Corporate Overview. March 2018 NASDAQ:FPRX

Transcription

1 Corporate Overview March 2018 NASDAQ:FPRX

2 Forward-Looking Statements Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of Words such as "may," "will," "expect," "plan," "anticipate" and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. These forward-looking statements reflect Five Prime's current beliefs and expectations. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ from these forward-looking statements. Forward-looking statements contained in this presentation include statements about (i) the timing of initiation, progress and scope of clinical trials for our product candidates; (ii) the potential use of our product candidates to treat patients; (iii) the extent of gene amplification and protein overexpression in and the size of certain patient populations; (iv) the prevalence and incidence of certain diseases; (v) the timing of the filing of INDs; (vi) the timing of program updates and data disclosures; and (vii) our preliminary financial results for the fiscal year ended December 31, Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected, changes in expected or existing competition, failure of our collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. Other factors that may cause our actual results to differ from current expectations are discussed in Five Prime's preliminary prospectus supplement relating to the proposed offering and its other filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein, as well as the risks identified in the registration statement and the preliminary prospectus supplement relating to the offering under the heading "Risk Factors." Except as required by law, we assume no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. 2

3 Five Prime in 2018 Value Proposition IND engine that is hard to copy and industry leading for discovery of I-O biologics Rapidly expanding pipeline transitioning into late-stage development History of value-creating collaborations; eligible to receive additional non-dilutive funding 3

4 The Five Prime Opportunity: Platform and Pipeline to Power Immuno-Oncology Clinical pipeline expected to more than double from 2 to 5 candidates by EOY 2018 Cabiralizumab CSF1R antibody I-O: Phase 2 in 2 nd - line pancreatic Phase 1a/1b in seven tumor settings Including ~60 patients in late-line pancreatic PVNS: Phase 2 ongoing Bemarituzumab (FPA144) FGFR2b antibody Initiation of FIGHT global Ph 1/3 trial in combo with chemo in first-line gastric Discovery platform and capabilities that uniquely position us to identify new I-O targets and therapeutics History of value-creating collaborations FPA150 B7-H4 antibody TIM-3 antibody FPT155 CD80-Fc 4

5 History of Value-Creating Collaborations $655M received* in non-dilutive funding from collaborations Eligible to receive additional funding from partnered clinical programs (below): Cabiralizumab Bemarituzumab (FPA144) TIM-3 antibody Territory Worldwide Greater China Worldwide Potential Milestone Payments $1.4 billion $39 million $295 million Development Costs BMS pays for I-O Zai pays for Greater China BMS pays Royalty percentages High teens to low twenties High teens to low twenties Mid-single-digit to low-double-digit * Includes milestone and funding payments that have been earned and invoiced but not yet received. 5

6 Oncology-Focused Pipeline with Multiple Clinical Candidates Program Cabiralizumab * (FPA008) CSF-1R antibody Indications Lead selection Pancreatic cancer (combination with Opdivo and chemo) Multiple tumor settings (combination with Opdivo ) IND-enabling activities Phase 1 Phase 1b Phase 2 Phase 3 ADVISE trial (combination with Opdivo ) Pigmented villonodular synovitis (PVNS) Bemarituzumab (FPA144 ** ) FGFR2b antibody FPA150 B7-H4 antibody FPT155 CD80-Fc TIM-3 antibody * I-O antibody * Novel I-O Biologics FIGHT Phase 1/3 trial (with chemo) in gastric/gej cancer Bladder cancer Multiple tumor settings Multiple tumor settings Multiple tumor settings Multiple tumor settings Multiple tumor settings * Partnered with Bristol-Myers Squibb Company (BMS) see Part I Item 1. Collaborations of our most recent Annual Report on Form 10-K for a description of the collaboration arrangement with BMS. ** Partnered with Zai Lab (Shanghai) Co., Ltd. (Zai) see our Current Report on Form 8-K filed with the SEC on December 19, 2017 for a description of the collaboration arrangement with Zai. 6

7 Cabiralizumab (FPA008) Antibody for Macrophage-Dependent Diseases

8 Cabiralizumab, a Product of the Five Prime Platform, Blocks Survival of Macrophages Cabiralizumab (FPA008) is an antibody to CSF-1R CSF-1 IL-34 Five Prime discovered IL-34, one of the two ligands for CSF-1R that cabiralizumab (FPA008) blocks 8

9 Rationale for Combination I-O Therapy: TAMs and Checkpoints Inhibit T Cell-Mediated Killing Through Different Mechanisms TAM Cabiralizumab blocks CSF-1R & depletes TAMs CD8 T Cell PD-1 TAMs produce factors that inhibit T cells CSF-1R PD-L1 PD-L1/PD-1 suppresses T cells High TAM levels are associated w/poor prognosis in pancreatic and other cancers Tumor Cell 9

10 Exploratory Phase 1 Trial of Cabira + Opdivo in Multiple Tumor Settings PHASE 1a Dose escalation and exploratory expansion Dose escalation cohorts (monotherapy & combination) PHASE 1b Cabiralizumab + Opdivo Completed enrollment end of 2017 Expansion in Selected Tumors Expansion in Pancreatic (n~30) Lung (NSCLC) Lung (NSCLC) Anti-PD-1 Resistant Head & Neck Pancreatic Renal N ~280 patients Study Objectives Safety Objective response rate and duration Survival Baseline and on-treatment biopsies Ovarian Glioblastoma 10

11 Pancreatic Cancer has Lowest 5-year Survival Rate Among 20 Common Cancers with Little Improvement Over Past ~35 Years Five-year survival rates for most common cancer sites Average for the years and Data: Journal of the National Cancer Institute: Chart: Chris Canipe / Axios 2017 Five Prime Therapeutics, Inc. All Rights Reserved 11

12 Significant Unmet Need in Pancreatic Cancer: Current Regimens Have Shown Limited Clinical Benefit Average survival rate for patients with advanced pancreatic cancer % < 3% Onivyde (liposomal irinotecan) Most recent FDA approval; for patients who progressed following gemcitabine-based therapy Onivyde/5-FU/Leucovorin 1 Phase 3 1 YEAR 5 YEAR ORR 7.7% (Phase 2 ORR 7.5%) No demonstrated activity with anti-pd1 therapy in pancreatic cancer Except in the <1-2% of patients who have microsatellite instability-high (MSI) 2 tumors PFS 3.1 months OS 6.1 months Diarrhea, neutropenia, and stomatitis are common Grade 3/4 events 1 Onivyde USPI, 2017; 2 Le DT et al. Science 2017; 357(6349): ; 3 Von Hoff DD et al. N Engl J Med 2013;369: ; 4 American Cancer Society. Pancreatic Cancer. Accessed November 3, 2017; 5 Foley K et al. Cancer Lett 2016;381;

13 Deep and Durable Responses Observed in Late-Line Pancreatic Cancer Progressive disease Treated beyond progressive disease Partial response Efficacy: Durable clinical benefit observed Confirmed ORR = 13% DCR = 16% Days Day Disease control: 5 to 9+ months Heavily pretreated population (average 3 prior lines of therapy) All responders have microsatellite stable (MSS) tumors that do not respond to PD1/L1 therapy Responses accompanied by steep declines in levels of the pancreatic tumor marker CA

14 Tolerable Safety Profile and Reductions in Metastatic Lesions Safety Profile: Safety profile consistent with nivolumab and cabiralizumab monotherapy Most common TRAEs* were elevations in creatine kinase (CK) and serum liver enzymes (without elevation in bilirubin) Believed to be secondary to cabira s depletion of Kupffer cells (macrophages); reported with other CSF-1R - targeting agents Isolated enzyme elevations were not associated with other clinical sequelae Grade 5 TRAEs** (3 of 229) at a frequency similar to monotherapy PD-1 inhibitors No Grade 5 events in pancreatic cohort Liver Metastases 58-year-old male: 3 prior chemo regimens Lung Metastases 63-year-old male: 4 prior chemo regimens * TRAEs treatment related adverse events ** Pneumonitis in a patient with thyroid cancer, and respiratory distress and acute respiratory distress in 2 patients with lung cancer 14

15 CSF-1R Blockade Reprograms the Tumor Microenvironment and Acts Synergistically with Anti-PD-1 to Shrink Tumors SEM) ORTHOTOPIC PANCREATIC CANCER MODEL Tumor Weight (mean g± p= p=0.03 IgG Anti- Anti- Anti-PD1 Combo CSF1R CSF1R (cabira) (cabira) + gemcitabine 15

16 BMS Advancing Randomized Phase 2 Trial of Cabiralizumab/Opdivo in 2 nd -Line Pancreatic Cancer (NCT ) Prior Line: Gemcitabine-Based Chemotherapy Trial Arms (2 nd -Line) Arm A: Investigator s Choice of Chemotherapy Gemcitabine/Abraxane or 5-FU/leucovorin/Onivyde Arm B: Cabiralizumab + Opdivo N ~160 patients Study Objectives Progression free survival (primary) Objective response rate and duration Prior Line: 5-Fluorouracil-Based Chemotherapy Arm C: Cabiralizumab + Opdivo combined with gemcitabine + Abraxane Arm D: Cabiralizumab + Opdivo combined with oxaliplatin/5-fu/leucovorin Overall survival rate Safety PK Dosing of the first patient initiated January 2018 Study will generate data that could support a front-line or second-line pivotal study 16

17 Attractive Market Opportunity: Unresectable or Metastatic Pancreatic Exocrine Cancer in Major Markets Incidence (2016) 1 US EU5* Japan First-line 45,950 52,130 32,240 Second-line 22,827 26,049 15,618 Sources: 1 - Decision Resources Group; Pancreatic Cancer Epidemiology Overview, August * - EU5 = France, Germany, Italy, Spain, UK 17

18 Advancing Cabiralizumab in Pigmented Villonodular Synovitis (PVNS) A CSF-1-driven locally aggressive tumor of the joint that causes pain and dysfunction Cabiralizumab depletes the macrophages that form the bulk of the tumor 14cm Preliminary Phase 2 data demonstrated efficacy with dosing every two weeks* Trial amended to optimize therapeutic index with dosing every four weeks Most AEs are irritating or cosmetic side effects (mainly eyelid edema) Data with new dosing schedule for this non-oncology disease will inform go/no go for pivotal trial *ASCO 2017 data presentation 18

19 % Change in Tumor from Baseline % Change in Tumor from Baseline Initial Phase 2 Data: Tumor Reductions in Most Patients at 4mg/kg* Dose-dependent responses observed in Phase 2 Most patients had tumor reductions at expansion dose Tolerable safety profile: most frequent AEs were asymptomatic CK elevation, periorbital edema, pruritis Dose-dependent response FPA008 Cohort: 1 mg/kg 2 mg/kg 4 mg/kg Last dose day of Last dose day of patients with PRs PR Study Days Most patients enrolled at the 4 mg/kg dose experienced tumor reduction * ASCO 2017 Sankhala et al. 19

20 Decreases in Pain and Functional Improvements Observed in Phase 2 Decreases in pain and Improvement in Median Ogilvie-Harris Composite Score Reported in Responders and Non-Responders improvement in function important to patients Improved performance of activities of daily living Lowered use of pain medication Preliminary Phase 2 data showed improvements in pain/function in both responders and nonresponders Before treatment * After 5 cabiralizumab doses at 4 mg/kg *29-year-old female with PVNS treated with cabiralizumab 20

21 Phase 2 Trial in PVNS to Inform Possible Pivotal Trial PHASE 2 Dose expansion 4mg/kg Q 2 weeks 30 patients Alternative Dosing Schedule to Improve Tolerability 4mg/kg ~ Q 4 weeks up to 30 patients Study Objectives Objective response Pain Functional improvement Completed Enrollment April 2017 Go/No Go on Pivotal Trial, 2H 2018 Range of motion Tolerability Preliminary Data Presented at ASCO June

22 PVNS is an Attractive Market Surgery is the most common treatment option and tumors often progress in patients with diffuse PVNS (D-PVNS) Estimated 2017 incidence and prevalence of D-PVNS based on Five Primesponsored Danish registry study 1 : Adult D-PVNS US EU5* Japan Incidence 2,000 2, Prevalence 28,200 28,100 11,200 Market research in the US indicates that up to 65% of prevalent D-PVNS patients would be eligible for treatment with an anti-csf1-r drug 2 1 Ehrenstein, et al. J Rheumatol, August FPRX Market Research of ~50 patients and physicians *EU5= France, Germany, Italy, Spain, UK 22

23 Bemarituzumab (FPA144) Targeted Immunotherapy for FGFR2b-Overexpressing Tumors

24 Bemarituzumab (FPA144) Was Designed to Recruit Tumor-Killing NK Cells into the Tumor Microenvironment Natural Killer Cell Enhanced ADCC to increase NK cell recruitment FPA144 FGFR2b FGF7, 10, 22 FPA144: antibody specific to FGFR2b splice variant Tumor Cell 24

25 Bemarituzumab Demonstrated Monotherapy Activity in Heavily Pre-treated Patients with FGFR2b+ Gastric Cancer* % Change in Tumor from Baseline Best % Change in Sum of Diameters from Baseline FGFR2b ORR = 19% DCR = 57.1% Safety: No DLTs during dose escalation (MTD not reached) 0-20 No grade 4 or higher treatmentrelated AEs Acceptable safety of bema and limited overlapping toxicities allows for chemo combination mg/kg 10 mg/kg 15 mg/kg * ASCO 2017 Catenacci et al 25

26 Strategic Decision to Pursue Front-line Bemarituzumab + Chemo Combo Trial Based on Compelling Rationale Tumor Volume (Mean mm 3 SEM) Heterogeneity of FGFR2b expression: bema + chemo more likely to kill FGFR2b low- and high-expressing cells Preclinical data show additive efficacy of bema + chemo OCUM-2 gastric cancer xenograft model Albumin FPA144 5FU/Cisplatin FPA144 +5FU/Cis Days Post Tumor Implantation 26

27 Phase 1/3 FIGHT Pivotal Trial of Bemarituzumab (FPA144) in Front-Line FGFR2b+ Gastric and GEJ Cancer Phase 1 Safety Lead in; any GI cancer Phase 3 Randomized; ~548 selected patients Study Endpoints FPA144 Dose Escalation + FOLFOX6 First patient dosed December 2017 Initiation expected mid-2018 FPA144 + FOLFOX6 vs Placebo + FOLFOX6 OS PFS ORR FGFR2b overexpression and FGFR2 gene amplification associated with poor prognosis Select biomarker-positive patients by IHC (tumor sample) or ctdna (blood-based) tests ~10% of patients expected to be biomarker-positive 27

28 Strategic Collaboration With Zai Lab for Bemarituzumab (FPA144) in Greater China $5 million upfront $39 million in development and regulatory milestone payments Royalty on net sales in Greater China in the high teens to low twenties percentages High incidence of gastric cancer in China ~700,000 new cases annually >40% of cases worldwide Exclusive license in Greater China Zai covers Phase 3 FIGHT trial costs in Greater China Collaboration will increase speed of FIGHT trial and lower Five Prime s global development costs FPRX Zai 28

29 Sizeable Market Opportunity for Bemarituzumab (FPA144) in the Front-Line Treatment of FGFR2b+ Gastric and GEJ Cancer Median PFS of FOLFOX alone in front-line gastric cancer treatment: 6-7 months 2 Estimated Incidence of Addressable Metastatic Gastric and GE Junction Adenocarcinoma Patients US 1 EU5* 1 Japan 1 (urban) China 1 st line patients 16,630 38,700 72, ,800 Unmet need: FGFR2b+ patients have significantly reduced survival Treatment eligible (10% FGFR2b+) 1,663 3,870 7,280 16,380 *EU5 = France, Germany, Italy, Spain, UK 1. Decision Resources Group, Market Forecast Assumptions Gastric Cancer, October ASCO

30 FPA150 Targeted Immunotherapy for B7H4-Overexpressing Tumors

31 FPA150: First-In-Class B7-H4 Antibody Designed for Two Mechanisms of Action Blocks a T cell checkpoint pathway expressed on tumor cells Engineered to have enhanced ADCC IND filed December 2017; FDA clearance to proceed with clinical development received in January 2018 FPA150 B7-H4 is expressed in multiple solid tumors, including breast and gynecologic cancers Triple Negative Breast Cancer Ovarian Cancer 31

32 FPA150 Phase 1 Clinical Trial Testing Monotherapy Against Selected B7-H4 Expressing Tumors PHASE 1a Dose escalation Any solid tumor Initiation expected in the first half of 2018 PHASE 1b Expansion; ~30 patients/cohort Breast Cancer Ovarian Cancer Endometrial Cancer Urothelial (Bladder) Cancer Additional cohorts TBD based on emerging data IHC assay to be used to select B7-H4 expressing tumors in Phase 1b Evaluating several I-O and chemo combination strategies to implement depending on Phase 1b monotherapy data Study Objectives Safety Objective response rate and duration Survival Baseline and on-treatment biopsies 32

33 Research and Preclinical Pipeline

34 FPT155: First-In-Class CD80-Fc Fusion Protein Engineered to Activate T cells Through Multiple Pathways Normal T cell activation via CD80 Antigen presenting cell CD80 CD28 T cell (+) signal FPT155 uses the binding interactions of soluble CD80 to: Block CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T cell activation Directly engage CD28 to further enhance its costimulatory activity (without super agonism) MHC TCR CD80 extracellular domain CD80 is a co-stimulatory molecule expressed on antigen presenting cells IND planned 2H18 Fc 34

35 Our Unique Platform Positions Us to Design New Drugs that Reprogram Immune Cells in the Tumor Microenvironment Immune Cell Immune Cell Extracellular Proteins Tumor Cell Discovering novel protein drugs Targeting key immune cells CD8 T cell TAM TReg Dendritic cell NK cell 35

36 IND Engine: Unique Platform Generating Novel Therapeutics Comprehensive Libraries of Extracellular Proteins Proprietary Screens Protein Therapeutics Secreted Factors Advanced Into Clinical Development cabiralizumab (anti-csf-1r) Cell-based Screens Antibodies FPA144 (anti-fgfr2b) FPA150 (anti-b7h4) Cell Surface Receptors/Ligands In Vivo Screens Soluble Receptors Ligand Traps Anti-TIM-3 Soluble Extracellular Domains Receptor-Ligand Matching FPT155 (T cell modulator) 36

37 2017 Results and Upcoming Milestones

38 Cash and Shares Outstanding Cash, cash equivalents & marketable securities, EOY 2017 Shares outstanding Net proceeds from recent follow-on public offering Estimated cash, cash equivalents & marketable securities, EOY 2018 FY 2018 estimated net cash used in operating activities $293 million 34.9 million as of February 20, 2018 $108 million* January 2018 ~ $250 million < $135 million * After deducting underwriting discounts and commissions and estimated offering expenses 38

39 Anticipated Five Prime News Flow and Milestones Cabiralizumab Pancreatic Cancer BMS enrolling randomized Phase 2 trial (2 nd -line pancreatic) combo with Opdivo and chemo Treating additional 35 late-line pancreatic patients with cabira+opdivo and complete biomarker analysis Cabira/Opdivo in Other Tumor Settings Completed Phase 1b enrollment YE17; anticipate program updates in 2H18 PVNS (Monotherapy) Enroll additional patients with flexible q4 week schedule; decide on pivotal trial by EOY18 Bemarituzumab (FPA144) Gastric/GEJ Cancer Complete Phase 1 portion of FIGHT chemo combo trial Initiate randomized, global Phase 3 portion mid-2018 Complete Japan Phase 1 trial in 2018 New Programs Initiate FPA150 (B7-H4 antibody) Phase 1 in 1H18 FPT155 (CD80-Fc) IND in 2H18 Anti-TIM-3 Phase 1 initiation 39

40 Thank you NASDAQ:FPRX