Catalyzing Precision Medicine with Integrated Rx/Dx in Oncology
Jefferies Healthcare ConferenceJune 8th, 2016
Safe Harbor Statement
2
This document contains forward-looking statements, as that term is defined in Section 27A of the Securities Act of 1933 andSection 21E of the Securities Exchange Act of 1934, about Ignyta, Inc. (“us” or the “Company”). Statements that are notpurely historical are forward-looking statements. These include statements regarding, among other things: Ignyta’s corporateand scientific vision and goals, including our ability to reduce the size of tumors and to eradicate residual disease; the clinicaland/or non-clinical data or plans underlying entrectinib or any of our other development programs; our ability to design andconduct development activities for entrectinib and our other development programs; our ability to develop or accesscompanion diagnostics for our product candidates; our ability to obtain and maintain intellectual property protection for ourproduct candidates; our ability to adequately fund our development programs; our ability to obtain regulatory approvals inorder to market any of our product candidates; and our ability to successfully commercialize any approved products.
Forward-looking statements involve known and unknown risks that relate to future events or the Company’s future financialperformance, some of which may be beyond our control, and the actual results could differ materially from those discussed inthis document. Accordingly, the Company cautions investors not to place undue reliance on the forward-looking statementscontained in, or made in connection with, this document.
Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements,include, among others, the potential for results of past or ongoing clinical or non-clinical studies to differ from expectations orprevious results; the interpretation of data from our clinical and non-clinical studies; our ability to initiate and complete clinicaltrials and non-clinical studies; regulatory developments; the potential advantages of our product candidates; the markets anyapproved products are intended to serve; and our capital needs; as well as those set forth under the headings “Special NoteRegarding Forward-Looking Statements,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Conditionand Results of Operations” contained in the Company’s Form 10-K filed with the Securities and Exchange Commission(“SEC”) on March 14, 2016, and similar disclosures made in the Company’s Form 10-Q filings and other SEC filings andpress releases.
The forward-looking statements contained in this document represent our estimates and assumptions only as of the date ofthis document, and we undertake no duty or obligation to update or revise publicly any forward-looking statements containedin this document as a result of new information, future events or changes in our expectations.
Third-party information included herein has been obtained from sources believed to be reliable, but the accuracy orcompleteness of such information is not guaranteed by, and should not be construed as a representation by, the Company.
Ignyta Case Report: Mr. Z
3
Nov 2013 March 2015
• ECOG performance status of 2• Required supplemental O2• Significant pain and dyspnea due
to widely metastatic disease• Staging head CT also revealed
numerous (15 to 20) asymptomatic brain metastases
• In hospice
Prior therapies• carboplatin/pemetrexed• pembrolizumab• docetaxel• vinorelbine
Identified to have tumor harboring SQSTM1-NTRK1 fusionEnrolled in Ignyta’s STARTRK-1 study at MGH in March 2015
• 46M patient with metastatic NSCLC, first diagnosed in November 2013
• 30 pack-year smoking history
Images courtesy of A. Shaw, MD, PhD and A. Farago, MD, PhD (MGH); Note: Individual results may not be representative of results in other patients.
Baseline Day 26: - 47% response
Clinical Response to Entrectinib, Ignyta’s Lead Program,in a 46 year-old Male Patient with NTRK1-Rearranged NSCLC
4
Day 317: - 79% response
Baseline(15-20 mets)
Day 26(CR)
Day 155(CR)
Complete Response of All Brain Metastases in 46 Year-OldMale Patient with NTRK1-Rearranged NSCLC
CNS complete response persists at Day 317Images: Farago and Shaw, MGH
5Note: Individual results may not be representative of results in other patients.
Key Investment Highlights
6
♦ Integrated approach to Rx/Dx development- CAP-accredited, CLIA-certified, QSR-compliant diagnostic lab with multi-modality assays- Internal Dx allows Ignyta to illuminate the molecular drivers of cancer and quickly advance the
most appropriate molecularly targeted therapies to address them♦ Robust pipeline of molecularly targeted therapies
- 3 potentially first-in-class or best-in-class clinical stage programs Entrectinib: In global Phase 2, potentially registration-enabling study Additional Phase 1 programs (RXDX-105, taladegib) with demonstrated clinical responses
- Preclinical program (RXDX-106) at the nexus of molecularly targeted and immuno-oncology♦ Multiple near-term catalysts to drive value
- Utilizing basket study designs for resource-efficient clinical development plans to generate multiple clinical data readouts in next 12 months, while building long-term value for patients and stockholders
♦ Experienced management team- Breadth and depth of expertise in clinical/preclinical development, regulatory affairs,
commercial, and other key technical and business disciplines
Ignyta’s vision is to catalyze precision medicine for the benefit of cancer patients everywhere, with an integrated approach to "Rx/Dx" in oncology
Jonathan Lim, M.D.Chairman, CEO, and Co-Founder
Zachary HornbyChief Operating Officer
Igor Bilinsky, Ph.D.SVP, Research Ops. & GM, I-O
Jacob Chacko, M.D.Chief Financial Officer
Val Harding, Ph.D.SVP, Chemistry, Mfg. & Controls
Will McCarthyChief Business Officer
Pratik Multani, M.D.Chief Medical Officer
Management Team Brings to Ignyta Experience from Leading Organizations and Institutions
7
Former Chair, CEO of Eclipse; CEO at Halozyme; McKinsey; NIH post-doc at Harvard/Dana Farber; Surgical resident at NYH-Cornell/Memorial Sloan Kettering; Board member at UCSD Moores Cancer Ctr.
Former Senior Director of Business Development at Fate Therapeutics; Director of BD at Halozyme; Marketing at Neurocrine; L.E.K. Consulting; Shire (TKT); Harvard Business School.
Former SVP of Corporate Development at Vical; VP Business Development and Special Operations at Halozyme; CEO of Androclus Therapeutics; Boston Consulting Group; MIT.
Former Vice President at TPG Capital; McKinsey; Marshall Scholar at Oxford University; UCLA Medical School; Harvard Business School.
Former VP, Product Differentiation/VP, Drug Product Design/VP, Pharmaceutical Development, in addition to numerous other leadership roles at Pfizer.
Former VP of Corporate and Business Development at Foundation Medicine; Exec Dir of BD and Sr. Director of Marketing at Halozyme; IMS Health, Deloitte Consulting; London Business School.
Former CMO at Fate; VP, Clin. Dev. at Kalypsys; CMO at Kanisa; VP, Clin. Dev. at Salmedix; Sr. Director of Medical Research at Biogen Idec; MD, MS at Harvard; Residency, MGH; Oncology, Dana Farber.
Robust Pipeline of Molecularly Targeted Therapies
81In-licensed from Nerviano Medical Sciences (NMS); 2In-licensed from Eli Lilly and Company; 3Acquired from Cephalon, a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd.
Commercial Opportunity Is Substantial for These Three Clinical Stage Assets
9
~175k patients annually in the U.S. could benefit from entrectinib, RXDX-105, and taladegib
*2.2M non-melanoma skin cancers, of which 80% is BCC (1.76M); laBCC is 1% of BCC (9.5% not candidates for surgery/radiation); mBCC is 0.55% (95% not candidates for surgery/radiation), yielding 10,868 patients in U.S.; Hh alterations include Hh (OE of SHh, IHh, DHh), PTCH1 (SNP/Del), SMO (SNP/OE); **Assumes 100% of patients are addressable, rather than 90%, due to lack of patient selection in BCC; Note: table does not include ~70k patients for oral taladegib as combo or ~70k patients for topical taladegib; %’s in red not included in Total Addressable Patients due to multiple other approved products; Assumes ~7.5% of PTC patients referred to med onc; Ignyta-generated data from multiple publicly available third party sources.
Indication | Alteration/Mechanism
NTRK 1 fusions
NTRK 2 fusions
NTRK 3 fusions
ROS 1 fusions
ALK fusions
RET fusions
BRAF fusions
BRAF mutations
Hh alter'ns / gene
express. signature *
Estimated U.S. Total
Patients/Yr. for entrectinib
Estimated U.S. Total
Patients/Yr. for RXDX-105
Estimated U.S. Total
Patients/Yr. for taladegib
Advanced basal cell carcinoma* 90%** - - 10,900 Bladder 1% 1% 2-10% - 700 6,900 Breast - secretory carcinoma 92% 1% 300 - Breast - NOS 2% 4-10% - - 23,300 Cholangiocarcinoma 4% 9% 2% 700 - CNS 1-5% - - 1,000 Colorectal 1% 1% 1-2% 1-2% <1% <1% 9% 3-4% 6,700 13,400 4,700 Gallbladder/Biliary 4% - - 400 GBM 1-3% 1% 2% 3-10% 350 - 1,100 Head and Neck 4-22% - - 26,500 Kidney 2-8% - - 4,600 Liver 2-3% - - 800 Lung adenocarcinoma ~1% <1% <1% 1-2% 3-7% 1-3% 4% 2-6% 3,000 1,700 4,900 Lung squamous cell 8-31% - - 20,200 Medulloblastoma 5-33% - - 100 Melanoma 1% 46% 2-6% - 700 4,100 Melanoma - Spitz 16% 3% 1% 3% 900 150 Ovarian 9% - - 1,800 Pancreatic 3% 1-24% - - 10,300 Prostate 1% 1% 4% - 2,350 10,000 Salivary gland - MASC 90-100% 100 -
Sarcoma 1-9% 2-11% 2-3% 1-5% 2-6% 2,550 - 800 Stomach 5% - - 1,000 Thyroid - PTC 5-13% 2-14% 7% 6% 2% 59% 2-3% 900 2,600 1,800 Uterine endometrial 7% - - 3,800 Total Addressable Patients 4,400 400 3,500 4,300 2,900 2,700 4,500 14,400 139,000 15,500 21,600 139,000
Gene Rearrangements to NTRK1, NTRK2, NTRK3, ROS1, ALK
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Clinical Sites Specimens Platform Output
FFPE
NGS
Trial Enrollment
Ignyta Central Lab
• CLIA
• CAP
RNA Prep
STARTRK-2(second of the
"Studies of Tumor Alterations
Responsive to Targeting Receptor
Kinases.“)
Ignyta’s Dx Capabilities Enable Leadership in Precision Medicine
Ignyta’s Integrated Rx/Dx Precision Medicine Vision: Molecularly Targeted Therapies for Cancer Patients
11*TYRO3, AXL, MERTBA: to be announced
Molecularly targeted therapies/cancer immunotherapies
Molecularly targeted/ CSC therapies
Molecularly Targeted Therapies for Cancer Patients
Entrectinib: A Potential First-in-Class Trk Inhibitor in Potentially Registration-enabling Phase 2 Study
♦ In vitro: inhibition of targets and downstream effectors in the PLCγ, MAPK and PI3K/AKT pathways
Target TrkA TrkB TrkC ROS1 ALK
IC50* (nM) 1.7 0.1 0.1 0.2 1.6
12* Biochemical kinase assay
Potent, selective, orally available ATP-competitive inhibitor of 5 oncogenic drivers
♦ In vivo: complete tumor growth inhibition and regression in multiple xenograft models
♦ FDA orphan drug designation for NSCLC, CRC and neuroblastoma, and rare pediatric disease designation for neuroblastoma; EMA orphan drug designation for neuroblastoma
♦ Composition of matter patent issued in US and allowed in Europe, with commercial protection out to 2029 (excluding PTE)
Phase 1 StudiesUpdated data as of March 7, 2016
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STARTRK-1
Dosing: continuous
NTRK1/2/3, ROS1 or ALK alterations
US, EU, Asia
65 patients
*RP2D = Recommended Phase 2 Dose** RECIST criteria not validated in primary brain tumors (FDA-AACR Brain Tumor Endpoints Workshop 2006)
ALKA-372-001
Dosing: intermittent and continuous
NTRK1/ROS1/ALK alterations
Italy
54 patients
Total clinical experience: 119 patients 45 patients treated with RP2D*: 600 mg PO once daily
“Phase 2-eligible population”: 25 patients - NTRK1/2/3-, ROS1-, or ALK-rearranged solid tumor- Naïve to prior Trk/ROS1/ALK inhibitors, as applicable- Treated at or above RP2D*
Response Evaluation- RECIST v1.1, locally assessed and confirmed:
24 patients- Volumetric assessment: 1 patient with
primary brain tumor**
Treatment-Related Adverse Events at RP2D>10% incidence; grades according to NCI CTCAE v4.0
14
(≥10% incidence, grades per NCI CTCAE v4.0, data as of March 7, 2016)
Adverse Events (AEs) at the RP2D (n=45)
Adverse Event Term, n (%) Grades 1-2 Grade 3 TotalDysgeusia 21 (47) 21 (47)
Fatigue/Asthenia 17 (38) 1 (2) 18 (40)
Constipation 10 (22) 10 (22)
Weight Increased 8 (18) 1 (2) 9 (20)
Diarrhea 7 (16) 1 (2) 9 (18)
Nausea 8 (18) 8 (18)
Myalgia 7 (16) 7 (16)
Paresthesia 7 (16) 7 (16)
Dizziness 6 (13) 6 (13)
Peripheral Sensory Neuropathy 4 (9) 2 (4) 6 (13)
Anemia 2 (4) 3 (7) 5 (11)
Dysphagia 4 (9) 1 (2) 5 (11)
Vomiting 5 (11) 5 (11)
♦ No cumulative toxicity
♦ No renal toxicity
♦ No QTc prolongation
♦ No hepatic toxicity
♦ No AEs > Grade 4
♦ All AEs reversible with dose modification
-100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
Fusion ConfirmedResponses (n) ORR (%)
NTRK1/3 3/3 100%
ROS1 12/14 86%
ALK 4/7 57%
% tu
mor
redu
ctio
n
PD
PR
CR
Best Response in TKI Treatment-Naïve NTRK-, ROS1-, and ALK-rearranged Tumors (n=24)
Antitumor Activity in ALK and ROS1 Inhibitor-Naïve Patients with NTRK1/2/3, ROS1, or ALK Gene Rearrangements
15
-100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
Fusion ConfirmedResponses (n) ORR (%)
NTRK1/3 3/3 100%
1 additional patient with NTRK+ astrocytoma• SD by RECIST (not validated for primary brain
tumors)• 45% by exploratory 3-D volumetric assessment
% tu
mor
redu
ctio
n
PD
PR
CR
Best Response in TKI Treatment-Naïve NTRK-, ROS1-, and ALK-rearranged Tumors (n=24)
Antitumor Activity in ALK and ROS1 Inhibitor-Naïve Patients with NTRK1/2/3, ROS1, or ALK Gene Rearrangements
16
NSCLCNSCLCNSCLCNSCLCNSCLCNSCLCNSCLCMASCNSCLC
AstrocytomaRCC
NSCLCNSCLC
MelanomaNSCLC
Unknown PrimaryCRC
NSCLCNSCLCNSCLCNSCLC
CRCNSCLCNSCLCNSCLC
0 3 6 9 12 15 18 21 24 27 30Time on Study (months)
XX
X
XX
X
X
X
.
.
X off study
progression by RECIST, continued due to clinical benefit
NTRK ALKROS1
.
time to response
TKI Treatment-Naïve NTRK-, ROS1-, and ALK-rearranged Tumors (n=25)
.
Antitumor Activity in ALK and ROS1 Inhibitor-Naïve Patients with NTRK1/2/3, ROS1, or ALK Gene Rearrangements
The median duration of response has not been reached (95%CI: 6 months, NR)
Data cutoff 07 March 2016 17
ongoing
CNS Involvement in Solid Tumor Malignancy
18
1Fokas et al, BBA - Reviews on Cancer 20132Chi et al, Cancers 2010
Brain metastases -20-40% of all patients with cancer
-lung (up to 50%)
-breast
-melanoma
Primary brain tumors-astrocytoma (NTRK2 fusions: 3%)
-glioblastoma (NTRK1 fusions: 1-2%)
-pediatric gliomas (NTRK3 fusions: 7%)
Optimal therapy would proactively address both systemic and CNS disease
19
Entrectinib: More Potent and CNS-Penetrant than Crizotinib
ROS1+ NSCLC patient treated with entrectinib
Baseline Day 50
Images courtesy of MJ. Ahn, MD, Samsung Medical Center
-100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
ROS1 Patients – Best Response (%)
Entrectinib in ROS1-Rearranged Cancer
20
0% change (ROS1 patient)
♦ High potency (IC50 0.2 nM), with ability to cross the BBB to address CNS disease
♦ Well tolerated
- No responders have discontinued due to tolerability
♦ Overall response rate (ORR) of 86% (12/14 patients)
- In NSCLC, ORR of 85% (11/13 patients)
- Based on clinical experience to date, compares favorably to crizotinib’s 72% investigator-assessed ORR*
- One additional response in melanoma
♦ Two complete responses
♦ Rapid responses (after 1 month of treatment)
♦ Durable responses; median duration of response not reached
* Based on a study of 50 patients
-100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
NTRK Patients - Best Response (%)
mCRC
Astrocytoma*
InfantileFibrosarcoma**
NSCLCMASC
RECIST v1.1
* response by 3-D volumetric assessment (courtesy of P. Brastianos MD, MGH)
** estimated from radiology assessment
Entrectinib in NTRK-Rearranged Cancer
♦ We believe entrectinib is the most potent Trk inhibitor in clinical development
- Potent activity against 3 primary mechanisms of resistance to other clinical stage Trk inhibitors
♦ Safety experience of ~120 patients (~3x more patient data than any other Trk inhibitor of which we are aware)
- No cumulative, renal, or hepatic tox, or QTc↑
- No responders have discontinued due to tolerability
♦ Responses in 100% (5/5) of NTRK+ patients- Rapid (1 month of treatment) and prolonged (
>1 year) responses
- Responses in five different histologies, adult and pediatric patients
- 3 out of 4 patients with NTRK fusions on continuous daily dosing remain on study
21
♦ CNS activity in 100% (3/3) of NTRK+ patients with CNS disease - Demonstrated consistent and robust CNS activity
- 3/5 of NTRK+ patients treated in Phase 1 or compassionate use setting had primary or metastatic CNS disease
STARTRK-2: Entrectinib Global Phase 2 Basket Study
22
RXDX-105 Is a Potent RET Inhibitor with Activity against BRAF and Other Kinases
Kinase IC50 (nM)
RET 0.33CCDC6-RET 0.33NCOA4-RET 0.41
PRKAR1A-RET 0.81RET (M918T) 4.34RET (V804M) 265.90
Biochemical In vitro Anti-proliferative Assay
LC2/adLung adenocarcinoma
CCDC6-RET
TT Thyroid cancerRET C634W
RXDX-105 40 11Alectinib 204 90
Cabozantinib 98 77
IC50 (nM)
♦ RXDX-105 is a multikinase inhibitor with potent activity against RET and BRAF
23
RXDX-105 Phase 1 Dose-Escalation StudyUpdated data as of May 25, 2016
24
Total Phase 1 clinical experience: 55 patients
Patients treated at clinically relevant doses (275 mg and 350 mg, fed):
20 patients
Patients with actionable RET or BRAF alterations:
11 patients
RXDX-105 Exposure Has Reached Levels Expected To BeEfficacious in RET and BRAF Driven Tumors
25
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
0 4 8 12 16 20 24
Plas
ma
Con
cent
ratio
n (n
g/m
L)
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 TargetConcentrationBRAF TargetConcentration
PK Data: BSA-normalized Day 15; Linear exposure plot
26
Most Common (>15%) Treatment-Emergent AEs in All Phase 1 Patients (N=55), N (%)
Grade ≤2 Grade ≥3 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)
Treatment-Emergent Adverse Events in All Phase 1 Patients
Note: Data as of May 3rd, 2016.
♦ Generally well-tolerated. All AEs reversible with dose reduction or holiday
♦ No treatment-related AEs >Grade 4
♦ Four DLTs (all resolved with dose interruption): G3 maculopapular rash (200 mg), G3 fatigue (275 mg), G3 diarrhea (275 mg Fed), G3 hyperbilirubinemia (350 mg Fed)
♦ Three treatment-related SAEs: G2 headache, G3 hyperbilirubinemia, G3 DRESS syndrome
RXDX-105 Preliminary Anti-Tumor Activity
27
Note: Phase 1 was an all-comers dose escalation study. 55 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 above.
RET M918T Medullary Thyroid Cancer Patient
51M with Medullary Thyroid RET M918T
♦ Dose: 350 mg (fed)
♦ Prior therapies: vandetanib, cabozantinib, sorafenib, MGCD516
- No prior PR/CR, but 30 months of SD on cabozantinib
♦ Response: First restaging scan (Cycle 2) showed a 38% decrease in target lesion (uPR)
♦ Status: Patient continues on treatment with confirmatory scan at Cycle 4 in June
28
Baseline
End of Cycle 2
Data as of May 25, 2016.
BRAF V600E Ovarian Cancer Patient
68F with serous ovarian CA BRAF V600E
♦ Dose: 350 mg (fed)
♦ Prior therapies: carbo/taxol, gemcitabine/carboplatin, topotecan,
♦ Response: 26% reduction in baseline tumor measurements at C2 and C4 scans
♦ Status: Patient continues on study in Cycle 5
29Data as of May 25, 2016.
Images provided by MSKCC
58F with metastatic NSCLC BRAF D594Gmutation
♦ Dose: 275 mg (fed)
♦ Prior therapies: pemetrexed, cisplatin, bevacizumab, cobimetinib, vinorelbine, and gemcitabine
♦ Response: Scans taken 4 weeks after last dose (six weeks from baseline); showed 28% reduction in tumor burden
♦ Status: Patient treated for 2 weeks; taken off study due to idiosyncratic drug-reaction (DRESS syndrome)
30
Images provided by Drilon (MSKCC)
NSCLC Patient with BRAF D594G Mutation
Baseline 6 Weeks Later
Data as of May 25, 2016.
NSCLC Patient with KRAS Mutation
75F with metastatic NSCLC, first diagnosed in 2007
♦ Dose: 275 mg (fed)
♦ Prior therapies: multiple lines of chemotherapy and 6 years of erlotinib
♦ Molecular analysis of tumor from her initial diagnosis revealed KRAS G12C mutation
♦ Response: At Cycle 2, the patient had 40% reduction in her target lesion, which was confirmed at Cycle 3
♦ Status: patient is still on study at 10+ cycles
31
Baseline End of Cycle 2
Data as of May 25, 2016.
32
Non-Small Cell Lung Adenocarcinoma Opportunity
Potent inhibitor
Clinical activity observed♦ RXDX-105 is a potent RET
and BRAF inhibitor
♦ Clinical activity also seen outside of these targets
♦ Patient with mutant KRAS NSCLC
♦ Patient with BRAFD594G mutation; typically non responsive to pure BRAF inhibition
♦ Suggests potential as both a targeted RET/BRAF inhibitor and MKI in NSCLC
Source: Gerber et al, 2014
Tumor samples for CDx analysis tested locally
Separate by solid tumor type and molecular alteration
Study 105-01: Phase 1b Basket Study
BRAF+ NSCLC
RET+ BRAF+NSCLC
BRAF+ CRC BRAF+ Other histologies
RET+ Other histologies
RET Baskets
Amended RXDX-105 Phase 1b Basket Study DesignRET, BRAF and NSCLC Baskets
33
RET+ NSCLC
BRAF Baskets
Objective♦ Preliminary demonstration of efficacy
OtherNon-Squamous
NSCLC
Squamous NSCLC
NSCLC Baskets
Objective♦ Preliminary demonstration of efficacy
♦ Exploration of efficacy in unselected NSCLC population
Summary of RXDX-105 Clinical Experience
♦ RXDX-105 appears safe and well-tolerated to date‒ 55 Phase 1 patients with advanced or metastatic solid tumors‒ Achieved efficacious exposure, based on RET- and BRAF-driven PDX models‒ RP2D selected and being further evaluated in Phase 1b study, which is open to enrollment
♦ RXDX-105 has demonstrated preliminary clinical activity in patients with cancers harboring activating BRAF- and RET- alterations‒ Unconfirmed PR (38% reduction) at Cycle 2 in a medullary thyroid cancer patient with the
RET M918T mutation‒ 26% reduction in target lesions in an ovarian cancer patient with BRAF V600E mutation
and 28% reduction in target lesions in a BRAF D594G NSCLC patient‒ Confirmed PR (40% reduction) in a patient with NSCLC positive for KRAS G12C who
continues on treatment after 10 cycles of therapy
♦ Further development ongoing‒ Phase 1b study includes baskets for RET- or BRAF-driven tumors as well as baskets for
patients with unselected lung cancer‒ Ph 1b basket study interim data, 4Q16
34
Key Investment Highlights
35
♦ Integrated approach to Rx/Dx development- CAP-accredited, CLIA-certified, QSR-compliant diagnostic lab with multi-modality assays- Internal Dx allows Ignyta to illuminate the molecular drivers of cancer and quickly advance the
most appropriate molecularly targeted therapies to address them♦ Robust pipeline of molecularly targeted therapies
- 3 potentially first-in-class or best-in-class clinical stage programs Entrectinib: In global Phase 2, potentially registration-enabling study Additional Phase 1 programs (RXDX-105, taladegib) with demonstrated clinical responses
- Preclinical program (RXDX-106) at the nexus of molecularly targeted and immuno-oncology♦ Multiple near-term catalysts to drive value
- Utilizing basket study designs for resource-efficient clinical development plans to generate multiple clinical data readouts in next 12 months, while building long-term value for patients and stockholders
♦ Experienced management team- Breadth and depth of expertise in clinical/preclinical development, regulatory affairs,
commercial, and other key technical and business disciplines
Ignyta’s vision is to catalyze precision medicine for the benefit of cancer patients everywhere, with an integrated approach to "Rx/Dx" in oncology
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