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Actionable news in RXDX: IGNYTA INC,

Ignyta: G. De Braud, Salvatore Siena, Sai-Hong I. Ou, Manish Patel, Myung-Ju Ahn, Jeeyun Lee, Todd M. Bauer, Anna F. Farago, Stephen Natasha Reddinger, Patel, David Luo, Edna Chow

The following excerpt is from the company's SEC filing.

: Exelixis, Genentech/Roche, AstraZeneca

Speakers Bureau

Ignyta

Research Funding

: Foundation Medicine

Travel/Accomodations

, Exelixis, Genentech/Roche, AstraZeneca

Recurrent Gene Rearrangements

Oncogenic drivers across a variety of

cancers

Upstream partner can provide

dimerization domains

ligand-

independent signaling

Activation of downstream pathways

Detectable in the clinic

RNAseq

DNA-based NGS

Select fusions are clinically-actionable

responses can be dramatic and durable
< br>Farago

, J Thorac Oncol. 2015 Dec;10(12):1670-4.

NTRK1/2/3

, ROS1, and ALK fusions are identified across multiple cancers

lower prevalence in more common cancers

NTRK1

NTRK2

NTRK3

high prevalence events in rare adult and pediatric cancers

Drilon

, Ann Oncol, 2016 Feb 15. PMID:

26884591

MASC (Mammary Analogue

Secretory Carcinoma)

Breast

Secretory CA

Congenital

Mesoblastic

Nephroma

Fibrosarcoma

Chromosome 12

Chromosome 15

Entrectinib

(RXDX-101)

Highly-potent, orally-available, ATP-competitive

tyrosine kinase inhibitor

Low to sub-nanomolar

efficacy against 5 kinases

Results in decreased downstream effector activity

PI3K/AKT

Active

in vitro

in vivo

rearranged cancers

Kinase

IC50 (nM)

Active against potential Trk

inhibitor resistance

mutations at clinically achievable exposures

F589L (gatekeeper)

Kinase domain

Phe589

Val573

Gly667

Mutation in

LOXO-101

Entrectinib

Human Exposure

Equivalent (nM)

Wildtype

AACR Abstract 2136, Data generated by Ignyta

Phase I Development

STARTRK-1 and ALKA-372-001

Entrectinib: Phase I Studies

STARTRK-1 (n=65)

Dosing: continuous

NTRK/ROS1/ALK

alterations

US, EU, Asia

initiated in July 2014

ALKA-372-001 (n=54)

intermittent

alterations

FIH study: Nerviano

Medical Sciences in

October 2012

assumed

responsibility in November 2013

RP2D: 600 mg PO once daily, continuous

Total clinical experience:

n=119 patients

Updated safety and efficacy data

(n=119)

Age, years,

median (range)

53 (46-63)

57 (46-66)

55 (46-66)

male/female (%)

ECOG performance

status, n

30 (56)

22 (34)

52 (44)

21 (39)

41 (63)

62 (52)

Unknown

Prior Cancer Therapies, n (%)

15 (13)

25 (39)

28 (24)

51 (94)

19 (29)

70 (59)

Tumor type,

35 (65)

36 (56)

71 (60)

Gastrointestinal Tract

9 (17)

9 (14)

18 (15)

Head & Neck

(e.g.,

sarcomas,

breast,

melanoma,

ovarian)

15 (23)

20 (17)

Baseline Characteristics

Safety

All patients in dose escalation and expansion phases

-advanced solid tumor

Treatment-Related Adverse Events

AEs were classified via CTCAE v4.0; all reversible with dose modifications

No evidence of cumulative hepatic

or renal toxicity, or QTc prolongation

occurred

(STARTRK-1):

cognitive

disturbance,

idiopathic

eosinophilic

myocarditis

Adverse Events (AEs) in >10%...


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