Julie Eastland Chief Financial Officer & Chief Business Officer Jefferies Global Healthcare Conference June 6, 2017

Transcription

1 Julie Eastland Chief Financial Officer & Chief Business Officer Jefferies Global Healthcare Conference June 6, Cascadian Therapeutics, Inc. All rights reserved.

2 Forward Looking Statement 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 forwardlooking 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. 2

3 Cascadian Therapeutics Today Late-stage biopharmaceutical company developing innovative, targeted therapeutic products for the treatment of cancer Addressing unmet medical need in HER2+ metastatic breast cancer (mbc), including patients with brain metastases NASDAQ:CASC Headquarters: Seattle, WA Employees: ~7 1Q-217 cash and shortterm investments: $136.1M No debt Differentiated safety and activity profile; well positioned for combining with current standard-ofcare agents ivotal trial: tucatinib + trastuzumab and capecitabine Small molecule, oral, potent tyrosine kinase inhibitor (TKI) that is highly selective for HER2 Broad potential for tucatinib beyond mbc, such as mcrc & gastric Strong I protection, through 231 in US Maintain worldwide rights 3

4 Tucatinib: Highly Selective for HER2 Exceptional potency and selectivity for HER2 relative to EGFR, which may result in lower potential for EGFR-related toxicities 1 (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 Cellular Selectivity Data Compound HER2 IC 5 (nm) EGFR IC 5 (nm) HER2 IC 5 (nm) 5% Human Serum tucatinib 8 >1 67 neratinib * lapatinib* *neratinib is a EGFR/HER1/2/4 inhibitor and is being evaluated in clinical studies; lapatinib (Tykerb ) is an inhibitor of EGFR/HER Harandi A. J of Onc. 29.

5 Tucatinib Investigator- Sponsored Studies CASC Tucatinib Developed Studies ipeline Focused on Development of Tucatinib INDICATION RE-IND HASE 1 HASE 2 IVOTAL* STATUS HER2CLIMB: tucatinib + C + Tz vs. placebo + C + Tz Enrolling pivotal study HER2+ mbc Triplet: tucatinib + C + Tz hase 1b fully enrolled and active tucatinib + T-DM1 hase 1b fully enrolled and active HR+, HER2+ mbc (1&2-L) Aspire award tucatinib + palbociclib + letrozole hase 1/2 opening for enrollment in 1H-217 HER2+ mcrc (3-L) MOUNTAINEER tucatinib + Tz lanned to open enrollment in 1H-217 Other studies & ISTs Ex: Tz + chemo, LMD, prevention of CNS recurrence In planning discussions Chk1 Inhibitor TIGIT antibody 5 * The HER2CLIMB hase 2 study was amended to a ivotal hase 2 trial Denote studies planned to start in phase as indicated C = capecitabine Tz = trastuzumab T-DM1 = trastuzumab emtansine

6 otential for Tucatinib in a Broad Range of HER2+ Cancers brain metastases from primary HER2 cancers metastatic breast cancer colorectal cancer gastro-esophageal junction cancer non-small cell lung cancer gastric cancer Our strategy is to develop tucatinib in select indications on our own, through partnerships or investigator-sponsored studies 6

7 HER2 Breast Cancer: Treatment aradigm Tucatinib is being developed to fit within the current and the emerging treatment paradigm - post pertuzumab and T-DM1 ost & T-DM1 EARLY STAGE (neoadjuvant / adjuvant) ADVANCED STAGE (metastatic) trastuzumab + chemo (e.g. capecitabine) trastuzumab + chemo +/- pertuzumab trastuzumab + chemo +/- pertuzumab T-DM1* lapatinib + capecitabine ost 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 (AHINITY), T-DM1 may be more frequently used in 1-L metastatic setting trastuzumab + lapatinib 7 T-DM1 = trastuzumab emtansine

8 Landscape: HER2+ Breast Cancer Targeted Therapy hase 1 hase 2 ivotal Approved otential Combination Therapies* ARX788 Anti-HER2 Drug Conjugate tucatinib HER2+ TKI ASIRE grant IST tucatinib HER2+ TKI T-DM1 (Kadcyla ) Anti-HER2 ADC LJM716 Anti-HER3 mab TIV1 HER2/neu peptide vaccine FS12 HER2-specific Fcab MM-32 HER2 targeted liposomal doxorubicin margetuximab Fc optimized Anti-HER2 mab trastuzumab (Herceptin ) Anti-HER2 mab pertuzumab (erjeta ) Anti-HER2 mab DS-821a HER2-targeting Antibody Drug Conjugate capecitabine (Xeloda ) Nucleoside metabolic inhibitor MEDI4276 Bispecific Tubulysin Antibody Drug Conjugate abemaciclib CDK 4/6 inhibitor everolimus mtor Inhibitor palbociclib (Ibrance ) CDK 4/6 inhibitor Indirect Competitors alpelisib I3Kα Inhibitor enzalutamide Androgen receptor inhibitor Direct Competitors poziotinib multi-tki neratinib multi-tki lapatinib (Tykerb ) multi-tki * Therapies that are approved or in development with potential for combining with tucatinib 8 hase 1b data with tucatinib Contemporary treatment experience

9 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 2% of breast cancers have abnormally high levels of protein called HER2. HER2+ mbc will spread to the brain in up to 5% of cases. 1 Tucatinib 3rd & 4th line treated mbc market is estimated to be ~15, to 16, patients in the US and approximately the same in the European major markets ASCO Cancer.Net, Treatment of Metastatic HER2-ositive Breast Cancer. 2. Addressable market includes patients with and without brain metastases; estimated using market research studies, SEER database, and other sources.

10 1 hase 1b Triplet Study Updated data presented at San Antonio Breast Cancer Symposium in December 216

11 hase 1b Triplet Combination Study Overview hase 1b Triplet - Overview hase 1b Triplet - atient opulation Treatment atient opulation tucatinib + capecitabine + trastuzumab rior trastuzumab + taxane + T-DM1 required; patients with brain metastases eligible Status Last patient enrolled in Dec 215 Enrollment at MTD n=27* Age, median (range) 5 (35-67) ECOG /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%) *hase 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 11 hase 1b Triplet Study update presented at 216 SABCS

12 hase 1b Triplet: Summary of Findings 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. Evaluated by Independent Central Review R&D Day Update June 216 N = 27 SABCS Update December 216 N = 27 rogression-free survival (FS) 6.3 months 7.8 months Overall response rate (ORR) 58% 61% Median duration of response NA 1 months Improvement in updated data supports our registrational strategy of tucatinib in advanced mbc a population that needs new options 12 hase 1b Triplet Study update presented at 216 SABCS

13 Most Common Treatment-Emergent AEs and LFT Abnormalities Tucatinib 3 mg BID Tucatinib 3 mg BID Adverse Events + C (N=7) + Tz (N=18) + C + Tz (N=27) Total Total Total LFT Abnormalities + C (N=7) + Tz (N=18) + C + Tz (N=27) Diarrhea Grade 1 Grade 2 Grade 3 5 (71%) (56%) (78%) Increased ALT Grade 1 Grade 2 Grade 3 5 (71%) (28%) (7%) Nausea Grade 1 Grade 2 Grade 3 5 (71%) (33%) 6 2 (74%) 13 7 Increased AST Grade 1 Grade 2 Grade 3 6 (86%) (5%) 9 23 (85%) E Grade 1 Grade 2 Grade 3 5 (71%) (67%) Increased Bilirubin Grade 1 Grade 2 Grade 3 3 (43%) 3 4 (22%) (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 13 *No Hy s law cases hase 1b Triplet Study update presented at 216 SABCS

14 hase 1b Triplet: FS by Best Overall Response Tucatinib + C + Tz (N = 27) Median FS: 7.8 months (95% CI: ) Median Duration of Response: 1 months (95% CI: ) Best overall response: Complete response artial response Stable disease (measurable and nonmeasurable lesions) rogressive disease atient still on study Censored due to adverse event or non-fs event rogression-free Survival (months) 14 hase 1b Triplet Study update presented at 216 SABCS

15 Without Brain Mets With Brain Mets FS Comparable in atients with or without Brain Metastases in Triplet Cohort Without brain mets With brain mets Treated, stable disease at baseline With brain mets Untreated asymptomatic With brain mets rogressive after prior tx atient still on study Censored due to adverse event rogression-free Survival (Months) 15 hase 1b Triplet Study update presented at 216 SABCS

16 Maximum Change in Sum of Diameters (%) Response in atients With Measurable Disease in Triplet Cohort 4% 2% Tucatinib + C + Tz (N = 23) ORR, including 1 CR: 14/23 (61%) Median Duration of Response: 1 months (95% CI: ) % -2% -3% -4% ORR 61% -6% -8% Without brain mets (n=14) With brain mets (n=9) = rior pertuzumab treatment (n=18) -1% 16 hase 1b Triplet Study update presented at 216 SABCS

17 17 Tucatinib Regulatory athway and ivotal Trial Design

18 HER2CLIMB: hase 2 Now ivotal Trial HER2CLIMB modified following FDA meeting and review by CASC External Steering Committee Sample size increase: 18 to 48* rimary endpoint: remains FS per RECIST 1.1 as assessed by central review Select secondary endpoints: FS 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 5% FS improvement 18 *includes patients already enrolled in 216

19 HER2CLIMB ivotal Trial Design atient opulation Metastatic HER2+ breast cancer with progression after pertuzumab, trastuzumab, a taxane and T-DM1 atients with and without brain metastases 2:1 N=48 capecitabine + trastuzumab + tucatinib capecitabine + trastuzumab + placebo rimary Endpoint rogression-free Survival (FS) 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-219, 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 19

20 HER2CLIMB Control Arm Assumptions CLEOATRA EMILIA TH3RESA JCO 16* CASC Tx Arm (n=42) Control Arm (n=46) Tx Arm (n=496) Control Arm (n=495) Tx Arm (n=44) Control Arm (n=198) Tx Group (n=82) Triplet Tx Cohort 1 (n=27) Study Treatment T + + docetaxel T + docetaxel T-DM1 C + L T-DM1 hysician Choice T-DM1 (post-) Tucatinib + C + T # of prior HER2 therapies (2-4) ORR 8% 69% 44% 31% 31% 9% 18% 61% Median FS (months) ** % CI: ( ) Estimates suggest a FS of 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 2 1. hase 1b Triplet Study update presented at 216 SABCS. *Dzimitrowicz et al. Journal of Clinical Oncology 34, no. 29 (October 216) **Time on treatment, not FS

21 HER2CLIMB Global Study Site Activation 6-7 sites open and enrolling 9-1 sites; start activating in 1H

22 Regulatory Strategy for Europe lan to seek scientific advice from European Medicines Agency (EMA) in 217 Goal is to gain agreement with EMA that US development plan is acceptable to seek registration Update on EMA scientific advice expected in 2H

23 23 Other rograms: CASC-578 and TIGIT Antibody

24 CASC-578 is a Highly otent 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 GL safety pharmacology study indicate CASC-578 has an acceptable safety profile at the doses tested, with no evidence of QTc or cardiac contractility 24

25 TIGIT Antibody is a otent 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 D-1 antibody resistant mouse tumor model 25

26 Financial Overview BALANCE SHEET AS OF 3/31/17 Cash, cash equivalents and investments Debt $136.1M $ None Common stock, shares outstanding 49.2M Market Capitalization 28M* 217 FINANCIAL GUIDANCE Cash used in operations $5.M - 54.M *Based on closing price of $4.2 on 5/26/17 26 CONFIDENTIAL

27 217 Key Business riorities BUSINESS RIORITIES Expand patient enrollment in HER2CLIMB pivotal trial; initiate sites in Europe, Australia and Israel Seek EMA scientific advice on filing strategy for EU (HER2CLIMB); provide update on regulatory status Report on Cascadian and investigator-sponsored studies at upcoming scientific meetings Explore tucatinib s utility in other solid tumors, such as HER2+ amplified metastatic colorectal and gastric/esophageal cancers in clinical and non-clinical studies CASC-578 (Chk1) Complete pharmacology studies Go/no-go to start IND-enabling studies Explore all available financial vehicles to fund additional studies and further development of preclinical programs TIMING H mid-217 1H-217 2H-217 1H

28 Why Invest in Cascadian Therapeutics? otential for tucatinib to be an integral part of modern mbc treatment paradigm for patients +/- brain mets Exclusive worldwide rights for tucatinib for all indications Building value through development of tucatinib, with emphasis in areas that address unmet medical needs Solid cash position Experienced development and commercialization management team 28

29 Thank You! Contact: Monique Greer SV, Investor Relations & Corporate Communications d c NASDAQ:CASC