Corporate Overview. September 2018 NASDAQ:FPRX

Transcription

1 Corporate Overview September 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, including in combination with other products, to treat patients; (iii) the extent of protein overexpression and gene amplification in certain patient populations; (iv) the prevalence and incidence of certain diseases; (v) the timing of the filing of INDs or their foreign equivalents; (vi) Five Prime s full-year 2018 net cash used in operating activities; and (vii) the amount of Five Prime s cash, cash equivalents and marketable securities at the end of 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 Value Proposition Unique IND engine provides competitive advantage for discovery of I-O biologics Expanding pipeline transitioning into latestage development Value-creating collaborations; eligible to receive additional non-dilutive funding 3

4 The Five Prime Opportunity: Platform and Pipeline to Excel in Immuno-Oncology Clinical pipeline expanding from 2 to 5 candidates in 2018 Cabiralizumab CSF1R ANT IBO DY Phase 2 in 2 nd - line pancreatic Multiple Phase 1 trials in other tumors Bemarituzumab FGFR2B ANTIBODY FIGHT global Phase 3 trial in combo with chemo in 1 st -line gastric IND engine generating new leads FPA150 B7-H4 ANTIBODY Phase 1 trial Value-creating collaborations FPT155 CD80-FC Study Start up Phase 1 TIM-3 ANTIBODY Phase 1 trial 4

5 Oncology-Focused Pipeline with Multiple Clinical Candidates Program Collaborator Cabiralizumab (FPA008) CSF-1R ANTIBODY Pancreatic cancer (combination with OPDIVO and chemo) Multiple tumor settings (combination with OPDIVO ) Phase 1 Phase 2 Apexigen & Yale Cancer Center IST for APX005M (anti-cd40) + cabira + OPDIVO Phase 1 Pigmented villonodular synovitis (PVNS) Phase 2 Bemarituzumab (FPA144) ** FGFR2B ANTIBODY FPA150 B7-H4 ANTIBODY FIGHT Phase 1/3 trial (with chemo) in gastric/gej cancer Multiple tumor settings Phase 1/3 Phase 1a FPT155 CD80-FC Multiple tumor settings Pre-Phase 1 BMS TIM-3 ANTIBODY* Phase 1/2 trial in multiple tumor settings Phase 1 I-O antibodies * Multiple tumor settings Pre-IND Novel I-O biologics Multiple tumor settings Pre-IND * 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 10-K filed with the SEC on December 19, 2017 for a description of the collaboration arrangement with Zai. + Clinical development is being conducted exclusively by Apexigen and Yale Cancer Center. Clinical development is being conducted exclusively by BMS. 5

6 Cabiralizumab (FPA008) Antibody to Deplete Tumor Associated Macrophages (TAMs)

7 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 7

8 8 Cabira + Nivo Combination Positively Alters the Tumor Microenvironment CSF-1R and M2 (immunosuppressive) macrophages decreased in tumors of patients treated with combo * Change in expression of CSF-1R and macrophage marker (day 28) Protein Median change from baseline Patients with decrease from baseline CSF-1R 60% (P = ) 76% CD163 (M2 marker) 43% (P = 0.207) 59% Statistically significant increases in pro-inflammatory markers in patients who responded to treatment (data not shown) An increase in CD8+ effector cells *ASCO 2018 Data support further clinical development of cabiralizumab + nivolumab in multiple indications, including pancreatic cancer

9 Significant Unmet Need in Pancreatic Cancer: Current Regimens Have Shown Limited Clinical Benefit Average survival rate for patients with advanced pancreatic cancer % 1 YEAR 5 YEAR < 3% Onivyde (liposomal irinotecan) Onivyde/5-FU/Leucovorin 1 Phase 3 ORR 7.7% (Phase 2 ORR 7.5%) PFS 3.1 months OS 6.1 months Diarrhea, neutropenia, and stomatitis are common Grade 3/4 events 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 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;

10 Percent change in tumor burden (SLD) from baseline Durable Responses Observed in Late-Line Pancreatic Cancer* Best change in tumor burden over time in efficacy-evaluable patients treated with cabiralizumab 4 mg/kg + nivolumab 3 mg/kg (n=31) Progressive disease Treated beyond progressive disease Partial response Days Day Efficacy & Safety: Durable clinical benefit observed Confirmed ORR = 13% DCR = 16% Disease control: 5 to 9+ months Heavily pretreated population (average 3 prior therapies) All responders had microsatellite stable tumors (do not respond to PD1/L1 therapy) No new or additive safety signals identified Whole exome sequencing analysis demonstrated that nearly all patients had low TMB * SITC, November 2017 Wainberg Z, et al. 10

11 CSF-1R Blockade Reprograms the Tumor Microenvironment and Acts Synergistically with Anti-PD-1 to Shrink Tumors Tumor Weight (mean g± SEM) ORTHOTOPIC PANCREATIC CANCER MODEL 2.0 p= p= IgG Anti-CSF1R Anti-CSF1R Anti-PD1 Combo (cabira) (cabira) + gemcitabine >80% reduction vs. control Five Prime Data 11

12 BMS Trial: Randomized Phase 2 Trial of Cabiralizumab/OPDIVO in 2 nd -Line Pancreatic Cancer (NCT ) 1st Line: Gemcitabine-Based Chemotherapy Trial Arms (2 nd -Line) Arm A: Chemotherapy alone Gemcitabine/Abraxane or 5-FU/leucovorin/Onivyde Arm B: Cabiralizumab + OPDIVO Study Objectives N ~160 patients Progression free survival (primary) Objective response rate and duration 1st 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 initiated in January 2018 Study will generate data that could support a front-line or second-line pivotal study Sites in U.S., Asia and Europe 12

13 Attractive Market Opportunity: Unresectable or Metastatic Pancreatic 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 13

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

15 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 15

16 FGFR2 Gene Amplification Associated with Significantly Reduced Survival in Gastric Cancer Prospective observational data from 20 Japanese institutions from patients with advanced stage gastric cancer* FGFR2 Gene Amplification N 1-year OS 2-year OS Hazard Ratio Negative % 48.1% 1 Positive % 19.8% 1.9 ( ) *Yuki, et al ASCO 2018 The nationwide cancer genome screening project in Japan SCRUM-Japan GI-SCREEN: Efficient identification of cancer genome alterations in advanced gastric cancer (GC). 16

17 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 in FGFR2b+ Gastric Cancer ORR (confirmed) = 19% DCR = 57% Safety No DLTs during dose escalation (MTD not reached) No grade 4 or higher treatment-related 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 + confirmed response per RECIST 17

18 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 Bema Dose Escalation + FOLFOX6 First patient dosed December 2017 Initiation expected 3Q18 Phase 3 ~10% of patients expected to be biomarker-positive Randomized; ~548 selected patients Bema + FOLFOX6 vs Placebo + FOLFOX6 Study Endpoints 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 18

19 Attractive Market Opportunity for Bemarituzumab in Front-Line Treatment of FGFR2b+ Gastric and GEJ Cancer Estimated Addressable Metastatic Gastric and GE Junction Adenocarcinoma FGFR2b+ Patients 1, US EU Japan/Korea China Treatment eligible 2,840 15,310 13,425 47,400 ~80,000 patients annually Global pricing for recently launched biologics range ~$6,500 to >$14,000/month 1 Median PFS of FOLFOX alone in front-line gastric cancer treatment: 6-7 months 3 1) Internal estimates based on population, published incidence and recurrence rates and estimated treatment rates.. ZS Associates ) Kelly CM, Janjigian YY. J Gatrointest Oncol ) Yoon et al. J Clin Oncol Shah et al. JAMA Oncol Al-Batran SE et al. J Clin Oncol

20 FPA150 Targeted Immunotherapy for B7-H4-Overexpressing Tumors

21 B7-H4 is a T Cell Checkpoint Ligand Found on Tumors; FPA150 is an Antibody Engineered to Block the Checkpoint and Enhance ADCC FPA150 is designed to bind with NK cells to increase tumor cell killing Cell killing (+) FcgRIIIa B7-H4 Tumor Cell B7-H4 MHC TCR (+) (-) T Cell Inhibitory signal Cell killing FPA150 blocks B7-H4 from inhibiting T cells 21

22 B7-H4 is Expressed in Multiple Solid Tumors, Including Breast and Gynecologic Tumors Approximately half of patients with breast or gynecologic tumors are expected to express moderate to high levels of B7-H4 Very little expression on normal cells/tissue N e g a t i v e M o d e r a t e - H i ( ~ 6 0 % ) N e g a t i v e M o d e r a t e - H i ( ~ 5 0 % ) N e g a t i v e M o d e r a t e - H i ( ~ 5 0 % ) L o w L o w L o w T N B C O v a r i a n c a n c e r E n d o m e t r i a l c a n c e r 22

23 T u m o r V o l u m e ( m m 3 ) FPA150 has the Potential To Synergize with PD-(L)1 Blocking Agents 4T1-moB7-H4/H3 Breast Cancer Model * Day m s Ig G c m F P A F a n t i- P D - 1 C o m b o 23

24 FPA150: Phase 1 Clinical Trial to Look for Monotherapy Activity Against B7-H4 Expressing Tumors PHASE 1a Dose escalation Any solid tumor Phase 1 initiated March 2018 Basket B7-H4+ Tumors Exploratory cohort PHASE 1b Expansion; ~30 patients/cohort; B7-H4+ Breast Cancer Ovarian Cancer Endometrial Cancer Urothelial (Bladder) Cancer Additional cohorts TBD Study Objectives Safety Objective response rate and duration Survival Baseline and on-treatment biopsies IHC assay to select patients with B7-H4 expressing tumors in exploratory cohort and Phase 1b Evaluating I-O and chemo combination strategies depending on Phase 1b monotherapy data 24

25 FPA150: Opportunity to Address Large Patient Populations with High Unmet Medical Need Late-line Treatment Estimated Eligible Population 1 (Proportion estimated to be B7-H4+) US EU5 Japan TNBC 3L+ 5,170 5,230 2,000 HR+/HER2- Breast Hormone-refractory and 3L chemo+ Ovarian 2L+ platinum-resistant Endometrial 2L+ Estimated Addressable Patients and Unmet Need 45,800 49,560 14,200 10,740 10,970 3,730 Late-line data not available Bladder 3L+ 7,450 13,460 2,600 Historical mpfs 2 < 4 months Potential to expand to earlier lines of therapy in combination with standard of care (e.g., PD-(L)1 therapy, chemotherapy, PARP inhibitors) 1 Decision Resources Group 2018, 2 Twelves C, Breast Cancer: Basic and Clinical Research 2016, 3 Mutch DG, J Clin Oncol 2007, 4 Aghajanian C, J Clin Oncol 2011, 5 Powels T, Lancet

26 Research and Preclinical Pipeline

27 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 MHC TCR T cell (+) signal FPT155 uses the binding interactions of soluble CD80 to: Directly engage CD28 to enhance its co-stimulatory activity (without super agonism) Block CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T cell activation CD80 CD28 CD80 extracellular domain CD80 is a co-stimulatory molecule expressed on antigen presenting cells Human IgG1 Fc 27

28 The Murine Surrogate mfpt155 Can Induce Tumor Regressions at Low Doses as a Single Agent T u m o r V o lu m e (M e a n m m 3 S D ) CT26 Tumor Growth Ig G 2 a 0.9 m g /k g m F P T m g /k g (s in g le ) m F P T m g /k g (s in g le ) migg2 mcontrol F P T m g /k g (s in g le ) 0.1 mg/kg mfpt155 One m F P T m g /k g (s in g le ) 0.2 mg/kg mfpt155 administration 0.6 mg/kg m F PmFPT155 T m g /k g (3 d o s e s 0.9 mg/kg m F PmFPT155 T m g /k g (3 d o s e s 0.1 mg/kg mfpt155 Three 0.2 mg/kg m F PmFPT155 T m g /k g (3 d o s e s administrations 0.3 mg/kg mfpt D a y s p o s t-in o c u la tio n ** p < according to T test 28

29 T u m o r V o lu m e (m m 3 ) mfpt155 is Efficacious in Multiple Tumor Models, Including Those Typically Refractory to I-O Treatment P e rc e n t s u rv iv a l mfpt155 demonstrates monotherapy anti-tumor activity in MC38, EMT6, 4T1, and B16-F10 models B16-F10 Tumor Growth B16-F10 Survival D a y s p o s t-in o c u la tio n D a y s p o s t-in o c u la tio n D a y s p o s t-in o c u la tio n D a y s p o s t-in o c u la tio n migg2b control 10 mg/kg mfpt155 3 mg/kg anti-ctla4 10 mg/kg 29

30 mfpt155 Has Strong Synergistic Combination Activity with anti-pd1 migg2a CT26 Tumor Growth mfpt155 5/15 rejections anti-pd1 Combination 9/15 rejections 30

31 IND Engine: Unique Platform and Source of Competitive Advantage for Generating Novel Therapeutics Comprehensive Libraries of Extracellular Proteins Proprietary Screens Protein Therapeutics Advanced Into Clinical Development Secreted Factors Cell-based Screens Antibodies bemarituzumab (anti-fgfr2b) cabiralizumab (anti-csf-1r) Cell Surface Receptors/Ligands In Vivo Screens Soluble Receptors Ligand Traps FPA150 (anti-b7-h4) Soluble Extracellular Domains Receptor-Ligand Matching Anti-TIM-3 31

32 Cash, Guidance and 2018 News and Milestones

33 Cash and Shares Outstanding Cash, cash equivalents & marketable securities Shares outstanding Estimated cash, cash equivalents & marketable securities, EOY 2018 FY 2018 estimated net cash used in operating activities $352.8 million as of June 30, million as of June 30, 2018 ~ $250 million < $135 million 33

34 2018 Five Prime News Flow and Milestones Cabiralizumab PANCREATIC CANCER BMS initiated randomized Phase 2 trial (2 nd -line pancreatic) combo with OPDIVO+chemo Treating additional 35 late-line pancreatic patients with cabira+opdivo, complete biomarker analysis Pharmacodynamics and genomic profiling data abstract at ASCO 2018 CABIRA/OPDIVO IN OTHER TUMOR SETTINGS Completed Phase 1b enrollment YE17; anticipate program updates in 2H18 Bemarituzumab (FPA144) GASTRIC/GEJ CANCER Complete Phase 1 portion of FIGHT chemo combo trial Initiate randomized, global Phase 3 portion of FIGHT 2H18 Completed Japan Phase 1 trial FIGHT trial-in-progress abstract at ASCO 2018 PVNS (MONOTHERAPY) No go on pivotal trial with current schedule; continued efficacy, but high discontinuation rates FPA150 (B7-H4 Antibody) Initiated Phase 1 Oral Presentation at AACR 2018 New Programs Initiate FPT155 (CD80-Fc) Phase 1 trial in Australia in 2H18 Anti-TIM-3 Phase 1 initiated 34

35 Thank you NASDAQ:FPRX