Corporate Overview June 2018 NASDAQ:FPRX
Forward-Looking Statements Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. 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 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 estimated 2018 net cash used in operating activities and estimated year-end balance of cash, cash equivalents and marketable securities. 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
Five Prime in 2018 Value Proposition IND engine that is hard to copy and industry leading for discovery of I-O biologics Expanding pipeline transitioning into latestage development History of value-creating collaborations; eligible to receive additional non-dilutive funding 3
The Five Prime Opportunity: Platform and Pipeline to Power Immuno-Oncology Clinical pipeline expected to more than double from 2 to 5 candidates in 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 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
Oncology-Focused Pipeline with Multiple Clinical Candidates Program Collaborator Indications selection Lead Cabiralizumab (FPA008) * CSF-1R antibody Pancreatic cancer (combination with Opdivo and chemo) Multiple tumor settings (combination with Opdivo ) Multiple tumor settings in ADVISE trial (combination with Opdivo ) Pigmented villonodular synovitis (PVNS) IND-enabling Phase 1 activities Phase 1a Phase 1b Phase 2 Phase 3 Bemarituzumab (FPA144) ** FGFR2b antibody FPA150 B7-H4 antibody FPT155 CD80-Fc TIM-3 antibody * I-O antibodies * Novel I-O Biologics FIGHT Phase 1/3 trial (with chemo) in gastric/gej 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. Excludes investigator-sponsored trials. Clinical development is being conducted exclusively by BMS. 5
Cabiralizumab (FPA008) Antibody for Macrophage-Dependent Diseases
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 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 8
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) Completed enrollment Q1 2018 Lung (NSCLC) Lung (NSCLC) Anti-PD-1 Resistant Head & Neck Pancreatic Renal N ~295 patients Study Objectives Safety Objective response rate and duration Survival Baseline and on-treatment biopsies Ovarian Glioblastoma 9
Tumor Biopsies Demonstrate that Cabira + Nivo Combination Positively Alters the Tumor Microenvironment* CSF-1R and M2 (immunosuppressive) macrophages decreased in tumors of patients treated with cabiralizumab + nivolumab 1 Change in expression of CSF-1R and macrophage markers (day 28) a Protein Median change from baseline, % Patients with decrease from baseline, % CSF-1R 60 (P = 0.0089) 76 CD163 (M2 marker) 43 (P = 0.207) 59 a Increases > 200% from baseline were observed for CSF-1R (n = 5), CD163 (n = 7), and CD68 (n = 6) CD68 (M1 + M2 marker) 16 (P = 0.263) 60 Statistically significant increases in pro-inflammatory markers observed in patients who responded to treatment compared to patients who didn t respond 2 Combination also demonstrated an increase in CD8+ effector cells *ASCO 2018 Carleton et al 1 Tumor biopsies were from patients in all expansion cohorts from the Phase 1a/1b clinical trial, except the cohort of patients with glioblastoma multiforme. 2 Data not shown. 10
Significant Unmet Need in Pancreatic Cancer: Current Regimens Have Shown Limited Clinical Benefit Average survival rate for patients with advanced pancreatic cancer 3-5 16% < 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): 409 413; 3 Von Hoff DD et al. N Engl J Med 2013;369:1691 1703; 4 American Cancer Society. Pancreatic Cancer. www.cancer.org. Accessed November 3, 2017; 5 Foley K et al. Cancer Lett 2016;381;244-251. 11
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 CA19-9 12
Reductions in Metastatic Lesions and Tolerable Safety Profile Liver Metastases 58-year-old male: 3 prior chemo regimens Lung Metastases 63-year-old male: 4 prior chemo regimens 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 * 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 13
BMS Advancing Randomized Phase 2 Trial of Cabiralizumab/Opdivo in 2 nd -Line Pancreatic Cancer (NCT03336216) 1st 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: Cabira + Opdivo N ~160 patients Study Objectives Progression free survival (primary) Objective response rate and duration 1st Line: 5-FU-Based Chemotherapy Arm C: Cabira + Opdivo + gemcitabine + Abraxane Arm D: Cabira + Opdivo + FOLFOX 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 14
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 Preliminary Phase 2 data demonstrated efficacy with dosing every two weeks, but many patients did not tolerate chronic dosing* Trial amended to optimize therapeutic index with dosing every four weeks 14cm *ASCO 2017 data presentation 15
% 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 80 20 0-30 -80 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 0 100 200 300 400 Study Days - 10 20 10 0-10 -20-30 -40-50 -60-70 -80 Most patients enrolled at the 4 mg/kg dose experienced tumor reduction * ASCO 2017 Sankhala et al. 16
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 17
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 2017 18
Bemarituzumab (FPA144) Targeted Immunotherapy for FGFR2b-Overexpressing Tumors
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 20
Bemarituzumab Demonstrated Monotherapy Activity in Heavily Pre-treated Patients with FGFR2b+ Gastric Cancer* % Change in Tumor from Baseline 40 20 0-20 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 -40-60 -80 + + + + Acceptable safety of bema and limited overlapping toxicities allows for chemo combination 6 mg/kg 10 mg/kg 15 mg/kg * ASCO 2017 Catenacci et al + confirmed response per RECIST 21
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 2H18 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 22
FPA150 Targeted Immunotherapy for B7H4-Overexpressing Tumors
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 Phase 1 initiated March 2018 FPA150 B7-H4 is expressed in multiple solid tumors, including breast and gynecologic cancers Triple Negative Breast Cancer Ovarian Cancer 24
FPA150 Phase 1 Clinical Trial Testing Monotherapy Against Selected B7-H4 Expressing Tumors PHASE 1a Dose escalation Any solid tumor Phase 1a initiated March 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 25
Research and Preclinical Pipeline
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: 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 MHC TCR CD80 extracellular domain CD80 is a co-stimulatory molecule expressed on antigen presenting cells IND or equivalent planned 2H18 Fc 27
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 bemarituzumab (anti-fgfr2b) Cell Surface Receptors/Ligands In Vivo Screens Soluble Receptors Ligand Traps FPA150 (anti-b7h4) Anti-TIM-3 Soluble Extracellular Domains Receptor-Ligand Matching 28
Cash, Guidance and 2018 News and Milestones
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 $389.4 million as of March 31, 2018 34.3 million as of March 31, 2018 ~ $250 million < $135 million 30
2018 Five Prime News Flow and Milestones Cabiralizumab Pancreatic Cancer BMS initiated 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 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 PVNS (Monotherapy) Enrolling additional patients with flexible q4 week schedule; decide on pivotal trial by EOY18 FPA150 (B7-H4 Antibody) Initiated Phase 1 March 2018 Oral Presentation at AACR 2018 New Programs Bemarituzumab (FPA144) Gastric/GEJ Cancer Complete Phase 1 portion of FIGHT chemo combo trial Initiate randomized, global Phase 3 portion 2H18 Completed enrollment in Japan Phase 1 trial FIGHT trial-in-progress abstract at ASCO 2018 FPT155 (CD80-Fc) IND or equivalent in 2H18 Anti-TIM-3 Phase 1 initiated 31
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