Ignyta 8-K Regulation FD Disclosure

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

Anna F. Farago, Manish Patel, Todd M. Bauer, Stephen V. Liu, Alexander Drilon, Jennifer Wheler,

Sai-Hong I. Ou, David Jackman, Daniel B. Costa, Pratik Multani, Zachary Hornby, David Luo,

Jonathan E. Lim, A. John Iafrate, and Alice T. Shaw

September 9, 2015

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

Exhibit 99.1

Disclosures: Consulting for Agios

Pharmaceuticals, Intervention

Insights, Cell Signaling Technology

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

Ligand-mediated signaling

TrkA/TrkB/TrkC

Fusion oncogene signaling:

ligand independent

NTRK gene rearrangements in human malignancies

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

KM-12

is

a

human

CRC

line

driven

by

a

constitutively

active

TrkA

fusion:

TPM3-NTRK1

Entrectinib

potently

inhibits

TrkA

phosphorylation

and

downstream

signaling

Entrectinib

induces in vivo tumor regression and durable tumor stabilization

In vitro

In vivo

xenograft

Target

TrkA

TrkB

TrkC

ROS1

ALK

IC50* (nM)

1.7

0.1

0.1

0.2

1.6

Entrectinib: pan-Trk inhibitor with in vitro and in vivo activity

* Biochemical kinase

assay

Entrectinib

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

NTRK1

gene rearrangement in NSCLC patient identified by anchored multiplex

polymerase chain reaction

NTRK1

(NM_001007792.1)

Chr1:156785542-156851642

Exon

number: 10

SQSTM1

(NM_001142298)

Chr5:179233388-179265077

Exon

number:6

Chr5

Chr1

AMP PCR technique described in Zheng

et al., Nat Med 2014

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

Patient characteristics and clinical symptoms

•

Male, 45 years old when diagnosed with stage IV (T1bN1M1a) NSCLC, adenocarcinoma histology, in

November 2013

•

30 pack-year cigarette history, quit in 2000

•

Developed progressive disease despite several lines of treatment, including chemotherapy and PD-1 inhibitor

•

At the time of enrollment, the patient had ECOG PS 2 with baseline chest wall pain requiring PRN

narcotics, dyspnea at rest, and an oxygen requirement of 3L/min by nasal cannula

•

Staging head CT demonstrated 15-20 previously untreated brain metastases up to 1.7 cm in diameter

•

Enrolled on phase I clinical trial with entrectinib

at 400 mg/m

2

PO daily

•

Entrectinib

was well tolerated, with possibly related AEs:

•

Dysgeusia, grade 1

•

Paresthesias, grade 1

•

Fatigue, grade 2

•

Within three weeks of starting treatment, the patient reported resolution of pain and dyspnea, and no

longer required supplemental oxygen

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

Baseline (Day -7)

Day 26: -47%

Day 155: -77.3%

Partial response by RECIST 1.1 at four weeks and ongoing

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

Complete response of all brain metastases

Baseline (Day -7)

Day 26

Day 155

MINI30.09

–

Clinical

response

to

entrectinib

in

a

patient

with

NTRK1-rearranged

non-small

cell

lung

cancer

(NSCLC)

-

Farago

Conclusions:

•

Entrectinib

caused rapid and clinically significant improvement in a patient with

NSCLC harboring an NTRK1

gene rearrangement.

•

The patient experienced resolution of baseline symptoms related to disease, including

pain, dyspnea, and hypoxia.

•

Entrectinib

was well tolerated with minimal side effects.

•

The response is durable and ongoing, with current duration of response 4.1 months.

•

Entrectinib

caused complete response of previously untreated brain metastases in

this patient, indicating potent CNS penetration and activity.

•

Entrectinib

may be an effective therapy for tumors harboring NTRK

gene

rearrangements, including those with CNS involvement.