Supercharging Immunotherapy

1©2019 HOOKIPA Pharma Inc.

Supercharging Immunotherapy

March 2019


Why We Do, What We Do

Many diseases

exist or persist due to

“underperformance”

of the immune system

Immunotherapies must be sufficiently

potent to prevent or cure these

diseases

Sufficient potency of immunotherapies

must not compromise safety

Immunotherapies must be amenable

for broad use and not excessively

burden the health care system

Our TheraT® and VaxWave®

technologies are designed with a

goal to achieve all the above

1

2

3

4


Our Reengineered Arenaviruses Are Designed To Reprogram The Immune System To Prevent Or Cure Infections And Cancer

Designed to effectively, safely,

and affordably combat infectious

diseases and cancer

Unique mode of action potentially leading to

cell therapy-like potency, with a well-tolerated

profile

Potent, durable T cell and antibody

responses; no meaningful vector-neutralizing

antibodies

Off-the-shelf, directly in-patient, systemic

and agnostic to route of administration

(intramuscular, intravenous, intratumoral)

Potential for easier and cost efficient

manufacturing


We Are An Experienced, International Team With A Proven Track Record Of Building Biotech Companies

Joern Aldag

CEO

uniQure, Evotec

Molecular Partners, G7, Unum

Daniel Pinschewer, MD

Founder and CSO

University of Basel, CH

Professor of Virology

Igor Matushansky, MD, PhD

CMO / Global Head of R&D

Daiichi Sankyo, Novartis Oncology

Columbia, Memorial Sloan Kettering

Reinhard Kandera, PhD

CFO

Valneva, Intercell

Leadership

Michael A. Kelly (Former SVP at Amgen)

Paul-Henri Lambert (Prof. Em. University of Geneva, Center of

Vaccinology)

Christoph Lengauer (Celsius Therapeutics, Blueprint Medicines,

Third Rock Ventures)

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

Graziano Seghezzi (Sofinnova Partners)

Sander Van Deventer (uniQure, Forbion Capital Partners)

Jan van de Winkel, PhD

Chairman of the Board

Founder & CEO Genmab

Board of Directors

International Multidisciplinary Team

73 people

New York City, Vienna


Our Platform, Strategy, And Finances –A Strong Basis To Deliver On Our Goals

Platform Strategy Investors

1 VaxWave® and TheraT® registered in Europe; pending in the US2 Refers to VaxWave® vector design; patents for TheraT ® vector design are pending

To improve the life of patients by

developing and commercializing

a new class of ‘‘off-the-shelf’’

immunotherapies to prevent

and treat infectious diseases

and cancer

• Phase 2 CMV program in solid

organ transplant recipients

• HIV, HBV therapeutics

(Gilead partnership $400m+)

• Cancer therapies based on viral

(HPV+), self (prostate), and

shared next-generation antigens

Two technologies using our proprietary arenavirus platform

VaxWave® 1

Replication-deficient

TheraT® 1

Replication-attenuated

Arenavirus family widely patented2

UNDISCLOSED U.S. PUBLIC LIFE

SCIENCES FUND

SironaCapital


Building Blocks Of Our Strategy

Patient

Proof of Concept

Exploit Platform

• Expand target space to self-and shared next-generation antigens

• Expand immuno-oncology pipeline

• Deliver on Gilead partnership

• Build manufacturing in-house

Market Proprietary

Therapeutics

• VaxWave®: CMV Prophylaxis • Solid organ transplant patients • Phase 2 POC

• TheraT®: HPV+ cancers• Phase 1 safety and efficacy • Monotherapy• Combination therapy

Checkpoint Inhibitors Two different arenaviruses

administered sequentially

• Retain attractive commercial rights to products

• Build and scale-up regulatory and commercial presence in key markets


Our Pipeline

Preclinical Phase 2Phase 1 Phase 3Antigen

gB/pp65

Undisclosed

Undisclosed

E6/E7

E6/E7

PSA/PSMA/

PAP

Target

CMV

HBV

HIV

HPV16+

Cancer

HPV16+

Cancer

Prostate

CancerImm

uno

-Oncolo

gy

Infe

ctious D

iseases Preliminary data

Q2/Q3 2020

Anticipated

Milestones

IND Q2/Q3 2019

Data late 2020/

early 2021

IND H1 2020

Data 2021

Compound

HB-101 (VaxWave®)

HB-400

Therapy

HB-500

Therapy

HB-201

(TheraT® LCMV)

HB-301 (TheraT®)

HB-202 (TheraT® PICV/

TheraT® LCMV)

Global

Rights

Development Stage


Platform


Arenaviruses: Harnessing Exceptional Viral Power To Drive Potent CD8+ T Cell Responses

The arenavirus LCMV was used by HOOKIPA co-founder

Prof. Rolf Zinkernagel for his Nobel Prize-winning research and

discoveries regarding the role of the MHC-complex in T cell immunity

HOOKIPA co-founder Daniel Pinschewer reengineered the arenavirus

LCMV to redirect the exceptionally potent T cell response of this virus

against cancer and infectious disease-specific antigens

VaxWave®

Replication-deficient

TheraT®

Replication-attenuated

Arenavirus genomes are reengineered as vectors

Broad HOOKIPA

Patent Estate

covers the entire

Arenavirus family1

Flatz et al. nature medicine 2010

1 Refers to replication-deficient arenaviruses; patents for replication-attenuated are pending


Arenavirus Technologies Can Be “Titrated” To Trigger >50% Antigen-Specific CD8+ T Cells

TheraT® superior potency compared to other technologies

Note: Comparison in mice of TheraT® (LCMV) and TheraT® (LCMV - PICV) heterologous prime-boost vs modified vaccinia virus Ankara (MVA), and recombinant Adenovirus 5-based (rAd5) vectors,

each expressing the E7 antigen, for their ability to induce E7-specific CD8+ T cells

MV

A 1

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era

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-Te

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lls

(%

)


TheraT® Supercharges The Immune System: Superior CD8+ T Cell Quantity And Quality

TheraT® induces Tox1 in CD8+ T cells,

rendering them checkpoint insensitive

TheraT® triggers alarmin (interleukin-33)

release, potentiating CD8+ T cell proliferation


Arenavirus-based Therapies Are Simple “Off-the-shelf” For Direct In-patient Use


Key Differentiating Features of HOOKIPA’s Arenavirus Platform

Arenaviruses: work horse of immunologists for decades

• Naturally target and activate dendritic cells (DCs) No complex ex-vivo logistics required

Entirely self-adjuvanted

• Reprogram the body’s immune system Robust, durable CD8 T cell responses

Potent, durable antibody responses against pathogens

• “Glycan shield”: No meaningful vector-neutralizing antibodies Allows for efficient repeat administration

• Proven to be well-tolerated in humans Phase 1 CMV trial: very limited adverse events, notably no cytokine release syndrome

Use of wildtype LCMV in patients to led to flu-like symptoms only1

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

M e d iu m D o s e

H ig h D o s e

L o w D o s e

m o n ths

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an

%IF

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+ C

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ell

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)

Flatz et al. Nature Medicine 2010

1 Webb et al Clinical Oncology 1975


Infectious Diseases


HB-101 To Address Significant Unmet Medical Need In Cytomegalovirus (CMV) Infections

• Liquid formulations of

VaxWave® gB vector

(B cell antigen)

VaxWave® pp65 vector

(T cell antigen)

• Activates both arms of adaptive immune system

Induces neutralizing antibodies to gB

Induces T cells against pp65

• Intra-muscular administration

• Prevalence, incidence

60% of US population1, up to 99% in less

industrialized regions latently infected

110k patients added p.a. to organ

transplant list in key relevant countries2

• No licensed prophylactic CMV vaccine exists

• CMV risks and symptoms in transplant

patients

Infection and/or re-activation

Fever, pneumonitis, colitis, hepatitis,

retinitis, ultimately transplant rejection or

death

• CMV congenital infection is a significant

further unmet medical need

CMV Unmet Medical Need Our Solution: HB-101

1 CDC Cytomegalovirus (CMV) and Congenital CMV Infectionhttps://www.cdc.gov/cmv/index.html; 2 US, EU, Canada, Australia, Japan


H C M V g B E L IS A

0 2 0 4 0 6 0

1 0

1 0 0

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P la c e b o

L o w D o s e

M e d iu m D o s e

H ig h D o s e

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)

Trial design: 54 healthy, CMV-negative adults; 3 administrations (month 0, 1, 3; as shown by on x-axis below); 3 doses (2.6x106, 2.6x107, 2.6x108 FFU), placebo-controlled

Results: Robust CD8+ and CD4+ Tcell andCMV-neutralizing antibody responses;nomeaningfulvector-neutralizing antibodies, well-tolerated

HB-101 – Phase 1 Trial Completed: Well-Tolerated, Potent and Durable T Cell Responses

H ig h D o s eL o w D o s e

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Dose dependent, durable pp65 specific CD8+ T cells following 3 injections of HB-101

HB-101 – Strong Antigen-specific T Cell Immunogenicity Demonstrated In Phase 1 Clinical Trial

H B -1 0 1 P h a s e 1 im m u n o g e n ic ity

0 4 0 8 0 1 2 0 1 6 0 2 0 0 2 4 0 2 8 0 3 2 0 3 6 0

0 .0

0 .1

0 .2

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M e d iu m D o s e

H ig h D o s e

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D a y s a fte r firs t v a c c in a tio n

CM

V s

pe

cif

ic C

D8

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ell

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Third Party Adoptive Cell Therapy Trial Demonstrated pp65-Specific T Cell Levels Which Were Therapeutic/Curative

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

Neuenhahn et al., Leukemia 2017

pp65-specific CD8+ T cells isolated from CMV+ donortransferred to patients with active CMV viremia were curative1

1 The results presented on this slide have been derived from publicly available reports of clinical trials run independently by third parties. We have not performed any head-to-head trials

comparing any of these other therapeutic approaches with HB-101. As such, the results of these other clinical trials may not be comparable to clinical results for HB-101. The design of

these other trials vary in material ways from the design of the clinical trials for HB-101.


HB-101 – Phase 2 CMV Trial Ongoing In Solid Organ Transplantation

HB-101 CMV Ph2 Solid Organ Transplant Patients

Patient Population

Subjects

Endpoints

Read-out

Live donor kidney transplant patients, high risk of CMV viremia, (i.e. CMV negative recipients and CMV positive donors)

• 150, randomized 2:1 study drug vs placebo

• Treated pre-transplant

• Stratified by post-transplant treatment intent Pre-emptive antiviral therapy (50 subjects)

6 months prophylactic antiviral therapy (100 subjects)

• Primary: immunogenicity and safety

• Secondary: reduction of viremia rate (Goal > 50%),

decreased use of antivirals

• Q1/Q2 2020: Primary endpoint safety/reactogenicity

• Q2/Q3 2020: Preliminary 3M efficacy post transplant (pre-emptive)

• 2021: Final 12M efficacy post transplant (pre-emptive & prophylactic)


Immuno Oncology


• TheraT® targets lymph nodes, dendritic cells; activates T cells in an antigen-specific manner

• Sets off IL-33 pathway, which leads to increased proliferation of T cells

• Leads to greater tumor infiltration

TheraT® Turning “Cold” Tumors “Hot”-Tumor Infiltration by Cytotoxic T Cells Stronger Than rAD1

Tumor

TheraT ® -TAA

CD8 T cells migrate from lymph nodes to tumor

Antigen-specific CD8 T cell activation

Lymph Nodes/ Dendritic Cells

Untreated rAd-OVA TheraT®-

GFP (irrel)

TheraT®-

OVA

1 Recombinant Adenovirus

ource: Kallert, S. et al. Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy; NATURE COMMUNICATIONS | 8:15327 | DOI:10.1038/ncomms15327, 9 (2017)


0 1 2 4 6 82 0 2 2 2 4 2 6 2 8 3 0 3 9 4 3 4 5 4 7 5 3 6 0

0

5 0 0

1 0 0 0

1 5 0 0

D a y s a fte r s e c o n d a ry c h a lle n g e

Tu

mo

r v

olu

me

(m

m3

)

* *

0 5 0 1 0 0 1 5 0 2 0 0

0

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6 0

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D a y s

Pe

rce

nt

su

rviv

al

(%)

T h e r a T®

(P IC V ) E 7 E 6 IV

T h e r a T®

(P IC V ) E 7 E 6 IT

B u ffe r c o n tro l IT

* * * *P < 0 .0 0 0 1

Single Applications Of TheraT® Show Potent Effect In Controlling Tumors And Prevents Rechallenge (HPV+ Cancer (TC1))

TC-1 model (HPV+ cancer)Intratumoral (IT)

Re-challenge

Strong tumor control in a metastatic setting

• 40% of mice cured1 for up to 150 days

Approach appropriate for treatment of

• Metastatic disease

• Primary disease and subsequent prevention of recurrence

Intravenous (IV)

0 5 0 1 0 0 1 5 0

0

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6 0

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1 0 0

D a y s

Pe

rce

nt

su

rviv

al

(%)

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T h e r a T®

(L C M V )-E 7 E 6 IV

T h e r a T®

(L C M V )-E 7 E 6 IT

B u ffe r IT

Mice rechallenged with tumor after being

previously cured1 by treatment with TheraT®

(LCMV) intratumoral

Mice rechallenged with tumor after being

previously cured1 by treatment with TheraT®

(PICV) intravenous

Mice challenged with tumor for the first time

D180

D140

1 Defined as complete remission without recurrence for at least six months.


• Direct correlation

between dose and

immunogenicity


between dose and

efficacy


between

immunogenicity and

efficacy

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

HB-201 Dose

HP

V s

pecific

(%

of to

tal)

low medium highbuffer

5

4

3

2

1

0

0 5 1 0 1 5 2 0 2 5

0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

D a y s p o s t tre a tm e n t

Tu

mo

r V

olu

me

[m

m3

]

B u ffe r

M e d iu m D o s e

H ig h D o s e

L o w D o s e1 5 0 0

2 0 0 0

Immunogenicity-Dose Tumor Control-Dose (Efficacy)


HB-201 – Clinical Study Design (Study H-200-001) To Validate Intravenous And Intratumoral Applications In HPV+ Tumors

Phase 2 Dose EXPANSIONPhase 1 Dose ESCALATION

Intratumoral application in other HPV+

cancers (cervical, anal, penile, etc.)1

Intravenous application in HPV+ H&NSCC

for metastatic tumor, 3rd line

Intravenous application in HPV+ H&NSCC

combination with Nivo for 2nd line

Intratumoral application in

other HPV+ cancers1

Intravenous application in HPV+ Head &

Neck Squamous Cell Carcinoma (H&NSCC)Arm 1:

(n=20)

Arm 2:

(n=20)

Arm 3:

(n=20)

Group 1:

(n=20)

Group 2:

(n=20)

1 First dose HB-201 into cancer accessible for intratumoral injection, subsequent doses intravenous

H2 2019:

Phase 1/2 IND

granted

H2 2020:

Group 1, first 3 cohorts

efficacy=PoC

Q4 2020/Q1 2021:


efficacy=PoC


0 2 0 4 0 6 0 8 0 1 0 0 1 2 0

0

5 0

1 0 0

1 4 0 1 6 0 1 8 0

T im e a fte r tu m o r c e ll e n g ra ftm e n t (d a y s )

Pe

rce

nt

su

rviv

al

(%)

T he raT®

(P IC V )-T h e ra T®

(L C M V )

B u ffe r

T he raT®

(P IC V )-T h e ra T®

(P IC V )

T he raT®

(L C M V )-T h e ra T®

(L C M V )

1

Under More Aggressive Conditions - Only Sequential Administration Of TheraT® (PICV) & TheraT® (LCMV) Increased Anti-Tumor Activity And Survival

TC-1 model (HPV+ cancer)

D120: Re-

challenged with

tumor cells

• Sequential

administration of

TheraT® (PICV) and

TheraT® (LCMV) is

more potent than

either one alone

• Re-challenging long

term survivors with

more tumor results in

no additional tumor

growth

In pre-clinical trials, a sequential administration of two arenaviruses is superior to repeated administration of either one alone in elimination of large tumor and protection from subsequent tumor re-challenge

1 One additional animal euthanized due to open tumor.


Phase 2 Dose EXPANSION

HB-202 & HB-201 Sequential Administration Study Design (Trial H-200-002) To Prove Optimum Tumor Control

The first dose will be HB-201 given as

intratumoral injection. Subsequent dose will be

HB-202 and then HB-201 given as intravenous

in a sequential alternating manner

HB-202 and HB-201 will be given as

intravenous in a sequential alternating manner.

HB-202 will be administered first, and HB-201

will be given several weeks later

Arm 1:

(n=20)

Arm 2:

(n=20)

Arm 3:

(n=20)

Group 1:

(n=20)

Group 2:

(n=20)

Intravenous application in HPV 16+

for metastatic tumor for 3rd Line

Intravenous application in HPV 16+ tumors,

combo with PD-L(1) for 2nd Line

Intratumoral and intravenous application in

HPV 16+ cancers accessible for

intratumoral injection

Phase 1 Dose ESCALATION

H1 2020:

Phase 1/2 IND

granted

2021:


efficacy=PoC

2021:


efficacy=PoC


• Single systemic TheraT® injection can lead to complete remission w/o recurrence for at least 6 months,

eliminating both primary tumor and lung metastasis

• Agnostic to the injection site (sub-cutaneous, intravenous, or intratumoral)

• Potential to turn tumors hot by intravenous or intratumoral injections

• Antigen specific “abscopal-like” mechanism

Efficacy in Melanoma Model Demonstrates Potential In Metastatic Disease by Targeting Melanoma Self-Antigen

Day 1:

Tumor cells

Day 4:

Tumor cells

DAY

17:

Day 1:

Tumor cells

Day 4:

Tumor cells

Day 7:

TheraT® (LCMV)1

In collaboration

with Lukas Flatz,

Kantonspital St. Gallen

TheraT® treatedUntreated

1 Intratumoral treatment leads to a 40% cure rate on main tumor (complete remission until end of observation period (100 days))


Key Financials, Investment Highlights


HOOKIPA Manufacturing – High Degree Of Validation And Clear Production Network Strategy

Clinical Manufacturing

OrganizationsDedicated CMO Production

Suite

Production Network

Strategy

Manufacturing collaboration

to access dedicated

manufacturing suite

• Partner Valneva Sweden

• Analytical services, develop

process scale-up, produce GMP

clinical trial material of VaxWave® &

TheraT® vectors

• Ring-fenced space and

human resources

VaxWave®

• Process developed & transferred

to Sigma Aldrich

• Phase 1/2 CMV material

manufactured successfully

TheraT®

• Process developed & transferred

to ABL and IDT

• Tox lots, engineering runs

successfully completed

HOOKIPA-controlled

manufacturing facility &

outsourcing

• Strategic review underway with a

goal to determine the mix of

proprietary and out-sourced

manufacturing


Executing on Financial Strategy To Support Pipeline Progression

Key Financial Data

in $ million 2017 2018

Revenue from collaboration & licensing – 7.6

R&D expenses (9.8) (22.0)

G&A expenses (4.4) (6.9)

Net loss (12.7) (16.2)

Cash and cash equivalents 61.4 48.6

Total assets 73.7 68.3

Total liabilities 11.6 23.9

Equity and convertible preferred stock 62.1 44.4

Financing History

• $ 142.5m raised to date

Series D $ 37.4m (Feb. 2019)

Series C $ 59.4m

Series B $ 36.1m

Series A $ 9.5m

• $ 8.3m R&D loans from

government agencies

• 31 December 2018

cash balance: $ 48.6m


Investment Highlights

Unique arenavirus MoA

potentially leads to cell therapy-like potency,

well tolerated safety profile

Strong leadership, board and investor

syndicate

Universal off-the shelf approach for

B- and T-cell immunity targeting large markets

Phase 2 POC CMV trial ongoing

Arenavirus technology capable of

reprogramming the immune system to

potentially prevent or cure many infectious

diseases and cancers


Supercharging Immunotherapy

www.hookipapharma.com

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Supercharging Immunotherapy