Supercharging Immunotherapy - Hookipa Pharma · HB-201 - Clinical Study Design (Study H-200-001) To...

1©2019 HOOKIPA Pharma Inc.

Supercharging Immunotherapy

January 2019


HOOKIPA is a Differentiated, Clinical Stage Immunotherapy Company

Strong Talent Pool

PEOPLEPLATFORM

Two Technologies Using

Proprietary Arenavirus

Develop Broad Portfolio of Products for Diseases

With Significant Unmet Medical Need

STRATEGY

VaxWave®

Replication-deficient

TheraT®

Replication-attenuatedCo-founders

Prof Daniel Pinschewer,Prof Rolf Zinkernagel

(Nobel laureate)

Infectious Diseases

CMV Vaccine in Ph2; HIV and HBV therapeutics

($400m+ partnership with Gilead)

Immuno-oncology

Viral antigens,

Self-antigens, and

Shared next-gen antigens

International Team 65 people

New York City and Vienna


Key Investment Highlights

Platform with RobustT cell Potency

Universal Approach Targeting Large Markets

Platform De-Risked;CMV Phase 2 POC Ongoing

Potential as Cancer Mono-and Combination Therapy

“Off-the shelf” in vivo approach Competes with TCR / ACT potency Well-tolerated, no cytokine release syndrome

Prophylactic and therapeutic applications Application in infectious diseases and cancers

Clinically supported antibody and T cell immunity Safety comparable to placebo Response duration of over 12 months

Strong preclinical tumor control in metastatic setting, no relapse upon tumor re-challenge (memory)

Independent of route of administration, i.v. or intra-tumoral Checkpoint inhibitors synergistic, ultimate combination is

using two different arenaviruses (heterologous)


What Makes Our Platform Unique?

The Arenavirus family has for decades been the workhorse for immunologists to induce robust, antigen-specific, CD8+ effector T cells

Arenaviruses target Dendritic cells in-vivo

o Reprogram the body’s immune system

o In contrast to cell therapies, no complicated ex-vivo logistics

o Access solid tumors

Repeat administrations without induction of vector-neutralizing antibodies, no adjuvants

Very safe, most natural way of treating serious diseases

Arenaviruses naturally induce robust CD8+ T cell AND antibody responses Broad Patent Portfolio

expected to cover the entire Arenavirus family*

including LCMV(Lymphocytic Choriomeningitis Virus)

and PICV (Pichinde Virus)

* Refers to arenavirus that are replication deficient. Attenuated patents are pending.


In-vivo Dendritic Cell Targeting Technology, Can Be “Tuned” To Make > 50% Of All CD8+ T Cells Antigen-specific

Prophylaxis/ID IndicationsTherapeutic/Oncology Indications

% Antigen Specific CD8 T Cells

0,1

1

10

100

B16F10(Melanoma)

P815 (Self-Antigen)

TC1 CMV HepB HPVMelanoma Masto- HPV+ CMV HepB HPVcytoma

(B16F10) (P815) (TC1)Self-Antigens

Therapeutic Immuno-Oncology Prophyl. Infectious Dis.


Our Pipeline

Preclinical Phase 2Phase 1 Phase 3Antigen

gB/pp65

Undisclosed

Undisclosed

E6/E7

E6/E7

PSA/PSMA/PAP

Shared Next-Gen Antigen

Target

CMV

HBV

HIV

HPV16+

Cancer

HPV16+

Cancer

Prostate Cancer

Undisclosed

Imm

uno-O

ncolo

gy

Infe

ctious D

iseases

P2 enrollment commenced

Q4 2018 POC Q1/2020

Anticipated Milestones

IND Q3/2019Data Q3 / 2020

IND Q1/2020Data Q4/2020

* HB-202 to combine LCMV and PICV Arenaviruses for optimal T cell response

Compound

HB-101 (VaxWave®)

HBV Therapy

HIV Therapy

HB-201 (TheraT® LCMV)

HB-301 (TheraT®)

HB-6xx

HB-202* (TheraT® PICV)

GlobalRights

Development Stage

Infectious Diseases

Clinical Data and Validating Partnership


HB-101 To Prevent Cytomegalovirus (CMV) Infection,A Widely Acknowledged Unmet Medical Need

• CMV

o Leading cause of birth defects, risk for organ transplant patients

o Organ transplant market > $ 400 m

• No functioning prophylactic CMV vaccine exists

o Standard of care: antivirals – sub-optimal treatment

o Ideal prophylaxis requires T-cell and antibody immunity

• HB-101 is a bivalent vaccine generating antigen-specific T-cells (pp65) and antibodies (gB)

o Strong protection demonstrated in guinea pigs

o Phase 1 confirmed all elements of target product profile

o Placebo-controlled Phase 2 proof-of-concept trial in 150 organ transplant patients ongoing

Bivalent Construct

pp65 T cell

Antigen

gBB cell

Antigen


HB-101 - Ph1 CMV Trial: Dose-Escalating, Randomized, Placebo-Controlled, Double-Blind, Finalized With 12 Month Follow-up

• 54 healthy, CMV-negative,male and female adults, 18-45 years

• Three cohorts of 18 subjects per cohort

o 14 vaccine

o 4 placebo

• Dose-escalation by cohort

o Cohort 1: 2.6x106 FFU



• Three administrations (month 0, 1, and 3)

• Endpoints safety and T cell and antibody immunogenicity reached

Randomized (N=54)

Cohort 1(N=18)

Cohort 2(N=18)

Cohort 3(N=18)

N=18

N=18

N=18 N=18

N=18

N=18

N=18

N=18 N=18

N=18 N=18 N=18

Adm 3

Month 4

Adm 1

Adm 2


HB-101 - Ph1 CMV Trial: Potent And Durable T Cell Responses, Potentially Superior To Adoptive Cell Therapy

Strong T cell Response• Increasing with dose• Increasing with every

boost (black arrows)• Durable >12 months

C D 8 /IF N g p p 6 5

0 2 4 6 8 1 0 1 2 1 4

0 .0

0 .1

0 .2

0 .3

0 .4

P la c e b o

C o h -2

C o h -3

C o h -1

m o n th s

Me

an

%IF

Ng

+ C

D8

T-c

ell

s (

+-S

EM

)

H C M V p p 6 5 E L I S P O T

0 2 4 6 8 1 0 1 2 1 4

0

1 0 0

2 0 0

3 0 0

4 0 0

5 0 0

P l a c e b o

C o h - 1

C o h - 2

C o h - 3

m o n t h s

Me

an

S

FC

/

1

0

6

P

BM

C

(+

-S

EM

) Placebo

Low dose

Medium dose

High dose

Placebo

Low dose

Medium dose

High dose

Bivalent Construct

pp65 T cell

Antigen

gBB cell

Antigen

Neuenhahn et al., Leukemia 2017

Curative T-cell frequencies (measured by CMV-spec. CD8+ IFNg+ T cells) induced by Adoptive Cell Therapy appear to be inferior to frequencies achieved by HB-101

Viral Load CMV-spec. CD8+ T cells CMV-spec. CD8+ IFNg+ T cells


No meaningful vector-neutralizing antibodies

T-cell responses superior to previous vaccines and Adoptive Cell Therapy**/***

B-cell and T-cell induction

B-cell responses comparable, but more durable than previous vaccines*/***

Well-tolerated safety profile

HB-101 - Ph1 CMV Trial: All Aspects Of Target Product Profile In Humans Confirmed

HB-101 CMV Vaccine

* CMV-specific neutralizing antibodies competitive with Sanofi gB/MF59 vaccine, which demonstrated efficacy** Substantial CD8 and CD4 T cell responses to gB and pp65 at a magnitude shown to correlate with protection in adoptive cell transfer (ACT)*** Separately designed trials conducted by third parties; we have not conducted head to head analysis; if we were to conduct head to head trials, results may differ materially


HB-101 - Ph2 CMV Trial Ongoing

HB-101 CMV Ph2 Solid Organ Transplant Patients

Patient Population Live Donor Kidney Transplant patients, high risk of CMV viremia, (i.e. CMV negative recipients and CMV positive donors)

Subjects • 150, randomized 2:1 transplant vs placebo• Treated pre-transplant• Stratified by post-transplant treatment intent

o Pre-emptive antiviral therapy (50 subjects)o 6 months prophylactic antiviral therapy (100 subjects)

Endpoints • Primary: Immunogenicity and Safety• Secondary: reduction of viremia rate (Goal > 50%), decreased

use of antivirals

Outcome Full phase 2 trial enabling start of pivotal phase 3 trial


Important Collaboration with Gilead Further Validates Our Platform and Technology Capabilities

Scope

o HBV and HIV therapeutics

o Investment of $50m in research project

• To develop 30 research grade VaxWave® andTheraT® vectors

• GMP manufacture

• Extensive testing in various animal species

o Clinical development and commercialization by Gilead

Terms

o $10m up-front

o R&D expense fully reimbursed by Gilead

o $400m in milestones

o With potential for up to double digit royalties


Immuno Oncology

Clinical Validation of Strong Preclinical Profile in 2019/20


TheraT® - Tumor Infiltration by Cytotoxic T Cells Beats Adeno5, Turning “Cold” Tumors “Hot”

Tumor

TheraT-TAA

Untreated rAd-OVA TheraT®-GFP TheraT®-OVA

Lymph Nodes/

Dendritic Cells

Antigen-specific

CD8 T cell activation

CD8 T cells migratefrom DCs to tumor

• TheraT® always targets lymph nodes, Dendritic Cells

• Activate T cells in an antigen specific manner

• Sets off Alarminpathway, which boosts T cell effect

• Leads to stronger tumor infiltration


TheraT® - Complete Responder Mice Exhibit Long Term Protection Against HPV+ (E7E6) Tumor Re-Challenge (HB-201)

Strong tumor control in a metastatic setting

o 40% of mice completely cured for up to 150 days

Approach appropriate for treatment of

o Metastatic disease

o Primary disease and subsequent prevention of recurrence

TC1 Challenge

LCM

V-T

her

aTE7

E6P

ICV

-Th

eraT

E7E6

The

raT

®(L

CM

V)

E7E6

Surv

ival

Rat

e

Ther

aT®

(PIC

V)

E7E6

Surv

ival

Rat

e


TheraT® - Elimination Of Primary Tumor And Metastasis In Melanoma Self-Antigen Model

• In B16F10 metastatic melanoma model, a single systemic injection of TheraT®

(Trp2 self antigen) can “cure” mice, eliminating primary tumor and metastasis

o Agnostic to the injection site of TheraT® (i.m., i.v., or intra-tumoral)

o Potential to turn tumors hot by intravenous or intra-tumoral injections


• Viral Antigens

o Biologically highly validated

o HB-201 and HB-202 for HPV+ tumors

• Self Antigens

o Requires outstanding T cell potency to break tolerance

o HB-301 for Prostate Cancer targeting PAP, PSA, PSMA

• Next-generation antigens

o “Shared” full-length transcript antigens

o In collaboration with Darwin Health

Self AGs

Viral AGs

Next Gen AGs

Target Antigen Strategy - From Viral To Self To Shared Next Generation Antigens

Pote

nti

al

Risk


HB-201 - HPV+ Cancer Pre-IND Package: Dose Dependent Tumor Control, Correlating With Immunogenicity

0 5 10 15 20 250

200

400

600

800

10001000

1500

2000

Tumor Volume

Days post treatment

Tu

mo

r V

olu

me [

mm

3]

Buffer

1E+03 RCV FFU

1E+04 RCV FFU

1E+05 RCV FFU

1E+06 RCV FFU

1E+02 RCV FFU

Tumor Control-Dose

buffer

Immunogenicity-Dose

buffer 102

103

105

0

1

2

3

4

5 H

PV

16

E7

+ (

% o

f C

D8

+B

22

0-)

*

**

**

TheraT(cl13/WE)-E7E6


HB-201 - Clinical Study Design (Study H-200-001) To Validate i.v. And Intra-tumoral Applications In HPV+ Tumors

** First dose HB-201 Intratumoral (IT), subsequent doses IV

• HB-201 dose escalation

o IV application in HPV+ Head & Neck Squamous Cell Carcinoma (H&NSCC)

o Intratumoral application in other HPV+ cancers (cervical, anal, penile, etc.)

• HB-201 dose expansion

o Arm 1: IV for metastatic tumor, 3rd line

o Arm 2: IV combination with Nivo for 2nd line

o Arm 3: Intratumoral

• HB-202 follows similar design

Recommended Phase 2 Dose Decision

Phase 2 Dose EXPANSIONPhase 1 Dose Escalation

Group 1: (n=20)

Group 2: (n=20)

• HPV 16+ HNSCC

• IV-IV-IV…

• HPV 16+ with cancer accessible for IT injection

• IT-IV-IV… **

Arm 1: (n=20)

Arm 2: (n=20)

• IV-IV-IV…

• Metastatic/3rd Line

• IV-IV-IV… + PD-(L)

• 2nd Line

Arm 3: (n=20)

• IT-IV-IV… **

• HPV 16+ with cancer accessible for IT injection


TC1 TheraT Homologous versus Heterologous Boost

• Heterologous prime / boost focuses booster effect on „shared antigen“

P8

15

mo

de

l(M

asto

cyto

ma)

Mice re-challenged with tumor after beingpreviously cured by treatment withTheraT(PICV)-TheraT(LCMV)-E7E6

Mice challenged with tumor for the first time.

Mice re-challenged with tumor after beingpreviously cured by treatment withTheraT(PICV)-TheraT(LCMV)-P1A

Mice challenged with tumor for the first time.

TC-1

mo

de

l(H

PV

+ca

nce

r)


HB-202 & HB-201 Combination Study Design (Trial H-200-002) Heterologous Prime-Boost To Prove Optimum Tumor Control

Recommended Phase 2 Dose Decision

• *HB-202 and HB-201 will be given as IV in a sequential alternating manner. HB-202 will be administered first, and HB-201 will be given several weeks later

• **The first dose will be HB-201 given as Intratumoral (IT) injection. Subsequent dose will be HB-202 and then HB-201 given as IV in a sequential alternating manner

Phase 2 Dose EXPANSIONPhase 1 Dose Escalation

Group 1: (n=20)

Group 2: (n=20)

• HPV 16+ HNSCC

• IV-IV-IV…

• HPV 16+ with Can accessible for IT injection

• IT-IV-IV…

Arm 1: (n=20)

Arm 2: (n=20)

• IV-IV-IV…

• Metastatic/3rd Line

• IV-IV-IV… + PD-(L)

• 2nd Line

Arm 3: (n=20)

• IT-IV-IV…

• HPV 16+ with Can accessible for IT injection


• Viral Antigens

o Biologically highly validated

o HB-201 and HB-202 for HPV+ tumors

• Self Antigens

o Requires outstanding T cell potency to break tolerance

o HB-301 for Prostate Cancer targeting PAP, PSA, PSMA

• Next-generation antigens

o “Shared” full-length transcript antigens

o In collaboration with Darwin Health

Self AGs

Viral AGs

Next Gen AGs

Target Antigen Strategy - From Viral To Self To Shared Next Generation Antigens

Risk

Pote

nti

al


Strong Science, Investors, Leadership

Delivering on our promises


Well Funded By Top Tier Healthcare And Corporate Investors

Financing History

• $ 105m raised to date

• Series C $ 59.4m 12/2017

• Series B $ 36.1m

• Series A $ 9.5m

• $ 8.4m R&D loans from

government agencies

• 30 September 2018

cash balance: $ 55.8m

Key Financial Data

in $ 000'

Full Year

2017

Nine Months

2018

Revenue from collaboration & licensing — 2 549

R&D expenses (9 772) (17 350)

G&A expenses (4 385) (4 175)

Net loss (12 723) (14 345)

Cash and cash equivalents 61 362 55 792

Total assets 73 732 66 543

Total liabilities (11 614) (19 875)

Equity and convertible preferred stock (62 118) (46 668)


Top Tier Leadership and Investor Base

Undisclosed U.S. public

life sciences fund

Jan van de Winkel

Chairman

President, CEO &Co-founder of Genmab A/S

Igor Matushansky (MD, PhD)

Global Head of R&D,

Chief Medical OfficerPrevious:• Daiichi Sankyo, Gl. HeadTransl.

Development Oncology• Novartis Oncology, Cell / Gene Th.• Columbia University Medical Center• Memorial Sloan Kettering CC

Daniel Pinschewer (MD) Founder,

Chief Scientific Officer

University Basel, Professor of Virology

Previous:• University of Geneva, Medical School,

Associate Professor Immunology

Jörn Aldag

Chief Executive OfficerPrevious:• uniQure NV, CEO• Evotec AG (EVTG), CEO• G7 Therapeutics, Co-founder• Molecular Partners,ChairmanBoard: UNUM Therapeutics

Reinhard Kandera (PhD)

Chief Financial Officer

Previous:• Valneva SE,CFO• Intercell AG,CFO

World Class Management Team

Board with Immense Biotech Expertise

• Paul-Henri Lambert (Prof. Emeritus University of Geneva, Center of Vaccinology)

• Christoph Lengauer (Celsius Therapeutics, Blueprint Medicines, Venture Partner at Third Rock Ventures)

• Julie O'Neill (Formerly, EVP Global Operations at Alexion Pharma)

• Graziano Seghezzi (Sofinnova Partners)

• Sander Van Deventer (Forbion Capital Partners)

Investors


Major R&D Milestones 2019 - 2021

Year Qu Infectious Diseases Immune Oncology

2019 Q2/3 HB201 HPV+ Cancer Ph 1/2 IND Granted

Q3/4

Q4/1 Gilead pre-clinical milestone (HBV/HIV)

2020 Q1/2 HB101 CMV Ph 2 Pre-emptive & Prophylactic: Primary Endpoint Safety/Reactogenicity

HB201+HB202 HPV+ Cancer Ph 1/2 IND Granted

Q2/3 HB101 CMV Ph 2 Pre-emptive: Preliminary Secondary Endpoint 3mo efficacy post transplant

Q3/4 HB201 HPV+ Cancer Ph 1 IV First 3 Cohorts Data=PoC

Q4/1 Gilead pre-clinical milestone (HBV/HIV) HB201 HPV+ Cancer Ph 1 IT First 3 Cohorts Data=PoCHB300 Prostate Cancer IND Granted

2021 Q1-4 HB101 CMV Ph 2 Pre-emptive & Prophylactic: Final Secondary Endpoint 12M efficacy post transplantGilead pre-clinical milestone (HBV/HIV)

HB201 HPV+ Cancer Ph 1 IV Primary Endpoint and RP2DHB201 HPV+ Cancer Ph 1 IT Primary Endpoint and RP2DHB201+HB202 HPV+ Cancer Ph 1 IV First 3 Cohorts Data=PoCHB201+HB202 HPV+ Cancer Ph 1 IT First 3 Cohorts Data=PoC

RP2D - (First) Response Phase II Dose; PoC - Proof of Concept; IV - Intravenous application; IT - Intertumoral application)


Key Investment Highlights

Platform with RobustT cell Potency

Universal Approach Targeting Large Markets

Platform De-Risked;CMV Phase 2 POC Ongoing

Potential as Cancer Mono-and Combination Therapy

“Off-the shelf” in vivo approach Competes with TCR / ACT potency Well-tolerated, no cytokine release syndrome

Prophylactic and therapeutic applications Application in infectious diseases and cancers

Clinically supported antibody and T cell immunity Safety comparable to placebo Response duration of over 12 months

Strong preclinical tumor control in metastatic setting, no relapse upon tumor re-challenge (memory)

Independent of route of administration, i.v. or intra-tumoral Checkpoint inhibitors synergistic, ultimate combination is

using two different arenaviruses (heterologous)


Supercharging Immunotherapy

www.hookipapharma.com

Supercharging Immunotherapy - Hookipa Pharma · HB-201 - Clinical Study Design (Study H-200-001) To...

Documents

Transcript of Supercharging Immunotherapy - Hookipa Pharma · HB-201 - Clinical Study Design (Study H-200-001) To...