UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 13G

Under the Securities Exchange Act of 1934

(Amendment No.  )*

Denali Therapeutics Inc.

(Name of Issuer)

Common Stock par value $0.01 per share

(Title of Class of Securities)

24823R105

(CUSIP Number)

December 31, 2017

(Date of Event Which Requires Filing of this Statement)

Check the appropriate box to designate the rule pursuant to which this Schedule is filed:

☐ Rule 13d-1(b)

☐ Rule 13d-1(c)

☒ Rule 13d-1(d)

*The remainder of this cover page shall be filled out for a reporting person's initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter disclosures provided in a prior cover page.

The information required in the remainder of this cover page shall not be deemed to be "filed" for the purpose of Section 18 of the Securities Exchange Act of 1934 ("Act") or otherwise subject to the liabilities of that section of the Act, but shall be subject to all other provisions of the Act (however, see the Notes).

CUSIP No.   24823R105 13G Page 2 of 12 Pages

1	NAMES OF REPORTING PERSONS
	I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)
	ARCH Venture Fund VIII, L.P.
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*
	(a)☐
	(b)☐
3	SEC USE ONLY
4	CITIZENSHIP OR PLACE OF ORGANIZATION
	Delaware
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		5	SOLE VOTING POWER
			0
		6	SHARED VOTING POWER
			11,068,749
		7	SOLE DISPOSITIVE POWER
			0
		8	SHARED DISPOSITIVE POWER
			11,068,749
9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
	11,068,749
10	CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*
	☐
11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
	12.3%
12	TYPE OF REPORTING PERSON*
	PN

CUSIP No.   24823R105 13G Page 3 of 12 Pages

1	NAMES OF REPORTING PERSONS
	I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)
	ARCH Venture Partners VIII, L.P.
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*
	(a)☐
	(b)☐
3	SEC USE ONLY
4	CITIZENSHIP OR PLACE OF ORGANIZATION
	Delaware
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		5	SOLE VOTING POWER
			0
		6	SHARED VOTING POWER
			11,068,749
		7	SOLE DISPOSITIVE POWER
			0
		8	SHARED DISPOSITIVE POWER
			11,068,749
9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
	11,068,749
10	CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*
	☐
11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
	12.3%
12	TYPE OF REPORTING PERSON*
	PN

CUSIP No.   24823R105 13G Page 4 of 12 Pages

1	NAMES OF REPORTING PERSONS
	I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)
	ARCH Venture Partners VIII, LLC
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*
	(a)☐
	(b)☐
3	SEC USE ONLY
4	CITIZENSHIP OR PLACE OF ORGANIZATION
	Delaware
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		5	SOLE VOTING POWER
			0
		6	SHARED VOTING POWER
			11,068,749
		7	SOLE DISPOSITIVE POWER
			0
		8	SHARED DISPOSITIVE POWER
			11,068,749
9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
	11,068,749
10	CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*
	☐
11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
	12.3%
12	TYPE OF REPORTING PERSON*
	OO

CUSIP No.   24823R105 13G Page 5 of 12 Pages

1	NAMES OF REPORTING PERSONS
	I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)
	Keith Crandell
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*
	(a)☐
	(b)☐
3	SEC USE ONLY
4	CITIZENSHIP OR PLACE OF ORGANIZATION
	United States of America
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		5	SOLE VOTING POWER
			0
		6	SHARED VOTING POWER
			11,068,749
		7	SOLE DISPOSITIVE POWER
			0
		8	SHARED DISPOSITIVE POWER
			11,068,749
9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
	11,068,749
10	CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*
	☐
11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
	12.3%
12	TYPE OF REPORTING PERSON*
	IN

CUSIP No.   24823R105 13G Page 6 of 12 Pages

1	NAMES OF REPORTING PERSONS
	I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)
	Clinton Bybee
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*
	(a)☐
	(b)☐
3	SEC USE ONLY
4	CITIZENSHIP OR PLACE OF ORGANIZATION
	United States of America
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		5	SOLE VOTING POWER
			0
		6	SHARED VOTING POWER
			11,068,749
		7	SOLE DISPOSITIVE POWER
			0
		8	SHARED DISPOSITIVE POWER
			11,068,749
9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
	11,068,749
10	CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*
	☐
11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
	12.3%
12	TYPE OF REPORTING PERSON*
	IN

CUSIP No.   24823R105 13G Page 7 of 12 Pages

1	NAMES OF REPORTING PERSONS
	I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)
	Robert Nelsen
2	CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP*
	(a)☐
	(b)☐
3	SEC USE ONLY
4	CITIZENSHIP OR PLACE OF ORGANIZATION
	United States of America
NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH		5	SOLE VOTING POWER
			0
		6	SHARED VOTING POWER
			11,068,749
		7	SOLE DISPOSITIVE POWER
			0
		8	SHARED DISPOSITIVE POWER
			11,068,749
9	AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
	11,068,749
10	CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES*
	☐
11	PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)
	12.3%
12	TYPE OF REPORTING PERSON*
	IN

CUSIP No.   24823R105 13G Page 8 of 12 Pages

Item 1(a). Name of Issuer

Denali Therapeutics Inc. (the "Issuer").

Item 1(b). Address of Issuer's Principal Executive Offices

151 Oyster Point Blvd., 2nd Floor, South San Francisco, CA  94080

Item 2(a). Name of Person Filing

ARCH Venture Fund VIII, L.P. ("ARCH Venture Fund VIII"); ARCH Venture Partners VIII, L.P. ("AVP VIII LP"); ARCH Venture Partners VIII, LLC ("AVP VIII LLC") (collectively, the "Reporting Entities" and individually, each a "Reporting Entity"); and Keith Crandell ("Crandell"), Robert Nelsen ("Nelsen") and Clinton Bybee ("Bybee") (collectively, the "Managing Directors" and individually, each a "Managing Director").  The Reporting Entities and the Managing Directors collectively are referred to as the "Reporting Persons".

Item 2(b). Address of Principal Business Office or, if none, Residence

8755 W. Higgins Avenue, Suite 1025, Chicago, IL 60631

Item 2(c). Citizenship

ARCH Venture Fund VIII and AVP VIII LP are limited partnerships organized under the laws of the State of Delaware. AVP VIII LLC is a limited liability company organized under the laws of the State of Delaware.  Each Managing Director is a US citizen.

Item 2(d). Title of Class of Securities

Common stock, par value $0.01 per share.

Item 2(e). CUSIP Number

24823R105

Item 3. If This Statement Is Filed Pursuant to Sections 240.13d-1(b) or 240.13d-2(b) or (c), Check Whether the Person Filing Is a(n):

Not Applicable.

Item 4. Ownership

(a) Amount beneficially owned:

ARCH Venture Fund VIII is the record owner of 11,068,749 shares of Common Stock (the "Record Shares") as of December 31, 2017.  AVP VIII LP, as the sole general partner of ARCH Venture Fund VIII, may be deemed to beneficially own the Record Shares.  AVP VIII LLC, as the sole general partner of AVP VIII LP, may be deemed to beneficially own the Record Shares.  As managing directors of AVP VIII LLC, each Managing Director may also be deemed to share the power to direct the disposition and vote of the Record Shares.  In addition, Nelsen holds options to exercise 47,165 shares of Common Stock, of which 0 are vested as of December 31, 2017, and 0 will vest within 60 days of December 31, 2017.

(b) Percent of class:

In the aggregate, the Reporting Persons beneficially own 12.3% of the outstanding shares of common stock of the Issuer, based upon 90,062,808 shares of common stock outstanding as of December 12, 2017 as reported on the Issuer's Form 424B4 filed on December 8, 2017 with Securities and Exchange Commission, plus shares issued to the underwriters reported on the Issuers Form 8-K filed December 12, 2017 with the Securities and Exchange Commission.

CUSIP No.   24823R105 13G Page 9 of 12 Pages

(c) Number of shares as to which such person has:

(i)    Sole power to vote or to direct the vote:

See line 5 of the cover sheets.

(ii)   Shared power to vote or to direct the vote:

See line 6 of the cover sheets.

(iii)  Sole power to dispose or to direct the disposition:

    See line 7 of the cover sheets.

(iv)  Shared power to dispose or to direct the disposition:

    See line 8 of the cover sheets.

Each Reporting Person disclaims beneficial ownership of such shares of Common Stock except for the shares, if any, such Reporting Person holds of record.

Item 5. Ownership of Five Percent or Less of a Class

Not Applicable.

Item 6. Ownership of More Than Five Percent on Behalf of Another Person

Not Applicable.

Item 7. Identification and Classification of the Subsidiary Which Acquired the Security Being Reported on By the Parent Holding Company

Not Applicable.

Item 8. Identification and Classification of Members of the Group

Not Applicable.

Item 9. Notice of Dissolution of Group

Not Applicable.

Item 10. Certification

Not Applicable.

CUSIP No.   24823R105 13G Page 10 of 12 Pages

SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

Dated:            February 2, 2018

ARCH VENTURE FUND VIII, L.P.

By:   ARCH Venture Partners VIII, L.P.

         its General Partner

 By:   ARCH Venture Partners VIII, LLC

                  its General Partner

  By:                   *                                         

                          Keith Crandell

                          Managing Director

ARCH VENTURE PARTNERS VIII, L.P.

By:   ARCH Venture Partners VIII, LLC

         its General Partner

 By:                    *                                         

                  Keith Crandell

                  Managing Director

ARCH VENTURE PARTNERS VIII, LLC

By:                       *

         Keith Crandell

         Managing Director

                          *

Keith Crandell

                          *

Robert Nelsen

                          *

Clinton Bybee

* By:  /s/ Mark McDonnell                            

           Mark McDonnell as

          Attorney-in-Fact

This Schedule 13G was executed by Mark McDonnell pursuant to Powers of Attorney attached hereto as Exhibit 2 and incorporated herein by reference.

CUSIP No.   24823R105 13G Page 11 of 12 Pages

Exhibit 1

AGREEMENT

Pursuant to Rule 13d-1-(k)(1) under the Securities Exchange Act of 1934, the undersigned hereby agree that only one statement containing the information required by Schedule 13G need be filed with respect to the ownership by each of the undersigned of shares of stock of Denali Therapeutics Inc.

This Agreement may be executed in any number of counterparts, each of which shall be deemed an original.

Dated:   February 2, 2018	ARCH VENTURE FUND VIII, L.P.
	By:   ARCH Venture Partners VIII, L.P.
	its General Partner

 By:   ARCH Venture Partners VIII, LLC

                  its General Partner

  By:                   *                                         

                          Keith Crandell

                          Managing Director

ARCH VENTURE PARTNERS VIII, L.P.

By:   ARCH Venture Partners VIII, LLC

         its General Partner

 By:                    *                                         

                  Keith Crandell

                  Managing Director

ARCH VENTURE PARTNERS VIII, LLC

By:                       *

         Keith Crandell

         Managing Director

                          *

Keith Crandell

                          *

Robert Nelsen

                          *

Clinton Bybee

* By:  /s/ Mark McDonnell                            

           Mark McDonnell as

          Attorney-in-Fact

This Agreement was executed by Mark McDonnell pursuant to Powers of Attorney attached hereto as Exhibit 2 and incorporated herein by reference.

CUSIP No.   24823R105 13G Page 12 of 12 Pages

Exhibit 2

POWERS OF ATTORNEY

KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below hereby constitutes and appoints Mark McDonnell his true and lawful attorney-in-fact, with full power of substitution, to sign any and all instruments, certificates and documents that may be necessary, desirable or appropriate to be executed on behalf of himself as an individual or in his capacity as a direct or indirect general partner, member, director, officer or manager of any partnership, corporation or limited liability company, pursuant to section 13 or 16 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), and any and all regulations promulgated thereunder, and to file the same, with all exhibits thereto, and any other documents in connection therewith, with the Securities and Exchange Commission, and with any other entity when and if such is mandated by the Exchange Act or by the Financial Industry Regulatory Authority, granting unto said attorney-in-fact full power and authority to do and perform each and every act and thing necessary, desirable or appropriate, fully to all intents and purposes as he might or could do in person, thereby ratifying and confirming all that said attorney-in-fact, or his substitutes, may lawfully do or cause to be done by virtue hereof. This Power of Attorney shall remain in full force and effect with respect to each undersigned person unless and until six months after such person is both no longer a Managing Director of ARCH Venture Partners and no longer serving on the board of directors of any portfolio company of any ARCH Venture Partners fund.

IN WITNESS WHEREOF, this Power of Attorney has been signed as of the 9^th day of March, 2015.

ARCH VENTURE FUND VIII, L.P.

By:   ARCH Venture Partners VIII, L.P.

         its General Partner

 By:   ARCH Venture Partners VIII, LLC

                  its General Partner

  By:  /s/ Keith Crandell                                

                          Managing Director

ARCH VENTURE PARTNERS VIII, L.P.

By:   ARCH Venture Partners VIII, LLC

         its General Partner

 By:   /s/ Keith Crandell                                

                  Managing Director

ARCH VENTURE PARTNERS VIII, LLC

By:   /s/ Keith Crandell                                

         Managing Director

/s/ Keith Crandell                                        

Keith Crandell

/s/ Robert Nelsen                                        

Robert Nelsen

/s/ Clinton Bybee                                        

Clinton Bybee

/s/ Kristina Burow                                       

Kristina Burow

/s/ Paul Thurk                                              

Paul Thurk