Corporate Overview. June 2017 NASDAQ:FPRX

Transcription

1 Corporate Overview June 2017 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 FivePrime'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 of certain diseases; (v) the timing of the filing of INDs; (vi) the timing of data disclosures; and (vii) our estimated 2017 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 FivePrime's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. 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 Our Unique Platform is Ideal for the Design of 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 3

4 Five Prime s Unique Platform Tests Nearly Every Extracellular Protein to Identify Protein Drugs and Antibody Targets Library of > 5700 Extracellular Proteins Soluble Extracellular Domains Secreted Factors Cell Surface Proteins 4

5 Oncology-Focused Pipeline with Multiple Clinical Candidates Program Cabiralizumab (FPA008) CSF-1R antibody Indications Lead selection Multiple tumor settings in combination with Opdivo Pigmented Villonodular Synovitis (PVNS) IND-enabling activities Phase 1 Phase 1b Phase 2 FPA144 FGFR2b antibody FP-1039 FGF ligand trap FPT155 CD80-Fc FPA154 Tetravalent GITR agonist antibody FPA150 B7-H4 antibody I-O antibody Gastric and bladder cancers Mesothelioma Multiple tumor settings Multiple tumor settings Multiple tumor settings Multiple tumor settings I-O antibody Multiple tumor settings 2016 Five Prime Therapeutics, Inc. All Rights Reserved 5

6 Cabiralizumab (FPA008) Antibody for Macrophage-Dependent Diseases

7 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

8 Rationale for Combination Therapy: TAMs and Checkpoints Inhibit T Cell-Mediated Killing Through Different Mechanisms TAM CD8 T Cell PD-1 TAMs produce factors that inhibit T cells CSF-1R PD-L1 PD-L1/PD-1 suppresses T cells Tumor Cell 8

9 CSF-1R Blockade Reprograms the Tumor Microenvironment and Acts Synergistically with Anti-PD-1 to Shrink Tumors ORTHOTOPIC PANCREATIC CANCER MODEL Tumor Weight (mean g± SEM) p= p=0.03 IgG Anti- Anti- Anti-PD1 Combo CSF1R CSF1R (FPA008) (FPA008) + gemcitabine Five Prime Data 9

10 Cabiralizumab/Opdivo Combination Trial in Multiple Tumor Settings Remains on Track PHASE 1a Exploring Multiple Dose Levels in Cancer Patients Initiated Sept 2015 Cabiralizumab Monotherapy Cabiralizumab + Opdivo Exploring Selected Tumor Settings at the Highest Dose Cabiralizumab Monotherapy Cabiralizumab + Opdivo N ~280 patients Study Objectives Safety PHASE 1b Cabiralizumab + Opdivo Initiated October 2016 LUNG (NSCLC) Anti-PD-1 Naïve LUNG (NSCLC) Anti-PD-1 Resistant HEAD & NECK PANCREATIC RENAL OVARIAN GLIOBLASTOMA Objective response rate and duration Survival Baseline and on-treatment biopsies to assess monotherapy and combination 10

11 Cabiralizumab in Pigmented Villonodular Synovitis (PVNS) A CSF-1-driven locally aggressive tumor of the joint that causes pain and dysfunction No approved therapies Cabiralizumab has orphan drug designation o ~25,000 patient prevalence in the U.S for the diffuse form Cabiralizumab depletes the macrophages that form the bulk of the tumor 14cm 11

12 Cabiralizumab: Current Five Prime-Sponsored Phase 2 Trial in PVNS Phase 2: ~ 30 patients Study Objectives Objective response Pain Initiated Phase 2 May 2016 Completed Enrollment April 2017 Range of motion 12

13 29-year-old Female with PVNS of Right Hand Demonstrating Dose-Related Clinical Improvement Before treatment After 5 cabiralizumab doses at 4 mg/kg

14 % Change in Tumor from Baseline % Change in Tumor from Baseline 5 of 11 PVNS Patients at the 4 mg/kg Dose Had a PR by MRI (4 Confirmed)* 80 Dose dependent response FPA008 Cohort: FPA008 1 mg/kg 2 mg/kg 4 mg/kg Most patients enrolled at the 4 mg/kg dose experienced tumor reduction Last dose day of Last dose day of patients with PR patients with PRs Study Days Dose Level FPA008 4 mg/kg In addition, pain/function improved in both responders and non-responders on Ogilvie-Harris score * ASCO 2017 Sankhala et al. 14

15 Preliminary Data Support Continued Development of Cabiralizumab in PVNS Efficacy: Demonstrated clinical benefit by MRI and pain and function Safety: Most frequent AEs (periorbital and eyelid edema, rash and pruritus) similar to other agents in this drug class o 3 out of 11 patients discontinued drug due to asymptomatic laboratory elevations of CK o Protocol amended for continued treatment with asymptomatic CK elevations: additional 21 patients enrolled at 4 mg/kg Future Plans: Assess recently enrolled 21 patients in current Phase 2 trial Plan for pivotal trial anticipated to begin in

16 FPA144 Targeted Immunotherapy for FGFR2b-Overexpressing Tumors

17 FPA144 Was Designed to Recruit Tumor-Killing NK Cells into the Tumor Microenvironment Natural Killer Cell Enhanced ADCC to increase NK cell recruitment FGF7, 10, 22 FPA144 FGFR2b FPA144: antibody specific to FGFR2b splice variant Tumor Cell 17

18 Overall Survival FGFR2b Overexpression and FGFR2 Gene Amplification are Associated With Poor Prognosis Overall Survival FGFR2 Gene Amplification (DNA) FGFR2b Protein Overexpression (IHC) FGFR2 non-amplified 6-8% with Amplified FGFR2 FGFR2-amplified FGFR2b IHC- (n=353) FGFR2b IHC+ (n=9) Follow-up (months) Follow-up (months) Jung et al. 2009; FGFR2 FISH; P=0.012 Pathobiology 2015; 82:

19 Ongoing Phase 1 Expansion Studies of FPA144 Monotherapy, 15 mg/kg every two weeks, FGFR2b+ by IHC Study Objectives Metastatic gastric or GEJ cancer up to 30 patients with high FGFR2b expression Metastatic bladder cancer up to 30 patients with FGFR2b expression Safety PK Objective response rate and duration 19

20 % Change in Tumor from Baseline FPA144 Demonstrates Monotherapy Activity in Heavily Pre-treated Patients with FGFR2b+ Gastric Cancer* Best % Change in Sum of Diameters from Baseline FGFR2b+ High number of prior therapies (Median = 3) Objective Response Rate: 19.0% (n=21) Disease Control Rate: 57.1% Median Duration of Response = 15.4 weeks FPA144 Dose Level 6 mg/kg 10 mg/kg 15 mg/kg Including patients enrolled into Part 2 (Cohort A), as well as 6 patients in Part 1B * ASCO 2017 Catenacci et al 20

21 Data Support Continued Development of FPA144 in Patients with FGFR2b+ Gastric Cancer Efficacy: Monotherapy responses compare favorably to approved targeted gastric cancer agents o FPA144: ORR 19% (median 4 th -line of therapy) o Ramucirumab: ORR 3.4% (2 nd -line of therapy) o Pembrolizumab: ORR: 6.4% (4 th -line of therapy); 11% (3 rd -line) Safety: FPA144 was well tolerated o No DLTs during dose escalation (MTD not reached) o No grade 4 or higher treatment-related AEs o No hyperphosphatemia or retinal toxicity Future Plans: Plan to initiate a FPA144 chemotherapy combination trial in front-line setting 21

22 Preclinical Data: FPA144 Has Additive Activity in Combination with Chemotherapy OCUM-2 gastric cancer xenograft model OCUM-2 gastric cancer xenograft model Tumor Volume (Mean mm 3 SEM) Albumin FPA144 5FU/Cisplatin FPA144 +5FU/Cis Days Post Tumor Implantation Albumin/Vehicle Paclitaxel/Albumin FPA144/Vehicle FPA144/Paclitaxel * From Abigael T. Gemo, et al., AACR, April

23 Pivotal Trial Planning for FPA144 for Front-Line Treatment of FGFR2b+ Gastric Cancer Seek regulatory guidance on a registration-enabling pivotal trial plan Likely a randomized, controlled trial: FOLFOX chemotherapy + placebo versus FOLFOX chemotherapy + FPA144 Eligible gastric cancer patients for FPA144 therapy can be identified by: 1. Tissue for FGFR2b protein overexpression by IHC (5%) 2. Blood for FGFR2 gene amplification by circulating DNA (additional 5%) Selecting patients using both methods increases eligible patient population to 10% of metastatic gastric cancer 23

24 FGFR2b in Urothelial Bladder Cancer (UBC) Ureter Screening (Day -5) Kidney Ureter Kidney FGFR2b overexpression in ~14% of metastatic bladder cancer FGF7 (ligand for FGFR2b) overexpression correlates with reduced survival Lymph LymphNode Node Ureter Lymph Lymph Node Lymph Node Node Node Cycle 8 Day 15 (Day 213) Kidney Ureter Lymph Lymph Node Node Kidney Patient with IHC+ bladder cancer in dose escalation had complete response; still on study > 2 years Enrolling FGFR2b-selected bladder cancer patients: o 4 patients enrolled to date o Too early to evaluate efficacy Lymph Node Lymph Node Lymph Node Lymph Node * ASCO 2017 Catenacci et al. 24

25 Research and Preclinical Pipeline

26 Advancing a Broad and Promising I-O Pipeline Discovery Programs Preclinical Programs Clinical Trials TReg cell screen CD8 T cell screen FPT155 (CD80-Fc) FPA154 (Anti-GITR) cabiralizumab (anti-csf-1r) FPA144 (anti-fgfr2b) Immunome x Immunome In vivo screens Single agent Combinations with PD1 blockers FPA150 (B7-H4) FP-1039 (FGF ligand trap) Three in IND-enabling studies First IND in 2017 Data read-outs in

27 FP150 A Therapeutic Candidate Antibody Targeting the B7-H4 Checkpoint Pathway

28 FPA150: Novel B7-H4 Antibody is Designed for Two Mechanisms of Action FPA150 Blocks a T cell checkpoint pathway Engineered to enhance ADCC against B7-H4-expressing tumor cells IND planned 4Q17 28

29 FPA154 A Novel, Multivalent Therapeutic Candidate Antibody Targeting GITR

30 FPA154 (anti-gitr): Increased Valency Leads to Stronger Activation Versus Conventional Antibodies Conventional Antibody Two GITR binding sites FPA154 Four GITR binding sites Fab variable domains Humanized sdab variable domains Human IgG1 Fc region Human IgG1 Fc region Designed for improved CD8 T cell agonistic activity with potent Treg depletion activity IND planned 4Q17 30

31 FPT155 A Soluble CD80-Fc That Modulates Multiple Signaling Pathways On T Cells

32 2016 Five Prime Therapeutics, Inc. All Rights Reserved Tumor Growth Volume % FPT155 (CD80-Fc) Was Originally Identified as One of the Most Potent Agonists in Our In Vivo Screen 400 CTLA4 300 Agonist hits Checkpoint hits CD80-Fc Individual Proteins Screened 32

33 FPT155 is a CD80-Fc Fusion Protein Engineered to Activate T cells Through Multiple Pathways Normal T cell activation via CD80 FPT155 uses the binding interactions of Soluble CD80 to modulate 3 pathways CD28 Activation (activates T cells without superagonism) CTLA4 Engagement PD-L1 Blockade CD80 is a co-stimulatory molecule expressed on antigen presenting cells 33

34 2016 Five Prime Therapeutics, Inc. All Rights Reserved The Murine Surrogate mfpt155 Has Potent Anti-Tumor Activity in Various Murine Tumor Models T u m o r V o lu m e (M e a n m m 3 S D ) T u m o r V o lu m e (M e a n m m 3 S D ) CT26 Tumor Growth MC38 Tumor Growth C T 2 6 T u m o r G r o w t h M C migg2 mfpt155 (0.3 mg/kg) migg2 mfpt155 (0.3 mg/kg) 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 34

35 mfpt155 Promotes Effector T Cell Recruitment into Tumors R a tio mfpt155 promotes T cell recruitment into CT26 tumors 3 days post-2nd dose at 0.3 mg/kg mfpt155 increases the ratio between effector T cells and T reg within CT26 tumors Tumor margin CD4 + T eff : T reg after 2 doses c o n vcc odn 4 v+ CT D : 4 T+ T r e: gt r e g CD8 + T : T reg after 2 doses C D 8 C+ DT 8 : + T r: e gt r e g **** **** *** * * Control R a tio 2 0 R a tio 2 0 R a tio 1C 5o0 n1 tro 5C0 l o n tro l C D 8 0C-F Dc 8 0 -F c Tumor margin FPT # d o s# e s d ore sce es ivre e dc e iv e d migg mfpt155 (0.3 mg/kg) # d o# s ed s o sre ecs ere ivce ed iv e d CD3 35

36 Summary of Cash and Cash Guidance CASH, CASH EQUIVALENTS & MARKETABLE SECURITIES $380.3 million as of March 31, 2017 FY 2017 ESTIMATED NET CASH USED IN OPERATIONS <$120 million ESTIMATED CASH, CASH EQUIVALENTS & MARKETABLE SECURITIES Estimate ending 2017 with approximately $300 million SHARES OUTSTANDING 28.6 million (as of March 31, 2017) 36

37 2017 News Flow and Anticipated Milestones Cabiralizumab Multiple I-O Tumor Settings Expect to complete Phase 1b (7 settings) enrollment 2H17 Plan to disclose initial clinical trial data in 2H17 PVNS (Monotherapy) Completed Phase 2 enrollment in April Seek regulatory agency guidance on 2018 pivotal trial FPA144 Gastric Cancer Seek regulatory agency guidance on pivotal front-line chemo combo trial Launch safety trial in Japan in 3Q17 FP-1039 Mesothelioma Plan to disclose updated clinical trial data at ESMO Research 2 IND filings planned by 4Q17; 1 IND on track for

38 Thank You NASDAQ:FPRX