Corporate Overview - Jefferies Prome... · p=0.03 0.0 0.5 1.0 1.5 2.0 t g ... diffuse form • Cabiralizumab ... • Safety: Most frequent AEs (periorbital and eyelid edema, rash

NASDAQ:FPRX

Corporate OverviewJune 2017

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 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.

Forward-Looking Statements Disclaimer

2© 2017 Five Prime Therapeutics, Inc. All Rights Reserved

• Discovering novel protein drugs

• Targeting key immune cells

3

Our Unique Platform is Ideal for the Design of New Drugs that Reprogram Immune Cells in the Tumor Microenvironment

© 2017 Five Prime Therapeutics, Inc. All Rights Reserved

Extracellular

Proteins

Tumor Cell

Immune CellImmune Cell

CD8 T cell TAM Dendritic cellTReg NK cell

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

Cell Surface

Proteins

Secreted

Factors


Oncology-Focused Pipeline with Multiple Clinical Candidates

5


Program IndicationsLead

selectionIND-enabling

activities Phase 1 Phase 1b Phase 2

Cabiralizumab

(FPA008)

CSF-1R antibody

FPA144FGFR2b antibody

FP-1039

FGF ligand trap

Multiple tumor settings in combination with Opdivo®

Pigmented Villonodular Synovitis (PVNS)

Gastric and bladder cancers

Mesothelioma

FPT155

CD80-Fc

FPA154

Tetravalent GITRagonist antibody

FPA150

B7-H4 antibody

I-O antibody

I-O antibody

Multiple tumor settings






Cabiralizumab (FPA008)Antibody for Macrophage-Dependent Diseases

7

Cabiralizumab, a Product of the Five Prime Platform Blocks Survival of Macrophages


CSF-1

Five Prime discovered IL-34,

one of the two ligands for CSF-

1R that cabiralizumab

(FPA008) blocks

Cabiralizumab (FPA008)

is an antibody to CSF-1R

IL-34

8

CD8 T Cell

Tumor Cell

PD-1

PD-L1

TAM

CSF-1R

PD-L1/PD-1

suppresses

T cells

TAMs produce

factors that

inhibit T cells


Rationale for Combination Therapy: TAMs and Checkpoints Inhibit T Cell-Mediated Killing Through Different Mechanisms

CSF-1R Blockade Reprograms the Tumor Microenvironment and Acts Synergistically with Anti-PD-1 to Shrink Tumors

Five Prime Data

ORTHOTOPIC PANCREATIC CANCER MODEL

+ gemcitabine

IgG Anti-PD1 Combo

p=0.0001

p=0.03

0.0

0.5

1.0

1.5

2.0

Tu

mo

r W

eig

ht

(mea

n g

±S

EM

)

9

Anti-

CSF1R

(FPA008)

Anti-

CSF1R

(FPA008)


Cabiralizumab/Opdivo® Combination Trial in Multiple Tumor Settings Remains on Track


PHASE 1b

Cabiralizumab

+ Opdivo®

Study ObjectivesCabiralizumabMonotherapy

N ~280 patients

Safety

Objective response

rate and duration

Survival

Baseline and

on-treatment

biopsies to assess

monotherapy

and combination

PANCREATIC

RENAL

OVARIAN

GLIOBLASTOMA

HEAD & NECK

LUNG (NSCLC)Anti-PD-1 Naïve

LUNG (NSCLC)Anti-PD-1 Resistant

Exploring Selected Tumor

Settings at the Highest Dose

PHASE 1a Exploring Multiple Dose

Levels in Cancer Patients

Initiated

October 2016

Initiated

Sept 2015

Cabiralizumab + Opdivo®

CabiralizumabMonotherapy

Cabiralizumab + Opdivo®

• 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

11

Cabiralizumab in Pigmented Villonodular Synovitis (PVNS)


14cm

Cabiralizumab: Current Five Prime-Sponsored Phase 2 Trial in PVNS

Objective response

Initiated Phase 2

May 2016

Phase 2: ~ 30 patients

Study Objectives

Range of motion

Pain

12

Completed Enrollment

April 2017


After 5 cabiralizumab

doses at 4 mg/kg

Before treatment

29-year-old Female with PVNS of Right Hand Demonstrating Dose-Related Clinical Improvement


5 of 11 PVNS Patients at the 4 mg/kg Dose Had a PR by MRI (4 Confirmed)*

Last dose day of

patients with PR

14

* ASCO 2017 Sankhala et al.

In addition, pain/function improved in both responders and non-responders on Ogilvie-Harris score

Most patients enrolled at the 4 mg/kg

dose experienced tumor reduction

Dose dependent response

80

20

-30

-80

% C

ha

ng

e in

Tu

mo

r fr

om

Ba

se

line

FPA008 Cohort:

FPA008 1 mg/kg

2 mg/kg

4 mg/kg

Study Days

0 100 200 300 400

0

-10

20

10

0

-20

-30

-40

-50

-60

-70

-80%

Ch

an

ge

in

Tu

mo

r fr

om

Ba

se

line

Dose Level FPA008 4 mg/kg

Last dose day of

patients with PRs


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 2018

FPA144Targeted Immunotherapy for FGFR2b-Overexpressing Tumors

FPA144 Was Designed to Recruit Tumor-Killing NK Cells into the Tumor Microenvironment


Enhanced ADCC to

increase NK cell

recruitment

FPA144: antibody

specific to FGFR2b

splice variant

Natural Killer Cell

Tumor Cell

FGFR2b

FPA144

FGF7, 10, 22

FGFR2b Overexpression and FGFR2 Gene Amplification are Associated With Poor Prognosis

18

6-8% with

Amplified

FGFR2

FGFR2 Gene Amplification (DNA) FGFR2b Protein Overexpression (IHC)

Follow-up (months)Follow-up (months)

1.6

0.8

1.0

1.4

0.2

0.0

0 20 40 60

Ove

rall

Su

rviv

al

Ove

rall

Su

rviv

al

1.6

0.8

1.0

1.4

0.2

0.0

0 20 40 60 80

Jung et al. 2009; FGFR2 FISH; P=0.012 Pathobiology 2015; 82:269-279

FGFR2 non-amplified

FGFR2-amplified

FGFR2b IHC- (n=353)

FGFR2b IHC+ (n=9)


Study Objectives

Safety

PK

Objective

response rate and

duration

Ongoing Phase 1 Expansion Studies of FPA144


Metastatic gastric or GEJ cancer –up to 30 patients with high FGFR2b expression

Metastatic bladder cancer –up to 30 patients with FGFR2b expression

Monotherapy, 15 mg/kg every two weeks, FGFR2b+ by IHC

20

FPA144 Demonstrates Monotherapy Activity in Heavily Pre-treated Patients with FGFR2b+ Gastric Cancer*


* ASCO 2017 Catenacci et al

• 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

Best % Change in Sum of Diameters

from Baseline FGFR2b+

0

20

40

-20

-40

-60

-80

% C

ha

nge in T

um

or

fro

m B

aselin

e

FPA144 Dose Level

Including patients enrolled into Part 2 (Cohort A), as well as 6 patients in Part 1B

6 mg/kg 10 mg/kg 15 mg/kg


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 4th-line of therapy)

o Ramucirumab: ORR 3.4% (2nd-line of therapy)

o Pembrolizumab: ORR: 6.4% (4th-line of therapy); 11% (3rd-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

22

Preclinical Data: FPA144 Has Additive Activity in Combination with Chemotherapy


* From Abigael T. Gemo, et al., AACR, April 2014

Albumin/Vehicle

Paclitaxel/Albumin

FPA144/Vehicle

FPA144/Paclitaxel

10 15 20 25 30 35 400

200

400

600

800

1000

1200

Albumin

FPA144

5FU/Cisplatin

FPA144 +5FU/Cis

Days Post Tumor Implantation

Tu

mo

r V

olu

me

(M

ean

mm

3

SE

M)

OCUM-2 gastric cancer xenograft model OCUM-2 gastric cancer xenograft model

• Seek regulatory guidance on a registration-enabling pivotal trial plan

• Likely a randomized, controlled trial:

23

Pivotal Trial Planning for FPA144 for Front-Line Treatment of FGFR2b+ Gastric Cancer


FOLFOX

chemotherapy

+

placebo

FOLFOX

chemotherapy

+

FPA144

versus

• 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


FGFR2b in Urothelial Bladder Cancer (UBC)

• FGFR2b overexpression in ~14%

of metastatic bladder cancer

• FGF7 (ligand for FGFR2b)

overexpression correlates with

reduced survival

• 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

Screening (Day -5)

Cycle 8 Day 15 (Day 213)

* ASCO 2017 Catenacci et al.

KidneyUreter

Lymph

NodeLymph

Node

KidneyUreter

Lymph

Node

Lymph

NodeLymph Node

Kidney Ureter

Lymph Node Lymph Node

Kidney Ureter

Lymph Node

Lymph Node

Kidney Ureter

Lymph Node Lymph Node

Kidney Ureter

Lymph Node

Research and Preclinical Pipeline

Advancing a Broad and Promising I-O Pipeline

26

CD8 Tcell screen

TRegcell screen

Immunome x Immunome

In vivo screens• Single agent

• Combinations

with PD1 blockers

Discovery Programs

cabiralizumab(anti-CSF-1R)

FPA144(anti-FGFR2b)

FP-1039 (FGF ligand trap)

Clinical Trials

Data read-outs in 2017

Preclinical Programs

Three in IND-enabling studies

First IND in 2017

FPA154(Anti-GITR)

FPT155(CD80-Fc)

FPA150(B7-H4)


FP150A Therapeutic Candidate Antibody Targeting the B7-H4

Checkpoint Pathway

28

FPA150: Novel B7-H4 Antibody is Designed for Two Mechanisms of Action

• Blocks a T cell

checkpoint pathway

• Engineered to enhance

ADCC against

B7-H4-expressing

tumor cells

FPA150


IND planned 4Q17

FPA154A Novel, Multivalent Therapeutic Candidate Antibody Targeting GITR

FPA154 (anti-GITR): Increased Valency Leads to Stronger Activation Versus Conventional Antibodies


Designed for improved CD8 T cell agonistic activity with potent Treg depletion activity

IND planned 4Q17

Conventional AntibodyTwo GITR binding sites

FPA154Four GITR binding sites

Human IgG1

Fc region

Human IgG1

Fc region

Fab variable

domains

Humanized

sdAb variable

domains

FPT155A Soluble CD80-Fc That Modulates Multiple Signaling Pathways On T Cells


32

FPT155 (CD80-Fc) Was Originally Identified as One of the Most Potent Agonists in Our In Vivo Screen

0

100

200

300

400

Individual Proteins Screened

Agonist hits Checkpoint hits

CD80-Fc

Tu

mo

r G

row

th

Vo

lum

e %

CTLA4


Normal T cell activation via CD80 FPT155 uses the binding interactions of Soluble CD80 to modulate 3 pathways


CD28Activation

(activates T cells without superagonism)

PD-L1Blockade

CTLA4

Engagement

CD80 is a co-stimulatory molecule

expressed on antigen presenting cells

FPT155 is a CD80-Fc Fusion Protein Engineered to Activate T cells Through Multiple Pathways


34

The Murine Surrogate mFPT155 Has Potent Anti-Tumor Activity in Various Murine Tumor Models

0 5 1 0 1 5 2 0 2 5

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

C T 2 6 T u m o r G r o w th

D a y s p o s t-in o c u la tio n

Tu

mo

r V

olu

me

(Me

an

mm

3

SD

)

0 5 1 0 1 5 2 0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

M C 3 8

D a y s p o s t-in o c u la tio n

Tu

mo

r V

olu

me

(Me

an

mm

3

SD

)

mIgG2

mFPT155 (0.3 mg/kg)

mIgG2

mFPT155 (0.3 mg/kg)

CT26 Tumor Growth MC38 Tumor Growth


35

mFPT155 Promotes Effector T Cell Recruitment into Tumors

Control

FPT155

Tumor

margin

Tumor

margin

mFPT155 promotes T cell recruitment

into CT26 tumors

3 days post-2nd dose at 0.3 mg/kg

CD3

mFPT155 increases the ratio between

effector T cells and Treg within CT26 tumors

CD4+ Teff : Treg

after 2 doses

CD8+ T : Treg

after 2 doses

mIgG

mFPT155 (0.3 mg/kg)

1 2 3

0

1 0

2 0

3 0

c o n v C D 4 + T : T r e g

# d o s e s re c e iv e d

Ra

tio

**** ***

C o n tro l

C D 8 0 -F c

1 2 3

0

1 0

2 0

3 0

c o n v C D 4 + T : T r e g


Ra

tio

**** ***

C o n tro l

C D 8 0 -F c

1 2 3

0

5 0

1 0 0

1 5 0

2 0 0

C D 8 + T : T r e g


Ra

tio

*

C o n tro l

C D 8 0 -F c

1 2 3

0

5 0

1 0 0

1 5 0

2 0 0

C D 8 + T : T r e g


Ra

tio

*

C o n tro l

C D 8 0 -F c


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

Summary of Cash and Cash Guidance


2017 News Flow and Anticipated Milestones

37

Research

Cabiralizumab

Multiple I-O Tumor Settings

FPA144 Gastric Cancer

FP-1039 Mesothelioma

Seek regulatory agency guidance on pivotal front-line chemo combo trial

2 IND filings planned by 4Q17;

1 IND on track for 2018

Plan to disclose updated

clinical trial data at ESMO

Expect to complete Phase 1b (7 settings) enrollment 2H17

Plan to disclose initial clinical

trial data in 2H17

Seek regulatory agency guidance on 2018 pivotal trial

Completed Phase 2

enrollment in April


Launch safety trial in Japan

in 3Q17

PVNS (Monotherapy)

NASDAQ:FPRX

Thank Youwww.fiveprime.com

Documents

Corporate Overview - Jefferies Prome... · p=0.03 0.0 0.5 1.0 1.5 2.0 t g ... diffuse form • Cabiralizumab ... • Safety: Most frequent AEs (periorbital and eyelid edema, rash