitors to Alpine’s lead program include:

Additionally, there are a number of other therapies for inflammatory diseases or cancer approved or in development that are also competitive with Alpine’s lead program and other programs in development. Many of the other therapies include other types of immunotherapies with different targets than Alpine’s programs. Other potentially competitive therapies work in ways distinct from Alpine’s development programs.

Many of Alpine’s competitors have significantly greater financial, technical, manufacturing, marketing, sales, and supply resources or experience than Alpine has. If Alpine successfully obtains approval for any therapeutic candidate, Alpine will face competition based on many different factors, including safety and effectiveness, ease with which Alpine’s products can be administered and the extent to which patients accept relatively new routes of administration, timing and scope of regulatory approvals, availability and cost of manufacturing, marketing, and sales capabilities, price, reimbursement coverage, and patent position of Alpine’s products. Competing products could present superior treatment alternatives, including by being more effective, safer, less expensive, or marketed and sold more effectively than any products Alpine may develop. Competitive products may make any products Alpine develops obsolete or noncompetitive before Alpine recovers the expense of developing and commercializing Alpine’s therapeutic candidates. Competitors could also recruit Alpine’s employees, which could negatively impact Alpine’s ability to execute Alpine’s business plan.

Any inability to attract and retain qualified key management and technical personnel would impair Alpine’s ability to implement Alpine business plan.

Alpine’s success largely depends on the continued service of key management and other specialized personnel, including Mitchell H. Gold, M.D., Alpine’s Executive Chairman and Chief Executive Officer, Jay R. Venkatesan, M.D., Alpine’s President and a member of Alpine’s board of directors, Stanford Peng, M.D., Ph.D., Alpine’s Executive Vice President of Research and Development and Chief Medical Officer, Ryan Swanson, Alpine’s Vice President of Immunology, Michael Kornacker, Ph.D., Alpine’s Vice President of Protein Engineering and Paul Rickey, Alpine’s Senior Vice President and Chief Financial Officer.

The loss of one or more members of Alpine’s management team or other key employees or advisors could delay Alpine’s research and development programs and materially harm Alpine’s business, financial condition, results of operations, and prospects. The relationships Alpine’s key managers have cultivated within Alpine’s industry make Alpine particularly dependent upon their continued employment with Alpine. Alpine is dependent on the continued service of its technical personnel because of the highly technical nature of Alpine’s therapeutic candidates and technologies, and the specialized nature of the regulatory approval process. Because Alpine’s management team and key employees are not obligated to provide Alpine with continued service, they could terminate their employment with Alpine at any time without penalty. Alpine does not maintain key person life insurance policies on any of Alpine’s management team members or key employees. Alpine’s future success will depend in large part on Alpine’s continued ability to attract and retain other highly qualified scientific, technical, and management personnel, as well as personnel with expertise in clinical testing, manufacturing, governmental regulation, and commercialization. Alpine faces competition for personnel from other companies, universities, public and private research institutions, government entities, and other organizations, including significant competition in the Seattle employment market.

If Alpine’s therapeutic candidates advance into clinical trials, Alpine may experience difficulties in managing its growth and expanding its operations.

Alpine has limited experience in therapeutic development and very limited experience with clinical trials of therapeutic candidates. As its therapeutic candidates enter and advance through preclinical studies and any clinical trials, Alpine will need to expand its development, regulatory, and manufacturing capabilities or contract with other organizations to provide these capabilities for it. In the future, Alpine expects to have to manage additional relationships with collaborators or partners, suppliers, and other organizations. Alpine’s ability to manage its operations and future growth will require Alpine to continue to improve its operational, financial, and

management controls, reporting systems, and procedures. Alpine may not be able to implement improvements to its management information and control systems in an efficient or timely manner and may discover deficiencies in existing systems and controls.

If any of Alpine’s therapeutic candidates are approved for marketing and commercialization and Alpine is unable to develop sales, marketing and distribution capabilities on its own or enter into agreements with third parties to perform these functions on acceptable terms, Alpine may be unable to successfully commercialize any such future products.

Alpine currently has no sales, marketing, or distribution capabilities or experience. If any of Alpine’s therapeutic candidates are approved, Alpine will need to develop internal sales, marketing, and distribution capabilities to commercialize such products, which may be expensive and time-consuming, or enter into collaborations with third parties to perform these services. If Alpine decides to market its products directly, Alpine will need to commit significant financial, legal, and managerial resources to develop a marketing and sales force with technical expertise and supporting distribution, administration, and compliance capabilities. If Alpine relies on third parties with such capabilities to market Alpine’s approved products, or decides to co-promote products with collaborators, Alpine will need to establish and maintain marketing and distribution arrangements with third parties, and there can be no assurance Alpine will be able to enter into such arrangements on acceptable, compliant terms or at all. In entering into third-party marketing or distribution arrangements, any revenue Alpine receives will depend upon the efforts of the third parties and there can be no assurance such third parties will establish adequate sales and distribution capabilities or be successful in gaining market acceptance of any approved therapeutic. If Alpine is not successful in commercializing any therapeutic approved in the future, either on its own or through third parties, Alpine’s business, financial condition, results of operations, and prospects could be materially and adversely affected.

If Alpine fails to comply with U.S. and foreign regulatory requirements, regulatory authorities could limit or withdraw any marketing or commercialization approvals Alpine may receive and subject Alpine to other penalties that could materially harm Alpine’s business.

Alpine, its therapeutic candidates, its suppliers, and its contract manufacturers, distributors, and contract testing laboratories are subject to extensive regulation by governmental authorities in the EU, the U.S., and other countries, with the regulations differing from country to country.

Even if Alpine receives marketing and commercialization approval of a therapeutic candidate, Alpine and its third-party service providers will be subject to continuing regulatory requirements, including a broad array of regulations related to establishment registration and product listing, manufacturing processes, risk management measures, quality and pharmacovigilance systems, post-approval clinical studies, labeling, advertising and promotional activities, record keeping, distribution, adverse event reporting, import and export of pharmaceutical products, pricing, sales, and marketing, and fraud and abuse requirements. Any product promotion and advertising will also be subject to regulatory requirements and continuing regulatory review.

Alpine is required to submit safety and other post market information and reports, and is subject to continuing regulatory review, including in relation to adverse patient experiences with the product and clinical results that are reported after a product is made commercially available, both in the U.S. and in any foreign jurisdiction in which Alpine seeks regulatory approval. The FDA and certain foreign regulatory authorities, such as the EMA, have significant post-market authority, including the authority to require labeling changes based on new safety information and to require post-market studies or clinical trials to evaluate safety risks related to the use of a product or to require withdrawal of the product from the market.

The FDA also has the authority to require a Risk Evaluation and Mitigation Strategies (“REMS”) plan either before or after approval, which may impose further requirements or restrictions on the distribution or use of an approved therapeutic. The EMA now routinely requires risk management plans (“RMPs”) as part of the marketing authorization application process, and such plans must be continually modified and updated

throughout the lifetime of the product as new information becomes available. In addition, the relevant governmental authority of any EU member state can request an RMP whenever there is a concern about the risk/benefit balance of the product.

The manufacturers and manufacturing facilities Alpine uses to make a future product, if any, will also be subject to periodic review and inspection by the FDA and other regulatory agencies, including for continued compliance with cGMP requirements. The discovery of any new or previously unknown problems with Alpine’s third-party manufacturers, manufacturing processes or facilities may result in restrictions on the product, manufacturers or facilities, including withdrawal of the product from the market. If Alpine relies on third-party manufacturers, Alpine will not have control over compliance with applicable rules and regulations by such manufacturers.

If Alpine or Alpine’s collaborators, manufacturers, or service providers fail to comply with applicable continuing regulatory requirements in the U.S. or foreign jurisdictions in which Alpine seeks to market its products, Alpine may be subject to, among other things, fines, warning and untitled letters, clinical holds, delay or refusal by the FDA or foreign regulatory authorities to approve pending applications or supplements to approved applications, suspension, refusal to renew or withdrawal of regulatory approval, product recalls, seizures, or administrative detention of products, refusal to permit the import or export of products, operating restrictions, inability to participate in government programs including Medicare and Medicaid, and total or partial suspension of production or distribution, injunction, restitution, disgorgement, debarment, civil penalties, and criminal prosecution.

Price controls imposed in foreign markets may adversely affect Alpine’s future profitability.

In most countries, the pricing of prescription drugs is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after receipt of marketing approval for a product. In addition, there can be considerable pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic, and regulatory developments may further complicate pricing and reimbursement negotiations, and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by various EU member states and parallel distribution, or arbitrage between low-priced and high-priced member states, can further reduce prices. In some countries, Alpine or Alpine’s collaborators may be required to conduct a clinical trial or other studies comparing the cost-effectiveness of Alpine’s vIgD therapeutic candidates to other available therapies in order to obtain or maintain reimbursement or pricing approval. Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries. If reimbursement of any product candidate approved for marketing is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, Alpine’s business, financial condition, results of operations, or prospects could be adversely affected.

Alpine’s business entails a significant risk of product liability and Alpine’s ability to obtain sufficient insurance coverage could harm Alpine’s business, financial condition, results of operations, or prospects.

Alpine’s business exposes it to significant product liability risks inherent in the development, testing, manufacturing, and marketing of therapeutic treatments. Product liability claims could delay or prevent completion of Alpine’s development programs. If Alpine succeeds in marketing products, such claims could result in an investigation by certain regulatory authorities, such as FDA or foreign regulatory authorities, of the safety and effectiveness of Alpine’s products, Alpine’s manufacturing processes and facilities, or Alpine’s marketing programs and potentially a recall of Alpine’s products or more serious enforcement action, limitations on the approved indications for which they may be used, or suspension or withdrawal of approvals. Regardless of the merits or eventual outcome, liability claims may also result in decreased demand for Alpine’s products, injury to Alpine’s reputation, costs to defend the related litigation, a diversion of management’s time and Alpine’s

resources, substantial monetary awards to trial participants or patients, and a decline in Alpine’s valuation. Alpine currently has product liability insurance it believes is appropriate for its stage of development and may need to obtain higher levels of product liability insurance prior to marketing any of its therapeutic candidates. Any insurance Alpine has or may obtain may not provide sufficient coverage against potential liabilities. Furthermore, clinical trial and product liability insurance is becoming increasingly expensive. As a result, Alpine may be unable to obtain sufficient insurance at a reasonable cost to protect Alpine against losses caused by product liability claims with a potentially material adverse effect on Alpine’s business.

Alpine’s employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on Alpine’s business.

Alpine is exposed to the risk of employee fraud or other misconduct. Misconduct by employees could include, but is not limited to:

In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws, regulations, guidance and codes of conduct intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws, regulations, guidances, and codes of conduct may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive program, health care professional, and other business arrangements.

Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions, including debarment or disqualification of those employees from participation in FDA regulated activities and serious harm to Alpine’s reputation. This could include violations of provisions of the U.S. federal Health Insurance Portability and Accountability Act (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), other U.S. federal and state law, and requirements of non-U.S. jurisdictions, including the European Union Data Protection Directive.

It is not always possible to identify and deter employee misconduct, and the precautions Alpine takes to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting Alpine from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws, regulations, guidance, or codes of conduct. If any such actions are instituted against Alpine, and Alpine is not successful in defending itself or asserting its rights, those actions could have a significant impact on Alpine’s business, including the imposition of significant fines, exclusion from government programs, or other sanctions.

Alpine’s business involves the use of hazardous materials and Alpine and its third-party manufacturers must comply with environmental laws and regulations, which may be expensive and restrict how it conducts business.

Alpine’s third-party manufacturers’ activities and Alpine’s own activities involve the controlled storage, use and disposal of hazardous and flammable materials, including the components of Alpine’s pharmaceutical

product candidates, test samples and reagents, biological materials and other hazardous compounds. Alpine and its manufacturers are subject to federal, state, local and foreign laws and regulations governing the use, generation, manufacture, storage, handling and disposal of these hazardous materials. Alpine currently carries no insurance specifically covering environmental claims relating to the use of hazardous materials. Although Alpine believes that its safety procedures for handling and disposing of these materials and waste products comply with the standards prescribed by these laws and regulations, Alpine cannot eliminate the risk of accidental injury or contamination from the use, storage, handling or disposal of hazardous materials. In the event of an accident, state or federal or other applicable authorities may curtail Alpine’s use of these materials and/or interrupt Alpine’s business operations. In addition, if an accident or environmental discharge occurs, or if Alpine discovers contamination caused by prior operations, including by prior owners and operators of properties Alpine acquires, Alpine could be liable for cleanup obligations, damages and fines. If such unexpected costs are substantial, this could significantly harm Alpine’s financial condition and results of operations.

Compliance with governmental regulations regarding the treatment of animals used in research could increase Alpine’s operating costs, which would adversely affect the commercialization of Alpine’s technology.

The Animal Welfare Act (“AWA”) is the federal law that covers the treatment of certain animals used in research. Currently, the AWA imposes a wide variety of specific regulations that govern the humane handling, care, treatment and transportation of certain animals by producers and users of research animals, most notably relating to personnel, facilities, sanitation, cage size, and feeding, watering and shipping conditions. Third parties with whom Alpine contracts are subject to registration, inspections and reporting requirements under the AWA. Furthermore, some states have their own regulations, including general anti-cruelty legislation, which establish certain standards in handling animals. Comparable rules, regulations, and or obligations exist in many foreign jurisdictions. If Alpine or Alpine’s contractors fail to comply with regulations concerning the treatment of animals used in research, Alpine may be subject to fines and penalties and adverse publicity, and Alpine’s operations could be adversely affected.

Alpine’s information technology systems could face serious disruptions adversely affecting Alpine’s business.

Alpine’s information technology and other internal infrastructure systems, including corporate firewalls, servers, leased lines, and connection to the Internet, face the risk of systemic failure potentially disruptive to Alpine’s operations. A significant disruption in the availability of Alpine’s information technology and other internal infrastructure systems could cause interruptions in Alpine’s collaborations with Alpine’s partners and delays in Alpine’s research and development work.

Alpine’s current operations are concentrated in one location and any events affecting this location may have material adverse consequences.

Alpine’s current operations are located in Alpine’s facilities situated in Seattle. Any unplanned event, such as flood, fire, explosion, earthquake, extreme weather condition, medical epidemics, power shortage, power outage, telecommunication failure, or other natural or manmade accidents or incidents resulting in Alpine being unable to fully utilize the facilities, may have a material adverse effect on Alpine’s ability to operate its business, particularly on a daily basis, and have significant negative consequences on Alpine’s financial and operating conditions. Loss of access to these facilities may result in increased costs, delays in the development of Alpine’s therapeutic candidates, or interruption of Alpine’s business operations. As part of Alpine’s risk management policy, Alpine maintains insurance coverage at levels it believes are appropriate for its business. However, in the event of an accident or incident at these facilities, Alpine cannot assure you the amounts of insurance will be sufficient to satisfy any damages and losses or that the insurance covers all risks. If Alpine’s facilities are unable to operate because of an accident or incident or for any other reason, even for a short period of time, any or all of Alpine’s research and development programs may be harmed. Any business interruption may have a material adverse effect on Alpine’s business, financial position, results of operations, and prospects.

The investment of Alpine’s cash, cash equivalents, and fixed income in marketable securities is subject to risks which may cause losses and affect the liquidity of these investments.

As of March 31, 2017, Alpine had $13.6 million in cash and cash equivalents. Alpine expects to invest its excess cash in marketable securities. These investments are subject to general credit, liquidity, market and interest rate risks, including potential future impacts similar to the impact of U.S. sub-prime mortgage defaults previously affecting various sectors of the financial markets and which caused credit and liquidity issues. Alpine may realize losses in the fair value of these investments, an inability to access cash in these investments for a potentially meaningful period, or a complete loss of these investments, which would have a negative effect on Alpine’s financial statements.

In addition, should Alpine’s investments cease paying or reduce the amount of interest paid to Alpine, Alpine’s interest income would suffer. The market risks associated with Alpine’s investment portfolio may have an adverse effect on Alpine’s results of operations, liquidity, and financial condition.

Changes in accounting rules and regulations, or interpretations thereof, could result in unfavorable accounting charges or require Alpine to change Alpine’s compensation policies.

Accounting methods and policies for biopharmaceutical companies, including policies governing revenue recognition, research and development and related expenses, and accounting for stock-based compensation, are subject to review, interpretation, and guidance from Alpine’s auditors and relevant accounting authorities, including the Securities and Exchange Commission. Changes to accounting methods or policies, or interpretations thereof, may require Alpine to reclassify, restate, or otherwise change or revise Alpine’s financial statements, including those contained in this proxy statement/prospectus/information statement.

Alpine’s business may be affected by litigation and government investigations.

Alpine may from time to time receive inquiries and subpoenas and other types of information requests from government authorities and others and Alpine may become subject to claims and other actions related to Alpine’s business activities. While the ultimate outcome of investigations, inquiries, information requests, and legal proceedings is difficult to predict, defense of litigation claims can be expensive, time-consuming and distracting, and adverse resolutions or settlements of those matters may result in, among other things, modification of Alpine’s business practices, costs, and significant payments, any of which could have a material adverse effect on Alpine’s business, financial condition, results of operations, and prospects.

Alpine believes its development programs and platform have a particular mechanism of action, but this mechanism of action has not been proven conclusively.

Alpine’s vIgD platform is novel and the underlying science is not exhaustively understood or conclusively proven. In particular, the interaction of vIgDs with the immune synapse, the ability of vIgDs to slow, stop, restart, or accelerate immune responses, and the ability of vIgD domains to interact with multiple counterparties is still theoretical. Graphical representations of proposed mechanisms of action of Alpine’s therapies, the size, actual or relative, of Alpine’s therapeutics, and how Alpine’s therapeutics might interface with other cells within the human body or inside the tumor microenvironment are similarly theoretical and not yet conclusively proven. The lack of a proven mechanism of action may adversely affect Alpine’s ability to rise sufficient capital, complete preclinical studies, adequately manufacture drug substance, obtain regulatory clearance for clinical trials, or interfere with Alpine’s ability to market its product to patients and physicians or achieve reimbursement from payors.

Because Alpine has no products currently in human clinical trials, any inability to present Alpine’s data in scientific journals or at scientific conferences could adversely impact Alpine’s business and stock price.

Alpine may from time to time submit data related to its research and development in peer-reviewed scientific publications or apply to present data related to its research and development at scientific or other

conferences. Alpine has no control over whether these submissions or applications are accepted. Even if accepted for a conference, Alpine has no control over whether presentations at scientific conferences will be accepted for oral presentation, poster presentation, or abstract publication only. Even when accepted for publication, Alpine has no control over the timing of the release of the publication. Rejection by publications, delays in publication, rejection for presentation, or a less-preferred format for a presentation may adversely impact Alpine’s stock price, ability to raise capital, and business.

Alpine’s business may be affected by adverse scientific publications or editorial or discussant opinions.

Alpine may from time to time publish data related to its research and development in peer-reviewed scientific publications or present data related to its research and development at scientific or other conferences. Editorials or discussants unrelated to Alpine may provide opinions on Alpine’s presented data unfavorable to Alpine. In addition, scientific publications or presentations may be made which are critical of Alpine’s science or research or the field of immunotherapy in general. This may adversely affect Alpine’s ability to raise necessary capital, complete preclinical studies, adequately manufacture drug substance, obtain regulatory clearance for clinical trials, or interfere with Alpine’s ability to market its product to patients and physicians or achieve reimbursement from payors.

If Alpine is not able to obtain and enforce patent protection for its technology, including therapeutic candidates, therapeutic products, and platform technology, development of its therapeutic candidates and platform, and commercialization of its therapeutic products may be materially and adversely affected.

Alpine’s success depends in part on its ability to obtain and maintain patents and other forms of intellectual property rights, including in-licenses of intellectual property rights of others, for Alpine’s technology, including platform and therapeutic candidates and products, methods used to manufacture Alpine’s therapeutic candidates and products and methods for treating patients using Alpine’s therapeutic candidates and products, as well as its ability to preserve Alpine’s trade secrets, to prevent third parties from infringing upon Alpine’s proprietary rights and to operate without infringing upon the proprietary rights of others. As of April 18, 2017, Alpine’s patent portfolio consists of over 11 pending patent applications. Alpine may not be able to apply for patents on certain aspects of Alpine’s technology, including therapeutic candidates and products, in a timely fashion or at all. Any future patents Alpine obtains may not be sufficiently broad to prevent others from using Alpine’s technology or from developing competing therapeutics and technology. There is no guarantee that any of Alpine’s pending patent applications will result in issued or granted patents, that any of Alpine’s issued or granted patents will not later be found to be invalid or unenforceable or that any issued or granted patents will include claims that are sufficiently broad to cover Alpine’s technology, including therapeutic candidates and products, or to provide meaningful protection from Alpine’s competitors. Moreover, the patent position of pharmaceutical and biotechnology companies can be highly uncertain because it involves complex legal and factual questions. Alpine will be able to protect Alpine’s proprietary rights from unauthorized use by third parties only to the extent that Alpine’s current and future technology, including therapeutic candidates and products, are covered by valid and enforceable patents or are effectively maintained as trade secrets. If third parties disclose or misappropriate Alpine’s proprietary rights, it may materially and adversely impact Alpine’s competitive position in the market.

The U.S. Patent and Trademark Office (“USPTO”) and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process. There are situations in which noncompliance can result in abandonment or lapse of a patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, competitors might be able to enter the market earlier than would otherwise have been the case. The standards applied by the USPTO and foreign patent offices in granting patents are not always applied uniformly or predictably. For example, there is no uniform worldwide policy regarding patentable subject matter or the scope of claims allowable in biotechnology and pharmaceutical patents. As such, Alpine does not know the

degree of future protection that it will have on its technology, including therapeutic candidates and products. While Alpine will endeavor to try to protect its technology, including therapeutic candidates and products, with intellectual property rights such as patents, as appropriate, the process of obtaining patents is time-consuming, expensive and sometimes unpredictable, and Alpine can provide no assurances that its technology, including therapeutic candidates and products, will be adequately protected in the future against unauthorized uses or competing claims by third parties.

In addition, recent and future changes to the patent laws and to the rules of the USPTO or other foreign patent offices may have a significant impact on Alpine’s ability to protect its technology, including therapeutic candidates and products, and enforce its intellectual property rights. For example, the Leahy-Smith America Invents Act enacted in 2011 involves significant changes in patent legislation. In addition, Alpine cannot assure you court rulings or interpretations of any court decision will not adversely impact Alpine’s patents or patent applications. In addition to increasing uncertainty with regard to Alpine’s ability to obtain patents in the future, there also may be uncertainty with respect to the value of patents, once obtained. Depending on decisions by the U.S. Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken Alpine’s ability to obtain new patents or to enforce Alpine’s existing patents and patents that Alpine might obtain in the future.

Once granted, patents may remain open to opposition, interference, re-examination, post-grant review, inter partes review, nullification or derivation action in court or before patent offices or similar proceedings for a given period before or after allowance or grant, during which time third parties can raise objections against such initial grant. In the course of such proceedings, which may continue for a protracted period of time, the patent owner may be compelled to limit the scope of the allowed or granted claims thus attacked, or may lose the allowed or granted claims altogether. Alpine’s patent risks include that:

Alpine licenses patent rights from third-party owners or licensees. If such owners or licensees do not properly or successfully obtain, maintain or enforce the patents underlying such licenses, or if they retain or license to others any competing rights, Alpine’s competitive position and business prospects may be materially and adversely affected.

Alpine does, and will continue to, rely on intellectual property rights licensed from third parties to protect Alpine’s technology, including platform technology, therapeutic candidates and products. Alpine is a party to a number of licenses that give Alpine rights to third-party intellectual property necessary or useful for Alpine’s business. Alpine also may license additional third-party intellectual property in the future. Alpine’s success will depend in part on the ability of Alpine’s licensors to obtain, maintain and enforce patent protection for Alpine’s licensed intellectual property, in particular those patents to which Alpine has secured exclusive rights. Alpine’s licensors may elect not to prosecute, or may be unsuccessful in prosecuting, the patent applications licensed to Alpine. Even if patents issue or are granted, Alpine’s licensors may fail to maintain these patents, may determine not to pursue litigation against other companies that are infringing these patents, or may pursue litigation less aggressively than Alpine would. Further, substantially all of Alpine’s existing licenses are non-exclusive and Alpine may not be able to obtain exclusive rights in licenses obtained in the future, which would potentially allow third parties to develop competing products or technology. Without protection for, or exclusive right to, the intellectual property Alpine licenses, other companies might be able to offer substantially identical products for sale, which could adversely affect Alpine’s competitive business position and harm Alpine’s business prospects. In addition, Alpine may sublicense its rights under its third-party licenses to current or future collaborators or any future strategic partners. Any impairment of these sublicensed rights could result in reduced revenue under or result in termination of an agreement by one or more of Alpine’s collaborators or any future strategic partners.

Alpine may be unable to protect its patent intellectual property rights throughout the world.

Obtaining a valid and enforceable issued or granted patent covering Alpine’s technology, including therapeutic candidates and products, in the U.S. and worldwide can be extremely costly. In jurisdictions where Alpine has not obtained patent protection, competitors may use Alpine’s technology, including therapeutic candidates and products, to develop their own products, and further, may commercialize such products in those jurisdictions and export otherwise infringing products to territories where Alpine has not obtained patent protection. In certain instances, a competitor may be able to export otherwise infringing products in territories where Alpine will obtain patent protection. In jurisdictions outside the U.S. where Alpine will obtain patent protection, it may be more difficult to enforce a patent as compared to the U.S. Competitor products may compete with Alpine’s future products in jurisdictions where Alpine does not or will not have issued or granted patents or where Alpine’s issued or granted patent claims or other intellectual property rights are not sufficient to prevent competitor activities in these jurisdictions. The legal systems of certain countries, particularly certain developing countries, make it difficult to enforce patents and such countries may not recognize other types of intellectual property protection, particularly that relating to biopharmaceuticals. This could make it difficult for Alpine to prevent the infringement of Alpine’s patents or marketing of competing products in violation of Alpine’s proprietary rights generally in certain jurisdictions. Proceedings to enforce Alpine’s patent rights in foreign jurisdictions could result in substantial cost and divert Alpine’s efforts and attention from other aspects of its business.

Alpine generally files a provisional patent application first (a priority filing) at the USPTO. A U.S. utility application and international application under the Patent Cooperation Treaty (“PCT”) are usually filed within twelve months after the priority filing. Based on the PCT filing, national and regional patent applications may be filed in various international jurisdictions, such as the European Union, Japan, Australia and Canada. Alpine has so far not filed for patent protection in all national and regional jurisdictions where such protection may be available. In addition, Alpine may decide to abandon national and regional patent applications before grant. Finally, the grant proceeding of each national or regional patent is an independent proceeding which may lead to situations in which applications might in some jurisdictions be refused by the relevant registration authorities, while granted by others. It is also quite common that depending on the country, various scopes of patent protection may be granted on the same therapeutic candidate, product or technology.

The laws of some jurisdictions do not protect intellectual property rights to the same extent as the laws in the U.S., and many companies have encountered significant difficulties in protecting and defending such rights in such jurisdictions. If Alpine or Alpine’s licensors encounter difficulties in protecting, or are otherwise precluded from effectively protecting, the intellectual property rights important for Alpine’s business in such jurisdictions, the value of these rights may be diminished and Alpine may face additional competition from others in those jurisdictions. Many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In addition, many countries limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of such patent. If Alpine or any of Alpine’s licensors are forced to grant a license to third parties with respect to any patents relevant to Alpine’s business, Alpine’s competitive position in the relevant jurisdiction may be impaired and Alpine’s business and results of operations may be adversely affected.

Alpine or Alpine’s licensors, collaborators or any future strategic partners may become subject to third party claims or litigation alleging infringement of patents or other proprietary rights or seeking to invalidate patents or other proprietary rights, and Alpine may need to resort to litigation to protect or enforce Alpine’s patents or other proprietary rights, all of which could be costly, time consuming, delay or prevent the development of Alpine’s therapeutic candidates and commercialization of Alpine’s therapeutic products, or put Alpine’s patents and other proprietary rights at risk.

Alpine or Alpine’s licensors, licensees, collaborators or any future strategic partners may be subject to third-party claims for infringement or misappropriation of patent or other proprietary rights. Alpine is generally obligated under Alpine’s license or collaboration agreements to indemnify and hold harmless Alpine’s licensors, licensees or collaborators for damages arising from intellectual property infringement by Alpine. If Alpine or Alpine’s licensors, licensees, collaborators or any future strategic partners are found to infringe a third party patent or other intellectual property rights, Alpine could be required to pay damages, potentially including treble damages, if Alpine is found to have willfully infringed. In addition, Alpine or its licensors, licensees, collaborators or any future strategic partners may choose to seek, or be required to seek, a license from a third party, which may not be available on acceptable terms, if at all. Even if a license can be obtained on acceptable terms, the rights may be non-exclusive, which could give Alpine’s competitors access to the same technology or intellectual property rights licensed to or from Alpine. If Alpine fails to obtain a required license, Alpine or Alpine’s licensee or collaborator, or any future licensee or collaborator, may be unable to effectively market therapeutic products based on Alpine’s technology, which could limit Alpine’s ability to generate revenue or achieve profitability and possibly prevent Alpine from generating revenue sufficient to sustain Alpine’s operations. In addition, Alpine may find it necessary to pursue claims or initiate lawsuits to protect or enforce Alpine’s patent or other intellectual property rights. The cost to Alpine in defending or initiating any litigation or other proceeding relating to patent or other proprietary rights, even if resolved in Alpine’s favor, could be substantial, and litigation would divert Alpine’s management’s attention. Some of Alpine’s competitors may be able to sustain the costs of complex patent litigation more effectively than Alpine can because they have substantially greater resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could delay Alpine’s research and development efforts and limit Alpine’s ability to continue Alpine’s operations.

Although Alpine does not believe its technology infringes the intellectual property rights of others, Alpine is aware of one or more patents or patent applications that may relate to Alpine’s technology, and third parties may assert against Alpine claims alleging infringement of their intellectual property rights regardless of whether their claims have merit. Infringement claims could harm Alpine’s reputation, may result in the expenditure of significant resources to defend and resolve such claims, and could require Alpine to pay monetary damages if Alpine is found to have infringed the intellectual property rights of others.

If Alpine were to initiate legal proceedings against a third party to enforce a patent covering Alpine’s technology, including therapeutic candidates and products, the defendant could counterclaim that Alpine’s patent is invalid or unenforceable. In patent litigation in the U.S., defendant counterclaims alleging invalidity or

unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, for example, patent ineligibility, lack of novelty, lack of written description, obviousness, or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. The outcome following legal assertions of invalidity and unenforceability during patent litigation is unpredictable. With respect to the validity question, for example, Alpine cannot be certain there is no invalidating prior art, of which Alpine and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, Alpine would lose at least part, and perhaps all, of the patent protection on Alpine’s technology, including therapeutic candidates and products. Such a loss of patent protection could have a material adverse impact on Alpine’s business. Patents and other intellectual property rights also will not protect Alpine’s technology, including therapeutic candidates and products, if competitors design around Alpine’s protected technology, including therapeutic candidates and products, without legally infringing Alpine’s patents or other intellectual property rights.

It is also possible that Alpine has failed to identify relevant third party patents or applications. For example, patent applications in the U.S. and elsewhere are published approximately 18 months after the earliest filing for which priority is claimed, with such earliest filing date being commonly referred to as the priority date. Therefore, patent applications covering Alpine’s technology, including therapeutic candidates and products, could have been filed by others without Alpine’s knowledge. Additionally, pending patent applications which have been published can, subject to certain limitations, be later amended in a manner that could cover Alpine’s technology, including therapeutic candidates and products. Third party intellectual property right holders may also actively bring infringement claims against Alpine. Alpine cannot guarantee it will be able to successfully settle or otherwise resolve such infringement claims. If Alpine is unable to successfully settle future claims on terms acceptable to Alpine, Alpine may be required to engage in or continue costly, unpredictable, and time-consuming litigation and may be prevented from, or experience substantial delays in, marketing Alpine’s technology, including therapeutic candidates and products. If Alpine fails in any such dispute, in addition to being forced to pay damages, Alpine may be temporarily or permanently prohibited from commercializing its technology, including a therapeutic product, that are held to be infringing. Alpine might, if possible, also be forced to redesign therapeutic candidates or products so Alpine no longer infringes the third party intellectual property rights. Any of these events, even if Alpine were ultimately to prevail, could require Alpine to divert substantial financial and management resources Alpine would otherwise be able to devote to its business.

If Alpine fails to comply with its obligations under any license, collaboration, or other agreements, Alpine may be required to pay damages and could lose intellectual property rights necessary for developing and protecting its technology, including Alpine’s platform technology, therapeutic candidates, and therapeutic products, or Alpine could lose certain rights to grant sublicenses, either of which could have a material adverse effect on Alpine’s results of operations and business prospects.

Alpine’s current licenses impose, and any future licenses Alpine enters into are likely to impose, various development, commercialization, funding, milestone, royalty, diligence, sublicensing, insurance, patent prosecution and enforcement, and other obligations on Alpine. If Alpine breaches any of these obligations, or uses the intellectual property licensed to Alpine in an unauthorized manner, Alpine may be required to pay damages and the licensor may have the right to terminate the license, which could result in Alpine being unable to develop, manufacture, and sell products covered by the licensed technology or enable a competitor to gain access to the licensed technology. Moreover, Alpine’s licensors may own or control intellectual property that has not been licensed to Alpine and, as a result, Alpine may be subject to claims, regardless of their merit, that Alpine is infringing or otherwise violating the licensor’s rights. In addition, while Alpine cannot currently determine the amount of the royalty obligations Alpine would be required to pay on future sales of licensed products, if any, the amounts may be significant. The amount of Alpine’s future royalty obligations will depend on the technology and intellectual property Alpine uses in therapeutic products Alpine successfully develops and commercializes, if any. Therefore, even if Alpine successfully develops and commercializes therapeutic products, Alpine may be unable to achieve or maintain profitability.

If Alpine is unable to protect the confidentiality of Alpine’s trade secrets, Alpine’s business and competitive position would be harmed.

In addition to seeking patent protection for certain aspects of Alpine’s technology, including platform technology, therapeutic candidates and products, Alpine also considers trade secrets, including confidential and unpatented know-how, important to the maintenance of Alpine’s competitive position. Alpine protects trade secrets and confidential and unpatented know-how, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to such knowledge, such as Alpine’s employees, corporate collaborators, outside scientific collaborators, CROs, contract manufacturers, consultants, advisors, and other third parties. Alpine also enters into confidentiality and invention or patent assignment agreements with its employees and consultants obligating them to maintain confidentiality and assign their inventions to Alpine. Despite these efforts, any of these parties may breach the agreements and disclose Alpine’s proprietary information, including Alpine’s trade secrets, and Alpine may not be able to obtain adequate remedies for such breaches. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive, and time-consuming, and the outcome is unpredictable. In addition, some courts in the U.S. and certain foreign jurisdictions are less willing or unwilling to protect trade secrets. If any of Alpine’s trade secrets were to be lawfully obtained or independently developed by a competitor, Alpine would have no right to prevent them from using that technology or information to compete with Alpine. If any of Alpine’s trade secrets were to be disclosed to or independently developed by a competitor, Alpine’s competitive position would be harmed.

Alpine is also subject both in the U.S. and outside the U.S. to various regulatory schemes regarding requests for the information Alpine provides to regulatory authorities, which may include, in whole or in part, trade secrets or confidential commercial information. While Alpine is likely to be notified in advance of any disclosure of such information and would likely object to such disclosure, there can be no assurance Alpine’s challenge to the request would be successful.

Alpine may be in the future, subject to claims Alpine or its employees or consultants have wrongfully used or disclosed alleged trade secrets of Alpine’s employees’ or consultants’ former employers or their clients. These claims may be costly to defend and if Alpine does not successfully do so, Alpine may be required to pay monetary damages, may be prohibited from using some of Alpine’s research and development, and may lose valuable intellectual property rights or personnel.

Many of Alpine’s employees were previously employed at universities or biotechnology or pharmaceutical companies, including Alpine’s competitors or potential competitors. Alpine may receive correspondence from other companies alleging the improper use or disclosure, and has received, and may in the future receive, correspondence from other companies regarding the use or disclosure, by certain of Alpine’s employees who have previously been employed elsewhere in Alpine’s industry, including with Alpine’s competitors, of their former employer’s trade secrets or other proprietary information. Responding to these allegations can be costly and disruptive to Alpine’s business, even when the allegations are without merit, and can be a distraction to management. Alpine may be subject to claims in the future that employees of Alpine have, or Alpine has, inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers. Litigation may be necessary to defend against these claims. If Alpine fails in defending current or future claims, in addition to paying monetary damages, Alpine may lose valuable intellectual property rights, personnel, or the ability to use some of Alpine’s research and development. A loss of intellectual property, key research personnel, or their work product could hamper Alpine’s ability to commercialize, or prevent Alpine from commercializing, Alpine’s therapeutic candidates, which could severely harm Alpine’s business. Even if Alpine is successful in defending against these claims, litigation could result in substantial costs and be a distraction to management.

If Alpine’s trademarks and trade names are not adequately protected, then Alpine may not be able to build name recognition in Alpine’s markets of interest and Alpine’s business may be materially and adversely affected.

Alpine’s trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. Any trademark litigation could be expensive. Alpine may not be able to protect Alpine’s rights to these trademarks and trade names or may be forced to stop using these names, which Alpine needs for name recognition by potential partners or customers in Alpine’s markets of interest. If Alpine is unable to establish name recognition based on Alpine’s trademarks and trade names, Alpine may not be able to compete effectively and Alpine’s business may be materially and adversely affected.

There can be no assurance others will not independently develop, or have not already developed, similar or more advanced technologies than Alpine’s technology or that others will not design around, or have not already designed around, aspects of Alpine’s technology or Alpine’s trade secrets developed therefrom. If third parties develop technology similar or superior to Alpine’s technology, or they successfully design around Alpine’s current or future technology, Alpine’s competitive position, business prospects, and results of operations could be materially and adversely affected.

Breaches of Alpine’s internal computer systems, or those of Alpine’s contractors or consultants, may place Alpine’s patents or proprietary rights at risk.

The loss of preclinical data or data from any future clinical trial involving Alpine’s technology, including therapeutic candidates and products, could result in delays in Alpine’s development and regulatory filing efforts and significantly increase Alpine’s costs. In addition, theft or other exposure of data may interfere with Alpine’s ability to protect its intellectual property, trade secrets, and other information critical to Alpine’s operations. Alpine has experienced in the past, and may experience in the future, unauthorized intrusions into its internal computer systems, including portions of its internal computer systems storing information related to its platform technology, therapeutic candidates and products, and Alpine can provide no assurances that certain sensitive and proprietary information relating to one or more of Alpine’s therapeutic candidates or products has not been, or will not in the future be, compromised. Although Alpine has invested significant resources to enhance the security of its computer systems, there can be no assurances Alpine will not experience additional unauthorized intrusions into its computer systems, or those of Alpine’s CROs and other contractors and consultants, that Alpine will successfully detect future unauthorized intrusions in a timely manner, or that future unauthorized intrusions will not result in material adverse effects on Alpine’s financial condition, reputation, or business prospects. Payments related to the elimination of ransomware may materially affect Alpine’s financial condition and results of operations.

Certain data breaches must also be reported to affected individuals and the government, and in some cases to the media, under provisions of the U.S. federal Health Insurance Portability and Accountability Act (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), other U.S. federal and state law, and requirements of non-U.S. jurisdictions, including the European Union Data Protection Directive, and financial penalties may also apply.

Alpine may be unable to obtain U.S. or foreign regulatory approval and, as a result, may be unable to commercialize its therapeutic candidates.

Alpine’s therapeutic candidates are subject to extensive governmental regulations relating to, among other things, research, development, testing, manufacture, quality control, approval, labeling, packaging, promotion, storage, record-keeping, advertising, distribution, sampling, pricing, sales and marketing, safety, post-approval

monitoring and reporting, and export and import of drugs. Rigorous preclinical testing and clinical trials and an extensive regulatory approval process are required to be successfully completed in the U.S. and in many foreign jurisdictions before a new therapeutic can be marketed. Satisfaction of these and other regulatory requirements is costly, time consuming, uncertain, and subject to unanticipated delays. It is possible that none of the therapeutic candidates Alpine may develop will obtain the regulatory approvals necessary for Alpine or Alpine’s collaborators to begin selling them.

Alpine has very limited experience in conducting and managing the clinical trials necessary to obtain regulatory approvals, including approval by the FDA as well as foreign regulatory authorities, such as the EMA. The time required to obtain FDA and foreign regulatory approvals is unpredictable but typically takes many years following the commencement of clinical trials, depending upon the type, complexity, and novelty of the therapeutic candidate. The standards the FDA and its foreign counterparts use when regulating Alpine are not always applied predictably or uniformly and can change. Any analysis Alpine performs of data from preclinical and clinical activities is subject to confirmation and interpretation by regulatory authorities, who could delay, limit, or prevent regulatory approval. Alpine may also encounter unexpected delays or increased costs due to new government regulations, for example, from future legislation or administrative action, or from changes in the policy of FDA or foreign regulatory authorities during the period of product development, clinical trials, and regulatory review by the FDA or foreign regulatory authorities. It is impossible to predict whether legislative changes will be enacted, or whether FDA or foreign laws, regulations, guidance, or interpretations will be changed, or what the impact of such changes, if any, may be.

Because the therapeutics Alpine is developing may represent a new class of therapeutics, the FDA and its foreign counterparts have not yet established any definitive policies, practices, or guidelines in relation to these drugs. While Alpine believes the therapeutic candidates it is currently developing are regulated as new biological products under the Public Health Service Act (“PHSA”), the FDA could decide to reclassify them, namely to regulate them or other products Alpine may develop as drugs under the Federal Food, Drug, and Cosmetic Act (“FDCA”). The lack of policies, practices, or guidelines may hinder or slow review by the FDA or foreign regulatory authorities of any regulatory filings Alpine may submit. Moreover, the FDA or foreign regulatory authorities may respond to these submissions by defining requirements Alpine may not have anticipated. Such responses could lead to significant delays in the clinical development of Alpine’s therapeutic candidates. In addition, because there may be approved treatments for some of the diseases for which Alpine may seek approval, in order to receive regulatory approval, Alpine may need to demonstrate through clinical trials that the therapeutic candidates Alpine develops to treat these diseases, if any, are not only safe and effective, but safer or more effective than existing products.

Any delay or failure in obtaining required approvals could have a material adverse effect on Alpine’s ability to generate revenues from the particular therapeutic candidate for which Alpine is seeking approval. Furthermore, any regulatory approval to market a product may be subject to limitations on the approved uses for which Alpine may market the product or the labeling or other restrictions. Regulatory authorities also may impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the therapeutic. In addition, the FDA has the authority to require a REMS plan as part of a Biologics License Application (“BLA”) or New Drug Application (“NDA”) or after approval, which may impose further requirements or restrictions on the distribution or use of an approved drug or biologic, such as limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria, and requiring treated patients to enroll in a registry. These limitations and restrictions may limit the size of the market for the therapeutic and affect coverage and reimbursement by third-party payors.

Alpine is also subject to numerous foreign regulatory requirements governing, among other things, the conduct of clinical trials, manufacturing, and marketing authorization, pricing and third-party reimbursement. The foreign regulatory approval process varies among countries and may include all of the risks associated with FDA approval described above as well as risks attributable to the satisfaction of local regulations in foreign

jurisdictions. Moreover, the time required to obtain approval may differ from that required to obtain FDA approval. Approval by the FDA does not ensure approval by regulatory authorities outside the U.S. and vice versa.

If Alpine or Alpine’s existing or future collaborators, manufacturers, or service providers fail to comply with healthcare laws and regulations, Alpine or such other parties could be subject to enforcement actions, which could adversely affect Alpine’s ability to develop, market, and sell Alpine’s therapeutics and may harm Alpine’s reputation.

Although Alpine does not currently have any products on the market, once Alpine begins commercializing its therapeutic candidates Alpine will be subject to additional healthcare statutory and regulatory requirements and enforcement by the federal, state, and foreign governments of the jurisdictions in which Alpine conducts its business. Healthcare providers, physicians, and third-party payors play a primary role in the recommendation and prescription of any therapeutic candidates for which Alpine obtains marketing approval. Alpine’s future arrangements with third-party payors and customers may expose Alpine to broadly applicable fraud and abuse and other healthcare laws and regulations constraining the business or financial arrangements and relationships through which Alpine markets, sells, and distributes the therapeutic candidates for which Alpine obtains marketing approval. Restrictions under applicable federal and state healthcare laws and regulations, include the following:

Ensuring Alpine’s future business arrangements with third-parties comply with applicable healthcare laws and regulations could involve substantial costs. If Alpine’s operations are found to be in violation of any such requirements, Alpine may be subject to penalties, including civil or criminal penalties, monetary damages, the curtailment or restructuring of Alpine’s operations, or exclusion from participation in government contracting, healthcare reimbursement, or other government programs, including Medicare and Medicaid, any of which could adversely affect Alpine’s financial results. Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks cannot be entirely eliminated. Any action against Alpine for an alleged or suspected violation could cause Alpine to incur significant legal expenses and could divert Alpine’s management’s attention from the operation of Alpine’s business, even if Alpine’s defense is successful. In addition, achieving and sustaining compliance with applicable laws and regulations may be costly to Alpine in terms of money, time, and resources.

If Alpine or Alpine’s current or future collaborators, manufacturers, or service providers fail to comply with applicable federal, state, or foreign laws or regulations, Alpine could be subject to enforcement actions, which could affect Alpine’s ability to develop, market, and sell Alpine’s therapeutics successfully and could harm Alpine’s reputation and lead to reduced acceptance of Alpine’s therapeutics by the market. These enforcement actions include, among others:

Any therapeutics Alpine develops may become subject to unfavorable pricing regulations, third-party coverage and reimbursement practices, or healthcare reform initiatives, thereby harming Alpine’s business.

The regulations governing marketing approvals, pricing, coverage, and reimbursement for new drugs and biologics vary widely from country to country. Many countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. Although Alpine intends to monitor these regulations, Alpine’s programs are currently in the early stages of development and Alpine will not be able to assess the impact of price regulations for a number of years. As a result, Alpine might obtain regulatory approval for a product in a particular country, but then be subject to price regulations delaying Alpine’s commercial launch of the product and negatively impacting the revenues Alpine is able to generate from the sale of the product in that country.

Alpine’s ability to commercialize any therapeutics successfully also will depend in part on the extent to which coverage and reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers, and other organizations. However, there may be significant delays in obtaining coverage for newly-approved therapeutics. Moreover, eligibility for coverage does not necessarily signify that a therapeutic will be reimbursed in all cases or at a rate covering Alpine’s costs, including research, development, manufacture, sale, and distribution costs. Also, interim payments for new therapeutics, if applicable, may be insufficient to cover Alpine’s costs and may not be made permanent. Thus, even if Alpine succeeds in bringing one or more therapeutics to the market, these therapeutics may not be considered cost-effective, and the amount reimbursed for any therapeutics may be insufficient to allow Alpine to sell Alpine’s therapeutics on a competitive basis. Because Alpine’s programs are in the early stages of development, Alpine is unable at this time to determine their cost effectiveness, coverage prospects, potential compendia listings, or the likely level or method of reimbursement, if covered. Increasingly, third-party payors who reimburse patients or healthcare providers, such as government and private insurance plans, are seeking greater upfront discounts, additional rebates, and other concessions to reduce the prices for therapeutics. If the price Alpine is able to charge for any therapeutics it develops, or the reimbursement provided for such products, is inadequate, Alpine’s return on investment could be adversely affected.

Alpine currently expects that certain therapeutics it develops may need to be administered under the supervision of a physician on an outpatient basis. Under currently applicable U.S. law, certain drugs not usually self-administered (including injectable drugs) may be eligible for coverage under Medicare through Medicare Part B. Medicare Part B is part of original Medicare, the federal health care program that provides health care benefits to the aged and disabled, and covers outpatient services and supplies, including certain pharmaceutical products that are medically necessary to treat a beneficiary’s health condition. Specifically, Medicare Part B coverage may be available for eligible beneficiaries when the following, among other requirements, have been satisfied:

Under current law, as a condition of receiving Medicare Part B reimbursement (the Medicare program that generally covers physician-administered, outpatient drugs) for a manufacturer’s eligible drugs or biologicals, the manufacturer is required to participate in other government healthcare programs, including the Medicaid Drug Rebate Program and the 340B Drug Pricing Program. The Medicaid Drug Rebate Program requires

pharmaceutical manufacturers to enter into and have in effect a national rebate agreement with the Secretary of the Department of Health and Human Services as a condition for states to receive federal matching funds for the manufacturer’s outpatient drugs furnished to Medicaid patients. Under the 340B Drug Pricing Program, the manufacturer must extend discounts to entities eligible to participate in the program. Average prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S. Reimbursement rates under Medicare Part B would depend in part on whether the newly approved product would be eligible for a unique billing code. Self-administered, outpatient drugs are typically reimbursed by Medicare under Medicare Part D, and drugs administered in an inpatient hospital setting are typically reimbursed under Medicare Part A under a bundled payment. It is difficult for Alpine to predict how Medicare coverage and reimbursement policies will be applied to Alpine’s products in the future and coverage and reimbursement under different federal healthcare programs are not always consistent. Medicare reimbursement rates may also reflect budgetary constraints placed on the Medicare program.

Third-party payors often rely upon Medicare coverage policies and payment limitations in setting their own reimbursement rates. These coverage policies and limitations may rely, in part, on compendia listings for approved therapeutics. Alpine’s inability to promptly obtain relevant compendia listings, coverage and adequate reimbursement from both government-funded and private payors for new therapeutics Alpine develops and for which Alpine obtains regulatory approval could have a material adverse effect on Alpine’s operating results, Alpine’s ability to raise capital needed to commercialize products and Alpine’s financial condition.

Alpine believes the efforts of governments and third-party payors to contain or reduce the cost of healthcare, and legislative and regulatory proposals to broaden the availability of healthcare, will continue to affect the business and financial condition of pharmaceutical and biopharmaceutical companies. A number of legislative and regulatory changes in the healthcare system in the U.S. and other major healthcare markets have been proposed, and such efforts have expanded substantially in recent years. These developments could, directly or indirectly, affect Alpine’s ability to sell Alpine’s products, if approved, at a favorable price.

For example, in the U.S., in 2010, Congress passed the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the “ACA”), a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of health spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional policy reforms.

Among the provisions of the ACA addressing coverage and reimbursement of pharmaceutical products, of importance to Alpine’s potential therapeutic candidates are the following:

Separately, pursuant to the health reform legislation and related initiatives, the Centers for Medicare and Medicaid Services (“CMS”) are working with various healthcare providers to develop, refine, and implement Accountable Care Organizations (“ACOs”) and other innovative models of care for Medicare and Medicaid beneficiaries, including the Bundled Payments for Care Improvement Initiative, the Comprehensive Primary Care Initiative, the Duals Demonstration, and other models. The continued development and expansion of ACOs and other innovative models of care will have an uncertain impact on any future reimbursement Alpine may receive for approved therapeutics administered by such organizations.

In addition, in recent years, the U.S. Congress has enacted various laws seeking to reduce the federal debt level and contain healthcare expenditures. For example, as a result of the Budget Control Act of 2011 and the Bipartisan Budget Act of 2015, an annual 2% reduction to Medicare payments took effect on April 1, 2013 and has been extended through 2025. These across-the-board spending cuts could adversely affect Alpine’s future revenues, earnings, and cash flows.

The financial impact of U.S. healthcare reform legislation over the next few years will depend on a number of factors, including the policies reflected in implementing regulations and guidance and changes in sales volumes for therapeutics affected by the legislation.

From time to time, legislation is drafted, introduced and passed in Congress that could significantly change the statutory provisions governing coverage, reimbursement, and marketing of products regulated by CMS or other government agencies. In addition to new legislation, CMS coverage and reimbursement policies are often revised or interpreted in ways that may significantly affect Alpine’s business and its products. In particular, Alpine expects that the new Administration and Congress will seek to modify, repeal, or otherwise invalidate all, or certain provisions of, the U.S. healthcare reform legislation. Since taking office, President Trump has continued to support the repeal of all or portions of the ACA. President Trump has also issued an executive order in which he stated that it is his Administration’s policy to seek the prompt repeal of the ACA and in which he directed executive departments and federal agencies to waive, defer, grant exemptions from, or delay the implementation of the provisions of the ACA to the maximum extent permitted by law. There is still uncertainty with respect to the impact President Trump’s Administration and Congress may have, if any, and any changes will likely take time to unfold. Such reforms could have an adverse effect on anticipated revenues from therapeutic candidates that Alpine may successfully develop and for which Alpine may obtain regulatory approval and may affect Alpine’s overall financial condition and ability to develop therapeutic candidates. However, Alpine cannot predict the ultimate content, timing or effect of any healthcare reform legislation or the impact of potential legislation on Alpine.

The healthcare industry is heavily regulated in the U.S. at the federal, state, and local levels, and Alpine’s failure to comply with applicable requirements may subject Alpine to penalties and negatively affect Alpine’s financial condition.

As a healthcare company, Alpine’s operations, clinical trial activities, and interactions with healthcare providers may be subject to extensive regulation in the U.S., particularly if Alpine receives FDA approval for any of its products in the future. For example, if Alpine receives FDA approval for a therapeutic for which reimbursement is available under a federal healthcare program (e.g., Medicare, Medicaid), it would be subject to a variety of federal laws and regulations, including those prohibiting the filing of false or improper claims for payment by federal healthcare programs (e.g. the federal False Claims Act), prohibiting unlawful inducements

for the referral of business reimbursable by federal healthcare programs (e.g. the federal Anti-Kickback Statute), and requiring disclosure of certain payments or other transfers of value made to U.S.-licensed physicians and teaching hospitals. Alpine is not able to predict how third parties will interpret these laws and apply applicable governmental guidance and may challenge Alpine’s practices and activities under one or more of these laws. If Alpine’s past or present operations are found to be in violation of any of these laws, Alpine could be subject to civil and criminal penalties, which could hurt Alpine’s business, Alpine’s operations, and financial condition.

Similarly, HIPAA prohibits, among other offenses, knowingly and willfully executing a scheme to defraud any health care benefit program, including private payors, or falsifying, concealing, or covering up a material fact or making any materially false, fictitious, or fraudulent statement in connection with the delivery of or payment for items or services under a health care benefit program. To the extent that Alpine acts as a business associate to a healthcare provider engaging in electronic transactions, Alpine may also be subject to the privacy and security provisions of HIPAA, as amended by HITECH, which restricts the use and disclosure of patient-identifiable health information, mandates the adoption of standards relating to the privacy and security of patient-identifiable health information, and requires the reporting of certain security breaches to healthcare provider customers with respect to such information. Additionally, many states have enacted similar laws imposing more stringent requirements on entities like Alpine. Failure to comply with applicable laws and regulations could result in substantial penalties and adversely affect Alpine’s financial condition and results of operations.

Alpine’s ability to obtain services, reimbursement, or funding from the federal government may be impacted by possible reductions in federal spending.

The U.S. federal budget remains in flux, which could, among other things, cut Medicare payments to providers. The Medicare program is frequently mentioned as a target for spending cuts. The full impact on Alpine’s business of any future cuts in Medicare or other programs is uncertain. In addition, Alpine cannot predict any impact President Trump’s administration and Congress may have on the federal budget. If federal spending is reduced, anticipated budgetary shortfalls may also impact the ability of relevant agencies, such as the FDA or the National Institutes of Health, to continue to function at current levels. Amounts allocated to federal grants and contracts may be reduced or eliminated. These reductions may also impact the ability of relevant agencies to timely review and approve drug research and development, manufacturing, and marketing activities, which may delay Alpine’s ability to develop, market, and sell any therapeutics Alpine may develop.

If any of Alpine’s therapeutic candidates receives marketing approval and Alpine or others later identify undesirable side effects caused by the therapeutic candidate, Alpine’s ability to market and derive revenue from the therapeutic candidates could be compromised.

In the event any of Alpine’s therapeutic candidates receive regulatory approval and Alpine or others identify undesirable side effects, adverse events, or other problems caused by one of Alpine’s therapeutics, any of the following adverse events could occur, which could result in the loss of significant revenue to Alpine and materially and adversely affect Alpine’s results of operations and business:

Significant developments stemming from the United Kingdom’s recent referendum on membership in the EU could have a material adverse effect on Alpine.

On June 23, 2016, the United Kingdom held a referendum and voted in favor of leaving the EU. This referendum has created political and economic uncertainty, particularly in the United Kingdom and the EU, and this uncertainty may last for years. Any business Alpine conducts, now and in the future, in the United Kingdom, the EU, and worldwide could be affected during this period of uncertainty, and perhaps longer, by the impact of the United Kingdom’s referendum. There are many ways in which Alpine’s business could be affected, only some of which Alpine can identify as of the date of this proxy statement/prospectus/information statement.

The referendum, and the likely withdrawal of the United Kingdom from the EU it triggers, has caused and, along with events potentially occurring in the future as a consequence of the United Kingdom’s withdrawal, including the possible breakup of the United Kingdom, may continue to cause significant volatility in global financial markets, including in global currency and debt markets. This volatility could cause a slowdown in economic activity in the United Kingdom, Europe, or globally, which could adversely affect Alpine’s operating results and growth prospects. In addition, Alpine’s business could be negatively affected by new trade agreements between the United Kingdom and other countries, including the U.S, and by the possible imposition of trade or other regulatory barriers in the United Kingdom.

It is currently unknown how regulations affecting clinical trials, the approval of Alpine’s future products, and the sale of these products will be affected by this referendum either in the United Kingdom or elsewhere in Europe.

These possible negative impacts, and others resulting from the United Kingdom’s actual or threatened withdrawal from the EU, may adversely affect Alpine’s operating results and growth prospects.

In determining whether you should approve the merger, the issuance of shares of Nivalis common stock and other matters related to the merger, as the case may be, you should carefully read the following risk factors in addition to the risks described under “Risk Factors—Risks Related to the Merger,” “Risk Factors—Risks Related to Nivalis” and “Risk Factors—Risks Related to Alpine,” which will also apply to the combined organization.

Nivalis’ stock price is expected to be volatile, and the market price of its common stock may drop following the merger.

The market price of Nivalis’ common stock following the merger could be subject to significant fluctuations following the merger. Market prices for securities of early-stage pharmaceutical, biotechnology, and other life

sciences companies have historically been particularly volatile. Some of the factors that may cause the market price of Nivalis’ common stock to fluctuate following the merger include:

Moreover, the stock markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies or the biotechnology sector. These broad market fluctuations may also adversely affect the trading price of the combined organization’s common stock.

In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies. Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm the combined organization’s profitability and reputation.

The combined organization will incur costs and demands upon management as a result of complying with the laws and regulations affecting public companies.

The combined organization will incur significant legal, accounting, and other expenses Alpine did not incur as a private company, including costs associated with public company reporting requirements. The combined organization will also incur costs associated with corporate governance requirements, including requirements under the Sarbanes-Oxley Act, as well as new rules implemented by the SEC and The NASDAQ Stock Market LLC. These rules and regulations are expected to increase the combined organization’s legal and financial compliance costs and to make some activities more time-consuming and costly. For example, the combined organization’s management team will consist of the executive officers of Alpine prior to the merger, some of whom may not have previously managed and operated a public company. These executive officers and other personnel will need to devote substantial time to gaining expertise regarding operations as a public company and compliance with applicable laws and regulations. These rules and regulations may also make it difficult and expensive for the combined organization to obtain directors and officers liability insurance. As a result, it may be more difficult for the combined organization to attract and retain qualified individuals to serve on the combined organization’s board of directors or as executive officers of the combined organization, which may adversely affect investor confidence in the combined organization and could cause the combined organization’s business or stock price to suffer.

Anti-takeover provisions in the combined organization charter documents and under Delaware law could make an acquisition of the combined organization more difficult and may prevent attempts by the combined organization stockholders to replace or remove the combined organization management.

Provisions in the combined organization’s certificate of incorporation and bylaws may delay or prevent an acquisition or a change in management. These provisions include a classified board of directors, a prohibition on actions by written consent of the combined organization’s stockholders, and the ability of the board of directors to issue preferred stock without stockholder approval. In addition, because the combined organization will be incorporated in Delaware, it is governed by the provisions of Section 203 of the DGCL, which prohibits stockholders owning in excess of 15% of the outstanding combined organization voting stock from merging or combining with the combined organization. Although Nivalis and Alpine believe these provisions collectively will provide for an opportunity to receive higher bids by requiring potential acquirers to negotiate with the combined organization’s board of directors, they would apply even if the offer may be considered beneficial by some stockholders. In addition, these provisions may frustrate or prevent any attempts by the combined organization’s stockholders to replace or remove then current management by making it more difficult for stockholders to replace members of the board of directors, which is responsible for appointing the members of management.

Nivalis and Alpine do not anticipate the combined organization will pay any cash dividends in the foreseeable future.

The current expectation is the combined organization will retain its future earnings to fund the development and growth of the combined organization’s business. As a result, capital appreciation, if any, of the common stock of the combined organization will be your sole source of gain, if any, for the foreseeable future.

Future sales of shares by existing stockholders could cause the combined organization stock price to decline.

If existing stockholders of Nivalis and Alpine sell, or indicate an intention to sell, substantial amounts of the combined organization’s common stock in the public market after the post-merger lock-up and other legal

restrictions on resale discussed in this proxy statement/prospectus/information statement lapse, the trading price of the common stock of the combined organization could decline. Based on shares outstanding as of May 12, 2017, upon completion of the merger, the combined organization is expected to have outstanding a total of approximately 13.9 million shares of common stock (after giving effect to the proposed Nivalis Reverse Stock Split). Of these shares, only approximately 3.5 million shares of common stock will be freely tradable, without restriction, in the public market.

The lock-up agreements entered into between each of Nivalis and Alpine and certain of each other’s securityholders provide that the shares subject to the lock-up restrictions will be released from such restrictions 180 days from the closing date. Based on shares outstanding as of May 12, 2017, up to an additional approximately 10.4 million shares of common stock (after giving effect to the proposed Nivalis Reverse Stock Split) will be eligible for sale in the public market, approximately 9.5 million of which will be held by directors, executive officers of the combined organization, and other affiliates and will be subject to volume limitations under Rule 144 under the Securities Act, and various vesting agreements. In addition, approximately 1.2 million shares of common stock subject to outstanding options of Alpine as of April 18, 2017, and approximately 0.5 million shares of common stock subject to outstanding options of Nivalis as of May 12, 2017 (in each case, after giving effect to the proposed Nivalis Reverse Stock Split) will become eligible for sale in the public market to the extent permitted by the provisions of various vesting agreements, the lock-up agreements and Rules 144 and 701 under the Securities Act. If these additional shares are sold, or if it is perceived that they will be sold, in the public market, the trading price of the combined organization common stock could decline.

If the ownership of the combined organization common stock is highly concentrated, it may prevent you and other stockholders from influencing significant corporate decisions and may result in conflicts of interest that could cause the combined organization stock price to decline.

Executive officers, directors of the combined organization, and their affiliates are expected to beneficially own or control approximately 70% of the outstanding shares of the combined organization common stock following the completion of the merger (after giving effect to the exercise of all outstanding vested and unvested options and warrants). Accordingly, these executive officers, directors, and their affiliates, acting as a group, will have substantial influence over the outcome of corporate actions requiring stockholder approval, including the election of directors, any merger, consolidation, or sale of all or substantially all of the combined organization assets or any other significant corporate transactions. These stockholders may also delay or prevent a change of control of the combined organization, even if such a change of control would benefit the other stockholders of the combined organization. The significant concentration of stock ownership may adversely affect the trading price of the combined organization’s common stock due to investors’ perception that conflicts of interest may exist or arise.

An active trading market for the combined organization’s common stock may not develop and its stockholders may not be able to resell their shares of common stock for a profit, if at all.

Prior to the merger, there had been no public market for Alpine’s common stock. An active trading market for the combined organization’s shares of common stock may never develop or be sustained. If an active market for the combined organization’s common stock does not develop or is not sustained, it may be difficult for its stockholders to sell their shares at an attractive price or at all.

If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about the combined organization, its business or its market, its stock price and trading volume could decline.

The trading market for the combined organization’s common stock will be influenced by the research and reports that equity research analysts publish about it and its business. Equity research analysts may elect not to provide research coverage of the combined organization’s common stock after the completion of this offering, and such lack of research coverage may adversely affect the market price of its common stock. In the event it

does have equity research analyst coverage, the combined organization will not have any control over the analysts or the content and opinions included in their reports. The price of the combined organization’s common stock could decline if one or more equity research analysts downgrade its stock or issue other unfavorable commentary or research. If one or more equity research analysts ceases coverage of the combined organization or fails to publish reports on it regularly, demand for its common stock could decrease, which in turn could cause its stock price or trading volume to decline.

The combined organization will have broad discretion in the use of proceeds from the Pre-Closing Financing and may invest or spend the proceeds of the Pre-Closing Financing in ways with which you do not agree and in ways that may not increase the value of your investment.

The combined organization will have broad discretion over the use of proceeds from the Pre-Closing Financing. You may not agree with the combined organization’s decisions, and its use of the proceeds may not yield any return on your investment. The combined organization’s failure to apply the net proceeds of the Pre-Closing Financing effectively could compromise its ability to pursue its growth strategy and the combined organization might not be able to yield a significant return, if any, on its investment of these net proceeds. You will not have the opportunity to influence the combined organization’s decisions on how to use the net proceeds from the Pre-Closing Financing.

Nivalis’ pre-merger net operating loss carryforwards and certain other tax attributes may be subject to limitations. The pre-merger net operating loss carryforwards and certain other tax attributes of Alpine and of the combined organization may also be subject to limitations as a result of ownership changes resulting from the merger.

In general, a corporation that undergoes an “ownership change” is subject to limitations on its ability to utilize its pre-change net operating loss carryforwards (“NOLs”) to offset future taxable income. In general, an ownership change occurs if the aggregate stock ownership of certain stockholders, generally stockholders beneficially owning five percent or more of a corporation’s common stock, applying certain look-through and aggregation rules, increases by more than 50 percentage points over such stockholders’ lowest percentage ownership during the testing period, generally three years. Nivalis may have experienced ownership changes in the past and may experience ownership changes in the future. In addition, the closing of the merger may result in an ownership change for Nivalis. It is possible that Alpine’s net operating loss carryforwards and certain other tax attributes may also be subject to limitation as a result of ownership changes in the past and/or the closing of the merger. Consequently, even if the combined organization achieves profitability, it may not be able to utilize a material portion of Nivalis’, Alpine’s or the combined organization’s net operating loss carryforwards and certain other tax attributes, which could have a material adverse effect on cash flow and results of operations.

If the combined organization fails to maintain proper and effective internal controls, its ability to produce accurate financial statements on a timely basis could be impaired.

The combined organization will be subject to the reporting requirements of the Exchange Act, the Sarbanes-Oxley Act and the rules and regulations of The NASDAQ Stock Market LLC. The Sarbanes-Oxley Act requires, among other things, that the combined organization maintain effective disclosure controls and procedures and internal control over financial reporting. The combined organization must perform system and process evaluation and testing of its internal control over financial reporting to allow management to report on the effectiveness of its internal controls over financial reporting in its Annual Report on Form 10-K filing for that year, as required by Section 404 of the Sarbanes-Oxley Act. As a private company, Alpine has never been required to test its internal controls within a specified period. This will require that the combined organization incur substantial professional fees and internal costs to expand its accounting and finance functions and that it expend significant management efforts. The combined organization may experience difficulty in meeting these reporting requirements in a timely manner.

The combined organization may discover weaknesses in its system of internal financial and accounting controls and procedures that could result in a material misstatement of its financial statements. The combined organization’s internal control over financial reporting will not prevent or detect all errors and all fraud. An internal control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the internal control system’s objectives will be met. Because of the inherent limitations in all internal control systems, no evaluation of internal controls can provide absolute assurance that misstatements due to error or fraud will not occur or that all internal control issues and instances of fraud will be detected.

If the combined organization is not able to comply with the requirements of Section 404 of the Sarbanes-Oxley Act, or if it is unable to maintain proper and effective internal controls, the combined organization may not be able to produce timely and accurate financial statements. If that were to happen, the market price of its common stock could decline and it could be subject to sanctions or investigations by The NASDAQ Stock Market LLC, the SEC, or other regulatory authorities.

This proxy statement/prospectus/information statement and the documents incorporated by reference into this proxy statement/prospectus/information statement contain forward-looking statements (including within the meaning of Section 21E of the United States Securities Exchange Act of 1934, as amended (the “Exchange Act”), and Section 27A of the United States Securities Act of 1933, as amended (the “Securities Act”)) concerning Nivalis, Alpine, the proposed merger and other matters. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Nivalis, as well as assumptions made by, and information currently available to, management. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “plan,” “believe,” “intend,” “look forward,” and other similar expressions among others. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the risk that the conditions to the closing of the merger are not satisfied, including the failure to timely or at all obtain stockholder approval for the merger; uncertainties as to the timing of the consummation of the merger and the ability of each of Nivalis and Alpine to consummate the merger; risks related to Nivalis’ ability to correctly estimate its operating expenses and its expenses associated with the merger; risks related to the changes in market price of Nivalis’ common stock relative to the exchange ratio; the ability of Nivalis or Alpine to protect their respective intellectual property rights; competitive responses to the merger; unexpected costs, charges or expenses resulting from the merger; potential adverse reactions or changes to business relationships resulting from the announcement or completion of the merger; and legislative, regulatory, political and economic developments. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere. Nivalis can give no assurance that the conditions to the merger will be satisfied. Except as required by applicable law, Nivalis undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

For a discussion of the factors that may cause Nivalis, Alpine or the combined organization’s actual results, performance or achievements to differ materially from any future results, performance or achievements expressed or implied in such forward-looking statements, or for a discussion of risk associated with the ability of Nivalis and Alpine to complete the merger and the effect of the merger on the business of Nivalis, Alpine and the combined organization, see the section entitled “Risk Factors” beginning on page 25.

Additional factors that could cause actual results to differ materially from those expressed in the forward-looking statements are discussed in reports filed with the SEC by Nivalis including the risk factors included in Nivalis’ most recent Annual Report on Form 10-K, and Nivalis’ recent Quarterly Report on Form 10-Q and Current Reports on Form 8-K filed with the SEC. See the section entitled “Where You Can Find More Information” beginning on page 293.

If any of these risks or uncertainties materialize or any of these assumptions prove incorrect, the results of Nivalis, Alpine or the combined organization could differ materially from the forward-looking statements. All forward-looking statements in this proxy statement/prospectus/information statement are current only as of the date on which the statements were made. Nivalis and Alpine do not undertake any obligation to publicly update any forward-looking statement to reflect events or circumstances after the date on which any statement is made or to reflect the occurrence of unanticipated events.

The Nivalis special meeting will be held on July 19, 2017, at the offices of Ballard Spahr LLP, 5480 Valmont Road, Suite 200, Boulder, Colorado 80301 commencing at 1:30 p.m. Mountain time. Nivalis is sending this proxy statement/prospectus/information statement to its stockholders in connection with the solicitation of proxies by Nivalis’ board of directors for use at the Nivalis special meeting and any adjournments or postponements of the Nivalis special meeting. This proxy statement/prospectus/information statement is first being furnished to Nivalis’ stockholders on or about [●], 2017.

1. To consider and vote upon a proposal to approve the Merger Agreement and the transactions contemplated thereby, including the merger and the issuance of Nivalis’ common stock to Alpine’s stockholders in accordance with the Merger Agreement.

2. To approve an amendment to the amended and restated certificate of incorporation of Nivalis to effect the Nivalis Reverse Stock Split, in the form attached as Annex D to this proxy statement/prospectus/information statement.

3. To approve the amendment to the amended and restated certificate of incorporation of Nivalis to effect the Nivalis Name Change in the form attached as Annex E to this proxy statement/prospectus/information statement

4. To consider and vote upon an adjournment of the Nivalis special meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal Nos. 1 and 2.

5. To transact such other business as may properly come before the Nivalis special meeting or any adjournment or postponement thereof.

Only holders of record of Nivalis’ common stock at the close of business on the record date, May 26, 2017, are entitled to notice of, and to vote at, the Nivalis special meeting. There were approximately 22 holders of record of Nivalis’ common stock at the close of business on the record date. At the close of business on the record date, 15,656,251 shares of Nivalis’ common stock were issued and outstanding. Each share of Nivalis’ common stock entitles the holder thereof to one vote on each matter submitted for stockholder approval. See the section entitled “Principal Stockholders of Nivalis” in this proxy statement/prospectus/information statement for information regarding persons known to Nivalis’ management to be the beneficial owners of more than 5% of the outstanding shares of Nivalis’ common stock.

The proxy accompanying this proxy statement/prospectus/information statement is solicited on behalf of Nivalis’ board of directors for use at the Nivalis special meeting.

If you are a stockholder of record of Nivalis as of the record date referred to above, you may vote in person at the Nivalis special meeting or vote by proxy using the enclosed proxy card. Whether or not you plan to attend the Nivalis special meeting, Nivalis urges you to vote by proxy to ensure your vote is counted. You may still attend the Nivalis special meeting and vote in person if you have already voted by proxy. As a stockholder of record you may vote in any of the following ways:

If your shares of Nivalis’ common stock are held by your broker as your nominee, that is, in “street name,” the enclosed voting instruction card is sent by the institution that holds your shares. Please follow the instructions included on that proxy card regarding how to instruct your broker to vote your shares of Nivalis’ common stock. If you do not give instructions to your broker, your broker can vote your shares of Nivalis’ common stock with respect to “discretionary” items but not with respect to “non-discretionary” items. Discretionary items are proposals considered routine under the rules of NASDAQ on which your broker may vote shares held in “street name” in the absence of your voting instructions. On non-discretionary items for which you do not give your broker instructions, your shares of Nivalis’ common stock will be treated as broker non-votes. It is anticipated that Proposal Nos. 1, 2 and 3 will be non-discretionary items.

All properly executed proxies that are not revoked will be voted at the Nivalis special meeting and at any adjournments or postponements of the Nivalis special meeting in accordance with the instructions contained in the proxy. If a holder of Nivalis’ common stock executes and returns a proxy and does not specify otherwise, the

shares represented by that proxy will be voted “FOR” Proposal No. 1 to approve the Merger Agreement and the transactions contemplated thereby, including the merger and the issuance of shares of Nivalis’ common stock to Alpine’s stockholders pursuant to the Merger Agreement; “FOR” Proposal No. 2 to approve an amendment to the amended and restated certificate of incorporation of Nivalis effecting the Nivalis Reverse Stock Split; “FOR” Proposal No. 3 to approve an amendment to the amended and restated certificate of incorporation of Nivalis to effect the Nivalis Name Change; and “FOR” Proposal No. 4 to approve the adjournment of the Nivalis special meeting, if necessary, to solicit additional proxies if there are not sufficient votes in favor of Proposal Nos. 1 or 2 in accordance with the recommendation of Nivalis’ board of directors.

Nivalis’ stockholders of record, other than those Nivalis’ stockholders who have executed support agreements, may change their vote at any time before their proxy is voted at the Nivalis special meeting in one of three ways. First, a stockholder of record of Nivalis can send a written notice to the Secretary of Nivalis stating that the stockholder would like to revoke its proxy. Second, a stockholder of record of Nivalis can submit new proxy instructions either on a new proxy card or by telephone or via the Internet. Third, a stockholder of record of Nivalis can attend the Nivalis special meeting and vote in person. Attendance alone will not revoke a proxy. If a stockholder of Nivalis of record or a stockholder who owns shares of Nivalis’ common stock in “street name” has instructed a broker to vote its shares of Nivalis’ common stock, the stockholder must follow directions received from its broker to change those instructions.

The presence, in person or represented by proxy, at the Nivalis special meeting of the holders of a majority of the shares of Nivalis’ common stock outstanding and entitled to vote at the Nivalis special meeting is necessary to constitute a quorum at the meeting. Abstentions and broker non-votes will be counted towards a quorum. Approval of Proposal Nos. 1 and 4 requires the affirmative vote of the holders of a majority of the shares of Nivalis’ common stock having voting power present in person or represented by proxy at the Nivalis special meeting. Approval of Proposal Nos. 2 and 3 requires the affirmative vote of holders of a majority of Nivalis’ common stock having voting power outstanding on the record date for the Nivalis special meeting.

Votes will be counted by the inspector of election appointed for the Nivalis special meeting, who will separately count “FOR” and “AGAINST” votes, abstentions and broker non-votes. Abstentions will be counted towards the vote total and will have the same effect as “AGAINST” votes for Proposal Nos. 2 and 3; abstentions will have no effect on Proposal Nos. 1 and 4. Broker non-votes will have the same effect as “AGAINST” votes for Proposal Nos. 2 and 3. For Proposal Nos. 1 and 4, broker non-votes will have no effect and will not be counted towards the vote total, but will be used to determine whether a quorum is present at the Nivalis special meeting.

As of May 30, 2017, the directors and executive officers of Nivalis beneficially owned approximately 3.5% of the outstanding shares of Nivalis’ common stock entitled to vote at the Nivalis special meeting. Each of the directors and executive officers, and certain other stockholders, of Nivalis have entered into support agreements, pursuant to which such director, executive officer or other stockholder has agreed to be present (in person or by proxy) at the Nivalis special meeting to vote all shares of Nivalis’ common stock owned by him, her or it as of the record date (a) in favor of (i) the approval of the Merger Agreement, (ii) the approval of the transactions contemplated therein, including the issuance of shares of Nivalis’ common stock pursuant to the Merger Agreement, (iii) the adoption of an amendment to Nivalis’ certificate of incorporation to effect the Nivalis Reverse Stock Split, (iv) the adoption of an amendment to Nivalis’ certificate of incorporation to effect the Nivalis Name Change, (v) any proposal to adjourn or postpone the meeting to a later date, if there are not sufficient votes for the approval of the Merger Agreement and the transactions contemplated therein, including the issuance of common stock pursuant to the Merger Agreement on the date on which such meeting is held, and (vi) any other proposal included in the proxy statement in connection with, or related to, the consummation of the Merger for which Nivalis’ board of directors has recommended that the Nivalis’ stockholders vote in favor; and (b) against any competing acquisition proposal with respect to Nivalis. As of April 18, 2017, Nivalis is not aware of any affiliate of Alpine owning any shares of Nivalis’ common stock entitled to vote at the Nivalis special meeting.

In addition to solicitation by mail, the directors, officers, employees and agents of Nivalis may solicit proxies from Nivalis’ stockholders by personal interview, telephone, telegram or otherwise. Nivalis and Alpine will share equally the costs of printing and filing this proxy statement/prospectus/information statement and proxy card. Arrangements will also be made with brokerage firms and other custodians, nominees and fiduciaries who are record holders of Nivalis’ common stock for the forwarding of solicitation materials to the beneficial owners of Nivalis’ common stock. Nivalis will reimburse these brokers, custodians, nominees and fiduciaries for the reasonable out-of-pocket expenses they incur in connection with the forwarding of solicitation materials. Nivalis has retained MacKenzie Partners as its proxy solicitor. Nivalis will pay the fees of MacKenzie Partners, which Nivalis expects to be approximately $10,000, plus reimbursement of out-of-pocket expenses.

As of the date of this proxy statement/prospectus/information statement, Nivalis’ board of directors does not know of any business to be presented at the Nivalis special meeting other than as set forth in the notice accompanying this proxy statement/prospectus/information statement. If any other matters should properly come before the Nivalis special meeting, it is intended that the shares represented by proxies will be voted with respect to such matters in accordance with the judgment of the persons voting the proxies.

This section and the section entitled “The Merger Agreement” in this proxy statement/prospectus/information statement describe the material aspects of the merger, including the Merger Agreement. While Nivalis and Alpine believe that this description covers the material terms of the merger and the Merger Agreement, it may not contain all of the information that is important to you. You should read carefully this entire proxy statement/prospectus/information statement for a more complete understanding of the merger and the Merger Agreement, including the Merger Agreement attached as Annex A, the opinion of Ladenburg attached as Annex B, and the other documents to which you are referred herein. See the section entitled “Where You Can Find More Information” in this proxy statement/prospectus/information statement.

Nivalis’ board of directors and management regularly reviews Nivalis’ operating and strategic plans in an effort to enhance stockholder value. This review involves, among other things, discussions of opportunities and risks associated with Nivalis’ product candidates, development programs, financial condition and market, as well as consideration of strategic alternatives and options available to Nivalis. On November 22, 2016, members of Nivalis’ management at that time, including Mr. Jon Congleton, Ms. Janice Troha, Mr. R. Michael Carruthers, Dr. David Rodman, Dr. Sherif Gabriel, and Dr. Steven Shoemaker, reviewed the results of Nivalis’ Phase 2 clinical trial of cavosonstat, a multi-center, randomized, double-blind, three-arm trial that enrolled 138 adult cystic fibrosis patients with two copies of the F508del mutation being treated with Orkambi™ (the “Clinical Trial”). The results of the Clinical Trial indicated that the Clinical Trial had failed to achieve its primary endpoint of lung function improvement and a key secondary endpoint of sweat chloride reduction. A second, smaller clinical trial of cavosonstat in CF patients with one copy of the F508del-CFTR mutation similarly failed to meet its primary endpoint of lung function improvement and a key secondary endpoint of sweat chloride reduction, as Nivalis announced on February 23, 2017.

In response to these negative results, Nivalis’ board of directors shortly thereafter initiated a process to identify and evaluate strategic alternatives available to Nivalis that ultimately resulted in the execution of the Merger Agreement with Alpine. The terms of the Merger Agreement are the result of extensive arm’s-length negotiations among members of the Special Committee (as defined below), Nivalis’ management team, and the management team of Alpine along with their respective advisors and under the guidance of each company’s board of directors. From the beginning, Nivalis followed a careful process assisted by experienced outside financial, scientific and legal advisors to rigorously examine potential transactions and transaction candidates in a broad and inclusive manner. The following is a summary of the background of the process undertaken by Nivalis, and the identification and evaluation of strategic alternatives and the negotiation of the Merger Agreement, including the circumstances surrounding Nivalis’ decision to review strategic alternatives available to it.

On November 27 and 28, 2016, Nivalis’ board of directors held telephonic meetings with members of Nivalis’ management and a representative of Gross Cutler Seiler Dupont LLC (“GCSD”), outside corporate counsel to Nivalis, to review the negative Clinical Trial results, the materials intended for public release of the results, and the strategic implications of those results. Following the close of markets on November 28, 2016, Nivalis publicly announced that the Clinical Trial had failed to achieve its primary endpoint of lung function improvement and a key secondary endpoint of sweat chloride reduction.

On November 30, 2016, Nivalis’ board of directors, in executive session without members of management present, but with a representative of GCSD present, held a telephonic meeting and engaged in a detailed and substantive discussion of strategic alternatives available to Nivalis in light of the negative Clinical Trial results. The board considered various strategic alternatives intended to maximize value for Nivalis’ stockholders, including continuation of the development of Nivalis’ products in other indications as well as possible licensing opportunities or a sale or merger involving Nivalis. Following this call, on December 1, 2016, Howard Furst,

M.D., Chairman of Nivalis’ board of directors, met with members of Nivalis’ management, and asked management to provide the board of directors with management’s assessment of strategic options and alternatives.

On December 9, 2016, Nivalis’ board of directors held a telephonic meeting which was attended by members of Nivalis’ management and a representative of GCSD, during which members of Nivalis’ management presented to the members of Nivalis’ board of directors an alternative development plan for Nivalis’ GSNOR inhibitors in a potential asthma indication. Members of Nivalis’ management also presented management’s assessment of other strategic alternatives, including potential licensing opportunities or a sale or merger involving Nivalis, along with an analysis of the costs of closing down two clinical trials that were ongoing at that time compared to the costs of carrying them to completion. Detailed discussions were held regarding the merits and risks associated with management’s proposed development plan, including market opportunities and risks, development risks, costs and resources required to conduct required research and development activities and to execute such a plan, and the expected timeline to proof-of-concept and other events likely to result in value to Nivalis’ stockholders. Nivalis’ board of directors elected to continue the ongoing clinical trials to completion given that both trials were nearing completion and that all activities associated with them would be completed in the first quarter of 2017.

On December 11, 2016, Nivalis’ board of directors held a telephonic meeting that was also attended by a representative of GCSD to discuss further management’s proposed plan for the development of Nivalis’ GSNOR inhibitors for asthma indications and other strategic alternatives available to Nivalis. Following a discussion of the risks and potential benefits and opportunities of the proposed plan, Nivalis’ board of directors determined that the risks and uncertainties of pursuing such a development plan, including uncertainties relating to the ability of Nivalis to raise the required funds on favorable terms, or at all, necessary to fund such further development, were too great in relation to the potential benefits. Accordingly, following extensive discussion, Nivalis’ board of directors determined that it was in the best interest of Nivalis and its stockholders to pursue alternative strategic options, including a reverse merger involving Nivalis, in an effort to maximize stockholder value. Nivalis’ board of directors then determined to establish a Special Committee of the board of directors (the “Special Committee”) to assist in the investigation and evaluation of such strategic options and to make recommendations to Nivalis’ board of directors and management with respect to the day-to-day decisions as to process and strategy concerning an assessment of any potential strategic alternatives. Nivalis’ board of directors designated Messrs. Conway and Sekhri and Dr. Loh as the members of the Special Committee. Nivalis’ board of directors also discussed the evaluation and retention of special legal counsel and financial advisors to advise and assist Nivalis in its exploration of a potential strategic transaction, and the resources required to complete ongoing clinical trials, to preserve Nivalis’ assets, and to investigate, pursue and consummate a strategic transaction. Following discussion, Nivalis’ board of directors determined that it was in the best interest of Nivalis and its stockholders for Nivalis to engage special legal counsel and a financial advisor to assist and advise Nivalis. Nivalis’ board of directors then authorized the Special Committee and Nivalis’ management to interview and engage special counsel and a financial advisor to assist management with respect to the pursuit of a strategic transaction.

Between December 11 and December 13, 2016, members of the Special Committee contacted potential law firms to advise Nivalis on a potential strategic transaction and discussed potential investment banking firms. On December 13, 2016, the Special Committee held a telephonic meeting with representatives of Latham & Watkins LLP (“Latham & Watkins”) to discuss Latham & Watkins’ potential engagement as legal advisors to Nivalis. Following the Special Committee’s discussion of the qualifications, expertise, experience and reputation of Latham & Watkins, the Special Committee engaged Latham & Watkins as Nivalis’ special outside counsel to assist and advise Nivalis with respect to a potential strategic transaction.

On December 19, 2016, Mr. Conway and Dr. Loh met with representatives from four investment banking firms in New York, New York, to determine their suitability to act as Nivalis’ financial advisor with respect to the pursuit of a strategic transaction. On December 21, 2016, the Special Committee held a telephonic meeting to discuss the merits of the investment bank candidates. After consideration of the relative qualifications and

expertise of the candidates, including industry expertise and knowledge, access to potential transaction candidates, and recent transaction experience, the Special Committee narrowed the candidates from four to two. Between December 21 and December 23, 2016, members of the Special Committee conducted further diligence on the two investment bank candidates. On December 23, 2016, the Special Committee held a telephonic meeting to discuss the investment bank candidates and the results of the further diligence conducted by members of the Special Committee. In this meeting, the Special Committee approved the selection of Ladenburg as Nivalis’ financial advisor for a potential strategic transaction, and the Special Committee appointed Mr. Conway as its chairman.

On January 2, 2017, Nivalis’ board of directors held a telephonic meeting which was also attended by members of Nivalis’ management and a representative of GCSD. Mr. Conway provided the board of directors with an update regarding recent activities of the Special Committee, including the engagement of Latham & Watkins and the process engaged in and discussions held with investment banking firms to assist and advise the Special Committee and the board through a potential strategic transaction. Mr. Conway reviewed the proposed terms of the engagement letter with Ladenburg. Following discussion of the engagement letter and the qualifications and experience of Ladenburg, Nivalis’ board of directors approved the engagement of Ladenburg on the terms set forth in its engagement letter presented to the board of directors and authorized management to execute and deliver the engagement letter to Ladenburg. Also at this meeting, Mr. Congleton reviewed plans to streamline Nivalis’ operations and conserve its cash resources, including a proposed reduction in force, and the board of directors reviewed a proposed press release circulated to the participants prior to the meeting relating to the determination to initiate a process to explore and evaluate a range of strategic alternatives, the establishment of the Special Committee and the retention of Ladenburg.

On January 3, 2017, Nivalis publicly announced the initiation of a process to explore and review a range of strategic alternatives focused on maximizing stockholder value from its clinical assets and cash resources. Such strategic alternatives included, but were not limited to, the potential for an acquisition, merger, business combination or other strategic transaction. Nivalis also announced that its board of directors had appointed a Special Committee to assist in the pursuit of such a transaction and that Nivalis’ had retained Ladenburg as its financial advisor. Nivalis further announced its intent to streamline its operations in order to conserve capital.

On January 5, 2017, an organizational meeting was held by teleconference with the Special Committee, members of Nivalis’ management team, representatives of Latham & Watkins, a representative of GCSD and representatives of Ladenburg in attendance. At this meeting, Ladenburg reviewed the process to be undertaken to identify and evaluate potential strategic alternatives and parties that may be interested in pursuing a strategic transaction with Nivalis. The Special Committee discussed the anticipated timeline for contacting, and receiving and evaluating proposals from, interested parties in connection with pursuing a strategic transaction, reviewed proposed selection criteria to be used in identifying and evaluating candidates, and reviewed a proposed bid letter prepared by Ladenburg to be sent to interested parties. The Special Committee further established a standing weekly meeting schedule to ensure regular communication and coordination among the members of the Special Committee, Latham & Watkins, GCSD and Ladenburg.

Between January 5 and February 7, 2017, Ladenburg, with assistance from the Special Committee and members of Nivalis’ management, conducted a process of identifying and evaluating potential parties to strategic combinations. In its outreach efforts, members of the board of directors and management, and representatives of Ladenburg, contacted a broad set of companies that met certain criteria established by the Special Committee and that consisted of private companies actively considering an initial public offering, private companies not actively considering an initial public offering, private companies that had failed in earlier attempts to complete an initial public offering but that had raised significant capital, publicly traded foreign companies seeking a NASDAQ listing and public companies in the United States seeking capital or that were believed to have a strategic fit with Nivalis. As a result of this process, between January 5, 2017 and February 5, 2017, Ladenburg delivered bid process letters to a total of 127 companies and, in response thereto, Nivalis received a total of 81 non-binding proposals.

On January 6, 2017, Nivalis’ board of directors held a telephonic meeting that was also attended by members of management and a representative of GCSD. Mr. Conway provided an update on the activities of the Special Committee, including the process of soliciting non-binding proposals and timing of key activities. Mr. Conway also reviewed, and the board of directors discussed, the proposed selection criteria to be used in evaluating candidates. The board of directors engaged in a discussion of various alternative structures and potential valuation scenarios relating to Nivalis’ GSNOR inhibitor assets.

On January 12, 2017, Nivalis publicly announced a reduction in workforce that would take place between January 15 and March 31, 2017, and which would affect a total of 25 employees, including Nivalis’ President and Chief Executive Officer, Jon Congleton, and Nivalis’ Chief Medical Officer, David Rodman, M.D. As a result of the reduction in workforce, as of March 31, 2017, Nivalis had five remaining employees, including two members of the management team, Mr. Carruthers, Chief Financial Officer and newly appointed Interim President, and Ms. Troha, Chief Operating Officer.

On January 16, 2017, the Special Committee held a telephonic meeting that was attended by representatives of Ladenburg, members of Nivalis’ management and a representative of GCSD to discuss the status of Ladenburg’s outreach efforts, the deadline for receipt of non-binding proposals following delivery of bid process letters, and the plans for reviewing such proposals. The Special Committee also discussed strategic alternatives relating to Nivalis’ GSNOR inhibitor platform, including the timing of any separate transaction involving these assets and expected valuation of such assets in light of their early stage of development and failure in the CF indication.

On January 20, 2017, Nivalis’ board of directors held a telephonic meeting attended by members of Nivalis’ management and a representative of GCSD. Mr. Conway gave an update on the activities of the Special Committee, including the status of Ladenburg’s outreach efforts as well as the process for reviewing and evaluating potential candidates and any eventual proposals, the criteria to be used in assessing such candidates, and the fact that outside experts may need to be engaged to assist in the evaluation of candidates. The board of directors engaged in a detailed discussion of these topics, during which the board of directors agreed with the selection criteria established by the Special Committee. This criteria included an evaluation of each candidate’s financing risk at closing; the candidate’s product pipeline; upcoming milestones with respect to the candidate’s product candidates likely to occur after a closing that may create greater value for stockholders; the experience and expertise of the candidate’s management and scientific teams; the candidate’s investor base and capital structure; the candidate’s ability to maintain Nivalis’ NASDAQ listing and operate a public company after closing; the proposed relative valuations of Nivalis and the candidate; and the candidate’s ability to effectively fund operations after a closing. Mr. Conway also updated the board of directors on the Special Committee’s discussions regarding potential strategies or alternatives with respect to Nivalis’ GSNOR inhibitor portfolio, noting that the main emphasis of the Special Committee would be on obtaining maximum value for Nivalis’ stockholders in the primary strategic transaction, but that the bid process letters that Ladenburg had delivered to potentially interested parties included a request for interested parties to indicate interest in Nivalis’ GSNOR portfolio. The board of directors then engaged in a discussion of potential strategic alternatives for the GSNOR portfolio.

On January 25, 2017, the Special Committee held a telephonic meeting with members of Nivalis’ management, representatives of Ladenburg and a representative of GCSD also present. At such meeting, the Special Committee discussed the status of Ladenburg’s outreach efforts and the application of the criteria established by the Special Committee that would be used to narrow down the list of potential candidates that had submitted or would submit non-binding indications of interest. The Special Committee also discussed limiting outreach efforts to companies in the pharmaceutical and biotechnology industry in light of Nivalis’ board of directors’ and management’s ability to evaluate and assess the products, and related operational, industry, regulatory, financial, market and other risks and opportunities, of companies within such industries. The Special Committee also discussed with representatives of Ladenburg the process for receipt, review and response to non-binding indications of interest.

Between January 27 and February 2, 2017, members of Nivalis’ management team held teleconferences with, and provided detailed information to, four companies that expressed an interest in Nivalis’ GSNOR inhibitor portfolio (the “Participating GSNOR Interested Parties”) as part of the indications of interest such parties submitted to Nivalis. Three of the Participating GSNOR Interested Parties indicated to representatives of Ladenburg that they were no longer interested in the GSNOR inhibitor portfolio after such parties had been notified by representatives of Ladenburg that they were not selected to move forward with negotiations for a transaction involving Nivalis generally.

On February 3, 2017, Nivalis’ board of directors held a telephonic meeting attended by members of Nivalis’ management and a representative of GCSD. Mr. Conway updated the board of directors on the status of, and next steps to be taken in, the process of evaluating and selecting potential partners for a strategic transaction involving Nivalis, which would include an initial screening of candidates by Ladenburg and the Special Committee based on the selection criteria approved by the Special Committee and review by the Special Committee of the non-binding indications of interest submitted by candidates. Mr. Conway further explained that the Special Committee would use such process to narrow the group of interested parties to a reasonable number for further discussion and evaluation, including formal, in-person presentations to Nivalis’ board of directors by each such interested party.

On February 7 and 8, 2017, the Special Committee, along with members of Nivalis’ management team, Dr. Furst and representatives of Ladenburg, met at Ladenburg’s offices in New York, New York, to review and evaluate the non-binding proposals that had been received and to identify candidates, based on the selection criteria established by the Special Committee, that should be invited to present their proposals to Nivalis’ board of directors. As a result of this process, the Special Committee identified ten companies (the “Initial Final Candidates”) to be extended an invitation to make presentations to Nivalis’ board of directors, one of which was Alpine. Following the meeting, representatives of Ladenburg contacted representatives of each of the Initial Final Candidates and indicated to each such party that such party had been selected to proceed in further discussions with Nivalis regarding a strategic transaction.

On February 9, 2017, Nivalis’ board of directors held a telephonic meeting which was attended by members of Nivalis’ management and a representative of Ballard Spahr LLP (which law firm Nivalis retained when the representative of GCSD who had been Nivalis’ outside corporate counsel joined Ballard Spahr LLP) (“Ballard”). Mr. Conway updated the board of directors with respect to the activities of the Special Committee, including a detailed review of the selection process used during the February 7 and 8, 2017 meetings at Ladenburg’s offices, and provided a summary of the Initial Final Candidates identified by the Special Committee.

On February 13 and 14, 2017, Nivalis’ board of directors, including each member of the Special Committee, members of Nivalis’ management, and representatives of Ladenburg participated in ten separate in-person meetings with the management teams of each of the Initial Final Candidates. During such meetings, each Initial Final Candidate presented information about its company and the terms of its non-binding proposal, and responded to questions from Nivalis’ board of directors, Nivalis’ management team and Ladenburg representatives. Following the conclusion of these meetings, on February 15, 2017, Nivalis’ board of directors, including each member of the Special Committee, members of Nivalis’ management and representatives of Ladenburg, reviewed each presentation made by the Initial Final Candidates and discussed each non-binding proposal received from the Initial Final Candidates. As a result of this review and discussion, Nivalis’ board of directors determined to select Alpine and three other companies (“Company A,” “Company B” and “Company C,” respectively; and together with Alpine, the “Finalist Candidates”) to move forward in the process. At the direction of Nivalis’ board of directors, Ladenburg thereafter contacted each of the Finalist Candidates to notify them of their selection to continue discussions with Nivalis concerning a potential strategic transaction.

Between February 14 and March 17, 2017, the Special Committee, other members of Nivalis’ board of directors, and members of Nivalis’ management requested, reviewed and analyzed scientific and other information regarding the development activities, product pipelines and businesses of the Finalist Candidates and

advanced the negotiations with these companies regarding a potential strategic transaction. Nivalis also retained outside scientific experts during this period to conduct detailed scientific diligence on the Finalist Candidates to further inform the Special Committee’s and board of directors’ determinations.

On February 17, 2017, Nivalis’ board of directors held a telephonic meeting attended by members of management, a Ladenburg representative and a representative of Ballard. Mr. Conway provided an update on activities of the Special Committee and reviewed with the board of directors the Finalist Candidates that were selected based on the proposed terms of a transaction received from each such party, including relative valuation proposals for Nivalis and such Finalist Candidate, the expertise and qualifications of the management and scientific teams of such Finalist Candidate, the development products and pipeline of such Finalist Candidate, market opportunities and risks, development risks, preparedness for operating a public company and other factors. The status of Nivalis’ diligence efforts with respect to each such Finalist Candidate and findings to date were also presented and reviewed. Ladenburg then provided a summary of the status and nature of the discussions Ladenburg held with each of the Finalist Candidates since the February 13 and 14, 2017 meetings in New York, New York.

On February 22, 2017, the Special Committee held a telephonic meeting attended by members of Nivalis’ management, representatives of Ladenburg and a representative of Ballard. Mr. Conway reviewed the key terms of the proposals from each of the Finalist Candidates resulting from negotiations with each of the Finalist Candidates, and the Special Committee engaged in a detailed discussion of such terms and the status of negotiations and strategies with each Finalist Candidate. The Special Committee also reviewed the findings from scientific and regulatory diligence and considered and discussed the potential risks affecting the ability of the Finalist Candidates to successfully and timely develop their respective products. The Special Committee further considered, with input from representatives of Ladenburg, the valuation ranges proposed by each of the Finalist Candidates and discussed strategies to advance discussions with each Finalist Candidate. Following this discussion, the Special Committee requested that Ladenburg prepare draft term sheets summarizing the proposals and certain other material terms of a transaction with each of the Finalist Candidates, including Alpine.

Between February 24 and February 28, 2017, representatives of Ballard and Latham & Watkins prepared draft non-binding term sheets to be delivered to each of the Finalist Candidates outlining the material terms of a proposed transaction with each such Finalist Candidate. During the same period, Nivalis’ management and members of the Special Committee conducted further due diligence of each Finalist Candidate. On February 27, 2017, Nivalis’ management, Mr. Conway, as chairman of the Special Committee, representatives of Ladenburg and a representative of Ballard held a telephonic meeting during which the results of the due diligence review conducted to date on the Finalist Candidates and input from the other members of the Special Committee received by Mr. Conway were discussed. As a result of such additional due diligence and discussions, Mr. Conway consulted with each of the other members of the Special Committee and the Special Committee members determined that it would not be in Nivalis’ best interest to pursue a transaction with Company C. The Special Committee directed Ladenburg to communicate to Company C that Nivalis would not be pursuing further discussions with such party. Following such determination and dismissal of Company C, the Special Committee determined to provide a draft non-binding term sheet to each of Alpine, Company A and Company B outlining, in each case, the terms of a proposed strategic transaction involving such company and Nivalis.

On February 27, 2017, representatives of Ladenburg provided draft non-binding term sheets to each of Alpine, Company A and Company B summarizing the material proposed terms of a potential transaction with each such company, including the form of the transaction, the respective valuations of Nivalis and each such company, the ability of Nivalis to enter into a separate transaction prior to a closing involving a sale or license of its GSNOR inhibitor portfolio, the composition of the board of directors following a closing, conditions to execution of a definitive agreement, conditions to the closing of a transaction, certain deal protection provisions, the parties’ obligations to deliver lock-up agreements, payment of fees and expenses, and confidentiality provisions.

On February 28, 2017, at the Special Committee’s direction, Ladenburg informed Company C that Nivalis would not be pursuing further discussions with Company C.

Between February 28, 2017 and March 3, 2017, Mr. Conway, as chair of the Special Committee, and members of Nivalis’ management engaged in due diligence discussions with the remaining Finalist Candidates and engaged in negotiations with each such Finalist Candidate of the terms set forth in the draft non-binding term sheets, in each case with input from representatives of Ladenburg, Latham & Watkins and Ballard.

On March 2, 2017, Alpine provided a revised draft of the non-binding term sheet reflecting Alpine’s counterproposals to the respective valuations of Nivalis and Alpine, the composition of the board of directors following the closing of a potential transaction to include an independent representative, the treatment of a sale of the GSNOR inhibitor portfolio prior to a closing, the duration of an exclusivity agreement with Alpine and the size of a break-up fee in the event a definitive agreement is terminated under certain circumstances.

On March 3, 2017, Nivalis’ board of directors held a telephonic meeting attended by members of Nivalis’ management, representatives from Ladenburg and a representative of Ballard. At such meeting, Mr. Conway updated the board of directors of Nivalis on the status of the Special Committee’s diligence of, and negotiations with, the Finalist Candidates, including with respect to the dismissal of Company C, and recent discussions with the remaining Finalist Candidates, including Nivalis’ engagement of outside scientific experts to assist it in further diligence of the transaction candidates. Mr. Conway advised the board of directors that, based on the Special Committee’s assessment of the strengths and weaknesses of the remaining Finalist Candidates following further due diligence activities and review of the material terms of the transactions proposed by the remaining Finalist Candidates, it was the recommendation of the Special Committee that the potential transaction candidates be narrowed to Alpine and Company B and that the process with Company A be slowed but remain active only to the extent negotiations with Alpine and Company B did not proceed favorably. Ladenburg then reviewed with the board of directors recent discussions held by members of Nivalis’ management and the Special Committee with representatives of each of Alpine and Company B and reviewed the key terms of the proposals submitted by each of Alpine and Company B, including the respective valuation proposals therein. The board of directors engaged in considerable discussion with input from Ladenburg and members of Nivalis’ management regarding the merits of pursuing a strategic transaction with either Alpine or Company B, and the proposed terms presented by each of Alpine and Company B. Following this detailed discussion, the board of directors agreed with the Special Committee’s recommendation that further diligence and negotiations should proceed with Alpine and Company B.

Also on March 3, 2017, separate teleconferences were held with each of Alpine and Company B to discuss various issues arising from Nivalis’ diligence efforts and to further negotiate the open terms of a potential transaction with each respective party. Participating in the calls from Nivalis were members of Nivalis’ management, Mr. Conway, as chairman of the Special Committee, representatives of Ladenburg and representatives of Ballard. Participating from Alpine and Company B were members of their respective management teams and members of their respective boards of directors and representatives of their respective legal counsels.

On March 3, 2017, a teleconference with Alpine and members of Nivalis’ management was held. During such teleconference the parties discussed the respective valuations of Alpine and Nivalis, including the underlying valuation assumptions relating to the net cash of each company at the closing of a potential transaction and a concurrent financing of Alpine, the scope of an exclusivity agreement with Alpine and the size of a break-up fee to be reflected in a definitive agreement for the potential transaction. Alpine sent a revised term sheet to representatives of Ladenburg reflecting a revised equity valuation of Alpine, and Ladenburg circulated the revised term sheet to members of Nivalis’ management and Mr. Conway as chairman of the Special Committee.

On March 3, 2017, members of Nivalis’ management team participated in a teleconference with Company B. On such teleconference the parties discussed the valuation of Company B, including the underlying valuation assumptions relating to the net cash of each company at a closing.

On March 4, 2017, representatives of Ladenburg held a teleconference with members of Alpine’s management and discussed Alpine’s revised valuation proposal and other terms reflected in the term sheet provided by Alpine on March 3, 2017.

On March 6, 2017, Alpine, Company A and Company B each circulated a revised term sheet to representatives of Ladenburg, who shared the term sheets with members of Nivalis’ management team and Mr. Conway as chairman of the Special Committee.

On March 8, 2017, Mr. Conway circulated to the members of the Special Committee a summary setting forth the original proposed terms and the counterproposals received from Alpine and Company B with respect to valuation and other key terms reflected in the term sheets being negotiated with Alpine and Company B as well as a list of potential scientific experts for the Special Committee to consider retaining to assist in further due diligence of Alpine and Company B. The members of the Special Committee provided Mr. Conway with feedback on Nivalis’ counterproposals to Alpine regarding the respective valuations of Nivalis and Alpine, which included an assumed $17.0 million concurrent financing of Alpine, the ability of Nivalis to sell or license its GSNOR inhibitor portfolio prior to the closing of a potential transaction, the duration of an exclusivity agreement with Alpine and the size of a break-up fee payable in the event a definitive agreement is terminated under certain circumstances. The members of the Special Committee also provided Mr. Conway with feedback on Nivalis’ counterproposals to Company B relating to the respective valuations of Nivalis and Company B.

Also on March 8, 2017, Mr. Conway, as chair of the Special Committee, and members of Nivalis’ management participated in a telephonic meeting with representatives of Ladenburg to discuss the status of diligence efforts and to receive and provide input on Nivalis’ ongoing term sheet negotiations with Alpine and Company B. Ladenburg provided advice and feedback on the proposed valuations and other terms proposed by each party.

Between March 8 and March 16, 2017, members of Nivalis’ management and the Special Committee held multiple teleconferences with the representatives of Alpine and Company B to conduct further diligence on each of the two companies and continued to negotiate the non-binding term sheets summarizing the terms of a proposed transaction with each of such companies. Nivalis’ external scientific experts also completed their scientific diligence on Alpine and Company B, one of whom prepared a written report that was circulated to the Special Committee and the board of directors. During this period, Nivalis’ management and Mr. Conway, as chair of the Special Committee, with the advice and assistance of Ladenburg, Latham & Watkins and Ballard, continued to negotiate the valuation and other key open terms of the non-binding term sheets with Alpine and Company B as well as the terms of an exclusivity agreement that Alpine had proposed. The members of the Special Committee further determined during this time period not to proceed as actively with negotiations with Company A given significant capitalization complexities with Company A as well as concerns relating to its status as a foreign entity.

On March 13, 2017, representatives of Sidley Austin LLP, special outside counsel to Alpine (“Sidley”), delivered to representatives of Latham & Watkins an initial draft of an exclusivity agreement providing for a period of exclusive negotiation between Alpine and Nivalis, which Latham & Watkins circulated to Nivalis’ management team and Mr. Conway.

On March 13 and March 14, 2017, representatives of Ladenburg worked with Nivalis’ management team, with input from members of the Special Committee and advice from Latham & Watkins and Ballard, to revise the term sheet with Alpine to reflect Nivalis’ counterproposals on valuation and adjustments to the calculation of the exchange ratio based on each company’s net cash at closing of a potential transaction, the requirement that

Alpine complete a financing of $17.0 million concurrent with a closing of a transaction and the size of the break-up fee payable in the event the definitive agreement is terminated under certain circumstances. Representatives of Ladenburg circulated this revised term sheet to Alpine’s management on March 15, 2017.

On March 15, 2017, the Special Committee held a telephonic meeting which was attended by members of Nivalis’ management, representatives of Latham & Watkins, a representative of Ballard and representatives from Ladenburg. Nivalis’ management circulated to the Special Committee in advance of the meeting copies of the current drafts of the term sheets with Alpine and Company B as well as the draft exclusivity agreement provided by Sidley. The Special Committee discussed findings from Nivalis’ continued diligence efforts and the status of term sheet negotiations with each of Alpine and Company B. The Special Committee also discussed the terms of the exclusivity agreement proposed by Alpine to be entered into should Alpine be chosen as the candidate with whom Nivalis would pursue a strategic transaction. The Special Committee received advice from Latham & Watkins with respect to the terms of the proposed exclusivity agreement as well as the Special Committee’s and the board of director’s fiduciary duties with respect to entering into such an exclusivity agreement. The Special Committee discussed the relative merits of Alpine and Company B and of their respective proposals and, after discussion, determined to recommend to the board of directors that Nivalis enter into an exclusivity agreement with Alpine and pursue a strategic transaction with Alpine. In making this decision, the Special Committee considered the greater experience of the Alpine management and scientific teams and preparedness to operate a public company, Alpine’s sophisticated investor base, Alpine’s cash position, including the financing of approximately $17.0 million to be completed immediately prior to a closing of a potential transaction with Alpine, Alpine’s unique discovery capabilities and the potential of its product pipeline, and key upcoming development milestones of Alpine with the potential to create stockholder value.

On March 16, 2017, representatives of Ladenburg received a revised draft of the non-binding term sheet from Alpine reflecting Alpine’s counterproposals to the draft circulated on March 15, 2017 to Alpine’s management. Also on March 16, 2017, representatives of Ladenburg notified Company A that Nivalis did not desire to continue discussions with Company A.

On March 17, 2017, representatives of Ladenburg held a teleconference with members of Alpine’s management team to discuss Alpine’s counterproposals relating to the duration of the exclusivity period, the size of the break-up fee and matters relating to adjustments to the calculation of the exchange ratio.

On March 17, 2017, Nivalis’ board of directors held a telephonic meeting which was attended by members of Nivalis’ management, representatives from Ladenburg, a representative of Ballard and Nivalis’ external scientific experts. During this meeting, the scientific experts presented their conclusions and recommendations to the board of directors resulting from the diligence conducted to date by them on Alpine and Company B. Nivalis’ management also provided an overview of due diligence conducted by management on Alpine and Company B, and management’s resulting recommendations. The board of directors engaged in a detailed discussion regarding the relative merits and risks of pursuing a strategic transaction with each of the two companies, including development and market risks and opportunities, and the expertise and capabilities of the management and scientific teams of Alpine and Company B.

Also on March 17, 2017, representatives of Ladenburg delivered to representatives of Sidley a revised draft of the exclusivity agreement.

On March 18, 2017, Nivalis’ board of directors held a telephonic meeting which was attended by members of management, representatives of Ladenburg and a representative of Ballard to continue its discussions of the merits of pursuing a strategic transaction with either of Alpine or Company B on the terms set forth in their respective term sheets. The board discussed the terms of a transaction with Alpine as reflected in the non-binding term sheet negotiated with Alpine and the terms, including duration and certain exceptions, of the proposed exclusivity agreement with Alpine, drafts of which had been circulated to the board of directors in advance of the meeting. The board members participated in a discussion of these considerations, including the potential benefits

and the potential risks and uncertainties associated with each of the potential strategic transactions. They also discussed the proposed economic terms Nivalis’ existing security holders could expect in the potential strategic transactions with Alpine or Company B, including the relative value assigned to the shares that would be held by the existing Nivalis stockholders based on the respective valuation assigned to Alpine in the private financing Alpine agreed to pursue in connection with the closing of the potential strategic transaction. A discussion ensued regarding the ability of these potential strategic transactions to enhance value for Nivalis’ stockholders, including a discussion of the market potential of the respective products, services and technologies being offered by Alpine and Company B, respectively. Following such discussion, Mr. Conway noted the determination by the Special Committee that it was in the best interests of Nivalis and its stockholders to continue negotiations with Alpine and that it was the Special Committee’s recommendation to the board of directors that Nivalis enter into the exclusivity agreement with Alpine and proceed to negotiate a definitive agreement with Alpine on the terms set forth in the non-binding term sheet. The board of directors, after consideration of the merits of Alpine and Company B, the risks and opportunities associated with their respective potential product candidates and pipelines, strengths and weaknesses of their respective management and scientific teams, the rigorous process undertaken by the Special Committee with the assistance of Ladenburg, Latham & Watkins and Ballard, including the evaluation of over 80 companies for a potential strategic transaction, as well as other factors the board of directors deemed significant, approved execution of the exclusivity agreement with Alpine and directed Nivalis’ management and representatives of Ladenburg, Latham & Watkins and Ballard to proceed with negotiations of a definitive agreement for a strategic transaction with Alpine and further directed Ladenburg to communicate to Company B that Nivalis had determined not to pursue further discussions with Company B.

Also on March, 18, 2017, representatives of Sidley delivered to representatives of Latham & Watkins a revised draft of the exclusivity agreement.

On March 19, 2017, representatives of Latham & Watkins delivered to representatives of Sidley a revised draft of the exclusivity agreement.

On March 20, 2017, at the direction of Nivalis’ board of directors, representatives of Ladenburg communicated to representatives of Company B that Nivalis would not be pursuing further discussions with Company B with respect to a strategic transaction involving Nivalis.

Also on March 20, 2017, Alpine and Nivalis executed the exclusivity agreement pursuant to which Nivalis agreed to negotiate with Alpine on an exclusive basis until April 20, 2017.

Between March 20, 2017 and the signing of the Merger Agreement on April 18, 2017, Nivalis and Alpine provided due diligence materials requested by the other party through access to electronic data rooms and the parties, with assistance of legal counsel, completed certain additional due diligence activities. During this time, the parties also negotiated the terms of the Merger Agreement as well as the Support Agreements and Lock-Up Agreements to be entered into by the respective directors, executive officers and certain significant stockholders of Nivalis and Alpine. Mr. Conway, as chair of the Special Committee, and Nivalis’ management consulted regularly and worked closely with representatives of Ladenburg, Latham & Watkins and Ballard during the course of the negotiations. The Special Committee continued to meet weekly with representatives of Ladenburg to discuss the progress of the negotiations and, in consultation with representatives of Ladenburg, Latham & Watkins and Ballard, continued to provide feedback to Nivalis’ management on the significant terms of the definitive agreement. The Special Committee also provided detailed, bi-weekly (or as circumstances dictated, more frequent) updates to Nivalis’ board of directors on the progress of the negotiations and discussions regarding key terms of the proposed transaction.

On March 21, 2017, members of Nivalis’ management team, members of Alpine’s management team, and representatives of each of Latham & Watkins, Sidley, Ladenburg, and Ascent Law Partners LLP, counsel to Alpine (“Ascent”), participated in a telephonic meeting to discuss the transaction generally and a timeline for consummation of the transaction.

On March 23, 2017, representatives of Latham & Watkins delivered an initial draft of the Merger Agreement to representatives of Sidley.

On March 29, 2017, members of Nivalis’ management team held a teleconference with management of the remaining GSNOR Interested Party and discussed the potential terms of a transaction. Following this teleconference, on March 31, 2017, members of Nivalis’ management team provided such GSNOR Interested Party with additional information regarding the GSNOR inhibitor portfolio. Management expressed concerns regarding the ability of this GSNOR Interested Party to consummate a transaction because it lacked funding, scientific expertise and development capabilities to advance development of the portfolio.

On March 29, 2017, members of Nivalis’ management, members of Alpine’s management and representatives of each of Latham & Watkins, Sidley, Ascent, and Ladenburg, participated in a telephonic meeting to discuss the parties progress with respect to negotiation of the draft Merger Agreement, diligence related matters, and the timeline of the execution of a definitive Merger Agreement and the consummation of the transaction.

On March 30, 2017, representatives of Sidley delivered a revised draft of the Merger Agreement to representatives of Latham & Watkins.

On March 31, 2017, Nivalis’ board of directors held a telephonic meeting attended by members of Nivalis’ management and a representative of Ballard. At this meeting, Mr. Conway updated the board of directors with respect to the status of Nivalis’ continued due diligence activities and the negotiation of the terms of a draft Merger Agreement to be entered into with Alpine. Nivalis’ board of directors then discussed the material terms of the draft Merger Agreement under negotiation and the anticipated timeline of negotiation and drafting of the Merger Agreement. Mr. Conway also updated the board of directors of Nivalis on the status of negotiations with a fifth company that had previously indicated potential interest in Nivalis’ GSNOR inhibitor assets to Mr. Conway through a mutual contact. Mr. Conway noted, however, that discussions with such party had ended relatively quickly as the party did not express an interest in moving forward in light of the fact that the party was not able to recruit successfully the scientific expertise required to advance development of these assets.

On April 3 and 4, 2017, members of Nivalis’ management and Mr. Conway, as chair of the Special Committee, visited Alpine’s corporate headquarters and met with members of Alpine’s management team and scientists to conduct further diligence and discuss certain matters pertaining to the transaction. An external scientific expert retained by Nivalis also joined the meeting by phone on April 4, 2017 to conduct a competitive assessment of Alpine’s technology.

On April 4, 2017, representatives of Latham & Watkins and representatives of Sidley and Ascent participated in a telephonic meeting to discuss outstanding issues under the Merger Agreement.

On April 7, 2017, the Special Committee held a telephonic meeting which was attended by members of Nivalis’ management and representatives of Ladenburg, Latham & Watkins and Ballard to discuss the recent due diligence meeting at Alpine’s headquarters, noting that the findings from such visit were positive. The Special Committee also reviewed and discussed the results of the scientific expert’s competitive assessment as outlined in his written report that was circulated to the Special Committee and the other board members prior to such meeting. The Special Committee also discussed with representatives of Ladenburg the fairness opinion to be delivered by Ladenburg in connection with the execution of the Merger Agreement. Representatives of Ladenburg noted that a discounted cash flow (“DCF”) analysis is often utilized in the valuation of companies in connection with the determination of the fairness of a transaction from a financial point of view to stockholders, but that a DCF analysis for early, pre-clinical stage companies is often not a valid indicator of value, however, due to significant variability in the assumptions used in a DCF analysis for companies at an early stage such as Alpine where revenue is speculative and will not be generated for a significant number of years in the future. The Ladenburg representative also pointed out that Alpine had not developed projections that are required for a DCF

analysis and any such projections would be highly speculative. Following a substantive discussion of the benefits and disadvantages of conducting a DCF analysis in connection with Ladenburg’s fairness determination, and consideration of the highly speculative nature of such an analysis in this context, practices in comparable transactions and other factors, the Special Committee determined that a DCF analysis would not provide an accurate valuation methodology in connection with the fairness determination.

On April 8, 2017, representatives of Latham & Watkins delivered a revised draft of the Merger Agreement to representatives of Sidley.

On April 12, 2017, representatives of Sidley delivered a revised draft of the Merger Agreement to representatives of Latham & Watkins.

On April 13, 2017, representatives of Latham & Watkins and representatives of Sidley and Ascent participated in a telephonic meeting to discuss outstanding issues under the Merger Agreement.

On April 14, 2017, representatives of Latham & Watkins delivered a revised draft of the Merger Agreement to representatives of Sidley.

Later on April 14, 2017, Nivalis’ board of directors held a telephonic meeting with members of management and representatives of each of Ladenburg, Latham & Watkins and Ballard. At this meeting, Mr. Conway updated Nivalis’ board of directors on the continued due diligence activities, including the recent visit to Alpine’s corporate headquarters, and Ms. Troha reviewed the results of the scientific expert’s competitive assessment as outlined in his written report that had previously been circulated to the board. Mr. Conway also updated the board on the status of negotiations of the Merger Agreement and reviewed the material terms and open issues under discussion. Mr. Conway summarized for the board again the process undertaken by the Special Committee and Nivalis leading to the determination to select Alpine and the steps taken by the Special Committee to ensure a thorough review and consideration of the terms of the Merger Agreement, including retention of Ladenburg and Latham & Watkins and retention of outside scientific experts to review and evaluate Alpine and the other transaction candidates. Also at this meeting, representatives of Latham & Watkins gave a presentation to the board concerning its fiduciary duties under Delaware law in connection with the proposed transaction and as applied to certain provisions in the Merger Agreement. The board asked questions of the representatives of Latham & Watkins during this presentation which were responded to. Representatives of Latham & Watkins then provided a detailed review of the terms of the Merger Agreement negotiated with Alpine (a copy of which had been circulated to the board in advance of the meeting along with a summary of the material terms of the Merger Agreement), including the provisions governing the exchange ratio and other economic terms; the closing cash requirements of the parties, the financing of Alpine required to be consummated contemporaneously with the closing pursuant to the Subscription Agreement, and other conditions to the closing; the treatment of stock options and warrants of each party; the terms of the “no-shop” provisions and exceptions to those provisions in the event of certain superior offers; the requirement that Nivalis’ board of directors recommend the approval of the Merger Agreement and the transactions contemplated thereby to Nivalis’ stockholders and the conditions under which a change in the recommendation of Nivalis’ board of directors would be permitted; and certain covenants of the parties applicable to the period commencing upon execution of the Merger Agreement and ending on the earlier of the Effective Time and the termination of the Merger Agreement. Latham & Watkins also reviewed with Nivalis’ board of directors the terms of the Support Agreements and Lock-Up Agreements. Following this discussion, Mr. Conway reviewed the process undertaken by the Special Committee and Nivalis for a potential sale or license of Nivalis’ GSNOR inhibitor portfolio. Mr. Conway noted that there had not been significant interest expressed for such assets in light of the failure of two clinical trials in CF, the very early-stage nature of the assets in other indications, such as asthma and inflammatory bowel disease, and the likely significant capital requirements necessary to conduct further development of such assets. After these presentations and discussions, representatives of Ladenburg presented its financial analysis of the proposed transaction, which included a summary of the proposed transaction and a discussion of the exchange ratio, and reviewed its draft fairness opinion, both of which had been circulated to the board in advance of the meeting.

Members of Nivalis’ board of directors asked questions of the representatives of Latham & Watkins and Ladenburg during and following their presentations, and engaged in a discussion of the terms of the Merger Agreement and related transaction documents.

During the period of April 14, 2017 through April 16, 2017, members of Nivalis’ management and Mr. Conway, as chair of the Special Committee, negotiated certain additional terms of the Merger Agreement and the Support Agreements and Lock-Up Agreements to be entered into with two of Nivalis’ large stockholders with the assistance of Latham & Watkins and Ladenburg.

On April 16, 2017, representatives of Sidley delivered a revised draft of the Merger Agreement to representatives of Latham & Watkins.

On April 17, 2017, Nivalis’ board of directors held a telephonic meeting which was attended by members of management, representatives of Ladenburg, representatives of Latham & Watkins, and representatives of Ballard. At this meeting, representatives of Latham & Watkins presented the revised terms of the Merger Agreement that had been further negotiated since the board’s April 14, 2017 meeting (as reflected in a marked copy of the Merger Agreement and updated summary of the terms of the Merger Agreement that had been circulated to the board in advance of the meeting), including the addition of closing conditions relating to the requirement for Sidley to deliver a tax opinion at or prior to the closing of the transaction and modifications to the termination and expense reimbursement rights of the parties. Representatives of Latham & Watkins also reviewed certain revisions to the Support Agreement to be entered into by certain significant stockholders of Nivalis. Nivalis’ board of directors then engaged in a discussion of the revised terms of the Merger Agreement and the other transaction documents and asked questions of the representatives of Latham & Watkins regarding the Merger Agreement, which were answered during Latham & Watkins’ presentation. Representatives of Ladenburg then reviewed its final valuation analysis and fairness opinion as circulated to the board in advance of the meeting. Ladenburg then delivered its oral opinion (subsequently confirmed in writing and attached hereto as Annex B) to the effect that, as of the date of the execution of the Merger Agreement, and based upon and subject to the considerations, limitations and other matters set forth in its written opinion attached hereto as Annex B, that the exchange ratio was fair, from a financial point of view, to Nivalis’ stockholders. During the presentations, members of Nivalis’ board of directors asked questions and discussed the revised terms of the Merger Agreement and Ladenburg’s financial analysis and fairness opinion. After these presentations and discussions, Nivalis’ board of directors unanimously (i) determined that the Merger Agreement, the merger and the other transactions contemplated by the Merger Agreement, including the issuance of common stock to Alpine’s stockholders and the Nivalis Reverse Stock Split, if deemed necessary or advisable, were advisable and in the best interests of Nivalis’ stockholders; (ii) approved the Merger Agreement, the Support Agreements, the merger and the transactions contemplated thereby in accordance with Delaware law; (iii) approved and declared advisable the Merger Agreement and the transactions contemplated thereby; (iv) approved an amendment to Nivalis’ certificate of incorporation to effect the Nivalis Name Change and, if determined necessary by Nivalis and Alpine, effect the Nivalis Reverse Stock Split; and (v) resolved to recommend that Nivalis’ stockholders vote to approve the Merger Agreement and the transactions contemplated therein, including the issuance of shares of Nivalis’ common stock in the merger.

Following this meeting, certain terms of the Support Agreement to be entered into between Alpine and one of Nivalis’ stockholders (the “Revised Support Agreement”) were revised to provide certain exceptions to the transfer restrictions therein.

On April 18, 2017, following finalization of the Revised Support Agreement, the Merger Agreement and related documents were executed and delivered by Nivalis, Alpine and the other applicable parties. Following execution of the Merger Agreement, Nivalis and Alpine issued a joint press release announcing the execution of the Merger Agreement and the related documents following the close of trading of Nivalis’ common stock on April 18, 2017.

In January 2015, Alpine entered into a Series Seed Stock Purchase Agreement, as amended, with certain investors which provided for $1.25 million in equity financing and was funded in multiple closings over the course of 2015 and early 2016 (the “Series Seed Financing”). The proceeds from the Series Seed Financing were used to finance Alpine’s research and development efforts and for general operating capital purposes.

In October 2015, Alpine signed a collaboration agreement with Kite providing Kite with access to two of Alpine’s TIP™ programs for use in Kite’s CAR-T and TCR programs. Alpine received $5.5 million in up-front cash payments from Kite and is eligible to receive up to $530.0 million in developmental, clinical, and regulatory milestones in addition to royalties on any products containing Alpine’s TIPs. Alpine used the proceeds from the up-front payments to finance its research and development efforts and for general operating capital purposes.

In June 2016, Alpine entered into a Series A Preferred Stock Purchase Agreement (the “Series A SPA”) with certain investors which provided for up to $48.0 million in equity financing to be funded in three potential tranches subject to certain milestones and other conditions (the “Series A Financing”). Approximately $10.33 million of Series A-1 Preferred Stock was sold by Alpine in the initial closing of the Series A Financing, which initial closing occurred on June 10, 2016. The proceeds from the initial closing of the Series A Financing were used to finance Alpine’s research and development efforts and for general operating capital purposes.

In addition to the Series A Financing, in December 2016, Alpine entered into a Loan and Security Agreement with a financial institution (the “Loan Agreement”) which provided Alpine with the ability to borrow up to $5.0 million, subject to certain terms and conditions as set forth more fully in the Loan Agreement, for purposes of funding Alpine’s research and development efforts and for general operating capital purposes. Alpine had not requested any term loan advances at March 31, 2017 or December 31, 2016.

Alpine’s executive management team and board of directors continually and periodically reviews a broad range of options to enhance stockholder value, including debt and/or equity financings, mergers and acquisitions, and monetization of existing research and development programs. On or about January 16, 2017, Alpine received a letter from Ladenburg. The letter described the potential for a strategic transaction involving Nivalis and invited Alpine to submit a non-binding proposal regarding such potential transaction.

On or about February 3, 2017, representatives of Alpine submitted to representatives of Ladenburg a response to Ladenburg’s letter, outlining the terms of a potential transaction between Alpine and Nivalis. Alpine’s February 3, 2017 letter set forth a proposal of high level terms for a potential merger transaction and discussed some of the strategic benefits Alpine could provide in such a combination with Nivalis.

On or about February 13, 2017, representatives of Alpine visited Ladenburg and certain members of Nivalis’ management team in New York, New York. At this meeting, representatives of Alpine provided a more detailed presentation, including a discussion of Alpine’s underlying technology and research and development efforts to date, Alpine’s financing efforts, current cash projections and other financial information, management team and other personnel, board of directors and scientific advisory team, and certain of Alpine’s strategic business relationships and collaboration opportunities. The parties also further discussed the economic and other terms of a potential merger transaction.

On March 20, 2017, following several formal and informal discussions by Alpine’s board of directors and Alpine’s management team regarding the terms of a potential merger transaction between Nivalis and Alpine, with the support of Alpine’s board of directors, management and Alpine’s existing investors, Alpine entered into a letter agreement with Nivalis containing certain limited exclusivity provisions to allow the parties an opportunity to conduct further due diligence and to attempt to negotiate a definitive agreement related to a potential merger transaction. As a requirement imposed by Nivalis to the potential merger transaction, certain existing Alpine investors demonstrated interest in a private financing in Alpine immediately prior to the closing

of the potential merger transaction, which when combined with the approximately $44.0 million in cash resources of Nivalis, would provide Alpine with approximately $90.0 million of funds available to enable Alpine to pursue the combined organization’s business objectives post-merger.

In late March and early April of 2017, as Alpine performed due diligence on the potential merger transaction and was working to negotiate the terms of the definitive Merger Agreement, Alpine management continued to keep Alpine’s board of directors informed, both through formal and informal communications, regarding the status of negotiations on the potential merger transaction. On Alpine’s telephonic board of directors call on March 29, 2017, Alpine’s board of directors authorized Alpine management to incur certain legal, accounting and other expenses related to the potential merger transaction.

On April 14, April 16 and April 18, 2017, Alpine’s board of directors held a series of telephonic meetings with Alpine’s legal advisors. The directors acknowledged and discussed that they had met and discussed on numerous occasions, both formally and informally, the potential merits and risks to Alpine and its stockholders of the merger and the $17.0 million financing to be consummated immediately prior to the closing of the merger as contemplated by the Subscription Agreement (the “Pre-Closing Financing”), the chronology of events leading to the proposals to approve the merger and the Pre-Closing Financing, the negotiations with the investors in such Pre-Closing Financing and with Nivalis with respect to the merger, and the terms and conditions of such Pre-Closing Financing and the merger. The directors also acknowledged that prior to the signing of the definitive Merger Agreement, certain investors of Alpine would also complete a Second Tranche Put Closing (as defined and set forth in the Series A SPA) related to Alpine’s Series A Financing, whereby such investors would, in the aggregate, purchase approximately $20.67 million of Series A-1 Preferred Stock in Alpine upon the terms set forth in the Series A SPA. Alpine’s legal counsel summarized the terms and conditions of the proposed merger and the Pre-Closing Financing, reviewed with the directors their fiduciary duties in the context of the consideration and approval of the Pre-Closing Financing and the merger and answered each director’s questions. After discussion, Alpine’s board of directors (i) authorized and approved the Pre-Closing Financing contemplated by the Subscription Agreement, (ii) approved and adopted the Subscription Agreement, (iii) determined that the merger and the transactions contemplated by the Merger Agreement were fair to, advisable and in the best interests of Alpine and its stockholders, (iv) approved and declared advisable the Merger Agreement and the transactions contemplated thereby, (v) resolved to recommend that the stockholders of Alpine execute a written consent to approve and adopt the Merger Agreement and thereby approve the transactions contemplated thereby and (vi) approved certain other related matters.

Nivalis’ board of directors considered the following factors in reaching its conclusion to approve the Merger Agreement and the transactions contemplated thereby and to recommend that Nivalis’ stockholders approve the Merger Agreement, and thereby approve the merger and the other transactions contemplated by the Merger Agreement, including the issuance of shares of Nivalis’ common stock in the merger, all of which Nivalis’ board of directors viewed as supporting its decision to approve the business combination with Alpine:

Nivalis’ board of directors also reviewed various factors impacting the financial condition, results of operations and prospects for Nivalis, including:

Nivalis’ board of directors also reviewed the terms and conditions of the Merger Agreement and associated transactions, as well as the safeguards and protective provisions included therein intended to mitigate risks, including:

In the course of its deliberations, Nivalis’ board of directors also considered a variety of risks and other countervailing factors related to entering into the merger, including:

The foregoing information and factors considered by Nivalis’ board of directors are not intended to be exhaustive but are believed to include all of the material factors considered by Nivalis’ board of directors. In view of the wide variety of factors considered in connection with its evaluation of the merger and the complexity of these matters, Nivalis’ board of directors did not find it useful to attempt, and did not attempt, to quantify, rank or otherwise assign relative weights to these factors. In considering the factors described above, individual members of Nivalis’ board of directors may have given different weight to different factors. Nivalis’ board of directors conducted an overall analysis of the factors described above, including thorough discussions with, and questioning of, Nivalis’ management team, members of the Special Committee and the legal and financial advisors of Nivalis, and considered the factors overall to be favorable to, and to support, its determination.

In the course of reaching its decision to approve the merger, Alpine’s board of directors consulted with Alpine’s senior management, financial and tax advisors and legal counsel, reviewed a significant amount of information and considered a number of factors, including, among others:

Alpine’s board of directors also considered a number of uncertainties and risks in its deliberations concerning the merger and the other transactions contemplated by the Merger Agreement, including the following:

Pursuant to an engagement letter dated January 3, 2017, Nivalis retained Ladenburg to act as a financial advisor in connection with the merger and the transactions contemplated by the Merger Agreement and to render an opinion to Nivalis’ board of directors as to the fairness, from a financial point of view, of the exchange ratio to Nivalis’ stockholders. On April 17, 2017, Ladenburg rendered its oral opinion, subsequently confirmed by delivery of a written opinion dated April 17, 2017 (the “Opinion”), to Nivalis’ board of directors, that, as of the date of such Opinion, and based upon the various assumptions, qualifications and limitations set forth therein, the exchange ratio was fair, from a financial point of view, to Nivalis’ stockholders.

The full text of the written Opinion of Ladenburg, dated April 17, 2017, is attached as Annex B to this proxy statement and is incorporated by reference. Nivalis encourages Nivalis’ stockholders to read the Opinion in its entirety for the assumptions made, procedures followed, other matters considered and limits of the review by Ladenburg. The summary of the Opinion set forth herein is qualified by reference to the full text of such Opinion. Ladenburg provided its Opinion for the sole benefit and use of Nivalis’ board of directors in its consideration of the merger and the other transactions contemplated by the Merger Agreement. Ladenburg’s Opinion is not a recommendation to any stockholder as to how to vote with respect to the proposed merger or the transactions contemplated by the Merger Agreement or to take any other action in connection with the merger or otherwise.

In connection with its Opinion, Ladenburg took into account an assessment of general economic, market and financial conditions as well as its experience in connection with similar transactions and securities valuations generally and, among other things:

In conducting its review and arriving at its Opinion, Ladenburg, with the consent of Nivalis, assumed and relied, without independent investigation, upon the accuracy and completeness of all financial and other information provided to Ladenburg by Nivalis and Alpine, or which is publicly available or was otherwise reviewed by Ladenburg. Ladenburg did not undertake any responsibility for the accuracy, completeness or reasonableness of, or independent verification of, such information. Ladenburg relied upon, without independent verifications, the assessment of management of Nivalis and Alpine as to the viability of, and risks associated with, the future products and services of Alpine (including without limitation, the development, testing and marketing of such products and services, the receipt of all necessary governmental and other regulatory approvals for the development, testing and marketing thereof, and the life and enforceability of all relevant patents and other intellectual and other property rights associated with such products and services). In addition, Ladenburg did not conduct, or assume any obligation to conduct, any physical inspection of the properties or facilities of Nivalis or Alpine.

With respect to the financial forecasts supplied to Ladenburg by Nivalis regarding Alpine, Ladenburg assumed, with Nivalis’ consent, that they were reasonably prepared on the basis reflecting the best currently available estimates and judgments of the managements of Nivalis and Alpine, as applicable, as to the future operating and financial performance of Nivalis and Alpine, as applicable, and that they provided a reasonable basis upon which Ladenburg could form its opinion. Ladenburg assumed, with Nivalis’ consent, that the only material asset of Nivalis is its net cash, that no other assets of Nivalis, including, without limitation, any net operating losses of Nivalis, have any material value and that Nivalis does not, and does not intend to, engage in any activity that may result in the generation of any revenue. Furthermore, Ladenburg assumed, with Nivalis’ consent, that there will be no further adjustments to the exchange ratio between the date of the Merger Agreement and the date the final exchange ratio is determined. Ladenburg expressly disclaimed any undertaking or obligation to advise any person of any change in any fact or matter affecting its Opinion of which Ladenburg becomes aware after the date of its Opinion. Ladenburg assumed there were no material changes in the assets, liabilities, financial condition, results of operations, business or prospects of Nivalis or Alpine since the date of the last financial statements made available to them. Ladenburg did not make or obtain any independent evaluations, valuations or appraisals of the assets or liabilities of Nivalis or Alpine, nor was Ladenburg furnished with such materials. Further, as Nivalis’ board of directors was aware, Alpine’s management did not provide Ladenburg with, and Ladenburg did not otherwise have access to, financial forecasts regarding Alpine’s business, other than certain expense forecasts for the remaining portion of 2017, and, accordingly, Ladenburg did not perform either a discounted cash flow analysis or any multiples-based analyses with respect to Alpine. In addition, Ladenburg did not evaluate the solvency or fair value of Nivalis or Alpine under any state or federal laws relating to bankruptcy, insolvency or similar matters. Ladenburg’s Opinion did not address any legal, tax or accounting matters related to the Merger Agreement or the merger, as to which Ladenburg has assumed that

Nivalis and Nivalis’ board of directors received such advice from legal, tax and accounting advisors as each has determined appropriate. Ladenburg’s Opinion addressed only the fairness of the exchange ratio, from a financial point of view, to Nivalis’ stockholders. Ladenburg expressed no view as to any other aspect or implication of the merger or any other agreement, arrangement or understanding entered into in connection with the merger. Ladenburg’s Opinion was necessarily based upon economic and market conditions and other circumstances as they existed and could be evaluated by Ladenburg on the date of its Opinion. It should be understood that although subsequent developments may affect Ladenburg’s Opinion, Ladenburg does not have any obligation to update, revise or reaffirm its Opinion and Ladenburg has expressly disclaimed any responsibility to do so.

Ladenburg did not consider any potential legislative or regulatory changes currently being considered or recently enacted by the United States or any foreign government, or any domestic or foreign regulatory body, or any changes in accounting methods or generally accepted accounting principles that may be adopted by the SEC, the Financial Accounting Standards Board, or any similar foreign regulatory body or board.

For purposes of rendering its Opinion, Ladenburg assumed, in all respects material to its analysis, that the representations and warranties of each party contained in the Merger Agreement are true and correct, that each party will perform all of the standards of the covenants and agreements required to be performed by it under the Merger Agreement and that all conditions to the consummation of the merger will be satisfied without waiver thereof. Ladenburg assumed that the final form of the Merger Agreement was substantially similar to the last draft reviewed by Ladenburg. Ladenburg also assumed that all governmental, regulatory and other consents and approvals contemplated by the Merger Agreement will be obtained and that in the course of obtaining any of those consents no restrictions will be imposed or waivers made that would have an adverse effect on the contemplated benefits of the merger. Ladenburg assumed that the merger will be consummated in a manner that complies with the applicable provisions of the Securities Act, the Exchange Act, and all other applicable federal and state statutes, rules and regulations.

Ladenburg’s Opinion was intended for the benefit and use of Nivalis’ board of directors in its consideration of the financial terms of the merger and may not be used for any other purpose or reproduced, disseminated, quoted or referred to at any time, in any manner or for any purpose without Ladenburg’s prior written consent. Ladenburg’s Opinion did not constitute a recommendation to Nivalis’ board of directors on whether or not to approve the merger or to any stockholder or any other person as to how to vote with respect to the merger or to take any other action in connection with the merger or otherwise. Ladenburg’s Opinion did not address Nivalis’ underlying business decision to proceed with the merger or the relative merits of the merger compared to other alternatives available to Nivalis. Ladenburg expressed no opinion as to the prices or ranges of prices at which shares of securities of any person, including Nivalis, will trade at any time, including following the announcement or consummation of the merger. Ladenburg was not requested to opine as to, and Ladenburg’s Opinion does not in any manner address, the amount or nature of compensation to any of the officers, directors or employees of any party to the merger, or any class of such persons, relative to the compensation to be paid to the securityholders of Alpine in connection with the merger or with respect to the fairness of any such compensation.

The following is a summary of the principal financial analyses performed by Ladenburg to arrive at its Opinion. Some of the summaries of financial analyses include information presented in tabular format. In order to fully understand the financial analyses, the tables must be read together with the text of each summary. The tables alone do not constitute a complete description of the financial analyses. Considering the data set forth in the tables without considering the full narrative description of the financial analyses, including the methodologies and assumptions underlying the analyses, could create a misleading or incomplete view of the financial analyses. Ladenburg performed certain procedures, including each of the financial analyses described below, and reviewed with Nivalis’ management the assumptions on which such analyses were based and other factors, including the historical and projected financial results of Nivalis and Alpine.

Based upon the exchange ratio in the Merger Agreement, Ladenburg assumed Nivalis would issue to Alpine’s stockholders and cause to become issuable to Alpine’s optionholders and warrantholders approximately 11.2 million shares of Nivalis’ common stock (as adjusted for the potential Nivalis Reverse Stock Split) and that Nivalis’ stockholders, optionholders and warrantholders will own, or hold rights to acquire, approximately 26% of the Fully-Diluted Common Stock of Nivalis post-merger.

Ladenburg estimated an implied equity value for Alpine of approximately $142.3 million, which was calculated by multiplying 11,229,209 (the number of shares of Nivalis’ common stock expected to be issued to Alpine’s stockholders or to become issuable to Alpine’s optionholders and warrantholders based on the exchange ratio, assuming the occurrence of the Nivalis Reverse Stock Split) by $12.67 (the implied per share price of Nivalis’ common stock following the Nivalis Reverse Stock Split).

Ladenburg calculated an implied total enterprise value for Alpine of approximately $101.1 million by subtracting an assumed Alpine Net Cash balance of approximately $41.2 million (based on Alpine’s projected indebtedness, cash and cash equivalents at July 31, 2017, the assumed closing date of the Merger for purposes of the Opinion), from the implied equity value of approximately $142.3 million.

Ladenburg reviewed the initial public offerings (“IPOs”) of twelve companies which completed an IPO since 2015 and whose lead products at the time of its IPO were in the immuno-oncology space. The implied total enterprise value at IPO is defined as the pre-money equity value plus indebtedness, liquidation value of preferred stock and non-controlling interest, minus cash and cash equivalents at the time of its IPO. Although the companies referred to below were used for comparison purposes, none of these companies are directly comparable to Alpine. Accordingly, an analysis of the results of such a comparison is not purely mathematical, but instead involves complex considerations and judgments concerning differences in historical and projected financial and operating characteristics of the selected companies below. These companies, which are referred to as the “Selected Oncology IPO Companies” were:

As indicated in the following table, the Selected Oncology IPO Companies had implied total enterprise values between $65 million and $1,716 million, with a median of $292 million and an interquartile range of $158 million to $730 million. Using the 25^th percentile and the 75^th percentile of the implied total enterprise values, Ladenburg then calculated a range of implied total equity values for Alpine (by subtracting an estimated $5.0 million in debt at closing and adding an estimated $46.2 million in net cash as closing), which was $200.0 million to $771 million. This compares to Alpine’s total equity value as per the Merger Agreement of approximately $142.3 million.

Ladenburg reviewed selected financial data of fourteen publicly traded companies in the biopharmaceutical industry which were in early stages of development and were focused on the immuno-oncology space (the “Selected Publicly Traded Early Stage Immuno-oncology Companies”). Although the companies referred to below were used for comparison purposes, none of those companies are directly comparable to Alpine. Accordingly, an analysis of the results of such a comparison is not purely mathematical, but instead involves complex considerations and judgments concerning differences in historical and projected financial and operating characteristics of the selected companies below. The total enterprise values are based on closing stock prices on April 13, 2017. The Selected Publicly Traded Early Stage Immuno-oncology Companies were:

As indicated in the following table, the fourteen Selected Publicly Traded Early Stage Immuno-oncology Companies had implied total enterprise values between $35 million and $528 million, with a median implied total enterprise value of $287 million and an interquartile range of $161 million to $397 million. Using the 25^th percentile and the 75^th percentile of the implied total enterprise values, Ladenburg then calculated a range of implied total equity values for Alpine (by subtracting an estimated $5.0 million in debt at closing and adding an estimated $46.2 million in net cash at closing), which was $202 million to $438 million. This compares to Alpine’s total equity value as per the Merger Agreement of approximately $142.3 million.


Delaware	2834	20-8969493
(State or other jurisdiction of incorporation or organization)	(Primary Standard Industrial Classification Code Number)	(I.R.S. Employer Identification Number)


Competition			164
Intellectual Property			165
Regulatory Matters			166
Employees			168
Facilities			168
Legal Proceedings			168

ALPINE BUSINESS			169
Overview			169
Immunology Background			170
Alpine’s vIgD Platform			179
Collaboration with Kite Pharma			188
Alpine’s Strategy			189
Product Pipeline			190
Lead Program ALPN-101			190
Active Discovery Programs			199
Manufacturing			199
Competition			200
Intellectual Property			201
Government Regulation			201
Employees			210
Facilities			210
Legal Proceedings			210

NIVALIS MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS			211
Overview			211
Financial Operations Overview			213
Results of Operations			215
Liquidity and Capital Resources			219
Critical Accounting Policies and Significant Judgment and Estimates			221
Contractual Obligations and Commitments			222
Related Party Transactions			222
Off-Balance Sheet Arrangements			222
Tax Loss Carryforwards			222
JOBS Act			223
Recent Accounting Pronouncements			223

QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK			223

ALPINE MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS			224
Overview			224
Financial Overview			226
Critical Accounting Policies and Significant Judgments and Estimates			227
Results of Operations			230
Liquidity and Capital Resources			232
Cash Flows			234
Contractual Obligations and Commitments			235
Off-Balance Sheet Arrangements			235

QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISKS			236

MANAGEMENT FOLLOWING THE MERGER			237
Executive Officers and Directors			237
Composition of the Board of Directors			240
Committees of the Board of Directors			241


Director Compensation			245
Executive Compensation Discussion and Analysis			245
Employment Benefits Plan			253

RELATED PARTY TRANSACTIONS OF DIRECTORS AND EXECUTIVE OFFICERS OF THE COMBINED ORGANIZATION			258
Nivalis Transactions			258
Alpine Transactions			258

UNAUDITED PRO FORMA CONDENSED COMBINED FINANCIAL INFORMATION			261
Pro Forma Condensed Combined Balance Sheet			262
Pro Forma Condensed Combined Statement of Operations			263
Pro Forma Condensed Combined Statement of Operations			264
Notes to the Unaudited Pro Forma Condensed Combined Financial Information			265

COMPARISON OF RIGHTS OF HOLDERS OF NIVALIS STOCK AND ALPINE STOCK			273
Current Alpine Rights Versus Nivalis Rights Post-Merger			273
Indemnification of Officers and Directors and Advancement of Expenses; Limitation on Personal Liability			283
Dividends			283
Amendments to Certificate of Incorporation or Bylaws			284

PRINCIPAL STOCKHOLDERS OF NIVALIS			285

PRINCIPAL STOCKHOLDERS OF ALPINE			287

PRINCIPAL STOCKHOLDERS OF COMBINED ORGANIZATION			289

LEGAL MATTERS			292

EXPERTS			292

WHERE YOU CAN FIND MORE INFORMATION			293

TRADEMARK NOTICE			293

OTHER MATTERS			294
Section 16(a) Beneficial Ownership Reporting Compliance			294
Stockholder Proposals			294
Communication with Nivalis’ Board of Directors			294

INDEX TO NIVALIS FINANCIAL STATEMENTS			F-A-1

INDEX TO ALPINE FINANCIAL STATEMENTS			F-B-1

ANNEX A—AGREEMENT AND PLAN OF MERGER AND REORGANIZATION			A-1

ANNEX B—OPINION OF LADENBURG			B-1

ANNEX C—GENERAL CORPORATION LAW OF THE STATE OF DELAWARE			C-1

ANNEX D—NIVALIS CERTIFICATE OF AMENDMENT REGARDING REVERSE STOCK SPLIT			D-1

ANNEX E—NIVALIS CERTIFICATE OF AMENDMENT REGARDING NAME CHANGE			E-1


Name		Current Principal Affiliation
Mitchell H. Gold, M.D.		Alpine Immune Sciences, Inc. Executive Chairman and Chief Executive Officer
Peter Thompson M.D.		Alpine Immune Sciences, Inc., Director
James N. Topper, M.D., Ph.D.		Alpine Immune Sciences, Inc., Director
Jay Venkatesan, M.D.		Alpine Immune Sciences, Inc. President and Director
Robert Conway		Nivalis Therapeutics, Inc., Director
Paul Sekhri		Nivalis Therapeutics, Inc., Director
Independent Designee (TBD)		(TBD)


R. Michael Carruthers		Mitchell H. Gold, M.D.
Interim President and Chief Financial Officer		Executive Chairman and Chief Executive Officer
Nivalis Therapeutics, Inc.		Alpine Immune Sciences, Inc.


QUESTIONS AND ANSWERS ABOUT THE MERGER			1

PROSPECTUS SUMMARY			7
The Companies			7
The Merger			8
Reasons for the Merger			8
Opinion of the Nivalis Financial Advisor			9
Overview of the Merger Agreement			10
Subscription Agreement			12
Support Agreements			12
Lock-up Agreements			14
Management Following the Merger			14
Interests of Certain Directors, Officers and Affiliates of Nivalis and Alpine			14
Risk Factors			15
Regulatory Approvals			16
NASDAQ Stock Market Listing			16
Anticipated Accounting Treatment			16
Appraisal Rights			16
Comparison of Stockholder Rights			17

SELECTED HISTORICAL AND UNAUDITED PRO FORMA CONDENSED COMBINED FINANCIAL DATA			18
Selected Historical Financial Data of Nivalis			18
Selected Historical Financial Data of Alpine			20
Selected Unaudited Pro Forma Condensed Combined Financial Data of Nivalis and Alpine			22
Comparative Historical and Unaudited Pro Forma Per Share Data			24

RISK FACTORS			25
Risks Related to the Merger			25
Risks Related to Nivalis			28
Risks Related to Nivalis’ Capital Requirements, Finances and Operations			28
Development and Regulatory Risks Related to Nivalis’ Business			32
Risks Related to Nivalis’ Reliance on Third Parties			39
Intellectual Property Risks Related to Nivalis’ Business			40
Risks Related to Nivalis’ Industry			46
Risks Related to Ownership of Nivalis’ Common Stock			47
Risks Related to Alpine			53
Risks Related to Alpine’s Intellectual Property			69
Risks Related to Government Regulation			75
Risks Related to the Combined Organization			83

FORWARD-LOOKING STATEMENTS			89

THE SPECIAL MEETING OF NIVALIS’ STOCKHOLDERS			90
Date, Time and Place			90
Purpose of the Nivalis Special Meeting			90
Recommendation of Nivalis’ Board of Directors			90
Record Date and Voting Power			91
Voting and Revocation of Proxies			91
Required Vote			92
Solicitation of Proxies			93
Other Matters			93


THE MERGER			94
Background of the Merger			94
Nivalis Reasons for the Merger			108
Alpine Reasons for the Merger			111
Opinion of the Nivalis Financial Advisor			113
Interests of the Nivalis Directors and Executive Officers in the Merger			120
Interests of the Alpine Directors and Executive Officers in the Merger			124
Limitations of Liability and Indemnification			127
Alpine Stock Options and Warrants			127
Form of the Merger			127
Merger Consideration			128
Effective Time of the Merger			129
Regulatory Approvals			129
Tax Treatment of the Merger			129
NASDAQ Stock Market Listing			129
Anticipated Accounting Treatment			130
Appraisal Rights			130

THE MERGER AGREEMENT			134
General			134
Merger Consideration			134
Treatment of Nivalis’ Stock Options			135
Treatment of Alpine’s Stock Options and Warrants			135
Directors and Officers of Nivalis Following the Merger			136
Amended and Restated Certificate of Incorporation and Amendment to the Amended and Restated Certificate of Incorporation of Nivalis			136
Conditions to the Completion of the Merger			137
Representations and Warranties			139
No Solicitation			140
Meetings of Stockholders			142
Covenants; Conduct of Business Pending the Merger			142
Other Agreements			145
Termination			145
Termination Fee			147
Amendment			148

AGREEMENTS RELATED TO THE MERGER			149
Subscription Agreement			149
Support Agreements and Written Consent			151
Lock-up Agreements			153

MATTERS BEING SUBMITTED TO A VOTE OF NIVALIS’ STOCKHOLDERS			154
Proposal No. 1: Approval of the Merger and the Issuance of Common Stock in the Merger			154
Proposal No. 2: Approval of an Amendment to the Amended and Restated Certificate of Incorporation of Nivalis Effecting the Nivalis Reverse Stock Split			154
Proposal No. 3: Approval of Nivalis Name Change			160
Proposal No. 4: Approval of Possible Adjournment of the Nivalis Special Meeting			160

NIVALIS BUSINESS			161
Overview			161
GSNOR Inhibitor Portfolio			162
Nivalis’ Business Strategy			162
Clinical Development of Cavosonstat to Date			162
Preclinical Safety Studies			164
Other GSNOR Inhibitors			164
Manufacturing and Supply			164


	Years Ended December 31,															Three Months Ended March 31,
Statement of Operations Data:	2016			2015			2014			2013			2012			2017			2016
	(in thousands, except per share data)															(unaudited)
Revenue	$	—		$	—		$	—		$	—		$	—		$	—		$	—
Operating expenses:
Research and development		23,316			16,054			12,200			13,136			7,100			2,758			5,567
General and administrative		8,586			6,844			2,287			2,141			1,930			2,781			2,367
Restructuring charges		—			—			—			—			—			3,486			—

Loss from operations		(31,902	)		(22,898	)		(14,487	)		(15,277	)		(9,030	)		(9,025	)		(7,934	)
Interest and other income, net		439			80			296			10			151			109			96
Interest expense		—			—			(845	)		(931	)		(694	)		—			—

Net loss		(31,463	)		(22,818	)		(15,036	)		(16,198	)		(9,573	)		(8,916	)		(7,838	)
Gain on extinguishment of convertible debt as a capital transaction		—			—			378			—			—			—			—

Net loss attributable to common shareholders	$	(31,463	)	$	(22,818	)	$	(14,658	)	$	(16,198	)	$	(9,573	)	$	(8,916	)	$	(7,838	)

Weighted average shares outstanding—basic and diluted		15,492			9,371			723			155			137			15,644			15,462

Net loss per share attributable to common stockholders—basic and diluted	$	(2.03	)	$	(2.43	)	$	(20.27	)	$	(104.50	)	$	(69.88	)	$	(0.57	)	$	(0.51	)


Selected Balance Sheet Data:	As of December 31,															As of March 31,
	2016			2015			2014			2013			2012			2017
							(in thousands)									(unaudited)
Cash, cash equivalents and marketable securities	$	61,035		$	87,254		$	27,812		$	1,098		$	4,705		$	52,674
Restricted cash		—			—			—			2,500			2,500			—
Working capital, net		55,164			83,267			26,027			(2,209	)		5,050			49,148
Total assets		61,935			87,909			28,543			4,134			8,012			53,009
Total liabilities		6,499			4,419			2,415			17,629			5,406			3,789
Convertible preferred stock		—			—			41,880			77,793			77,793			—
Accumulated deficit		(180,300	)		(148,837	)		(126,019	)		(110,983	)		(94,785	)		(189,216	)
Total stockholders’ equity (deficit)		55,436			83,490			(15,752	)		(91,288	)		(75,188	)		49,220


	Year Ended December 31,						Three Months Ended March 31,
	2016			2015			2017			2016
							(unaudited)
	(in thousands, except share and per share data)
Statements of Operations Data:
Revenues:
Collaboration revenue	$	2,950		$	492		$	737		$	737

Total revenues		2,950			492			737			737

Operating expenses:
Research and development		2,989			422			1,858			421
General and administrative		1,149			441			873			220

Total operating expenses		4,138			863			2,731			641

Income (loss) from operations		(1,188	)		(371	)		(1,994	)		96
Other income		22			2			5			4

Income (loss) before taxes		(1,166	)		(369	)		(1,989	)		100
Income tax expense		(66	)		—			—			—

Net Income (loss) attributable to common stockholders	$	(1,232	)	$	(369	)	$	(1,989	)	$	100

Basic net income (loss) per share attributable to common stockholders	$	(1.08	)	$	(0.37	)	$	(1.61	)	$	0.03

Diluted net income (loss) per share attributable to common stockholders	$	(1.08	)	$	(0.37	)	$	(1.61	)	$	0.03

Weighted-average shares used to compute basic net income (loss) per share attributable to common stockholders		1,136,066			1,000,000			1,238,090			1,000,000

Weighted-average shares used to compute diluted net income (loss) per share attributable to common stockholders		1,136,066			1,000,000			1,238,090			3,950,196


	December 31, 2016			December 31, 2015			March 31, 2017
							(unaudited)
	(in thousands)
Selected Balance Sheet Data:
Cash and cash equivalents	$	11,819		$	5,423		$	13,568
Deferred revenue		2,008			4,958			1,271
Working capital, net		9,451			2,260			11,484
Total assets		12,595			5,439			14,519
Convertible preferred stock		11,535			610			15,535
Common stock		—			—			—
Additional paid-in capital		144			17			217
Accumulated deficit		(1,601	)		(369	)		(3,590	)
Total stockholders’ deficit		(1,457	)		(352	)		(3,373	)


	For the Year Ended December 31, 2016			For the Three Months Ended March 31, 2017
	(in thousands, except per share data)
Unaudited Pro Forma Condensed Combined Statements of Operations Data:
Total revenue	$	2,950		$	737
Research and development expenses		26,305			4,616
General and administrative expenses		9,735			3,426
Restructuring charges		—			3,486
Loss from operations		(33,090	)		(10,791	)
Net loss		(32,695	)		(10,677	)
Basic and diluted net loss per share	$	(0.59	)	$	(0.19	)


	As of March 31, 2017
	(in thousands)
Unaudited Pro Forma Condensed Combined Balance Sheet Data:
Cash, cash equivalents and marketable securities	$	99,909
Working capital, net		88,367
Total assets		102,260
Accumulated deficit		(5,516	)
Total stockholders’ equity		58,243


	Year Ended December 31, 2016			Three Months Ended March 31, 2017
Nivalis Historical Per Common Share Data:
Basic and diluted net loss per share	$	(2.03	)	$	(0.57	)
Book value per share	$	3.56		$	3.14
Alpine Historical Per Common Share Data:
Basic and diluted net loss per share	$	(1.08	)	$	(1.61	)
Book value per share		n/a			n/a
Combined Organization Per Common Share Data:
Basic and diluted net loss per share	$	(0.59	)	$	(0.19	)
Book value per share		n/a		$	1.05


Date of IPO Announcement	Company Name	Enterprise Value ($MM)
3/8/17	BeyondSpring		$ 367
1/26/17	Jounce Therapeutics		125
1/25/17	AnaptysBio		164
6/29/16	Syros Pharmaceuticals		172
5/18/16	Merus		65
3/22/16	Corvus Pharmaceuticals		141
2/2/16	BeiGene		477
10/7/15	CytomX Therapeutics		216
7/27/15	NantKwest		1,716
5/5/15	Adaptimmune Therapeutics		719
4/14/15	Aduro Biotech		764
3/24/15	Cellectis		1,108


Company Name	Enterprise Value ($MM)
Adaptimmune Therapeutics plc	$	204
Agenus Inc.		396
AnaptysBio, Inc.		398
Bellicum Pharmaceuticals, Inc.		174
Calithera Biosciences, Inc.		246
Cellectis S.A.		510
Compugen Ltd.		157
CytomX Therapeutics, Inc.		391
Fate Therapeutics, Inc.		92
Five Prime Therapeutics, Inc.		528
Jounce Therapeutics, Inc.		435
Leap Therapeutics, Inc.		52
Merus B.V.		327
Trillium Therapeutics Inc.		35