supercharging immunotherapy · 2019-04-11 · supercharging immunotherapy april 2019 ©2019 hookipa...

1©2019 HOOKIPA Pharma Inc.

Supercharging Immunotherapy

April 2019


Disclaimer

This presentation contains forward-looking statements that can involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements

regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, future revenue, timing and likelihood of success, plans

and objectives of management for future operations, future results of anticipated products and prospects, plans and objectives of management are forward-looking statements. These statements involve known and

unknown risks, uncertainties and other important factors that may cause our actual results, level of activity, performance, events, circumstances or achievements to be materially different from any future results, level

of activity, performance, events, circumstances or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,”

“will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” “would” or “continue” or the negative of these terms or other similar

expressions. The forward-looking statements in this presentation are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and

financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this presentation and are subject to a number of

risks, uncertainties and assumptions.

Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-

looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those

projected in the forward-looking statements. Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all

risk factors and uncertainties.


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 & Director

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 & Director

Valneva, Intercell

Leadership

Michael A. Kelly (Former SVP at Amgen)

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

Vaccinology)

Christoph Lengauer, PhD (Celsius Therapeutics, Blueprint Medicines,

Third Rock Ventures)

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

Graziano Seghezzi (Sofinnova Partners)

Sander van Deventer, MD, PhD (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

Sirona

Capital


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

• Build manufacturing in-house

• Deliver on Gilead partnership

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

H1 2020

Anticipated

Milestones

IND H1 2019

Data late 2020/

early 2021

IND H1 2020

Data mid-2021

Compound

HB-101 (VaxWave®)

HBV

Therapy

HIV

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 HOOKIPA Patent Estate

covering all arenaviruses1

Pichinde Virus (PICV)

Lymphocytic Choriomeningitis

Virus (LCMV)

Flatz et al. Nature Medicine 2010

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

Arenavirus Family


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

0

2

4

6

1 0

2 0

3 0

4 0

5 0

6 0E

7-T

et+

CD

8

T c

ell

s

(%)

M o d if ie d v a c c in ia v ir u s

A n k a r a

(M V A ) 1 09

A d e n o v iru s ( rA d 5 ) 1 09

H O O K IP A a re n a v iru s

S in g le v ir u s L C M V 1 07

H O O K IP A a re n a v iru s

c o m b o L C M V + P IC V

v e c to r s 1 05

Arenavirus vectors Other viral vectors

HPV+ cancer

antigen (E7) -

specific CD8 T cells

109

109107

105


TheraT® triggers alarmin (interleukin-33)

release, potentiating CD8+ T cell

proliferation

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

TheraT® induces Tox1 in CD8+ T cells,

rendering them checkpoint insensitive

1 Kallert, S. et al. Nature Communications 2017;

2 Page, N. et al. Immunity 2018

1 2


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

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

Approximately 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


A n tib o d y Im m u n o g e n ic ity

(H C M V g B1 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

I2Trial 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 Antibody & 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

N o N e u tra liz in g A n tib o d ie s

(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

1 B cell antigen; 2 GMT= geometric mean titer, AEU= arbitrary ELISA units, CI= confidence interval;


Dose dependent, durable CMV phosphoprotein 65 (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 T c e ll 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 p

p6

5 s

pe

c.

INF

g+

CD

8 T

ce

lls

(%

)


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

CMV viral load

Total CMV pp65 specific CD8 T cells (%)

CMV pp65 specific IFNg+ CD8 T cells (%)

Neuenhahn et al., Leukemia 2017

Phosphoprotein 65 (pp65) - specific CD8+ T cells isolated from CMV+ donoradministered 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

Patients

Endpoints

Expected 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 patients)

6 months prophylactic antiviral therapy (100 patients)

• Primary: immunogenicity and safety

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

decreased use of antivirals

• H1 2020: Primary endpoint safety/reactogenicity

• H2 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 Adenovirus1

TheraT ® -TAA2

Tumor

CD8 T cells migrate from lymph nodes to tumor

Antigen-specific CD8 T cell activation

Lymph Nodes/ Dendritic Cells

1 Recombinant Adenovirus; 2 Tumor Associated Antigen

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

Untreated Adenovirus Arenavirus

Delivery

Antigen -

-

OVA

Adeno Arenavirus

GFP (irrelevant)

Arenavirus

OVA


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

(%)

In tra v e n o u s

In tra tu m o ra l

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 Recurrence (HPV+ Cancer (TC1))

HPV+ Cancer Challenge: TheraT ® Treatment 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

metastatic recurrence

PICV

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

In tra v e n o u s

In tra tu m o ra l ( IT )

B u ffe r IT

Previously cured1 by treatment with

TheraT® (LCMV) intratumoral

Previously cured1 by treatment with

TheraT® (PICV) intravenous

Challenged with tumor

for the first time

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

LCMV

D140: Re-

challenged with

tumor cells

D180: Re-

challenged with

tumor cells


• 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+

specific

T c

ells

(%

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

Other HPV+ cancers

(cervical, anal, penile, etc.)1

Intratumoral

HPV+ HNSCC for metastatic tumor

3rd line

Intravenous

HPV+ HNSCC combination with nivolumab

2nd line

Intravenous

Other HPV+ cancers1

Intratumoral

H1 2019:

IND filing with FDA

H2 2019:

Initiate Phase 1/2

clinical trial

late 2020/ early 2021:

Preliminary results

expected

HPV+ Head & Neck Squamous Cell

Carcinoma (HNSCC)

Intravenous

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


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

1st dose HB-201 given as intratumoral

injection; subsequent dose HB-202, then

HB-201 and HB-202 both intravenous in

sequential alternating manner

HB-202 and HB-201 sequential alternating

intravenous application;

HB-202 administered first, HB-201 several

weeks later

Arm 1:

(n=20)

Arm 2:

(n=20)

Arm 3:

(n=20)

Group 1:

(n=20)

Group 2:

(n=20)

HPV 16+ metastatic tumor

3rd Line

Intravenous

HPV 16+ tumors

2nd Line in combination with nivolumab/PD-1

Intravenous

HPV 16+ cancers accessible for intratumoral injection;

Intratumoral and intravenous

Phase 1 Dose ESCALATION

H1 2020:

IND filing with FDA

H2 2020:

Initiate Phase 1/2 trial

2021:

Preliminary results

expected (Group 1+2,

1st 3 cohorts efficacy = POC


• Single systemic TheraT® injection can lead to complete remission without 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

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))

Day 1:

Tumor cells

Day 4:

Tumor cells


Key Financials, Investment Highlights


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


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

• December 31, 2018 pro forma cash

balance: $85.9m(pro forma adjusted for Series D net

proceeds)

Executing on Financial Strategy To Support Pipeline Progression

Key Financial Data

in $ million

Year ended

December 31,

2017

Year ended

December 31,

2018

Revenue from collaboration & licensing – 7.6

R&D expenses (9.8) (22.0)

G&A expenses (4.4) (6.8)

Net loss (12.7) (16.2)

in $ million

As of Dec. 31,

2017

As Dec. 31,

2018

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


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

supercharging immunotherapy · 2019-04-11 · supercharging immunotherapy april 2019 ©2019 hookipa...

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