Supercharging Immunotherapy€¦ · Supercharging Immunotherapy Company Presentation October 2018. Preventing. Curing. To Reprogram The Immune System To Overcome Infectious Diseases

1Hookipa Biotech GmbH Non-Confidential

Supercharging Immunotherapy

Company Presentation

October 2018

Preventing. Curing.

To Reprogram The Immune SystemTo Overcome Infectious Diseases And Cancer

3©2018 Hookipa Pharma Inc. Confidential

Clinical Stage Immuno-Therapy Company

Strong Talent Pool

65 people New York, Vienna

Co-foundersProf Daniel Pinschewer,Prof Rolf Zinkernagel

(Nobel laureate)

Accomplished Leadership

Blue chip financial and strategic investors

PEOPLETECHNOLOGY

Two Platforms Using Arenavirus

Develop Broad Portfolio For Significant

Unmet Medical Need

Infectious Diseases

CMV Vaccine; HIV and HBV therapeutics in$ 400 m+ partnership with

Gilead

Immuno-oncology

Viral antigens,

Self-antigens, and

Shared neo-antigens

STRATEGY

Vaxwave®

Replication-deficient

TheraT®

Replication-attenuated


TheraT-E7E6

Arenavirus Advantage Over TCR/ACT Is EvidentWe Will Use It To Build A Leading Immuno-Oncology Position

TCR/ ACT Arenavirus vector


Differentiating Key Themes

Technology with unprecedented T cell potency

Universal approach targeting large markets

Platform de-risked,CMV POC Ph2 Trial Ongoing

Potential as cancer mono-and combination therapy

Management, investors, and partner strongly validate

approach

Novel “off-the shelf” in vivo approach using arenavirus Potent as TCR/ACT, but without complicated ex-vivo logistics Safe, no cytokine release storms

Infectious diseases and cancer Naturally targeting solid tumors Prophylactic and therapeutic applications

Remarkable antibody and T cell induction, clinically proven In humans as safe as placebo, no CRS Response duration >12 mos

Monotherapy potency likely, given preclinical data and CMV trial results with Vaxwave®

Synergistic with check point inhibitors, other combinations Active in checkpoint refractory settings

World-class board and management Blue chip financial and strategic investors Landmark partnership deal with Gilead


Market Proprietary Immuno-oncology Drugs

Focused Strategy3 Horizons

Horizon 2019

Fully Exploit Platform• Build I/O pipeline• Expand target space to self- and shared

neo-antigens• Establish Clinical POC for Infectious

Disease pipeline in partnership with Gilead• Control manufacturing

Horizon 2022

Validate Efficacy In Humans

• Vaxwave® - Cytomegalovirus Prophylaxis o Ph2 POC o Solid Organ Transplant patients

• TheraT® - HPV+ mediated Cancero Ph1 safety and efficacy o Monotherapyo Followed by heterologous combination


Pipeline

Compound TargetAntigenPre-

clinicalVectorDesign

Phase 2Phase 1 Phase 3

Gilead

HB-101 (Vaxwave®)

HBV Therapy

HIV Therapy

HB-201 (TheraT®)

HB-202* (TheraT®)

HB-301 (TheraT®)

Next GenAntigen

gB/pp65

TBD

TBD

E6/E7

E6/E7

PSA/PSMA/PAP

Shared Neo-Antigen

CMV

HBV

HIV

HPV+HNSCC

HPV+HNSCC

Prostate Cancer

TBD

OncologyInf. Diseases

Gilead

IND granted Q3/2018POC Q4/2019 – Q1/2020

Near term milestones

IND Q3/2019Data H1/2020

IND Q1/2020Data Q4/2020

*) HB-202 is a combination product to boost HB-201 in heterologous prime-boost to potentiate T cell response


Science


Broad Patent EstateHookipa patent estate

covers the entire Arenavirus family

incl. LCMV(Lymphocytic Choriomeningitis Virus)

Arenaviruses Naturally Induce Antibodies And Exceptionally Potent CD8+ T Cell Responses

LCMV-specificcytotoxic T lymphocyte

LCMV used by Hookipa co-founder

Prof. Rolf Zinkernagelfor his Nobel Prize-winning discovery of the role of the

MHC-complex in T cell immunity

Redirecting the exceptionally potent

T cell response of LCMV against cancer- and

infectious disease-specific antigens


Arenavirus targets Dendritic cells in vivo, potentiates the body’s own immune system

Repeat administrations w/o induction of vector-neutralizing antibodies, no adjuvants

No need for complicated ex-vivo logistics, works best on solid tumors

In addition to T-cell induction, it generates potent antibody responses

Arenavirus – for decades the workhorse for immunologist to induce antigen-specific CD8+ effector T cells

Key Differentiating Features Of Hookipa’sArenavirus Immunotherapy Technology


Two Powerful “Engineered” Arenavirus Technologies

Replication DefectiveVaxwave® Replication AttenuatedTheraT®

S-Segment3`5`

GP

dN

L-Segment5` 3`

Z

L

Exchange by

Target Antigen

S-Segment - 13`5`

GP

dN

L-Segment5` 3`

Z

LExchange by

Target Antigen

S-Segment - 23`5` GP

Exchange by

Target Antigen

• 2 segments, 1 Glycoprotein (GP)

• Replace GP by ‘antigen of choice’, no GP remaining

• Consequence: replication deficient, antigen specific

• 3 segments, 2 Glycoproteins (GP)

• Duplicate S segment, insert 2 ‘antigens of choice’

• Consequence: replication attenuated, antigen specific


Kallert et al. Nature Communications 2017

Superior CD8 T Cell QUANTITY And QUALITY Via TheraT

Page et al. Immunity 2018

wtST2/IL33ko

LCMV specific IL33 activated CD8 T cell expansion LCMV specific TOX mediated checkpoint repression


Translational


Technology Can Be “Tuned” To Make > 50% Of All CD8+ T Cells Antigen-specific, Specifically Targeting Disease

Prophylaxis/ID IndicationsTherapeutic/Oncology Indications

% Antigen Specific CD8 T Cells

0,1

1

10

100

B16F10(Melanoma)

P815 (Self-Antigen)

TC1 CMV HepB HPV


0

2

4

6

8

1040

50

60

E7 Tet+ CD8 (%)

Peak value over 21 day time course shown

TheraT® Induces More Potent E7-specific CD8 Response Than Adeno 5, MVA, and Peptides

TheraT


Arenavirus Vector Mechanism Of Action For I/D and I/O Purposes

TheraT-E7E6

Immuno-Oncology

VaxWave-HepB

Infectious Diseases

CD-T-IDA

IDA=infectious disease antigenTAA=tumor associated antigen


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

• Strong tumor control in a metastatic setting

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

• Re-challenged on day 140, these mice are protected from new tumor formation for over 200 days

91

11

21

41

61

82

53

23

94

65

36

0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

2 5 0 0

D a y s a f t e r s e c o n d a r y c h a l l e n g e

Tu

mo

r v

olu

me

(m

m3

)

* *

T T 1 - E 7 E 6 i . t . p r i m e o n l y ( n = 3 )

C o n t r o l m i c e ( n = 4 )

TC

- 1

T C - 1 r e c h a l le n g e

T T 2 - E 7 E 6 i . v . h o m o l o g o u s p r i m e b o o s t ( n = 1 )

• Approach appropriate for the treatment of

o Metastatic disease

o Primary disease and subsequent prevention of recurrence

o Potential to replace surgery and radiation therapy as primary modality

Days after secondary challenge

TC1 Challenge TC1 Re-Challenge

LCM

V-T

her

aTE7

E6P

ICH

-Th

eraT

E7E6

Infectious Diseases


HB-101 – CMV Ph1 Healthy Volunteer Trial: Potent, Durable T Cell Immunogenicity; 3-Fold More Potent Than ACT

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

Feuchtinger et al Blood 2010

We reach equivalent T-cell frequencies previously directly correlated with elimination of viremia by adoptive cell therapy (ACT)

Peak Level


HB-101 – CMV Ph1 Healthy Volunteer Trial Potent And Durable Antibody Immunogenicity

Bivalent Construct

pp65 T cell

Antigen

gBB cell

Antigen

Antibody Response• Increasing with dose• Increasing with every

boost (black arrows)• Durable 12 months

g B E L IS A

0 2 4 6 8 1 0 1 2 1 4

1 0

1 0 0

1 0 0 0

P la c e b o

C o h -1

C o h -2

C o h -3

m o n th s

GM

T A

EU

/ml

+-

95

%C

I

H C M V N e u tra liz a t io n

0 2 4 6 8 1 0 1 2 1 4

1 0

1 0 0

P la c e b o

C o h -1

C o h -2

C o h -3

m o n th s

GM

T N

T +

- 9

5%

CI

Placebo

Low dose

Medium dose

High dose

Placebo

Low dose

Medium dose

High dose

C o h -3C o h -1

d00

d28

d84

m04

m12

d00

d28

d84

m04

m12

d00

d28

d84

m04

m12

d00

d28

d84

m04

m12

30_S

N

1_S

P

1 0

1 0 0

L C M V N T A

c u t-o ff

C o h -2 C trlP la c e b o

LCM

V N

eutr

aliz

atio

n Ti

ter

B-cell responses comparable to previous vaccines (ie CMV-specific neutralizing antibodies competitive with Sanofi gB/MF59 vaccine, which demonstrated efficacy.

No neutralizing vector ABs


HB-101 – CMV Ph1 Healthy Volunteer Trial As Safe As Placebo

Bivalent Construct

pp65T cell

Antigen

gBB cell

Antigen 0%

10%

20%

30%

40%

50%

60%

70%

Solicited Severe

Local Symptoms

Solicted Severe

General Symptoms

Unsolicited

Related AEs

Unsolicited Severe

Related AEs

Placebo Low Dose

Medium Dose High Dose

Percentage of Subjects Reporting Adverse Events


No vector-neutralizing antibodies

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

B-cell and T-cell induction

B-cell responses comparable to previous vaccines*

Excellent safety profile

HB-101 CMV Healthy Volunteer TrialSummary Of Clinical Responses

HB-101 Best-in Class 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)


HB-102 CMV Ph2 To Start Q3/2018 - Targeting High Risk Live Donor Kidney Transplant Patients

Ph2 Trial POC In Solid Organ Transplant Patients

Endpoints Primary Safety/immunogenicitySecondary Efficacy/ reduction of viremia rate (goal >50%),

decreased use of antivirals

Patient Population Live Donor Kidney Transplant with high risk for CMV viremia(High risk: Donor+/ Recipient- = D+/R-)

Outcome Full Ph 2 POC trial enabling start of pivotal trial

Stratification by post-transplant treatment intent

Randomize 2:1Pre-transplant HB101 vs placebo

Randomize 2:1Pre-transplant HB101 vs placebo

Post-transplant:close observation (pre-emptive therapy; baseline viremia rate=80%)

Post-transplant:6 months anti-virals(prophylactic therapybaseline viremia rate=40%)

transplant

transplant

Treatment


HB-102 Ph2 News Flow

2018 2019 2020 2021

CMV data pre-emptivepatients2019/20

CMV data pro-phylacticpatientsQ3 2020

CMV Ph2 IND07/ 2018

CMV Ph3 Start2021


Immuno-Oncology


Tumor Infiltration By Cytotoxic T Cells (CTLs)TheraT® Is Turning “Cold” Tumors “Hot”

LUNGSDAY 21

DAY 1: B16F10

B16F10Tumor

TheraT-TAA

EG7-OVA

LUNGSDAY 21

DAY 1: B16F10DAY 10: TheraT-Trp2


HB-201 – H&NSCC – 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

HP

V1

6 E

7+

(%

of

CD

8+

B2

20

-)

*

**

**

TheraT(cl13/WE)-E7E6

LCM

V-T

her

aTE7

E6 (

TT1

)P

ICH

-Th

eraT

E7E6

(T

T2)


HB-201 And HB-202 News Flow Next 30 Months

• HB-201

o Ph1 Mono trial start Q3 2019, POC in H1 2020 – 3rd line

o Combine w/ Nivolumab -2nd line

• HB-202

o Ph1 Mono trial, later combine with HB-201 (heterologous prime-boost) and Nivolumab – 1st line

2018 2019 2020

Q3 2019: HB-201 Ph1

Start

H1 2020: HB-201

Monotherapy data

06/ 2019 HB-201 IND

grant

Q4 2020: HB-201 Ph2 data

w/ Nivolumab

Q4 2020: HB-202 Ph2 data

Monotherapy


0,1 1 10 100

**Clinical TheraT HPV/E7

Clinical ACT HPV/E7

PreCLinical TheraT

Clinical VaxWave - CMV

Clinical ACT - CMV

PreClinical VaxWave

% Antigen Specific CD8 T Cells

Strong Rational for Clinical Efficacy for TheraT® in I/O

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

)

Hinrichs et al ASCO 2018 HPV TILs

Vaxwave, TheraTT cell Levels

ACT/TIL levels indicativeof clinical benefit

Hypothesis for clin. TheraT HPV/E7 therapeutic level


Corporate Overview


World Class Leadership Team

Daniel Pinschewer (MD)

Founder & Chief Scientific OfficerUniversity Basel, Professor of VirologyPrevious:• University of Geneva,

Medical School, Associate Professor Immunology

Igor Matushansky (MD, PhD)

Global Head of R&DChief Medical OfficerPrevious:• Daiichi Sankyo, Gl. Head Transl.

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

Jörn Aldag

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

Reinhard Kandera, Dr.

Chief Financial OfficerPrevious:• Valneva SE, CFO• Intercell AG, CFO

Jan van de Winkel

ChairmanPresident & CEO & Co-Founder Genmab A/S

Anders Lilja (PhD)

VP Technical DevelopmentPrevious:• Novartis Vaccines,

Research Investigator and Associate Project Leader

Christoph Lengauer

Non-Executive DirectorCo-Founder Celsius TXVenture Partner Third RockPrevious:• CSO Blueprint• Novartis, Sanofi• Johns Hopkins School of

Medicine

Paul Henri Lambert

Non-Executive DirectorProf. emeritus University of Geneva, Center of Vaccinology

Independent Non-Executive DirectorsLeadership


Well Funded By Top Tier Healthcare And Corporate Investors

Financing Strategy

• € 95 m Raised To Date

• Series C € 50m 12/ 2017

• Series B € 30 m

• Series A €7 m

• Grant funding €8m

• 30 June 2018

Cash Balance € 54m

Shareholder Base

Healthcare VCs and crossover investors

Corporate VCs / Pharma

Undisclosed U.S. public life sciences fund

SironaCapital


Building Infectious Diseases Pipeline With Ideal Partner US$ 400 m Research Collaboration, Up To Double-Digit Royalties

• HBV and HIV therapeutics

• Pre-clinical activities by Hookipa

o Delivery of 30 research grade Vaxwave® and TheraT® vectors

o GMP manufacturing

• Clinical development and commercialization by Gilead

• Terms

o Meaningful up-front

o R&D expense fully funded by Gilead

o $400m in milestones, royalties


News Flow Next 30 Months

(major milestones in red)

2018 2019 2020

Q2 2018: Gilead collaboration

mid 2018: CMV Phase 2 start

Q1 2020: CMV Phase 2 results

Q3 2019: H&N Phase 1 start

H1 2020: H&N Phase 1 Full POC

Q1 2020: H&N first Phase 2 Start

Q4 2020: HB-301 IND


Supercharging Immunotherapy

www.hookipapharma.com

Documents

Supercharging Immunotherapy€¦ · Supercharging Immunotherapy Company Presentation October 2018. Preventing. Curing. To Reprogram The Immune System To Overcome Infectious Diseases