8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 5, 2016

IGNYTA, INC.

(Exact Name of Registrant as Specified in its Charter)

Delaware	001-36344	45-3174872
(State of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)

11111 Flintkote Avenue

San Diego, California 92121

(Address of principal executive offices, including zip code)

Registrant’s telephone number, including area code: (858) 255-5959

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 7.01 Regulation FD Disclosure

On June 5, 2016, interim results from Ignyta Inc.’s Phase 1 clinical trial of RXDX-105 were announced, including in a poster presentation, at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois. The press release dated June 5, 2015 announcing the data from the poster presentation is attached hereto as Exhibit 99.1. The poster presentation is attached hereto as Exhibit 99.2.

The information contained in this Item 7.01 and in Exhibits 99.1 and 99.2 of this Current Report on Form 8-K shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 9.01. Financial Statements and Exhibits

(d) Exhibits.

Exhibit No.	Description
99.1	Press Release, dated June 5, 2016.
99.2	Poster Presentation, dated June 5, 2016.

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SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Dated: June 6, 2016	IGNYTA, INC.
	By:	/s/ Jonathan E. Lim, M.D.
	Name:	Jonathan E. Lim, M.D.
	Title:	President and Chief Executive Officer

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EXHIBIT INDEX

Exhibit No.	Description
99.1	Press Release, dated June 5, 2016.
99.2	Poster Presentation, dated June 5, 2016.

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EX-99.1

Exhibit 99.1

Ignyta Announces Interim Data from

Phase 1 Clinical Trial of

Investigational Precision Medicine RXDX-105 at ASCO 2016

June 5, 2016 9:00 AM Eastern Time

SAN DIEGO—(BUSINESS WIRE)—Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, today announced that interim results from the Phase 1 clinical trial of RXDX-105, the company’s orally available, small molecule multikinase inhibitor with potent activity against such targets as RET and BRAF, were presented at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract 2574). RXDX-105 is Ignyta’s second clinical stage compound after entrectinib, the furthest advanced inhibitor for solid tumors with NTRK (neurotrophin receptor kinase), ROS1, or ALK gene rearrangements.

“We continue to be encouraged by the safety and preliminary antitumor activity data from our Phase 1 clinical trial of RXDX-105,” said Pratik Multani, M.D., Chief Medical Officer of Ignyta. “Given the performance of RXDX-105 thus far, we look forward to the results from the Phase 1b portion of the study, in which we are further evaluating this investigational agent and its activity in targeted patient populations with relevant molecular alterations, as well as in patients with unselected lung cancer.”

The Phase 1 dose escalation portion of the clinical trial was designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent RXDX-105 in patients with advanced or metastatic solid tumors.

As of the May 3, 2016, data cut-off, the findings showed:

• A total of 55 patients with a range of solid tumors were dosed with RXDX-105 in the clinical trial;

• RXDX-105 was well tolerated:

• The most frequent treatment-emergent adverse events were fatigue, nausea, rash, vomiting, diarrhea, decreased appetite, constipation, anemia, muscle spasms, and abdominal pain;

• Four Grade 3 dose-limiting toxicities (DLTs) were observed: maculopapular rash, fatigue, diarrhea and hyperbilirubinemia, each of which resolved upon study drug interruption; and

• Three serious adverse events (SAEs) were considered treatment-related: Grade 2 headache, Grade 3 hyperbilirubinemia and Grade 3 drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). No Grade 4 or Grade 5 treatment-related adverse events were observed;

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• An MTD based on DLTs was not reached; based upon overall safety and exposure during Phase 1, the RP2D was determined to be 350 mg, once daily in the fed state, and is being further evaluated in the Phase 1b portion of the study;

• Pharmacokinetic measurements showed increased exposure with increasing dose, with a half-life compatible with once-daily dosing. Dosing in the fed state appears to increase exposure over dosing in the non-fed state;

• Exposures reached levels expected to be efficacious based on tumor growth inhibition in animal models of RET- and BRAF-driven tumors; and

• Twenty patients were dosed at or above the clinically relevant dose of 275 mg in the fed state, 11 of whom had an actionable RET or BRAF alteration. Tumor regression of greater than 20% was observed in four of the 20 patients, including:

• an unconfirmed partial response (38% reduction) in a patient with medullary thyroid cancer with a RET M918T mutation;

• a 28% reduction in target lesions in a patient with non-small cell lung cancer (NSCLC) with a BRAF D594G mutation;

• a 26% reduction in target lesions in a patient with ovarian cancer with a BRAF V600E mutation; and

• finally, as previously reported at the ENA Conference 2015 (Wang, 2015), a confirmed partial response (40% reduction) in a patient with NSCLC with a KRAS G12C mutation, who continues on treatment after 10 cycles.

In addition to RXDX-105, Ignyta is developing a pipeline of first-in-class and best-in-class molecularly targeted therapies to fight cancer – with the ultimate goal of not just shrinking tumors, but eradicating cancer relapse and recurrence in precisely defined patient populations. Ignyta recently presented combined data from two Phase 1 clinical trials of its lead product candidate entrectinib that indicated the drug showed signs of clinical activity in patients who had several different types of cancer with NTRK1/2/3, ROS1 or ALK gene alterations and had not previously been treated with a Trk-, ROS1-, or ALK-directed targeted therapy. Entrectinib is the most potent Trk inhibitor in the clinic and the only Trk inhibitor with clinically demonstrated activity against primary and metastatic tumors in the central nervous system (CNS), a frequent site of progression of advanced solid tumors.

“We are excited to continue testing the potential for our molecularly targeted therapies, like entrectinib and RXDX-105, to shrink tumors and eradicate residual disease in selected patient populations,” said Jonathan Lim, M.D., Chairman and CEO of Ignyta. “We remain committed to serving those patients who have the highest unmet need and may otherwise not have effective treatment options.”

On Monday, June 6, 2016, Ignyta will file a Form-8-K with the U.S. Securities and Exchange Commission (SEC) containing the materials presented at the ASCO Annual Meeting. The company’s SEC filings can be found on the company’s website at www.ignyta.com and on the SEC’s website at www.sec.gov.

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About Ignyta, Inc.

At Ignyta, we fight cancer – a formidable opponent that manifests as thousands of different molecularly defined diseases and takes away millions of lives globally, every year. In this fight, our vision is not just to shrink tumors but to eradicate residual disease – the source of cancer relapse and recurrence – in precisely defined patient populations by 2030. We will work tirelessly to achieve this vision by pursuing an integrated therapeutic (Rx) and companion diagnostic (Dx) strategy for treating cancer patients. Our Rx efforts are focused on discovering, in-licensing or acquiring, then developing and commercializing, molecularly targeted therapies that, sequentially or in combination, are foundational for eradicating residual disease. Our Dx efforts aim to pair these product candidates with biomarker-based companion diagnostics that are designed to precisely identify, at the molecular level, the patients who are most likely to benefit from the therapies we develop. We believe that only through this integrated Rx/Dx approach can we succeed in this fight.

For more information, please visit: www.ignyta.com.

Forward-Looking Statements

This press release contains forward-looking statements about Ignyta as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, references to the results of the Phase 1 clinical study of RXDX-105 and the development of Ignyta’s product candidates. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, the inherent uncertainties associated with developing new products or technologies and operating as a development stage company; Ignyta’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in Ignyta’s plans to develop and commercialize its product candidates; the potential for final results of the ongoing clinical trials of RXDX-105 or other product candidates, or any future clinical trials of RXDX-105 or other product candidates, to differ from preliminary or expected results; Ignyta’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; Ignyta’s ability to obtain and maintain intellectual property protection for its product candidates; the risk that orphan drug exclusivity may not effectively protect a product from competition and that such exclusivity may not be maintained; the potential for the company to fail to maintain the CAP

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accreditation and CLIA certification of its diagnostic laboratory; the loss of key scientific or management personnel; competition in the industry in which Ignyta operates; and market conditions. These forward-looking statements are made as of the date of this press release, and Ignyta assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements. Investors should consult all of the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents the company files with the SEC available at www.sec.gov, including without limitation Ignyta’s Annual Report on Form 10-K for the year ended December 31, 2015 and subsequent Quarterly Reports on Form 10-Q.

Contacts

Ignyta, Inc.

Jacob Chacko, M.D.

CFO

858-255-5959

jc@ignyta.com

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EX-99.2

Exhibit 99.2

A phase 1 dose escalation study of RXDX-105, an oral RET and BRAF inhibitor, in patients with advanced solid tumors
Manish R. Patel1, Marwan Fakih2, A. Craig Lockhart3, Anthony J. Olszanski4, Siqing Fu5, Lyudmila Bazhenova6, Alexander Drilon7, Rupal Patel8, Jennifer W. Oliver8, Pratik S. Multani8, and Ding Wang9
1Sarah Cannon Research Institute/Florida Cancer Specialists, Sarasota, FL; 2City of Hope Comprehensive Cancer Center, Duarte, CA; 3Washington University Medical Center, St. Louis, MO; 4Fox Chase Cancer Center, Philadelphia, PA; 5MD Anderson Cancer Center, Houston, TX; 6University of California San Diego Moores Cancer Center, San Diego, CA; 7Memorial Sloan Kettering Cancer Center, New York, NY; 8Ignyta, Inc., San Diego, CA; 9Henry Ford Hospital, Detroit, Michigan
Background
RXDX-105 is a small molecule multikinase inhibitor (MKI) with potent activity against targets such as RET and BRAF. RXDX-105 is being developed as an oral therapy for patients with solid tumors, including those that harbor RET or BRAF alterations.
The potential for RET and BRAF inhibition to result in durable cytoreductive responses in lung cancer patients has been demonstrated in phase 2 trials of the multikinase RET inhibitor cabozantinib (Drilon et al., 2015) and the BRAF inhibitor dabrafenib (Planchard et al., 2015).
RXDX-105 is a potent RET and BRAF inhibitor with biochemical IC50 values of 0.3 and 0.8 nM against wild type RET and wild type BRAF, respectively. In addition, RXDX-105 potently inhibits RET rearrangements (IC50: 0.3-0.8 nM), RET M918T (IC50: 4 nM) and BRAF V600E (IC50: 54 nM).
RXDX-105 has demonstrated potent antitumor activity in multiple preclinical models of BRAF mutant and RET-rearrangement driven cancers.
Hence, solid tumors with RET or BRAF rearrangements or mutations may respond to treatment with RXDX-105.
Due to the MKI properties of RXDX-105, it may also be active in patients with unselected tumors.
Phase 1 Trial Overview
Patient Population: Patients not selected based upon molecular profile; histological or cytological evidence of advanced solid tumor; any number of prior systemic therapies allowed, including RET or BRAF inhibitors; ECOG performance status 0 or 1
Patients were assigned to escalating doses of RXDX-105 using a standard 3+3 design.
DLTs were evaluated during Cycle 1 and graded according to the NCI CTCAE v4.03.
Cohort
1 2 3 4 5 6 7
7 Fed
8 Fed
Dose (QD)
20 mg 40 mg 75 mg 100 mg 150 mg 200 mg 275 mg 275 mg
350 mg*
N
4 3 3 3 4 8 10 12
8
*RP2D
55 patients were treated across 8 dose levels and 4 DLTs were observed
An MTD based on DLTs was not reached; the RP2D was selected based on the overall safety and PK data and was determined to be 350 mg administered once daily under Fed condition
Table 1. Patient Disposition and Baseline Characteristics, n (%)
TOTAL
Treated 55
Discontinued 44 (80)
Primary reason for discontinuation
Disease Progression 32 (58)
Adverse Event 8 (15)
Death 2 (4)
Withdrawal by Subject 2 (4)
Age, years, median (range) 61 (27-81)
Sex, male/female % 55/45
ECOG performance status
0 23 (42)
1 32 (58)
Tumor Type
GI: Colorectal (20), Pancreas (3), Gall Bladder (1), Stomach (1), 28
Cholangiocarcinoma (2), Hepatocellular (1)
Breast 2
Lung: Squamous (3), Non-squamous (7) 10
Gyn: Ovarian (4), Endometrial stromal (1), Cervical (1) 6
Head and Neck 4
Thyroid: Papillary (3), Hurthle Cell (1), Medullary (1) 5
PRELIMINARY RESULTS
Safety
RXDX-105 has been generally well-tolerated. All AEs that have occurred to date are reversible with dose reduction or holiday. The safety data are current as of May 3, 2016.
Four DLTs have occurred: G3 maculopapular rash (200 mg), G3 fatigue (275 mg), G3 diarrhea (275 mg Fed) and G3 hyperbilirubinemia (350 mg Fed). All DLTs resolved upon study drug interruption. Two patients resumed treatment at a reduced dose; one patient discontinued treatment due to progression prior to restarting study drug and the patient with hyperbilirubinemia discontinued due to the event.
Two G4 events have occurred (intestinal obstruction and anemia), neither of which were considered drug-related. There have been no G5 treatment-related events.
Three SAEs were considered treatment-related: G2 headache, G3 hyperbilirubinemia and G3 drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).
The most common treatment-emergent AEs in Phase 1 patients are presented below.
Most Common (>15%) Treatment-Emergent AEs in All Patients (N=55), N (%)
Grade £2 Grade ³3 Any Grade
Fatigue 23 (42) 2 (4) 25 (46)
Rash 17 (31) 2 (4) 19 (35)
Nausea 17 (31) 2 (4) 19 (35)
Vomiting 17 (31) 2 (4) 19 (35)
Diarrhea 12 (22) 5 (9) 17 (21)
Decreased Appetite 14 (26) 1 (2) 15 (27)
Constipation 14 (26) 1 (2) 15 (27)
Anemia 7 (13) 8 (15) 15 (27)
Muscle Spasms 14 (26) 0 14 (26)
Abdominal pain 10 (18) 3 (6) 13 (24)
Hypokalemia 9 (16) 3 (6) 12 (22)
Hypertension 9 (16) 1 (2) 10 (18)
Dyspnea 9 (16) 1 (2) 10 (18)
Hypoalbuminemia 7 (13) 2 (4) 9 (16)
Pharmacokinetics
BSA Normalized Day 15 Linear Plot
Exposures of RXDX-105 administered on a continuous daily dosing regimen increased with increasing dose Lower BSA correlates with increased exposure Fed condition increases exposure 350 mg Fed achieves 18% increase in AUC over 275 mg Fed
Based on the accumulation ratio, the plasma half-life of RXDX-105 is estimated to be in the range of 35-45 hours, compatible with QD dosing Exposure has reached levels expected to be efficacious in RET- and BRAF-driven tumors, based on animal models exhibiting tumor growth inhibition
5000
4500
4000
(ng/mL) 3500
3000
2500
Concentration 2000 Plasma 1500
1000
500
0
0 4 8 12 16 20 24
Time (h)
350 mg (Fed), N=6 275 mg (Fed), N=10 275 mg, N=7 200 mg, N=7 150 mg, N=3 100 mg, N=3 75 mg, N=3 40 mg, N=3 20 mg, N=3 RET Target Concentration BRAF Target Concentration
Phase 1 Patients with an Actionable RET or BRAF Alteration Treated with ³275 mg (Fed)
Phase 1 was an all-comers dose escalation study. Fifty-five patients were treated in the Phase 1 portion of the study; 20 were treated at the clinically relevant doses of 275 mg and 350 mg, Fed condition. Of those, 11 patients had an actionable RET or BRAF alteration. Data as of May 25, 2016, for tumor response and duration of therapy in these patients are displayed below.
Best Response
BRAF V600E Papillary Thyroid SD (-14%) BRAF V600E Papillary Thyroid SD* BRAF V600E Ovarian SD (-26%) NCOA4-RET Cecal/CRC PD** RET M918T Medullary Thyroid uPR (-38%)
BRAF D594G CRC PD
BRAF V600E NSCLC PD
CCDC6-RET CRC PD
RET Fusion NSCLC PD
BRAF D594G NSCLC SD (-28%)
BRAF V600E Papillary Thyroid PD
0 1 2 3 4 5 6 7 8
*Pt. does not have measurable disease **Pt. continuing therapy post-progression due to overall clinical benefit
Time on Treatment (months)
Ongoing RETi Naive BRAFi Naive Prior RETi Prior BRAFi
BRAF Ovarian Cancer Patient
A PET/CT scan from a 68 year-old female with BRAF V600E serous ovarian cancer demonstrated a 26% reduction in target lesions at C2 and C4 scans. This patient was treated with 350 mg, Fed condition. Prior treatment includes carboplatin/taxol, topotecan, and gemcitabine/carboplatin. The patient continues on study in Cycle 5.
NSCLC Patient Update
As previously reported at ENA (Wang, 2015), one confirmed RECIST PR was noted in a patient treated with 275mg, Fed condition. The patient is a 75 y/o female with metastatic NSCLC. Molecular analysis of her baseline tumor (2007) revealed KRAS G12C mutation. At Cycle 2, the patient had 40% reduction in her target lesion. She continues on study after 10 cycles.
Conclusions
RXDX-105 has been well-tolerated to date in 55 Phase 1 patients with advanced or metastatic solid tumors. Efficacious exposure, based on RET- and BRAF-driven PDX models, has been achieved.
The RP2D has been selected and is being further evaluated in the Phase 1b portion of the study, which is open to enrollment. Early signals of anti-tumor activity have been noted in Phase 1. Unconfirmed PR (38% reduction) observed at Cycle 2 in a medullary thyroid cancer patient with the RET M918T mutation 26% reduction in target lesions observed in an ovarian cancer patient with the BRAF V600E mutation and 28% reduction in target lesions observed in a BRAF D594G
NSCLC patient Confirmed PR (40% reduction) observed in a patient with NSCLC positive for KRAS G12C who continues on treatment after 10 cycles of therapy These preliminary data support further development of RXDX-105 in patients with advanced cancer.
The Phase 1b portion of the study includes baskets for patients with RET- or BRAF-driven tumors as well as baskets for patients with unselected lung cancer.
Abstract #2574 – Presented at the ASCO Annual Meeting, June 3 – 7, 2016, Chicago, IL.
Email correspondence: MPatel@flcancer.com. Thank you to all the patients and their families who participated in this study.