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© 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
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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
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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
Phase 1b Triplet Study update presented at 2016 SABCS
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
Phase 1b Triplet Study update presented at 2016 SABCS
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)
Phase 1b Triplet Study update presented at 2016 SABCS
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
Phase 1b Triplet Study update presented at 2016 SABCS
Response in Patients With Measurable Disease in Triplet Cohort
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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)
Phase 1b Triplet Study update presented at 2016 SABCS
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
d - 206.801.2701
c - 206.496.8550