five prime therapeutics, inc. corporate overview prime.pdfcompetitive advantage in immuno-oncology...

© 2015 Five Prime Therapeutics, Inc. All Rights Reserved

June 2015

Five Prime Therapeutics, Inc. Corporate Overview

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 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 timing of receipt of clinical results for our product candidates; (iii) the potential use of our product candidates to treat patients; (iv) the extent of gene amplification and protein overexpression in certain patient populations; (v) the advancement of our immuno-oncology program; and (vi) the period during which we expect to be able to fund operations.

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.

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Investment Highlights

• 3 clinical-stage protein therapeutics covering 11 indications

• Competitive advantage in immuno-oncology • Unique discovery platform for novel targets and protein drugs

• Clinical and research collaborations with BMS

• Platform generates assets valued by pharma; strong track record of deal-making

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Platform: A Library of Substantially All Extracellular Proteins to Identify New Targets and Therapeutics

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Receptor-Ligand Matching

Antibodies to Novel Targets (Secreted Proteins

Or Receptors)

Soluble Receptors (Ligand Traps)

In vivo Screens

Soluble Receptors (Ligand Traps)

Cell Surface Receptors

Secreted Factors

Library of > 5700 Extracellular Proteins Proprietary Screens

Protein Therapeutics Cell-based Screens

In Vivo Screens


Many New IO Targets Remain to be Discovered in the Tumor Microenvironment

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The Five Prime Immunome: ~500 Cell Surface Receptors Enriched for Regulators of the Immune

Response to the Tumor

Tumor Cell

T Cell

Tumor Cell

Macrophage

PD-1

PDL-1

FPxx FPyy

The Five Prime Advantage: Functionally Screening the Entire Immunome

Receptor-Ligand Matching

In vivo Screens

Cell-based Screens

In Vivo Screens


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Our Current Focus: T Cells and TAMs Tumor-Associated Macrophages T Cell Checkpoints

• Identified multiple novel drug targets • Two pathways partnered with BMS • All other targets unpartnered

• Antibody work underway with Adimab, Vaccinex, and BMS

• FPA008 CSF1R antibody blocks TAMs • Based on our discovery of IL-34 • Phase 1a/1b with Opdivo® in H2:2015

• Future Expansion: Tregs, MDSC, and dendritic cells • Goal: 1 IND per year beginning 2017


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INDICATIONS PRE-IND PHASE 1 PHASE 1B

FPA008 CSF1R antibody

6 cancers in combination with Opdivo® (nivolumab)

PVNS

Rheumatoid Arthritis

FPA144 FGFR2b antibody Gastric Cancer

Partnered

FP-1039 (GSK 3052230) FGF ligand trap

Squamous NSCLC

Mesothelioma

Clinical Pipeline: 3 Protein Therapeutics Covering 11 Indications


FPA008 Antibody for Macrophage-Dependent Diseases

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FPA008 Blocks Activation and Survival of Macrophages by Blocking Ligand Binding to CSF-1R

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Survival Activation

FPA008

Macrophages/Monocytes/Osteoclasts

CSF-1

IL-34 (Discovered by

FivePrime) CSF-1R


CSF-1R Dependent Cells Play Pivotal Roles in Cancer, PVNS and Autoimmunity

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Inflammatory Macrophages, Osteoclasts

• Rheumatoid Arthritis

• Cancer (Immuno-Oncology)

Tumor-Associated Macrophages

Monocytes

• Pigmented Villonodular Synovitis (PVNS)

Macrophages in Joints

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&docid=0-6dt_ac1OltLM&tbnid=YAkBWQ3mtAXZsM:&ved=0CAUQjRw&url=http://www.rndsystems.com/ihc_molecule_images.aspx?m=3627&ei=aaVNU-_sGsqtyASJiIGYDQ&bvm=bv.64764171,d.aWc&psig=AFQjCNFxP27PE090-Pt8fUbfcYNHmrP3uQ&ust=1397683865567275


Immuno-Oncology: FPA008 Reduces TAMs

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F4/80 Staining for Macrophages in the MC38 Tumor Model

Tumor-associated macrophages (TAMs) • are immunosuppressive • correlate with poor prognosis • are associated with resistance to IO therapy • Depend on CSF-1R for survival

Mouse FPA008 Control


Strong Rationale for Combining Blockers of CSF-1R and PD-1

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CD8 T Cell

Tumor cell

CD8 T Cell

PD-1

TAM

PD-L1

nivolumab

TAM

CSF-1R

FPA008

PD-1

CSF-1R

PD-L1

Tumor cell Tumor killing

TAMs and PD-1 Activation Suppress Tumor Killing

TAM Reduction and PD-1 Inhibition Enhance Tumor Killing


CSF-1R Inhibition Synergizes with Checkpoint Inhibitors

13 Zhu et al., (2014) Cancer Research

Tumor regression

Pancreatic tumor model


FPA008 Activity Synergizes with Immune Agonists

Anti-CD40

Mouse FPA008

FGK45

Control Mouse FPA008 Anti-CD40 Combo

*

* p


FPA008 Clinical Program

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FPA008 Phase 1 Advancing

• Completed testing in healthy volunteers • No dose-limiting toxicities • All adverse events were grade 1 or 2 and reversible • Well tolerated up to 3 mg/kg • PK profile supports biweekly or less frequent dosing

• Advanced into open-label dosing in Rheumatoid Arthritis patients • Data will be presented before end of 2015

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FPA008 Caused Rapid and Sustained Reduction of Monocyte Biomarkers in Healthy Volunteers

• FPA008 selectively reduced CD16-positive monocytes -- cells associated with inflammation and cancer

• FPA008 also reduced bone turnover markers (osteoclast effect)

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0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 20

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6 0

8 0

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W e e k s

CD

16-

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ytes

per

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blo

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P la c e b oF P A 0 0 8 1 m g /k gF P A 0 0 8 3 m g /k gF P A 0 0 8 1 0 m g /k g

CD16-positive Monocytes After a Single Dose


FPA008 & Nivolumab Combination Trial in Six Cancers Expected to Begin Mid-2015

• Five Prime plans to conduct a Phase 1a/1b clinical trial • 1a: Dose escalation to assess safety and tolerability of the combination • 1b: Expand into six tumor settings to assess preliminary efficacy

*Approved indications for Opdivo® (nivolumab)

• Five Prime retains full ownership of FPA008

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Demonstrated nivolumab activity

Non-small cell lung cancer*

Melanoma*

Head & neck

Exploratory

Pancreatic cancer

Colorectal cancer

Malignant glioma


PVNS is a CSF-1-Driven Orphan Disease

• Rare, locally aggressive tumor of synovium • Over-expression of CSF-1 recruits macrophages

forming the tumor mass

• High morbidity

• No approved therapies • Phase 1/2 PVNS trial planned for mid-2015

• IND cleared April 2015 • Phase 1: Select optimal dose for Phase 2 • Phase 2: Assess tumor shrinkage, pain and joint

function

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FPA144 Antibody for Gastric Cancer

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FPA144: An Antibody to FGF Receptor 2b with Enhanced Cell Killing (ADCC) for Treating Gastric Cancer

• Recruits natural killer (NK) cells more effectively than native antibody

• Incorporates BioWa’s POTELLIGENT® glycoengineering technology

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Rationale for Targeting FGFR2b in Gastric Cancer • FGFR2 gene amplification occurs in ~5% of gastric cancer patients

• Additional patients may have tumors with FGFR2b protein overexpression without gene amplification

• Worldwide prevalence of gastric cancer: 1.5 million patients

• High unmet need: FGFR2 gene amplification or FGFR2b protein over-expression is associated with lower overall survival

• FPA144 is effective in preclinical models

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OCUM2 Gastric Cancer Xenograft


FPA144 Phase 1 Study Now Enrolling Patients

• Expect to begin dosing selected gastric cancer patients by EOY 2015 • If clinical activity seen in Phase 1, potential for accelerated development

(U.S. orphan drug) as monotherapy

• Potential future combination trial with front-line chemotherapy

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FISH-positive (~5%) Part 2:

SelectedGastric Cancer

Part 1A:Dose escalation in solid tumors; 3+3 design Safety,

Response Rate FISH-negative,

IHC-positive Part 1B: Unselected Gastric Cancer

Now

Expected EOY 2015


FP-1039 Ligand Trap for Cancer

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FP-1039 Selectively Blocks FGFR1 Ligands

• Selectively blocks cancer-promoting FGFs that bind to FGFR1, not unrelated FGFs

• FGFR1 amplification in sqNSCLC is associated with diminished survival

• Safe and well-tolerated as monotherapy in Phase 1; target engagement demonstrated

• Avoids retinal detachment, hyperphosphatemia, mucositis, nailbed changes and asthenia seen with small molecule TKIs Tumor cell growth

Tumor cell survival

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Cancer-Promoting FGFs

FP-1039

Tumor Cell

FGFR1


GSK-Funded Phase 1b Clinical Trial of FP-1039/GSK3052230 (Study FGF117360)

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Safety and

Tolerability in combination

with SOC

Dose/PK

Overall Response Rate

& Duration

Mesothelioma • 1st-line, cisplatin/pemetrexed

FGF2 ligand over-expression

Squamous NSCLC • 1st-line, paclitaxel/carboplatin • Previously treated, docetaxel

FGFR1 amplification (10-20%)

Global study enrolling 70 to 120 patients

GSK plans to report preliminary data by EOY 2015


Financial Highlights

• Expect cash runway to extend into 1H2018 • Past efficacy data readouts for all three clinical programs • Move one or more new immuno-oncology candidates into clinical trials

• $217 million cash as of March 31, 2015 • Guidance

• Expect 2015 net cash used in operating activities to be between $59 and $63 million

• Estimate ending 2015 with between $165 and $170 million in cash

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Expectations

FPA008 CSF1R antibody

FPA144 FGFR2b antibody

FP-1039 FGF ligand trap

Immuno-Oncology Research

Gastric Cancer Initial data from solid tumor & unselected gastric cancer patients by end of 2015

Squamous NSCLC & Mesothelioma

GSK to present preliminary efficacy data by end of 2015

Cancer Advance internal drug candidates to preclinical development

INDICATION EXPECTATIONS PROGRAM

6 Cancers Complete Phase 1a dose escalation & expand to Phase 1b by late 2015/early 2016

PVNS Initial data by late 2015 to early 2016

RA Present open-label RA data by end of 2015


Investment Highlights

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• 3 clinical-stage protein therapeutics covering 11 indications

• Competitive advantage in immuno-oncology • Unique discovery platform for novel targets and protein drugs

• Clinical and research collaborations with BMS

• Platform generates assets valued by pharma; strong track record of deal-making

Five Prime Therapeutics, Inc.�Corporate OverviewForward-Looking Statements DisclaimerInvestment Highlights�Platform: A Library of Substantially All Extracellular Proteins to Identify New Targets and TherapeuticsMany New IO Targets Remain to be Discovered in the Tumor MicroenvironmentOur Current Focus: T Cells and TAMsClinical Pipeline:�3 Protein Therapeutics Covering 11 IndicationsFPA008�Antibody for Macrophage-Dependent DiseasesFPA008 Blocks Activation and Survival of Macrophages by Blocking Ligand Binding to CSF-1RCSF-1R Dependent Cells Play Pivotal Roles in Cancer, PVNS and AutoimmunityImmuno-Oncology: FPA008 Reduces TAMsStrong Rationale for Combining Blockers of CSF-1R and PD-1CSF-1R Inhibition Synergizes with Checkpoint InhibitorsFPA008 Activity Synergizes with Immune AgonistsFPA008�Clinical ProgramFPA008 Phase 1 AdvancingFPA008 Caused Rapid and Sustained Reduction of Monocyte Biomarkers in Healthy VolunteersFPA008 & Nivolumab Combination Trial in Six Cancers Expected to Begin Mid-2015PVNS is a CSF-1-Driven Orphan Disease FPA144�Antibody for Gastric CancerFPA144: An Antibody to FGF Receptor 2b with Enhanced Cell Killing (ADCC) for Treating Gastric CancerRationale for Targeting FGFR2b in Gastric CancerFPA144 Phase 1 Study Now Enrolling PatientsFP-1039�Ligand Trap for CancerFP-1039 Selectively Blocks FGFR1 LigandsGSK-Funded Phase 1b Clinical Trial of �FP-1039/GSK3052230 (Study FGF117360)Financial HighlightsExpectationsInvestment Highlights

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