Investor Event at SABCS. December 2017

Transcription

1 Investor Event at SABCS December 2017

2 Forward-Looking Statements This presentation, in addition to historical information, contains certain forwardlooking statements made pursuant to the Private Securities Litigation Reform Act of Such statements may involve significant risks and uncertainties, and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, new product development (including clinical trials outcome and regulatory requirements/actions); competitive risks to marketed products; forecasts of future operating results; availability of required financing and other sources of funds on acceptable terms, if at all; as well as those discussed in the Company's filings with the Securities and Exchange Commission. 2

3 Agenda 8:00 pm 8:05 pm Welcome and Opening Remarks: Michael Pehl, President and Chief Executive Officer-elect 8:05 pm 8:30 pm Treatment Options for Advanced, Triple-negative Breast Cancer: Harold J. Burstein, MD, PhD, Associate Professor of Medicine at Harvard Medical School, and medical oncologist at Dana-Farber Cancer Institute and Brigham & Women's Hospital 8:30 pm 8:50 pm Sacituzumab Govitecan Phase 2 Results in mtnbc: Linda T. Vahdat, MD, MBA, medical oncologist at Memorial Sloan Kettering Cancer Center and Chief of Medical Oncology and Clinical Director of Cancer Services at Norwalk Hospital 8:50 pm 9:00 pm Strategic Company Priorities: Michael Pehl, President and Chief Executive Officer-elect 9:00 pm Q&A Session 3

4 First-in-class Antibody-Drug Conjugate Platform Potential to address approximately 90% of all human cancers Suite of Humanized Antibodies for Creating ADCs 1. hrs7, used in sacituzumab govitecan, targets Trop-2 for solid cancers 2. Labetuzumab, used in IMMU-130, targets CEACAM5 for colorectal cancer 3. IMMU-114, used in IMMU-140, targets HLA-DR for solid and liquid cancers Linker for SN-38 SN-38 Payload 1. Unique ADC chemistry avoids low solubility & selectively delivers SN-38 directly to the tumor 2. Delivers 136-fold more SN-38 than irinotecan Linker for SN High drug-to-antibody ratio (7.6:1) 2. Moderately stable & ph sensitive 3. Rapid payload release at or inside tumor 4

5 Sacituzumab Govitecan, an Antibody-Drug Conjugate for Targeted Drug Delivery to Solid Cancers 1. Target: Trop-2 Pan-epithelial cancer antigen with broad expression in many different cancers 80% of patients have moderate to strong expression by immunohistochemistry Internalizes upon antibody binding - ideal target for drug delivery with antibody-drug conjugates Trop-2 expression in TNBC liver tumor biopsy 2. Antibody: Humanized RS7-3G11 Binds human breast, lung, colon, renal, prostate, urothelial, and many other solid cancers 5

6 Current Therapies Used to Treat mtnbc Most commonly-used chemotherapies were introduced more than 25 years ago Cyclophosphamide Approved in 1959 Doxorubicin Approved in 1974 Cisplatin Approved in 1978 Carboplatin Approved in 1986 Docetaxel Approved in 1995 Paclitaxel Approved in 1993 mtnbc ranks among the highest unmet medical needs in Oncology today

7 Treatment Options for Advanced, Triplenegative Breast Cancer Harold J. Burstein, MD, PhD Associate Professor of Medicine at Harvard Medical School, and medical oncologist at Dana-Farber Cancer Institute and Brigham & Women's Hospital

8 Clinical Takeaways for TNBC 1. Less favorable outcomes compared to other types of breast cancer 2. Most patients will receive neoadjuvant/adjuvant chemotherapy Residual disease after neoadjuvant treatment is prognostic marker for greater risk of recurrence 3. Recurrences typically arise in years 2-4 after diagnosis and have lower risk of recurrence thereafter 4. Metastasis to viscera (lung, liver, brain) more common than in (treated) ER+ or HER2+ breast cancer 5. There are no drugs specifically approved / indicated for TNBC 6. Responses are common with chemotherapy but duration of treatment in 1st, 2nd, 3rd etc. lines of chemotherapy is typically shorter than with ER+ or HER2+ cancers 8

9 Clinical Takeaways for TNBC (cont d) 7. While 80% of BRCA1-associated breast cancers are TNBC, most TNBC are not BRCA-associated and there is little clinical evidence for BRCA-ness in most cases 8. Genomic sequencing can identify higher mutational burden in TNBC but only rarely identifies an actionable or targetable mutation 9. There are no agents specifically approved for treatment of triple-negative breast cancer. 10. Chemotherapy approvals shared with advanced and/or refractory breast cancer 11. Approvals typically based on improvement in PFS or OS, or rarely on activity in defined, refractory disease 9

10 Chemotherapy for Advanced Breast Cancer: Duration of Chemotherapy Treatment by Tumor Subtype and Line of Therapy Single center experience at Dana-Farber Cancer Institute Seah DS, et al. J Natl Comp Canc Netw 2014;12:

11 Rapid Drop-Off in Efficacy in TNBC Number of patients receiving chemotherapy Median # weeks on chemotherapy st line 2nd line 3rd line st line 2nd line 3rd line Kassam et al, Clin Breast Ca

12 Site of 1 st Recurrence in NCCN* Triple Negative vs Luminal HER2+ vs Luminal Site OR (95% CI)** p OR (95% CI) p Distant vs Locoregional 1.33 (1.00, 1.78) (0.84, 1.56) 0.39 Lung vs Other 2.27 (1.50, 3.43) < (1.05, 2.60) 0.03 Brain vs Other 5.32 (2.85, 9.91) < (2.93, 10.43) <0.001 Bone vs Other 0.23 (0.16, 0.33) < (0.28, 0.53) <0.001 Liver vs Other 1.06 (0.69, 1.62) (1.12, 2.52) *Analysis based on cohort of 1,235 patients with documented recurrence (TN, n=408; HER2+, n=341; Luminal, n=486). Luminal cohort used as the referent group for all analyses. **OR=odds ratio; CI=confidence interval; Other refers to any/all other distant/locoregional site Lin et al, ASCO 2009

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15 Choice of Chemotherapy by Line of Therapy* 15 Agent Ray et al, J Comp Effect Res st line N= nd line N= rd line N= th line N=1059 Paclitaxel 26% 28% 22% 18% Capecitabine 22% 18% 16% 16% Trastuzumab 20% 19% 19% 19% Docetaxel 17% 13% 8% 6% Doxorubicin 11% 6% 7% 9% Bevacizumab 10% 14% 18% 18% Gemcitabine 10% 16% 19% 19% Carboplatin 9% 8% 8% 7% Vinorelbine 7% 12% 14% 14% Lapatinib NR NR 6% 8% * End date of f/u period = Mar 31, 2010 or disenrollment from eligible health plan

16 CALGB 40502: 1 st Line Chemotherapy for Advanced Breast Cancer OUTCOMES in TNBC Rugo HS, et al. J Clin Oncol 2015;33:

17 TNT: Randomized Trial of Docetaxel vs Carboplatin for 1 st Line Treatment of TNBC OUTCOMES in TNBC Response Rate Time to Progression Docetaxel 34% 4.5 m Carboplatin 31% 3.1 m Tutt A, et al. SABCS 2014;

18 Single-agent Capecitabine in Anthracycline-treated and Paclitaxelresistant Advanced Breast Cancer OUTCOMES not specific for TNBC N=163 RR: 20% Response rates: 9 to 19% Blum JL et al. J Clin Oncol 1999;17:485. Kathy D. Miller et al. JCO 2005;23:

19 Eribulin Monotherapy vs Treatment of Physician's Choice in Patients with Metastatic Breast Cancer (EMBRACE): a Phase 3 Open-label Randomized Study OUTCOMES not specific for TNBC Endpoint Eribulin TPC OS 13.1 m 10.6 m PFS 3.7 m 2.2 m RR 13% 5% RR / TNBC 12% 10% Median prior chemo: 3 to 4 regimens Prior Anthracycline 100% Prior Taxane 100% Prior Cyclophosphamide 73% 19 Cortes J, et al. Lancet 2011;377:

20 Phase 3 Open-Label Randomized Study of Eribulin Mesylate vs Capecitabine in Patients with Locally Advanced or Metastatic Breast Cancer Previously Treated with an Anthracycline and a Taxane OUTCOMES not specific for TNBC TNBC results: PFS 2.9m vs 2.2m; OS 14.4m vs 9.4m 20 Response rates independent review: E = 11%, C = 11.5%, Response rates investigator review: E = 16%, C = 20% Kaufman et al. JCO 2015;33: ; Twelves C, et al. Breast Cancer (Auckl) 2016;

21 Vinorelbine or Gemcitabine after Anthracyclines and Taxanes for Metastatic Breast Cancer OUTCOMES not specific for TNBC Vinorelbine Gemcitabine Author No. Response Rate PFS Zelek et al. Cancer 2001 Seo et al. Inv New Drugs 2011 Spielmann et al. Oncology 2001 Brodowicz et al. The Breast 2000 Modi et al. Clinical Breast Cancer % 6m 26 21% 2.8 m 41 29% 25 2 nd line: 33% 3 rd line: 6% 22 17% 2 nd line: 5.1 m 3 rd line: 3.5 m 21

22 Innovations in TNBC

23 Olaparib in Patients with Recurrent High-grade Serous or Poorly Differentiated Ovarian Carcinoma or Triple-negative Breast Cancer: a Phase 2, Multicentre, Open-label, Non-randomized Study PARP inhibitors have activity in BRCA-associated breast cancer but not unselected TNBC OUTCOMES in TNBC 23 Gelmon KA, et al. Lancet Oncol 2011;12:852

24 Olympiad Study: Olaparib vs Standard Therapy for BRCA-associated Breast Cancer OUTCOMES not specific for TNBC TNBC outcomes: HR 0.43 Response rates: Olaparib 55% Standard chemo 21% 24 Robson M et al. N Engl J Med 2017;377:

25 Overall Response Rates by PD-L1* Status for Trials Reported to Date Agent Subtype ORR ORR (PD-L1+) Pembrolizumab Single agent (Keynote-012) Single agent (Keynote-028) Single agent (Keynote-086-A) Single agent (Keynote-086-B) Phase II with eribulin TNBC ER+/HER2- TNBC TNBC TNBC 18.5% 12.0% 4.7% 23.0% 33.3% 18.5% 12.0% 4.8% 23.0% 29.4% Atezolizumab Single agent Phase Ib with nab-paclitaxel TNBC TNBC 10.0% 38.0% 13.0% 36.0% Avelumab Single agent (Javelin) All ER+/HER2- HER2+ TNBC 4.8% 2.8% 3.8% 8.6% 33.3% NR NR 44.4% * Studies used different antibodies and cutoffs for determining PD-L1 positivity 25

26 ESO-ESMO ABC3 Guideline The treatment of triple-negative breast cancer (TN-ABC) still remains the largest unmet need within ABC. In spite of extensive research, no treatments apart from chemotherapy have so far proven to be effective for this population. For this reason, no specific recommendations can be made for this ABC subtype, with the possible exception of platinum compounds for BRCAmutated patients. Cardoso F, et al. Ann Oncol

27 Sacituzumab Govitecan Phase 2 Results in mtnbc Linda T. Vahdat, MD, MBA Medical oncologist at Memorial Sloan Kettering Cancer Center and Chief of Medical Oncology and Clinical Director of Cancer Services at Norwalk Hospital

28 Background 1. Metastatic triple-negative breast cancer (mtnbc) is an aggressive disease with poor prognosis that disproportionally affects young women Visceral and brain metastases are very common 2. No single standard chemotherapy available for relapsed/refractory mtnbc Response rates with standard chemotherapy are low (~10-15%) Median progression-free survival (PFS) is ~2-3 months with standard therapies (capecitabine, cisplatin or carboplatin, eribulin, nab-paclitaxel) 3. Currently, there is a large unmet need in the breast cancer community 28

29 Low Response Rates in Pre-treated mtnbc* Drug Phase N Population ORR (%) PFS (mos) OS (mos) 1st line treatment Carboplatin st line Docetaxol st line Cisplatin/ Carboplatin st line (80.2%) Ixabepilone 3 Capecitabine 3 2 (pooled analysis) 3 (pooled analysis) >1st line treatment Resistant to anthracycline, cyclophosphamide & taxane or taxane only Prior or resistant to anthracycline & taxane Eribulin 4 3 (pooled analysis) 199 > 1 prior chemo * Includes breast cancer drugs with data from Phase 2/3 s with minimum mtnbc sample size > 60; ORR and PFS data Source of data: 1) Tutt A, SABCS 2014; 2) Isakoff SJ, J Clin Oncol 2015; 3) Perez EA, Breast Can Res Treat 2010; 4) Pivot X, Ann Oncol

30 Sacituzumab Govitecan Antibody-Drug Conjugate (ADC) Linker for SN-38 30

31 Clinical Trial Experience 1. Preliminary results in 69 patients with mtnbc showed an objective response rate of 30%, which was published earlier this year in the Journal of Clinical Oncology 1 2. In 2016, sacituzumab govitecan was awarded Breakthrough Therapy Designation by the FDA, and enrollment was resumed in a more defined population in 3rd-line setting mtnbc patients were treated with sacituzumab govitecan 10 mg/kg on days 1 and 8 every 21 days until progression or unacceptable toxicity Includes 53 of 69 patients who received 2 prior therapies from previously reported study 1. Bardia et al. J Clin Oncol. 2017;35:

32 Single Arm, Open-Label Study Design Metastatic TNBC (ASCO/CAP guidelines) N = 110 Sacituzumab govitecan 10 mg/kg Days 1 and 8, every 21 days Scanned every 8 weeks Until progression or unacceptable toxicity Key eligibility criteria 1. Adults, 18 years of age 2. ECOG >2 prior therapies in metastatic setting or >1 therapy if progressed within 12 months of (neo)adjuvant therapy 4. Prior taxane therapy 5. Measurable disease Evaluations 1. Response evaluation by investigators 2. Blinded independent central review of all CRs, PRs, and 20% tumor reductions 3. Other evaluations: safety, immunogenicity, Trop-2 expression 32

33 Patient Disposition and Treatment Metastatic TNBC >3 rd line N = died 30 in long-term follow-up* 14 still on treatment 1. Enrollment between Jul 2013 and Feb Data cutoff date of June 30, Patients received a median of 14.5 doses (range: 1-88) over a median duration of 4.9 months (range: ) * Includes 2 patients who were lost to follow up 33

34 Demographics and Patient Characteristics N = 110 Female/Male, n 109/1 Median age, years (range) 55 (31-81) Race White Black Asian Other Not specified ECOG performance status % 7% 4% 4% 10% 30% 70% Median time from metastatic disease to study entry, years (range) 1.5 ( ) >3 rd line for metastatic disease 3 rd line* >4 th line 100% 41% 59% Prior chemotherapy drugs** Taxanes Anthracyclines Cyclophosphamide Platinum agents Gemcitabine Fluoropyrimidine agents Eribulin Vinorelbine Prior checkpoint inhibitors Sites of metastatic disease at study entry*** Lung/mediastinum Liver Bone Chest wall N = % 86% 85% 75% 57% 51% 45% 15% 17% 58% 46% 45% 24% 34 * 2 patients who progressed within 12 months of (neo)adjuvant therapy only received one line in the metastatic setting; ** Used in >10% patients; *** Metastatic sites reported in >20% patients

35 Adverse Events (Regardless of Causality) Body system Adverse event All grades Grade 3 or 4 Neutropenia 63% 41% Hematologic Febrile neutropenia 8% 7% Anemia 52% 10% Leukopenia 24% 14% Nausea 63% 5% Gastrointestinal Diarrhea 56% 8% Vomiting 46% 5% Constipation 32% 1% Fatigue 50% 7% Alopecia 36% NA Other Decreased appetite 30% 0% Hyperglycemia 23% 4% Hypomagnesemia 21% 1% Hypophosphatemia 15% 8% Includes all events >20% (all grades) or >5% (grade 3 or 4); NA = not applicable Adverse events were managed with supportive medication or dose modifications 25% of patients had dose modifications predominantly to 7.5 mg/kg 2. Two patients (1.8%) discontinued due to adverse events (grade 3 transient infusion reaction/grade 2 fatigue 3. There were no treatment-related deaths

36 Tumor Response to Treatment Clinical benefit rate (CR+PR+SD 6 months) = 45% (50/110) 2. 74% (75/102) of patients with at least one CT response assessment had reduction of target lesions (sum of diameters) patients had 1 scheduled CT response assessment, 8 patients withdrew prior to assessment (4 PD, 4 MRI brain metastasis) * Patients with at least 20% tumor reduction (n = 56) were reviewed; ** Confirmed objective response rate per RECIST; *** Waterfall is based on local assessment; BICR = Blinded Independent Adjudicated Central Review.

37 Response Onset and Durability (n=37) Local BICR * Median duration of response, months (95% CI) 7.6 (4.8, 11.3) 9.1 (4.1, 14.3) Complete response 1. Median time to onset of response: 2.0 months (range: ) 2. 9 long-term responders were progression free for >1 year from start of treatment (4 responders >2 years) patients were still receiving sacituzumab govitecan at time of data cutoff, June 30, 2017 Partial response Continuing treatment as of June 30, 2017 cutoff Left study with PR (censored) Onset of objective response Months from start of sacituzumab govitecan * Patients with at least 20% tumor reduction (n = 56) were reviewed; BICR = Blinded Independent Adjudicated Central Review. 37

38 Time on Treatment for All Patients (N = 110) 38 Last prior time on treatment calculated as last dose date first dose date. Sacituzumab govitecan time on treatment calculated as (date off study or data cut off date of June ) first dose date. If more than 1 agent is given in the last prior regimen, the time of the last prior treatment is taken as the longest time for any agent used

39 Progression-free Survival (%) Overall Survival (%) Progression-free and Overall Survival* 100 Progression-free survival 100 Overall survival Median (95% CI): 5.5 months (4.8, 6.6) Median (95% CI): 12.7 months (10.8, 13.6) 80 85/110 (77%) number of events 80 71/110 (64%) deaths reported Months Number at risk Months Number at risk * Based on local assessment

40 Response to Sacituzumab Govitecan in Subgroups* ORR, % (n/n) Overall 34% (37/110) Age <55 55 Onset of metastatic disease 1.5 years 1.5 years Prior regimens for metastatic disease 3 rd line 4 th line 37% (20/54) 30% (17/56) 29% (16/55) 38% (21/55) 36% (16/45) 32% (21/65) Visceral involvement at study entry Yes No Trop-2 IHC (n = 62) 0-1 (weak, absent) 2-3 (moderate, strong) No Trop-2 IHC Prior checkpoint inhibitors ORR, % (n/n) 30% (26/88) 50% (11/22) 0% (0/5) 40% (23/57) 29% (14/48) 47% (9/19) * Based on local assessment 40

41 Clinical Response to Sacituzumab Govitecan 1. Patient with mtnbc seen for management of fungating chest-wall/axillary mass 2. 7 prior regimens for MBC including carboplatin, capecitabine, doxorubicin, paclitaxel, vinorelbine, Ixabepilone, and eribulin 41

42 Clinical Response to Sacituzumab Govitecan 1. Patient with mtnbc, including metastasis to liver 2. 2 prior regimens including paclitaxel and carboplatin 42

43 Conclusions 1. Sacituzumab govitecan demonstrated significant clinical activity as a single agent in heavily pretreated patients with relapsed/refractory mtnbc Confirmed ORR * : 34% Clinical benefit rate (6 months) * : 45% The responses were durable (estimated median duration of response was 7.6 months based on local assessment) All data consistent with central review 2. Results suggest that sacituzumab govitecan has a predictable and manageable safety profile 3. Additional studies including rational combinations are currently being evaluated for mtnbc and other breast cancer subsets * Based on local assessment 43

44 ASCENT Phase 3 Study Overview Metastatic TNBC Refractory/relapsed after 2 prior SOC chemotherapies for advanced disease OR 1 therapy for patients who progressed within 12 months of completion of (neo)adjuvant therapy N = 328 Stratification Factors No. of prior therapies Geographic region Presence/absence of known brain metastasis 1. Clinical trials number: NCT Sacituzumab govitecan (IMMU-132) 10 mg/kg IV, days 1 and 8 every 21 days Treatment of physician choice Capecitabine Eribulin Gemcitabine Vinorelbine Continue treatment until progression Primary Endpoint PFS (Blinded Independent Central Read) Secondary Endpoint Overall Survival 2. Now enrolling in the US; European enrollment to begin in first half of Presented at: New Agents and Strategies; December 7, 2017; 5:00-7:00 PM, Hall 1 (abstract# 733)

45 Strategic Company Priorities Michael Pehl President and Chief Executive Officer-elect

46 New Vision For Value Creation Become a fully-integrated biopharmaceutical company focused on the development and commercialization of our unique ADC platform in order to maximize value for all stakeholders 1. Bring sacituzumab govitecan to market Initially focused on mtnbc in the 3 rd line setting 2. Develop plans to expand sacituzumab govitecan commercially beyond mtnbc 3. Pursue strategic opportunities for sacituzumab govitecan clinical and regional partnerships 4. Prioritize earlier product candidates in clinical pipeline, focused on our ADC platform 46

47 Key Business Objectives for 2017/ Submit BLA for Accelerated Approval in mtnbc As planned in the first quarter of Continue confirmatory Phase 3 study in mtnbc First patient dosed in November 2017 in the U.S. 3. Continue CMC preparations for commercial launch Pre-approval inspection activities continue Commercial drug manufacturing continues 4. Develop sacituzumab govitecan lifecycle plan Broaden footprint in mtnbc and mbc Pursue fast to market opportunity in UC, evaluate NSCLC opportunity Phase 2 signal seeking monotherapy studies in advanced prostate, ovarian, and head and neck cancers Phase 1/2 combination studies with PARP- and checkpoint-inhibitors 5. Build out Company leadership team Build commercial and medical affairs infrastructure for sacituzumab govitecan launch in the U.S. 47

48 Strong Management Team to Execute Strategy More than 20 years experience in Hematology and Oncology Most recently President, Hematology & Oncology at Celgene Launched multiple blockbuster drugs in oncology including Revlimid, Pomalyst, and Abraxane Michael Pehl President and CEO Previously served at Amgen 48 Brendan P. Delaney Chief Commercial Officer More than 20 years of commercial oncology experience on block-buster brands Most recently VP, U.S. Hematology/Oncology Commercial at Celgene Previously served at Novartis and Genentech

49 Strong Management Team to Execute Strategy Responsible for business development, corporate and portfolio strategy, and corporate transformation Global VP of Corporate Strategy, Innovation, and Digital Ventures at Pfizer Inc. Usama Malik Chief Business Officer Previously served as senior executive & executive advisor at Novartis, BMS, Lily, Schering, Intarcia, Zoetis, Danaher, Quest Diagnostics, Aetna among others More than 30 years of strategic finance experience in multiple industries Previously Interim CEO and CFO at Emisphere and Astralis Served 20 years at AT&T, including CFO at AT&T Alascom 49 Michael R. Garone Chief Financial Officer

50 Strong Management Team to Execute Strategy Over 28 years of biologics drug development experience Most recently, EVP of Development responsible for manufacturing, process development and supply chain management at Seattle Genetics Dr. Morris Rosenberg Acting Head of CMC 50

51 51 Timelines for Accelerated Approval in mtnbc

52 Building a Best-in-Class Commercial Organization 2H Chief Commercial Officer appointed 2. Recruit senior leadership in marketing & market access 3. Prepare the brand for launch 1H Prepare Immunomedics for launch 2. Launch-readiness review process fully operational 3. Hire experienced oncology sales leadership team 2H Hire and train experienced oncology field force 2. Go to market strategy and tactics finalized 3. Full launch readiness in by early Q

53 Building a Blockbuster Brand in Oncology Other Trop-2- expressing tumors TNBC & mbc 1. Establish foothold in mtnbc as first and only ADC approved in this area of high unmet need mtnbc 2. Build foundational therapy in TNBC and mbc across treatment lines 3. Expand to other solid tumors that express Trop-2 and are sensitive to irinotecan 53

54 Sufficient Cash Runway to Reach AA in mtnbc Cash balance $140 Million Potential warrant exercise by Seattle Genetics $42 Million Potential warrant exercise by other investors $32 Million Debt (convertible senior notes) $20 Million Basic shares outstanding (fully diluted) 152 (187) Million Data as of September 30,

55 A Vision With Patients In Full Focus Become a fully-integrated biopharmaceutical company focused on the development and commercialization of our unique ADC platform in order to maximize value for all stakeholders 55