supercharging immunotherapy
TRANSCRIPT
2©2019 HOOKIPA Pharma Inc.
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
3©2019 HOOKIPA Pharma Inc.
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
4©2019 HOOKIPA Pharma Inc.
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
5©2019 HOOKIPA Pharma Inc.
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
6©2019 HOOKIPA Pharma Inc.
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
7©2019 HOOKIPA Pharma Inc.
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
9©2019 HOOKIPA Pharma Inc.
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
10©2019 HOOKIPA Pharma Inc.
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
09
rAd
5 1
09
Th
era
T
® - (L
CM
V)
107
Th
era
T
® - (P
ICV
)/
Th
era
T
® - (L
CM
V)
0
2
4
6
1 0
2 0
3 0
4 0
5 0
6 0
E7
-Te
t+ C
D8
T
ce
lls
(%
)
11©2019 HOOKIPA Pharma Inc.
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
12©2019 HOOKIPA Pharma Inc.
Arenavirus-based Therapies Are Simple “Off-the-shelf” For Direct In-patient Use
13©2019 HOOKIPA Pharma Inc.
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
Me
an
%IF
Ng
+ C
D8
T-c
ell
s (
+-S
EM
)
Flatz et al. Nature Medicine 2010
1 Webb et al Clinical Oncology 1975
15©2019 HOOKIPA Pharma Inc.
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
16©2019 HOOKIPA Pharma Inc.
H C M V g B E L IS A
0 2 0 4 0 6 0
1 0
1 0 0
1 0 0 0
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
T im e (w e e k s )
GM
T A
EU
/ml
+-
95
%C
I
H C M V p p 6 5 E L IS P O T
0 2 0 4 0 6 0
0
1 0 0
2 0 0
3 0 0
4 0 0
5 0 0
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
T im e (w e e k s )
Me
an
SF
C /
10
6 P
BM
C (
+-S
EM
)
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
d0
0
d2
8
d8
4
m0
4
m1
2
d0
0
d2
8
d8
4
m0
4
m1
2
d0
0
d2
8
d8
4
m0
4
m1
2
d0
0
d2
8
d8
4
m0
4
m1
2
30
_S
N
1_
SP
1 0
1 0 0
L C M V N T A
c u t-o ff
M e d iu m D o s e C trlP la c e b o
LC
MV
Ne
utr
ali
za
tio
n T
ite
r
17©2019 HOOKIPA Pharma Inc.
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
0 .3
0 .4P 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
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
T c
ell
s (
%)
18©2019 HOOKIPA Pharma Inc.
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.
19©2019 HOOKIPA Pharma Inc.
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)
21©2019 HOOKIPA Pharma Inc.
• 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)
22©2019 HOOKIPA Pharma Inc.
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
2 0
4 0
6 0
8 0
1 0 0
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
2 0
4 0
6 0
8 0
1 0 0
D a y s
Pe
rce
nt
su
rviv
al
(%)
* * * *P < 0 .0 0 0 1
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.
23©2019 HOOKIPA Pharma Inc.
• Direct correlation
between dose and
immunogenicity
• Direct correlation
between dose and
efficacy
• Direct correlation
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)
24©2019 HOOKIPA Pharma Inc.
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:
Group 2, first 3 cohorts
efficacy=PoC
25©2019 HOOKIPA Pharma Inc.
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.
26©2019 HOOKIPA Pharma Inc.
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:
Group 1, first 3 cohorts
efficacy=PoC
2021:
Group 2, first 3 cohorts
efficacy=PoC
27©2019 HOOKIPA Pharma Inc.
• 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))
29©2019 HOOKIPA Pharma Inc.
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
30©2019 HOOKIPA Pharma Inc.
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
31©2019 HOOKIPA Pharma Inc.
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