cancer and autoimmune diseases · and autoimmune diseases a balanced business model: mature...

Cancer and Autoimmune Diseases

We are armed to fight

Forward Looking Statement

This presentation contains express or implied information and statements that might be deemed forward-looking information and statements in respect of OSE Immunotherapeutics.

They do not constitute historical facts. These information and statements include financial projections that are based upon certain assumptions and assessments made by OSE

Immunotherapeutics’ management in light of its experience and its perception of historical trends, current economic and industry conditions, expected future developments and other

factors they believe to be appropriate.

These forward-looking statements include statements typically using conditional and containing verbs such as “expect”, “anticipate”, “believe”, “target”, “plan”, or “estimate”, their

declensions and conjugations and words of similar import.

Although the OSE Immunotherapeutics’ management believes that the forward-looking statements and information are reasonable, the OSE Immunotherapeutics’ shareholders and

other investors are cautioned that the completion of such expectations is by nature subject to various risks, known or not, and uncertainties which are difficult to predict and generally

beyond the control of OSE Immunotherapeutics. These risks could cause actual results and developments to differ materially from those expressed in or implied or projected by the

forward-looking statements. These risks include those discussed or identified in the public filings made by OSE Immunotherapeutics with the AMF. Such forward-looking statements are

not guarantees of future performance.

This presentation includes only summary information and should be read with the OSE Immunotherapeutics Reference Document filed with the AMF on 26 April 2019 including the 2018

Financial results, all available on the OSE Immunotherapeutics’ website.

Other than as required by applicable law, OSE Immunotherapeutics issues this presentation at the date hereof and does not undertake any obligation to update or revise the forward-

looking information or statements.

This presentation does not constitute an offer to sell the shares or soliciting an offer to purchase any of the Shares to any person in any jurisdiction where such an offer or solicitation is

not permitted. The Shares may not be offered or sold, directly or indirectly, may be distributed or sent to any person or into any jurisdiction, except in circumstances that will result in the

compliance with all applicable laws and regulations. Persons into whose possession this presentation may come are required to inform themselves about, and to observe all, such

restrictions. The Company accept no responsibility for any violation by any person, whether or not it is a prospective purchaser of Shares, of any such restriction.

The information contained in this presentation has not been independently verified and no commitment, representation or warranty, express or implied, is given by the Company or

anyone of its directors, officers or respective affiliates or any other person and may not serve as the basis for the veracity, completeness, accuracy or completeness of the information

contained in this document (or for any omission of any information in this presentation) or any other information relating to the Company or its affiliates. The information contained in this

document is provided only as of the date of this document and may be subject to update, supplement, revision, verification and modification. They can be modified significantly. The

Company is not subject to an obligation to update the information contained in this document and any opinion expressed in this document is subject to change without notice. The

Company, its advisers, its representatives cannot be held responsible in any manner whatsoever for any loss of any nature whatsoever resulting from the use of this document or its

contents or otherwise related in any way to this document.

This document contains information relating to the Company's markets and the positioning of the Company in these markets. This information is derived from various sources and

estimates of the Company. Investors cannot rely on this information to make their investment decision.

OSE Immunotherapeutics

OSE’s Technological Platform: From Target

Identification to Product Validation and BeyondAn integrated operational immunology research platform

Phase 3 asset (Tedopi®) in NSCLC post check-point

inhibitor – Step-1 results expected in April 2020

Multiple clinical stage assets in Immuno-Oncology and

Auto-Immunity

Technology endorsed by significant partnerships with

Servier and Boehringer Ingelheim for up to €1.3Bn in

milestones (60 Millions Euros already received since 2016)

Leveraging a unique experience of 25 years of clinical

immunology in immunotherapy cluster in Nantes

Investment Summary

Founded in 2012

IPO in 2015 (raised € 21.1m)

Listed on EuroNext Paris, EPA ticker OSE

As of December 31, 2019

Turnover € 26m

Cash € 25.8m

Financial viability until Q1 2021

01

02

03

04

3

Warning: Initiation of new clinical trials, patient accrual and planned timelines

throughout this presentation are expected to be impacted by the Covid-19 situation in

the coming months

A French Biotechnology Success Story

OSE PHARMA

CREATION

Founded by Emile

Loria and

Dominique

Costantini in Paris

Now HQ based in

Nantes, with

operational offices

in Paris

IPO

Euronext

€21.1M

MERGER

OSE Pharma and

Effimune merge to give

birth to

OSE

Immunotherapeutics

PARTNERSHIP

WITH SERVIER

A license option

agreement covering

development and

commercialization of

OSE-127 targeting

both ulcerative colitis

and Sjögren's

syndrome

PARTNERSHIP

WITH

BOEHRINGER

INGELHEIM

A worldwide license

and collaboration

agreement to develop

BI 765063 (OSE-172)

in multiple cancer

indications

2012 2015 2016 2017 2018KEY FIGURES

€ 26Mrevenues in 2019

45employees

(incl. specific R&D skills)

4products in clinical-stage status

3strategic partnerships with

international pharma companies

LICENSING

AGREEMENT

WITH CKD

Licensing

Agreement with

Cohong Kun Dong

in South Korea for

registration and

marketing of

Tedopi®

2019

4

A Business Model Making OSE Unique

Clinical-stage

biotechnology

company focused on

immuno-oncology

and autoimmune

diseases

A balanced

business model:

mature technologies,

breakthrough

developments,

partnerships,

patents

A R&D engine

to discover new

therapies against

major diseases with

high unmet need

Strong partnerships with big

pharma companies and clinical

and academic entities in Europe

and the US combined to an

efficient patent protection policy

Delivers multiple first-in-class

products that activate or regulate

the immune system

Unique expertise and knowledge

focused on novel target discovery

to generate innovative agonists

or antagonists of the immune

response

5

Long-Term Partnerships Designed to Ensure the Fastest Delivery of New Therapies to Patients in Need

HOW?

Sharing knowledge and

bringing together

fundamental to facilitate

the generation of

breakthrough discoveries

6

WHO? WHY?

Accelerate the clinical

development of its product

candidates

Significant financial support

HOW MUCH?

Potential revenues for OSE

thanks to upfront fees and

milestone payments

(excl. royalties)

€1.3Bn

1

2

A Low-Diluted, Family-Based Economical Model Making OSE Self-Sufficient in Terms of Cash since 2015

Shareholding structure (as of June 2019)By number of shares

Dominique Costantini

13%

Emile Loria Group24%

Aparena Consulting

(Alexis Peyroles)4%

Maryvonne Hiance3%

Others Managers / Boardmembers2%

Other55%

Funds raised and IPO

No additional fundraising needed since the IPO in March 2015

thanks to a strong partnership business model

Market capitalization of €49 M as of March 30, 2020

Stock price at €3.31/share as of March 30, 2020

3.2M€ raised prior to IPO

21.1M€ raised on Euronext

Paris (IPO)

7

Strategic Income-Generating Pharma Partnerships Driving R&D

December 2016 April 2018

License option agreement covering development and

commercialization of OSE-127

Worldwide license and collaboration agreement to develop BI

765063 (OSE-172) in advanced solid tumors

Ulcerative colitis and Sjögren's syndrome Multiple cancers indications

Positive Phase 1 results

Launch of Phase 2 expected in 2020(1)Phase 1 on-going– CTA received for France & Belgium

€20M payment received to date:

€10M upfront fees + €10M(2) first-step option fees

€30M payment received to date:

€15M upfront fees + €15M short-term payment for the initiation of Phase 1

Up to €252M forthcoming payments, excl. Royalties (3):

€M5 + 15 M€ second-step option fees + €232M milestone payments

(1) Subject to the evolution of the situation of COVID-19(2) Exclusive VAT amount(3) Royalties on sales amounted from 8 to 10% as agreed in the two contracts

Up to €1Bn forthcoming payments, excl. Royalties (2):

Milestone payments

8

Immuno-Oncology and Auto-Immune Diseases

First-in-Class Portfolio

PROGRAM Indication Pre-Clinical Phase 1 Phase 2 Phase 3

IMMUNO-ONCOLOGY

Tedopi®

NeoepitopesNSCLC

EU-US-Israel

Ongoing

Tedopi®Advanced pancreatic

cancer

Combo with PD1

Opdivo® Ongoing

BI 765063 (OSE-172)

SIRP⍺-CD-47

Various cancers Ongoing

BiCKI®

Bispecific anti-PD-1 &

Innovative Targets

Various cancers 2020

AUTO-IMMUNE DISEASES

FR104CD28

Autoimmune diseases &

Transplantation

Phase 2 planning

ongoing

OSE-127IL-7R

Ulcerative Colitis

Sjögren’s syndrome

Positive Phase 1

Results Q4 20192020

9

From a Single Product to a 4 Clinical-Stage Products Portfolio in Only One Year

Tedopi®o Ongoing Phase 3 in NSCLC after failure of PD-1/PDL1 immune checkpoint inhibitors

o Ongoing Phase 2 in pancreatic cancer in combination with checkpoint inhibitor Opdivo®

o Sponsor of the pancreatic trial : GERCOR with Bristol Myers Squibb providing Opdivo®

BiCKI®

FR104

BI 765063

OSE-127

o Phase 2-ready and currently evaluating the best options for continuing a sustainable

development, incl. worldwide partnering opportunities

o Unveiled a new bispecific fusion protein platform at the World Immunotherapy Congress in

March 2019 built on the key backbone component anti-PD-1 and innovative targets

o Global immuno-oncology agreement with Boehringer Ingelheim

o Ongoing Phase 1 in advanced solid tumors

o Dosing of a first patient triggered milestone payments of a total of €15M

o Positive Phase 1 results in Q4-2019 for the treatment of autoimmune diseases, launch of Phase 2

expected in 2020

o Awarded milestone payment of €10M(2) upon exercise of the first option by Servier under the two-

step option within the global license agreement

(1) Exclusive-VAT amounts10

I&I: New ConceptsI/O: T-cell approach I/O: New Myeloid targets

11

MacrophagePhagocytosis

Dendritic cellsAg presentation

Immune BalanceEffectors vs Regulators

Cancer VaccinePriming

BispecificImmune checkpoint

Abilities and Knowledge in R&D

To Address Key Drivers of the Immune System

11

12

Abilities and Knowledge in R&D

To Address Key Drivers of the Immune System

12

▪ Selective Immune Checkpoint(CD28, SIRPg)

▪ New Cytokine Blockade(IL-7R)

▪ Resolution of Inflammation(ChemR23)

I&I: New Concepts

▪ Cancer Vaccine (Tedopi®)

▪ Bispecific Immune Checkpoints (BiCKI®)

I/O: T-cell Approach

▪ New Immune Checkpoint(SIRPa, CLEC-1)

▪ Phagocytosis & Sensing of death

I/O: New Myeloid Targets

Transversal Biotechnologies

Antibody discovery Molecular Engineering Bioproduction Bioanalytics

Translational Research

Human 3D ‘organ’ ex-vivo platform Bio-Informatics(3D patient-derived primary tissue explant cultures) (Big Data, Target discovery/validation)

13

OSE’s Research Pillars

13

Upcoming Growth Beyond 2019 Based on Three Core Pillars

14

2016-2017

Preparing the ground in terms of technology, strategy and pipeline, resulting in forthcoming

development of candidate drugs

2018-2019

o Consolidating the business modelo Refine HR policyo Signing additional strategic

partnerships

2020 and beyond

Accelerate the added-value creation thanks to 2 clinical-stage products

and 1 world-class platform

TEDOPI®

Phase2 & 3

Most advanced product

+100Partnered cancer centers that use the product in clinical trials

04/2020 Step-1 results phase 3 NSCLC

FR104

Phase 2- ready asset

€10M Earnings after the Phase 1 completion in 2016

BiCKI®

Bifunctional products with many development opportunities in immuno-oncology

A new bispecific platform withan anti-PD-1 backbone In auto-immune disease or

transplant

250+ Years of Combined Experience in Major Pharmaceutical, Biotech and CRO Companies

Board of Directors

Management

Dominique Costantini,MD

Chairman & Director of Development

Maryvonne HianceVice Chairman &

Public Affairs

Sophie BrouardDirector

Jean-Patrick DemonsangDirector

Didier Hoch, MDDirector

Gérard Tobelem, MDDirector

Alexis PeyrolesChief Executive Officer

Director

Frédérique Corallo,MD

Chief Medical Officer, Autoimmune Diseases

Brigitte Dreno, MDDirector

Bérangère Vasseur,MD

Chief Medical Officer, Immuno-Oncology

Nicolas Poirier, PhDChief Scientific Officer

Director

Emilienne Soma,PharmD, PhD

Director of Pharma Programs Development

Anne-Laure Autret-CornetChief Financial Officer

15

Jean-Pascal Conduzorgues, PharmD

Qualified Person (QP)

A Company Project and Vision Backed by Experienced Leaders

o Medical Doctor specialized in immunology, with 25+ years experience in management positions in the pharma industry (HMR)

o Overseen many therapeutic innovations and the development of numerous medicines mainly in immunology and oncology

o 1997-2011

• Founder and CEO of BioAlliance Pharma (now Onxeo), a biotech company in oncology and supportive care

• Conducted the company’s IPO on Euronext in 2005 and the registration of products in Europe and the US

o Since 2012:

• Founder of OSE Pharma, a biotech company in cancer immunotherapy, and now Chairman of OSE Immunotherapeutics

• Conducted the company’s IPO on Euronext and the merger with Effimune, a biotechnology company specialized in immune regulation

16

Dominique Costantini, MDChairman & Director

of Development

Maryvonne HianceVice Chairman &

Public Affairs

o Specialized in nuclear science and served, for 14 years, as a manager of neutron studies at FRAMATOME (Areva)

o Over a 20-year period, General Manager at innovative biotechnology companies including SangStat Atlantic, DrugAbuse Sciences and TcLand

o Also founder and General Manager of Strategic Ventures, a consulting company providing support to technological companies

o Member of the French Strategic Council for Innovation and Advisor to the French SMEs and Industry Ministry.

o 2008-2016: Co-founded and CEO for Effimune

o Since 2016: Vice-Chairman and Director for Strategy of OSE Immunotherapeutics, then Public Affairs since July 2019

o Also President of France Biotech, the French Association of Life Sciences entrepreneurs

20+ years of international management and financial control experience in multiple related positions

o 1996-2001: Sanofi-Aventis in Financial Control and Business Development in Asia and Eastern Europe

o 2001-2005: Ideactif as a Finance Manager

o 2005-2012: Guerbet Group (leader in medical imaging) as a Financial Control Manager in France and then as General Manager in Latin America

o 2013-2014: Founder and Managing Partner at Aperana Consulting, specializing in life sciences and digital start-ups

o 2013-2016: OSE Pharma as CFO and Head of Business Development

o May 2016-April 2018: OSE Immunotherapeutics’ Chief Operating Officer

o Since April 2018: OSE Immunotherapeutics CEOAlexis Peyroles

Chief Executive Officer

Scientific Advisors and Collaborators

Our International Network

Giuseppe Giaccone

NIH - Washington

Bert‘t Hart

BPRC – Rijswijk

Richard Pierson

SOM - Baltimore

Prasad Adusumilli

MSKCC – New York

Masayuki Miyasaka

Suita – Osaka

Régis Josien

INSERM – Nantes

Tom Mc Donald

Queen Mary – London

Gilles Blancho –

Nantes

Katryn Wood

NDS – Oxford

Benjamin Besse

IGR – Paris

Leslie Kean

C.H. - Seattle

Luis Rizzo

A. Einstein - Sao Paulo

Christophe Louvet

IMM/GERCOR – Paris

17

In Phase 3 in NSCLC post-CKI – Step-1 results expected in April 2020

In Phase 2 in pancreatic cancer in combination with Opdivo® in a GERCOR sponsored studyTedopi®

In Phase 1 in advanced solid tumorsBI 765063 (Sirpa-CD47)

A new Bi-specific platform with an anti-PD-1 backbone (proprietary)BiCKI®

Phase 2 planning in auto-immune diseases or transplantFR104 (CD-28)

Phase 2 in UC (sponsor OSE) & in Sjögren’ s syndrome (sponsor Servier) expected to start in

2020OSE-127 (IL-7 receptor)

Potential € 1.3Bn milestone payments in auto-immune diseases and immuno-oncology through partnerships

with top pharmaceuticals

Boehringer Ingelheim on BI 765063 . Servier on OSE-127 . Local partners on Tedopi® : Rafa in Israel and CKD in South Korea

Projected catalysts to drive near term value

A High Potential Clinical-Stage BiotechKey Highlights

Progress with R&D new targets

18

Ongoing Phase 3 clinical study of Tedopi®

in NSCLC patients

post checkpoint-inhibitor

Step-1 results expected in April 2020

A potential of € 1.3Bn milestone payments

through partnerships with top pharma companies:

• Boehringer Ingelheim on BI 765063

• Servier on OSE-127

• Local partners on Tedopi® : Rafa in Israel and CKD

in South Korea

Multiple programs in clinical stage development:

• Non-small cell lung cancer post CKI

• Advanced pancreatic cancer

• Solid tumors

• Ulcerative colitis and Sjögren’s syndrome

• Autoimmune diseases & transplantation

Additional first-in-class products in discovery/early

clinical covering immuno-oncology (myeloid

checkpoints) and autoimmune indications

OSE ImmunotherapeuticsInvestor Highlights

20


IMMUNO-ONCOLOGY

Tedopi® NSCLCEU-US-Israel

ongoing

Tedopi®Advanced

pancreatic cancer

Combo with PD1

Opdivo®

Ongoing

First-in-Class Portfolio in Immuno-oncology

Our lead product: Tedopi®

• A proprietary combination of neoepitopes aimed at stimulating T-lymphocytes

• Currently in Phase 3 clinical trial in advanced NSCLC post checkpoint inhibitor (CKI) failure


• Currently in Phase 2 clinical trial in combination with CKI Opdivo® in aggressive advanced pancreatic cancer

21

An Alternative Approach to Cytotoxic T-Cell Activation

Tedopi®

Tedopi®

• A proprietary combination of 9 optimized « neoepitopes »

+ 1 epitope giving universal T helper response

• Restores the immuno-surveillance of cancer cells in HLA-A2 positive responder patients

• Induces early T-cell memory responses

• Strong patent family plus orphan status in the US

NEOEPITOPES / HLA / TCR binding:

Mandatory to activate cytotoxic T-cell response

Neoepitopes: Small peptides deriving from tumor

specific antigens expressed in various cancers,

1st T-lymphocyte activation signal

22

Tedopi®

Suspected Mechanisms of Resistance to PD-1/PD-L1 Checkpoint Inhibitors:HLA Downregulation

23

Tedopi® Technology: A Differentiated Approach to Immune StimulationBased on MHC*-I (HLA-A2) Neoepitopes

• Loss of MHC-I expression, in cancer cells, is known to play a role in tumor escape from immune system.

• MHC-I defects play a direct role in cancer progression, increasing the growth and invasive potential of cancer cell1

• Many oncogenes have been shown to interfere with antigen processing and presentation as HER2 and p532

• Down-regulated MHC class I surface expression could be corrected by IFN-treatment like T cell activation i.e in pancreatic human tissue samples, reduction or loss of HLA class I was observed in 76% of cases.

These reductions were reversible upon exposure to IFN-γ in vitro, suggesting a regulatory

rather than structural defect in these genes (Pandha H et al. Clin Exp Immunology 2007)

* Major Histocompatibility Complex

1 Garrido et al 2012;

2 Mimura et al 2011- Sabapathy K et al 2008 24

Tedopi® : Epitopes Identification and Selection Based on 10 Years of R&D

25

For Non-Small Cell Lung Cancer (NSCLC) after Checkpoint Inhibitor Failure

Tedopi®

234,030 154,050

NEW CASES IN 2018 DEATHS IN 2018

• Checkpoint inhibitors are rapidly becoming the first line

standard of care for NSCLC and are expected to command

a significant portion of the market by 2024

• Tedopi® is being explored as a second-line therapy in

NSCLC patients following CKI failure and has the chance to

capture a share of this market2014–2024 NSCLC market size2

2014 2024

1 American Cancer Society. Facts & Figures 2018. American Cancer Society. Atlanta, Ga. 2018.2 K Nawaz & RM Webster. The non-small-cell lung cancer drug market. Nature Reviews Drug Discovery v15, pages 229–230 (2016) DOI: 10.1038/nrd.2016.42

NSCLC = 80-85% of all lung cancers

LUNG CANCER:

2ND MOST COMMON CANCER

In the United States1

26

Increased Survival in Poor Prognosis Patients

Tedopi® Phase 2 Results

TEDOPI®

MEDIAN OVERALL SURVIVAL (p=0.086)

• TEDOPI®: 17.3 MONTHS vs. CONTROL* (HLA-A2-) : 12 months

ONE YEAR SURVIVAL (p=0.063)

• TEDOPI®: 59% vs. CONTROL* (HLA-A2-) : 49%

CORRELATION BETWEEN EPITOPE

RESPONSES AND SURVIVAL (p<0.001)

Correlation between immune responses and survival

0 - 1 epitope: 406 ± 58 days of survivalLow

2 - 3 epitopes: 778 ± 72 days of survivalMedium

4 - 5 epitopes: 875 ± 67 days of survivalHigh

27

After at Least First Line Failure: Long Term Survival in 64 ITT Patients

Tedopi® Phase 2 Results in Advanced NSCLC (Stage IIIb & IV)

MEDIAN OVERALL SURVIVAL: 17 MONTHS

Surviving Patients Following 2 Year Treatment With Tedopi®

67% of the patients enrolled in the

Phase 2 study were metastatic

65.5% received more than 2

previous lines of treatment

9% of Brain Metastasis patients**

* Survival in the literature is at 1% for stage IV NSCLC

**J. Nemunaitis, abstr 1202 brain metastasis WORLD CONFERENCE ON LUNG CANCER 2015

Promising clinical results in this

difficult patient population.

Strong improvement in the long-

term survival rate in patients with

poor prognosis factor*

25%

4 years OS

# of Days

25%

28

Brahmer –NEJM 2015 * Borghaei – NEJM 2015 * Felip -ESMO 2017 * Herbst – Lancet Oncol 2016 * Herbst – ESMO 2016 * Herbst – ASCO 2017 * Barve JCO 2008

PDL1 ≥ 50%: 14.9 vs. 17.3 vs. 8.2

HR 0.54, HR 0.50

Pembro - PD-L1 ≥1%

Nivo - All comers Nivo - All comers

Tedopi® Phase 2 Results in Advanced NSCLC (Stage IIIb & IV) Second Line Tx Landscape in Advanced NSCLC and Tedopi® Long Term Survivors at 4 Years

Tedopi© - HLA-A2+

25%

At year 4

Tedopi® shows comparable long-term survival to multiple approved NSCLC therapies in their respective Phase 2 studies

29

After Immune Checkpoint Inhibitor Escape

Tedopi® Phase 3 Clinical Trial in Advanced NSCLC Patients

https://www.clinicaltrials.gov/ct2/show/NCT02654587

Potential benefit in patients who have

previously failed CKI treatment

Enrolment of approximately 100 patients to be

expanded to a total of 325 patients depending

on survival data

Primary Endpoint:

Overall Survival (OS)

Secondary Endpoints:

Progression-free survival, Quality of Life,

Overall response rate, Tolerance

Potential breakthrough therapy following

PD-1 or PD-L1 tumour progression

Invasive or metastatic

Stage second or third

line treatment

After CKI failure

Step 1: 100 NSCLC patients

Amended protocol

accepted by Authorities

and IRB to restart

ATALANTE 1 recruitment

2 step-studyStep-1 results expected

In April 2020

30

Mechanism of Action of Multiple Neoepitope Vaccine when Resistance to ICI

Multiple neoepitope vaccine1

• Increase the tumor associated antigen

(TAA) presentation

• Increase the priming and activation of T

cell

To increase the recognition of cancer cells

by specific T cells

Mechanism Examples

Tumor cell-

intrinsic

Absence of antigenic proteins Low mutational burden

Lack of viral antigens

Lack of cancer-testis antigens

Overlapping surface proteins

Absence of antigen

presentation

Deletion in TAP transporters

Deletion in B2M

Silenced HLA

Genetic T cell exclusion Oncogenic PD-L1 expression

MAPK oncogenic signaling

Stabilized b-catenin

Mesenchymal transcriptome

Insensibility to T cells Mutations in ITNδ pathway signaling

Tumor cell-

extrinsic

Absence of T cells Lack of T cells with tumor antigen-specific

TCRs

Inhibitory immune checkpoints VISTA, LAG-3, TIM-3

Immunosuppressive cells TAMs, Tregs

Mechanisms of primary & adaptive resistance to immunotherapy2

1 Fikes, EOBT 2003; 2Sharma, Cell 2017 Viteri , AACR 2019

31

Tedopi®: Cases of Interest in NSCLC Post-Checkpoint FailureClinical Characteristics

Patient 1 Patient 2 Patient 3 Patient 4 (control)

Gender Male Female Male Female

Age (years) 54 44 49 52

Histology Squamous Adenocarcinoma Adenocarcinoma Adenocarcinoma

Metastatic sites Lung, pleural Pleural Brain, lung, Lymph Lung, Adrenal

Mutation profile Not done KRAS G12C EGFR wt ALK wt KRAS G12V

HLA A2 phenotype* A*02, A*01 A*02, A*01 A*02, A*30 A*02,A*03

Previous treatment lines 2 2 2 2

ICI treatment Anti-PD1 Anti-PD1 Anti-PD1 + anti-CTLA4 Anti-PD1 + AXL Inh

ICI best response SD PD PR PD

Time lapse ICI/Tedopi 57 d 39 d 51 d 43 d

*HLA typing by PCR-SSOP (Luminex)

Viteri et al., AACR 2019

32

Tedopi®: Cases of Interest in NSCLC Post-Checkpoint FailureEfficacy & Safety

Patient 1 Patient 2 Patient 3 Patient 4 (control)

Best response to Tedopi® PR SD > 9 mo SD > 9 mo PD

Treatment duration 3.7 mo 11.5 mo 16.9 mo 2.8 mo

Progression Free Survival 4.2 mo 11 mo 18.1 mo 2.1 mo

OS after Tedopi® initiation 20.6+ mo 22.1+ mo 20.3+ mo 7.1+ mo

Immune–related adverse events No side effects

Post-injection Cytokine

release syndrome x 5; Local

site induration;

Hyperthyroidism

HyperthyroidismHypothyroidism;

Post-injection Fever x 2

Treatment after Tedopi® Yes (CT) Yes (CT) Yes (CT) Yes (CT)

Viteri et al., AACR 2019

33

Tedopi®: For Pancreatic Cancer

1 American Cancer Society. Facts & Figures 2018. American Cancer Society. Atlanta, Ga. 2018.

2 Globocan 2012 (World Health Organization)

• Worldwide incidence: 337,000 Cases = 330,000

Cases With Mortality2

• The five-year survival with pancreatic cancer rate

is 9%

• There is a lack of effective therapies with minimal

side effects

Projected Number of Pancreatic Cancer Patients

Eligible for Treatment in 2018

Diagnosed in 2018: 55,440

Patients Treated: 34,373

Receiving 1L Treatment: 27,498

Receiving 2L Treatment: 10,999-13,749

leading to 44,330 deaths per year

3rd MOST DEADLY CANCER

In the United States155,440 44,330

NEW CASES IN 2018 DEATHS IN 2018

34

Tedopi®: Phase 2 Study in Pancreatic Cancer

1 American Cancer Society. Facts & Figures 2018. American Cancer Society. Atlanta, Ga. 2018.

2 Globocan 2012 (World Health Organization)

The Potential to Address High Therapeutic Needs Combining Tedopi® with PD-1 CKI Opdivo®

To evaluate Tedopi® as a maintenance

therapy, alone or in combination with

Opdivo® (Nivolumab) and evaluated versus

Folfiri (current second-line SoC)HLA-A2 positive patients

with stable disease

who received 4 months

of Folforinox

(the current SoC)

Sponsored by GERCOR:

a cooperative group of digestive oncology experts,

international recognition and supported by

Bristol-Myers Squibb

Phase 2 Study

Tedopi® Tedopi®

+Opdivo®

Control Group

Folfiri alone(standard protocol)

35

Immuno-Oncology


First-in-class product

BI 765063 (antagonist of SIRP⍺)

• First-in-class myeloid checkpoint transforming suppressive cells into effector cells within tumor micro-environment

• License and collaboration agreement with Boehringer Ingelheim (April 2018) to develop BI 765063 in multiple

cancer indications

• Phase 1 trial ongoing in patients with advanced solid tumors A dose finding study of BI 765063 administered as a single agent and in combination with Boehringer Ingelheim’s monoclonal

antibody PD-1 antagonist BI 754091, a lymphocyte T checkpoint inhibitor


IMMUNO-ONCOLOGY

BI 765063

(OSE-172)

SIRP⍺

Various

cancersOngoing

36

For BI 765063 (OSE-172)

A Strategic Partner of Choice

“We are excited to partner with OSE Immunotherapeutics to develop this promising, novel cancer immunotherapy (…)”

Jonathon Sedgwick, VP & Global Head, Cancer Immunology Boehringer Ingelheim

INTERNAL

Anti-PD1

Anti LAG 3

SMAC mimetics

IL23-i

PARTNERSHIPS

Vira Therapeutics

(oncolytic viruses)

CureVac

(mRNA vaccines)

GLOBAL FOOTPRINT

Europe

Americas

Asia

COLLABORATION

Sarah Cannon RI

(57 sites in the US)

COMBINATION POTENTIAL GLOBAL EXECUTION CAPABILITIES

“The objective for the next wave of cancer immunology therapeutics is to alert the immune system (…)”

Jonathon Sedgwick, VP & Global Head, Cancer Immunology Boehringer Ingelheim

Sales over € 16Bn R&D over € 3Bn

37

Joint Development Agreement

BI 765063 (OSE-172)

Boehringer Ingelheim has acquired the rights to develop, register and commercialize BI 765063

and will bear all costs for this product development

€ 15m Upfront payment

April 2018

€ 15m Milestone payments

Upon CTA for Phase 1 and

1st dosing of patient

H1 2019

Up to € 1.1Bn

Milestone payments

+ Royalties on sales

Global Immuno-oncology Partnership to develop

BI 765063

38

Activates Anti-Tumor Macrophages and Dendritic Cells Function

BI 765063 (OSE-172): Tackles Myeloid Suppressive Cells (MDSC, TAM)

First-In-Class

BI 765063

OSE IMMUNOTHERAPEUTICS DISCOVERY: SIRPα IS EXPRESSED BY MDSCS AND TAMS AND CONTROLS THEIR DIFFERENTIATION

STRONG PATENT POSITION 2014-2015-2016-2017

BI 765063 inhibits MDSC and macrophages M2 pro-tumorigenic cells and increases M1 anti-tumorigenic cells. In addition,

BI 765063 is not binding human T-cells, allowing strong T-cell proliferation.

24th Molecular Medicine TRI-CONFERENCE, Feb 2017

39

An Original Approach to CD47 Blockade in Humans

BI 765063 (OSE-172) : Antagonist of SIRP-alpha

40

BiCKI® PlatformNovel Bispecific Checkpoint Inhibitor Platform Targeting PD-1 and Innovative Targets

BiCKI®: Bispecific checkpoint inhibitor platform

• Bispecific fusion protein built on engineered anti-PD-1 mAb key backbone

• Combined with innovative targets strive for synergy

• Multimodal technology to adress primary & secondary resistance mechanisms

BiCKI® IL-7: To REVIVE the Cancer Immunity Cycle

• Synergistically potentiates TCR signaling

• Expands TEFF but not TREG

• Inhibits TREG functions

• Promotes mucosal T cell migration

• Restores TEX proliferation and functions

• Prevents T cell apoptosis & clonal deletion

BiCKI®IL-7Priming , activation,

homeostasis, expansion

BiCKI®IL-7Mucosal Migration

BiCKI®IL-7Disarms TREG function

BiCKI®IL-7Reinvigorates TEX

Prevents clonal deletion

41

OSE-279 / BiCKI®: a Response to Primary and Secondary Resistance to Immune Checkpoint Inhibitors

42

Inadequate T cell priming/expansion

Lack of T cell infiltration

Macrophages and Dendritic cell dysfunction

Tumor antigen loss

Immunosupressive microenvironment

Programmed T cell death

Lack of T cell costimulation

Anti PD-1 associated resistance mechanismsCancer immunity cycle

OSE-279 / BiCKI®: a Breakthrough Discovery at Proof of Concept Status Protected by 4 Patent Applications

BiCKI®An innovative bifunctional anti-PD1 antibody platform engineered to improve its

bioproduction in a bi-functional format in mammalian cells and providing protein stability

Selection of most promising candidates to go to clinical trials

Wider spectrum of patients responding to immunotherapies

Protection by 4 patent applications filed in December 2018

43

Anti PD-1 Backbone

Blocks PD-1 inhibitory signal

Delivers drug into the tumor microenvironment (TME) on PD-

1 expressing T cells

Second part of the bi-functional molecule

Restores T cell antitumoral activity or modifies the TME to

favor anti-tumor immune response

Costim. Activator CKI, Cytokines & Tumor targeting

Production of several anti PD-1 monoclonal

OSE-279 / BiCKI®: Multiple Treatment Possibilities In a Promising Market with High Interest

Possible therapeutic indications A dynamic market

BiCKI platform development acceleration thanks to OSE’s

degree of innovation and immunological expertise to

activate/regulate immune responses

Opportunities in cancer indications with already approved anti-PD-(L)1

immunotherapy, that are efficient in 15 to 30% of patients:

Melanoma

NSCLC

Head and Neck

squamous cell

carcinomaHodgkin

lymphoma

Urothelial

carcinoma

Gastric cancer

Colorectal cancer

Benefits for more than half of these cancer patients and

opportunities in non-registered anti-PD-(L)1 cancer

indication

44

1Only company developing in clinic IL7-receptor

antagonist for auto-immune and inflammatory

chronic diseases

$10.6BnGlobal immune checkpoint inhibitors market

valuation in 2017

20.1% Projected market CAGR from 2018 to 2025

0No approved drugs in anti-PD1/PDL1-refractory

patients or indications yet

Severalagreements

Auto-Immune Diseases

First-in-Class Portfolio – FR104


• Aim is to show clinical evidence of immune system control that would support use of FR104 in

auto-immune diseases (such as rheumatoid arthritis, for instance) or transplantation


AUTOIMMUNE DISEASES

FR104

CD28

Autoimmune

diseases &

Transplantation

Phase 2 planning

ongoing

45

Immune checkpoint

TREG function

ICOS-L

PDL-1(abatacept)

FR104 is a Selective CD28 AntagonistOriginal Control of Immune Synapses: TEFF Controlled and TREG Potentiated

CD28 delivers stimulatory signals to T cells - CTLA-4 and PDL-1 deliver inhibitory signals to T cells

• FR104 (CD28 antagonist) blocks selectively stimulatory signals, reinforcing T cell inhibition and

promoting Tregulatory function

• Abatacept (CTLA4 Ig= CD80/86 antagonists) blocks both stimulatory and inhibitory signals

Antigen-presenting

Cell-APCs

CD28, CTLA-4 and PD-L1 ligands on T cells binding to CD80/CD86 on human APCs

46

46

Poirier et al J of Immunology 2016 First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28

D 1 D 1 5 D 2 9 D 5 7 D 8 5 D 1 1 3

0

5 0 0 0 0

1 0 0 0 0 0

1 5 0 0 0 0

2 0 0 0 0 0

T im e

An

ti-K

LH

Ab

s (

U/m

l)

0 .0 2 m g /K g

0 .2 m g /K g

0 .5 m g /K g

1 .5 m g /K g

P la c e b o

D 1 D 1 5 D 2 9 D 5 7 D 8 5 D 1 1 3

0

1 0 0 0

2 0 0 0

3 0 0 0

4 0 0 0

5 0 0 0

T im e

An

ti-K

LH

Ab

s (

% f

rom

Da

y 1

)

0 .0 2 m g /K g

0 .2 m g /K g

0 .5 m g /K g

1 .5 m g /K g

P la c e b o

• FR104 demonstrated a good safety profile No clinical or biological events - FR104 did not alter

total lymphocyte counts or lymphocyte subsets

No elevation of cytokines observed in the serum of any

subjects

• FR104 shows efficacy in human to control

anti-KLH (IgG) responses

• At 1.5mg/kg the anti-KLH antibodies (IgG) was

suppressed at long term until Day 57

• FR104 controls T follicular helper (Tfh) and

thereby IgG responsesTfh cells ( CD4+ Cell subset) are correlated with

disease activity and autoantibody production in

various human autoimmune diseases

• Recommended Phase 2 doses based on KLH

responses : 0.5 mg/kg and 1.5 mg/kg

Selective CD28 antagonist FR104 induces persistent

expression of anti-KLH Abs

FR104 – Phase I Clinical Trial DataPlacebo-controlled, Randomized, Double-blind

Single and Multiple IV Doses of FR104 in 65 Subjects

47

47

First-in-Class Portfolio in Autoimmune Diseases


• OSE-127: antagonist of the Interleukin-7 α-receptor or CD127, control of pathogenic T-cells

• Phase 1 positive results (Dec. 2019):

• Good safety and tolerability profile

• Consistent pharmacokinetic and pharmacodynamic parameters

• Dose-proportionality across the several dose-levels up to 10 mg/kg

• Two Phase 2 trials expected to start in 2020

• Ulcerative Colitis (OSE sponsor) and Sjögren’s syndrome (Servier sponsor)

• License option agreement with Servier in December 2016


AUTO-IMMUNE DISEASES

OSE-127IL-7R

Ulcerative Colitis

Sjögren syndrome

Positive Phase 1

Results Q4 20192020

48

License Option to Servier after Phase 2

OSE-127 - Differentiated MoA as Full IL-7 Receptor Antagonist

€ 10.25m upfront

December 2016

€ 30m Two-step option fee

Phase 2 completion UC & Sjögren’s

Including € 10m paid upon exercise of first option step (February 2019)

Total potential € 272mMilestone payments and

royalties on sales

OSE-127

• A recent peer-reviewed publication in Nature

Communications highlighted a novel

mechanism of action for

OSE-127:

• OSE-127 is a full-antagonist at IL-7R

• OSE-127 demonstrated antigen-specific

blunting of memory T cell responses

49

OSE-127: Positive results of First-in-Human Dose-Escalation Phase 1 Clinical Trial

* Belarif, L. et al.IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation. Nature communications, 26 October 2018

First-in-human dose-escalation,

randomized, double-blind, placebo-controlled clinical

trial in 63 healthy volunteers

First subjects dosed in Phase 1

December 2018

A Breakthrough Approach for the Treatment of Inflammatory Autoimmune Diseases*

To evaluate the safety and tolerability of single-and multiple-ascending

intravenous and subcutaneous doses

of OSE-127

Positive Phase 1 results

• Good safety and tolerability profile for OSE-127

• Consistent PK & PD parameters, dose-proportionality across the several dose-levels up to 10 mg/kg

Two planned Phase 2 trials

• In Ulcerative Colitis (OSE sponsor) and in Sjögren’s syndrome (Servier sponsor)

• Both trial initiations expected in 2020

50

Financing and Innovation

Current Academic & Public Partnerships

Objective:

Clinical developmentuntil Phase 2

Objective:

Clinical developmentuntil Phase 2

Objective:

Phase 2 in pancreatic cancer in combo with Opdivo®

Partners: Partners: Partners:

Next step:

Phase 2 clinical trial in UC expected to start in 2020

Next step:

Phase 1 clinical trial ongoing in premier

European cancer centers

Next step:

Phase 2 clinical trial ongoing

Objective:

Product efficacy profile and development strategy

Partner:

Next step:

Development strategy in solid tumors

Potential CAR-T

OSE-127

EFFIMab

BI 765063 (OSE-172)

EFFI-CLINTEDOPI® OSE-703

51

Ongoing Phase 3 clinical study of Tedopi®

in NSCLC patients

post checkpoint inhibitor failure


A potential of € 1.3Bn milestone payments

through partnerships with top pharma companies:

• Boehringer Ingelheim on BI 765063

• Servier on OSE-127

• Local partners on Tedopi® : Rafa in Israel and CKD

in South Korea

Multiple programs in clinical stage development:

• Non-small cell lung cancer post CKI

• Advanced pancreatic cancer

• Solid tumors

• Ulcerative colitis and Sjögren’s syndrome

• Autoimmune diseases & transplantation

Additional first-in-class products in

discovery/early clinical covering

immuno-oncology (myeloid checkpoints)

and autoimmune indications


Investor Highlights

52

Contacts:

Alexis Peyroles, CEO

[email protected]

+33 6 11 51 19 77

Dominique Costantini, Chairman, Director of Development

[email protected]

+33 6 13 20 77 49

Company information: http://ose-immuno.com/en/

Head Office22, boulevard Bénoni Goullin

44200 Nantes, France

Paris Office100, avenue de Suffren

75015 Paris, France

cancer and autoimmune diseases · and autoimmune diseases a balanced business model: mature...

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