julie eastland - jefferies · palbociclib (ibrance®) cdk 4/6 inhibitor alpelisib pi3kα inhibitor...

© 2017 Cascadian Therapeutics, Inc. All rights reserved.

Jefferies Global Healthcare ConferenceJune 6, 2017

Julie EastlandChief Financial Officer & Chief Business Officer

Forward Looking Statement

2

This written and oral presentation contains forward-looking statements, including statements concerning preclinical results and anticipated research, preclinical and clinical development activities, the potential benefits and tolerability of product candidates, development plans, the anticipated announcement of clinical data, and clinical milestone dates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,”, “will,” “intends,” “potential,” “possible,” and similar expressions are intended to identify forward-looking statements. Forward-looking statements involve risks and uncertainties related to Cascadian’s business and the general economic environment, many of which are beyond its control. These risks, uncertainties and other factors could cause Cascadian’s actual results to differ materially from those projected in forward-looking statements. These risks and uncertainties include, among others, the possibility that preclinical and clinical trials of product candidates will not be successful, or be completed, or confirm earlier results, risks associated with obtaining additional financing, risks related to obtaining and protecting intellectual property rights, risks related to regulatory strategies and the receipt of regulatory approvals and risks related to general economic factors. Although Cascadian Therapeutics believes that its forward-looking statements are reasonable, it can give no assurance that its expectations are correct. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For a detailed description of Cascadian Therapeutics’ risks and uncertainties you are encouraged to review the documents filed with the securities regulators in the United States on EDGAR and in Canada on SEDAR. Except as required by law, the company undertakes no obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Cascadian Therapeutics Today

3

Late-stage

biopharmaceutical

company developing

innovative, targeted

therapeutic products for

the treatment of cancer

NASDAQ:CASC

Headquarters: Seattle, WA

Employees: ~70

1Q-2017 cash and short-

term investments: $136.1M

No debt

Addressing unmet

medical need in

HER2+ metastatic

breast cancer (mBC),

including patients

with brain

metastases

Pivotal trial: tucatinib +

trastuzumab and

capecitabine

Small molecule, oral,

potent tyrosine kinase

inhibitor (TKI) that is

highly selective for HER2

Differentiated safety and

activity profile; well

positioned for combining

with current standard-of-

care agents

Broad potential for

tucatinib beyond mBC,

such as mCRC & gastric

Strong IP protection,

through 2031 in US

Maintain worldwide rights

Tucatinib: Highly Selective for HER2

▪ Exceptional potency and selectivity for HER2 relative to EGFR, which may result in lower potential for EGFR-related toxicities1 (e.g., diarrhea, skin rash)

▪ Tolerability may lead to better compliance and ability to dose for longer periods of time

▪ Favorable profile compared to EGFR/HER2 dual inhibitors such as neratinib and lapatinib

▪ Ongoing experiments to determine differentiation of protein binding in CNS

4

Cellular Selectivity Data

Compound HER2 IC50 (nM) EGFR IC50 (nM) HER2 IC50 (nM) 50%

Human Serum

tucatinib 8 >10000 67

neratinib* 7 8 39

lapatinib* 49 31 810

*neratinib is a EGFR/HER1/2/4 inhibitor and is being evaluated in clinical studies; lapatinib (Tykerb®) is an inhibitor of

EGFR/HER2

1. Harandi A. J of Onc. 2009.

Pipeline Focused on Development of Tucatinib

5

INDICATION PRE-IND PHASE 1 PHASE 2 PIVOTAL* STATUS

HER2+ mBC

Enrolling pivotal study

Phase 1b fully enrolled

and active

Phase 1b fully enrolled

and active

HR+, HER2+ mBC

(1&2-L) Aspire award

Phase 1/2 opening for

enrollment in 1H-2017

HER2+ mCRC (3-L)

MOUNTAINEER

Planned to open

enrollment in 1H-2017

Other studies & ISTs In planning discussions

Chk1 Inhibitor

TIGIT antibody

HER2CLIMB: tucatinib + C + Tz vs. placebo + C + Tz

Triplet: tucatinib + C + Tz

tucatinib + T-DM1

tucatinib + Tz

Tu

cati

nib

Inve

stig

ato

r-

Sp

on

sore

d S

tud

ies

CA

SC

Tu

cati

nib

Dev

elo

ped

Stu

die

s

Denote studies planned to start in phase as indicated

tucatinib + palbociclib + letrozole

Ex: Tz + chemo, LMD, prevention of CNS recurrence

C = capecitabine

Tz = trastuzumab

T-DM1 = trastuzumab emtansine

* The HER2CLIMB Phase 2 study was amended to a Pivotal Phase 2 trial

Potential for Tucatinib in a Broad Range of HER2+ Cancers

6

brain metastases from primary HER2 cancers

non-small cell lung cancergastric cancer

gastro-esophageal junction cancer

colorectal cancer

metastatic breast cancer

Our strategy is to develop tucatinib in select

indications on our own, through partnerships or

investigator-sponsored studies

HER2 Breast Cancer: Treatment Paradigm

7

trastuzumab +

chemo +/-

pertuzumab

T-DM1*lapatinib +

capecitabine

trastuzumab +

lapatinib

trastuzumab +

chemo (e.g.

capecitabine)EARLY STAGE ADVANCED STAGE

Tucatinib is being developed to fit within the current and the

emerging treatment paradigm - post pertuzumab and T-DM1 Post P & T-DM1

▪ Post pertuzumab and T-DM1 in mBC, there is no single standard of care,

particularly for patients who develop brain metastases

▪ Tucatinib in combination has shown encouraging safety and activity following

pertuzumab and T-DM1 for patients with and without brain metastases

▪ If pertuzumab approved in extended adjuvant setting (APHINITY), T-DM1 may

be more frequently used in 1-L metastatic setting

T-DM1 = trastuzumab emtansine

trastuzumab +

chemo +/-

pertuzumab

(neoadjuvant / adjuvant) (metastatic)

8

Landscape: HER2+ Breast Cancer Targeted Therapy

Direct Competitors

Potential Combination Therapies*

Indirect Competitors

Phase 1 Pivotal ApprovedPhase 2

capecitabine (Xeloda®)

Nucleoside metabolic inhibitor

trastuzumab (Herceptin®)

Anti-HER2 mAb

pertuzumab (Perjeta®)

Anti-HER2 mAb

T-DM1 (Kadcyla®)

Anti-HER2 ADC

everolimusmTOR Inhibitor

enzalutamideAndrogen receptor

inhibitor

abemaciclibCDK 4/6 inhibitor

lapatinib (Tykerb®)

multi-TKI

neratinibmulti-TKI

ARX788Anti-HER2 Drug Conjugate

LJM716Anti-HER3 mAb

TPIV100HER2/neu peptide vaccine

FS102HER2-specific Fcab

poziotinibmulti-TKI

palbociclib (Ibrance®)

CDK 4/6 inhibitor

alpelisibPI3Kα Inhibitor

DS-8201aHER2-targeting

Antibody Drug Conjugate

tucatinibHER2+ TKI

* Therapies that are approved or in development with potential for combining with tucatinib

tucatinibHER2+ TKI

ASPIRE grant IST

MM-302HER2 targeted

liposomal doxorubicin

margetuximabFc optimized Anti-HER2

mAb

MEDI4276Bispecific Tubulysin

Antibody Drug Conjugate

Phase 1b data with tucatinib

Contemporary treatment experience

Tucatinib: HER2+ Metastatic Breast Cancer (mBC)

▪ Cascadian Therapeutics retains exclusive worldwide rights in all indications

• Ongoing initiatives to support registration strategies in US and Europe

▪ Advanced HER2+ mBC market is attractive and sizable

• Global treatment patterns in major countries Europe are aligned to US market

• High unmet medical need with no defined standard of care for patients in this setting,

including patients with breast cancers that metastasize to the brain

• About 20% of breast cancers have abnormally high levels of protein called HER2.

HER2+ mBC will spread to the brain in up to 50% of cases.1

▪ Tucatinib 3rd & 4th line treated mBC market is estimated to be ~15,000 to

16,000 patients in the US and approximately the same in the European

major markets2

9

1. ASCO Cancer.Net, Treatment of Metastatic HER2-Positive Breast Cancer.

2. Addressable market includes patients with and without brain metastases; estimated using market research studies,

SEER database, and other sources.

Phase 1b “Triplet Study”Updated data presented at San Antonio Breast Cancer Symposium in December 2016

10

Phase 1b Triplet Combination Study Overview

11

Phase 1b Triplet - Overview

Treatmenttucatinib + capecitabine +

trastuzumab

Patient

Population

Prior trastuzumab

+ taxane + T-DM1 required;

patients with brain

metastases eligible

Status Last patient enrolled in Dec 2015

Enrollment at

MTDn=27*

Phase 1b Triplet - Patient Population

Age, median (range) 50 (35-67)

ECOG 0/1, n (%) 14 (52%) / 13 (48%)

Hormone receptor+, n (%) 15 (56%)

# of prior HER2 agents,

median (range) 3 (2-4)

Brain metastases, n (%) 11 (41%)

*Phase 1b also included two doublet safety lead-in cohorts of tucatinib with capecitabine (n=7) and tucatinib with

trastuzumab (n=18) for a total sample size of n=52

Phase 1b Triplet Study update presented at 2016 SABCS

Phase 1b Triplet: Summary of Findings

12

Evaluated by Independent

Central Review

R&D Day Update

June 2016

N = 27

SABCS Update

December 2016

N = 27

Progression-free survival (PFS) 6.3 months 7.8 months

Overall response rate (ORR) 58% 61%

Median duration of response NA 10 months

▪ Encouraging safety and anti-tumor activity in patients with and without brain metastases

▪ Responses and long-term stable disease seen in patients with brain metastases

▪ Combination of tucatinib with trastuzumab and capecitabine was well tolerated Most treatment-emergent adverse events were Grade 1, with few tucatinib dose reductions and no required prophylactic use of antidiarrheal agents.

Improvement in updated data supports our registrational strategy of

tucatinib in advanced mBC – a population that needs new options


Most Common Treatment-Emergent AEs and LFT Abnormalities

Adverse Events

Tucatinib 300 mg BID

+ C

(N=7)

+ Tz

(N=18)

+ C + Tz

(N=27)

Total Total Total

Diarrhea

Grade 1

Grade 2

Grade 3

5 (71%)

4

1

0

10 (56%)

7

3

0

21 (78%)

14

4

3

Nausea

Grade 1

Grade 2

Grade 3

5 (71%)

4

1

0

6 (33%)

6

0

0

20 (74%)

13

7

0

PPE

Grade 1

Grade 2

Grade 3

5 (71%)

1

3

1

0

0

0

0

18 (67%)

2

13

3

13

LFT Abnormalities

Tucatinib 300 mg BID

+ C

(N=7)

+ Tz

(N=18)

+ C + Tz

(N=27)

Increased ALT

Grade 1

Grade 2

Grade 3

5 (71%)

3

1

1

5 (28%)

4

1

0

19 (70%)

15

2

2

Increased AST

Grade 1

Grade 2

Grade 3

6 (86%)

3

2

1

9 (50%)

9

0

0

23 (85%)

15

6

2

Increased Bilirubin

Grade 1

Grade 2

Grade 3

3 (43%)

3

0

0

4 (22%)

3

1

0

14 (52%)

7

5

2*

▪ In 148 pts treated with tucatinib at MTD or higher in Array or Cascadian sponsored

studies, Grade 3 diarrhea rate was 7/148 = 4.7%

▪ LFT abnormalities have been uncommon and manageable in triplet combination

*No Hy’s law cases


0 6 12 18 24

Progression-Free Survival (months)

Phase 1b Triplet: PFS by Best Overall Response

14

Median PFS: 7.8 months (95% CI: 4.1-12.4)

Median Duration of Response: 10 months (95% CI:2.8-19.3)

Complete response

Partial response

Stable disease (measurable and nonmeasurable lesions)

Patient still on study

Best overall response:

Progressive disease

Censored due to adverse event or non-PFS event

Tucatinib + C + Tz (N = 27)


0 6 12 18 24

Progression-Free Survival (Months)

PFS Comparable in Patients with or without Brain Metastases in Triplet Cohort

15

Without B

rain

Me

tsW

ith B

rain

Me

ts

Without brain mets

With brain mets – Treated, stable disease at baseline

With brain mets – Untreated asymptomatic

Patient still on study

With brain mets – Progressive after prior tx

Censored due to adverse event


Response in Patients With Measurable Disease in Triplet Cohort

16

P

P

P

P

P

PP

P

P

P

P P

P

P

P P P

P

-100%

-80%

-60%

-40%

-20%

0%

20%

40%

Maxim

um

Ch

an

ge i

n S

um

of

Dia

mete

rs (

%)

Without brain mets (n=14)

With brain mets (n=9)

P = Prior pertuzumab treatment (n=18)

Tucatinib + C + Tz (N = 23)

-30%

ORR, including 1 CR: 14/23 (61%)

Median Duration of Response: 10 months (95% CI: 2.8-19.3)


ORR

61%

Tucatinib Regulatory Pathway and Pivotal Trial Design

17

HER2CLIMB: Phase 2 Now Pivotal Trial

▪ Sample size increase: 180 to 480*

▪ Primary endpoint: remains PFS per RECIST 1.1 as assessed by central review

▪ Select secondary endpoints:• PFS per RECIST 1.1 in subset of patients with brain metastases• Overall Survival

▪ Exploratory endpoints include: Response Rate in brain metastases per RANO-BM

▪ Registrational study designed to detect a tucatinib treatment effect of at least a 50% PFS improvement

18

HER2CLIMB modified following FDA meeting and review by CASC

External Steering Committee

*includes patients already enrolled in 2016

HER2CLIMB Pivotal Trial Design

19

Patient Population

• Metastatic HER2+ breast

cancer with progression

after pertuzumab,

trastuzumab, a taxane and

T-DM1

• Patients with and without

brain metastases

capecitabine +

trastuzumab

+ tucatinib

2:1N=480

capecitabine +

trastuzumab

+ placebo

Primary

Endpoint

Progression-Free

Survival (PFS)

▪ Stratified for treated or untreated CNS metastases, ECOG status and region of world

▪ Additional CNS endpoints remain exploratory• Responses in brain metastases• Time to need for intervention for brain metastases (time to radiation or surgery; time to

hospitalization)

▪ Independent Data Monitoring Committee (IDMC) will monitor the safety of patients in the study at regular intervals; no planned interim analysis at this time

▪ Target enrollment completion: mid-2019, based on current projections

HER2CLIMB has the potential to provide a needed option

for patients who have progressed past T-DM1,

importantly those with brain metastases

HER2CLIMB Control Arm Assumptions

20

TxArm

(n=402)

ControlArm

(n=406)

TxArm

(n=496)

ControlArm

(n=495)

TxArm

(n=404)

Control Arm

(n=198)

Tx

Group

(n=82)

TxCohort1

(n=27)

Study Treatment

T + P + docetaxel

T + docetaxel

T-DM1 C + L T-DM1Physician

ChoiceT-DM1

(post-P)Tucatinib+ C + T

# of prior HER2

therapies0-1 0-1 1 1 2 2 2 3 (2-4)

ORR 80% 69% 44% 31% 31% 9% 18% 61%

Median PFS(months)

18.5 12.4 9.6 6.4 6.2 3.3 4**7.8

95% CI: (4.1-12.4)

CLEOPATRA TH3RESA JCO ’16* CASC

Triplet

▪ Estimates suggest a PFS of 3-4.5 months for capecitabine + trastuzumab post both pertuzumab + T-DM1

▪ HER2CLIMB uses these assumptions along with input from CASC Steering Committee

▪ The control arm is conservatively powered with an assumption of 4.5 months

1. Phase 1b Triplet Study update presented at 2016 SABCS.

*Dzimitrowicz et al. Journal of Clinical Oncology 34, no. 29 (October 2016) 3511-3517.

**Time on treatment, not PFS

EMILIA

HER2CLIMB Global Study Site Activation

21

60-70 sites open

and enrolling

90-100 sites; start

activating in 1H-2017

Regulatory Strategy for Europe

22

▪ Plan to seek scientific advice

from European Medicines

Agency (EMA) in 2017

▪ Goal is to gain agreement with

EMA that US development

plan is acceptable to seek

registration

Update on EMA scientific advice

expected in 2H-2017

Other Programs: CASC-578 and TIGIT Antibody

23

CASC-578 is a Highly Potent and Selective Chk1 Inhibitor

▪ Chk1 is a protein kinase that regulates cell cycle progression in response to DNA damage response (DDR) signaling

▪ Targeting cell cycle regulation and DDR is a clinically validated approach to cancer therapy

▪ CASC-578, a picomolar inhibitor of Chk1, is active as a single agent and in combination with chemotherapeutic agents in a variety of solid tumor and hematological tumor derived cell lines

▪ CASC-578 has demonstrated single agent anti-tumor activity in preclinical models of acute leukemia, mantle cell lymphoma and non-small cell lung cancer

▪ Results of recent GLP safety pharmacology study indicate CASC-578 has an acceptable safety profile at the doses tested, with no evidence of QTc or cardiac contractility

24

TIGIT Antibody is a Potent Immune Checkpoint Inhibitor

▪ TIGIT is an emerging immune checkpoint target that regulates the induction of adaptive (T cell) and innate (NK cell) immune response to cancers

▪ CASC has identified fully human antibodies that bind to human, mouse and cyno TIGIT with sub-nanomolar affinity and block TIGIT binding to CD155 and CD112

▪ CASC’s novel TIGIT antibody has demonstrated single agent anti-tumor activity in a PD-1 antibody resistant mouse tumor model

25

Financial Overview

26 CONFIDENTIAL

BALANCE SHEET AS OF 3/31/17

Cash, cash equivalents and investments $136.1M

Debt $ None

Common stock, shares outstanding 49.2M

Market Capitalization 208M*

2017 FINANCIAL GUIDANCE

Cash used in operations $50.0M - 54.0M

*Based on closing price of $4.20 on 5/26/17

2017 Key Business Priorities

27

BUSINESS PRIORITIES TIMING

Expand patient enrollment in HER2CLIMB pivotal trial; initiate

sites in Europe, Australia and Israel2017+

Seek EMA scientific advice on filing strategy for EU

(HER2CLIMB); provide update on regulatory status2H-2017

Report on Cascadian and investigator-sponsored studies at

upcoming scientific meetings 2017

Explore tucatinib’s utility in other solid tumors, such as HER2+

amplified metastatic colorectal and gastric/esophageal

cancers in clinical and non-clinical studies

mid-2017

CASC-578 (Chk1) Complete pharmacology studies

Go/no-go to start IND-enabling studies1H-2017

2H-2017

Explore all available financial vehicles to fund additional

studies and further development of preclinical programs1H-2017

Why Invest in Cascadian Therapeutics?

28

Building value through development of

tucatinib, with emphasis in areas that

address unmet medical needs

Potential for tucatinib to be an integral

part of modern mBC treatment

paradigm for patients +/- brain mets

Exclusive worldwide rights for tucatinib

for all indications

Solid cash position

Experienced development and

commercialization management team

NASDAQ:CASC

Thank You!

Contact:

Monique Greer

SVP, Investor Relations &

Corporate Communications

[email protected]

d - 206.801.2701

c - 206.496.8550

mailto:[email protected]

julie eastland - jefferies · palbociclib (ibrance®) cdk 4/6 inhibitor alpelisib pi3kα inhibitor...

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