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. 3 OSE Immunotherapeutics Company Overview

OSE’s Technological Platform: From Target Identification to Product Validation and Beyond An integrated operational immunology research platform

Intertwined with academic research Common locations, Founded in 2012 01 mixed team IPO in 2015 (€ 21.1m) Fully translational Constant collaboration with clinicians, Listed on EuroNext Paris, EPA ticker OSE 02 pre-clinical humanized models As of June 30, 2019 Turn over € 16m - Net profit € 0.5m Leveraging a unique experience of 25 years of clinical 03 immunology in immunotherapy cluster in Nantes Cash € 26.5m Financial visibility until end of 2020 04 Connected internationally with top academic centers 4 OSE Immunotherapeutics Investor Highlights

Multiple programs in clinical stage development: Ongoing Phase 3 clinical study of Tedopi® in NSCLC patients • Non-small cell lung cancer post CKI post checkpoint inhibitor failure • Advanced pancreatic cancer • Solid tumors Interim results expected end of Q1 2020 • Ulcerative colitis and Sjögren’s syndrome • Autoimmune diseases & transplantation

A potential of € 1.3Bn milestone payments through partnerships with top pharma companies: Additional first-in-class products in discovery/early clinical covering • Boehringer Ingelheim on BI 765063 immuno-oncology (myeloid checkpoints) • Servier on OSE-127 and autoimmune indications • Local partners on Tedopi® : Rafa in Israel and CKD in South Korea 5 Current Industrial Partnerships Up to € 1.3Bn in Potential Milestones + Royalties

OSE-127 BI 765063 (OSE-172) Tedopi®

€ 10.25m Upfront payment € 15m Upfront payment € 1.2m upfront and short-term December 2016 April 2018 milestones Q1 2020

€ 30m € 15m Milestone payments: CTA Phase 1 2 step option fee: Phase 2 completion UC & st Up to € 4.3m Sjögren Incl. € 10m paid upon exercise of 1st and 1 dosing of a patient option step February 2019 H1 2019 Milestone payments + Royalties on sales and a margin Up to € 272m Up to € 1.1Bn within the transfer price Milestone payments Milestone payments + Royalties on sales + Royalties on sales

Up to € 1.3Bn Milestone payments + Royalties on sales 6 6 Abilities and Knowledge To Address Key Drivers of the Immune System

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

Cancer Vaccine Bispecific Macrophage Dendritic cells Immune Balance Priming Immune checkpoint Phagocytosis Ag presentation Effectors vs Regulators 7 7 OSE’s Research Pillars

Transversal Biotechnologies

Antibody discovery Molecular Engineering Bioproduction Bioanalytics

I/O: T-cell Approach I/O: New Myeloid Targets I&I: New Concepts

▪ Selective Immune Checkpoint (CD28, SIRPg) ▪ Cancer Vaccine ▪ New Immune Checkpoint (SIRPa, CLEC-1) (Tedopi®) ▪ New Cytokine Blockade (IL-7R) ▪ Bispecific Immune Checkpoints ▪ Phagocytosis & Sensing of death (BiCKI®) ▪ Resolution of Inflammation (ChemR23)

Translational Research

Human 3D ‘organ’ ex-vivo platform Bio-Informatics (3D patient-derived primary tissue explant cultures) (Big Data, Target discovery/validation) 8 First-in-Class Portfolio Immuno-Oncology and Auto-Immune Diseases

Pre-Clinical PROGRAM Indication Phase 1 Phase 2 Phase 3 POC IMMUNO-ONCOLOGY

Tedopi® EU-US-Israel NSCLC Neoepitopes Ongoing

Advanced pancreatic Combo with PD1 Tedopi® cancer Opdivo® Ongoing

BI 765063 (OSE-172) Various cancers Ongoing SIRP⍺ OSE-703 Various cancers 2020 IL-7R BiCKI® Bispecific anti-PD-1 & Various cancers 2020 Innovative Targets AUTO-IMMUNE DISEASES

FR104 Autoimmune diseases Phase 2 planning CD28 & Transplantation ongoing First-in-class product OSE-127 Ulcerative Colitis Positive Phase 1 2020 IL-7R Sjögren’s syndrome Results Q4 2019 9 A High Potential Clinical-Stage Biotech Key Highlights

Projected catalysts that drive near term value

In Phase 3 in NSCLC post-CKI – First-step results expected end of Q1 2020 Tedopi® In Phase 2 in pancreatic cancer in combination with Opdivo® in a GERCOR sponsored study

BI 765063 In Phase 1 in advanced solid tumors

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

FR104 Phase 2 status in auto-immune diseases or transplant

OSE-127 Phase 2 in UC (sponsor OSE) & in Sjögren’ s syndrome (sponsor Servier) expected in 2020

Progress of the portfolio OSE-703 (with MSKCC), R&D new targets

A potential of € 1.3Bn milestone payments in auto-immune diseases and in 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 10 First-in-Class Portfolio Immuno-Oncology

Pre-Clinical PROGRAM Indication Phase 1 Phase 2 Phase 3 POC

IMMUNO-ONCOLOGY

EU-US-Israel Tedopi® NSCLC ongoing Combo with PD1 Advanced Tedopi® Opdivo® pancreatic cancer Ongoing

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 • Results from the first step expected end of Q1 2020 • Currently in Phase 2 clinical trial in combination with CKI Opdivo® in aggressive advanced pancreatic cancer 11 Tedopi® An Alternative Approach to Cytotoxic T-Cell Activation

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

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

Tedopi® 13 Tedopi® Technology: A Differentiated Approach to Immune Stimulation Based 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 14 Tedopi®: Epitopes Identification and Selection Based on 10 Years of R&D 15 Tedopi® For Non-Small Cell Lung Cancer (NSCLC) after Checkpoint Inhibitor Failure

LUNG CANCER: 2ND MOST COMMON CANCER In the United States1 234,030 154,050 NEW CASES IN 2018 DEATHS IN 2018 NSCLC = 80-85% of all lung cancers

2014 2024 • 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 market 2014–2024 NSCLC market size2

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 16 Tedopi® Phase 2 Results Increased Survival in Poor Prognosis Patients

Correlation between immune responses and survival

CORRELATION BETWEEN EPITOPE TEDOPI® RESPONSES AND SURVIVAL (p<0.001)

Low 0 - 1 epitope: 406 ± 58 days of survival

Medium 2 - 3 epitopes: 778 ± 72 days of survival

MEDIAN OVERALL SURVIVAL (p=0.086) ® • TEDOPI : 17.3 MONTHS vs. CONTROL* (HLA-A2-) : 12 months High 4 - 5 epitopes: 875 ± 67 days of survival ONE YEAR SURVIVAL (p=0.063) • TEDOPI®: 59% vs. CONTROL* (HLA-A2-) : 49% 17 Tedopi® Phase 2 Results in Advanced NSCLC (Stage IIIb & IV) After at Least First Line Failure: Long Term Survival in 64 ITT Patients

Surviving Patients Following 2 Year Treatment With Tedopi® 67% of the patients enrolled in the Phase 2 study were metastatic MEDIAN OVERALL SURVIVAL: 17 MONTHS 65.5% received more than 2 previous lines of treatment

9% of Brain Metastasis patients** 25% 25% 4 years OS Promising clinical results in this difficult patient population. Strong improvement in the long- term survival rate in patients with poor prognosis factor* # of Days

* Survival in the literature is at 1% for stage IV NSCLC **J. Nemunaitis, abstr 1202 brain metastasis WORLD CONFERENCE ON LUNG CANCER 2015 18 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

Nivo - All comers Nivo - All comers

25% PDL1 ≥ 50%: At year 4 14.9 vs. 17.3 vs. 8.2 HR 0.54, HR 0.50

Pembro - PD-L1 ≥1% Tedopi© - HLA-A2+

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

Brahmer –NEJM 2015 * Borghaei – NEJM 2015 * Felip -ESMO 2017 * Herbst – Lancet Oncol 2016 * Herbst – ESMO 2016 * Herbst – ASCO 2017 * Barve JCO 2008 19 Tedopi® Phase 3 Clinical Trial in Advanced NSCLC Patients After Immune Checkpoint Inhibitor Escape

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 Invasive or metastatic on survival data Amended protocol Stage Second or third accepted by Authorities line treatment Primary Endpoint: and IRB to restart After CKI failure Overall Survival (OS) ATALANTE 1 recruitment Secondary Endpoints: 2 step-study Step 1:  100 NSCLC patients Progression-free survival, Quality of Life, Overall response rate, Tolerance Step 1 results expected end of Q1 2020 Potential breakthrough therapy following PD-1 or PD-L1 tumour progression

https://www.clinicaltrials.gov/ct2/show/NCT02654587 20 Mechanism of Action of Multiple Neoepitope Vaccine when Resistance to ICI

Multiple neoepitope vaccine1 Mechanism Examples Tumor cell- Absence of antigenic proteins Low mutational burden • Increase the tumor associated antigen intrinsic Lack of viral antigens Lack of cancer-testis antigens (TAA) presentation Overlapping surface proteins

Absence of antigen Deletion in TAP transporters • Increase the priming and activation of T presentation Deletion in B2M cell 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

To increase the recognition of cancer cells Tumor cell- Absence of T cells Lack of T cells with tumor antigen-specific by specific T cells extrinsic TCRs Inhibitory immune checkpoints VISTA, LAG-3, TIM-3

Immunosuppressive cells TAMs, Tregs Mechanisms of primary & adaptive resistance to immunotherapy2

1 2 Fikes, EOBT 2003; Sharma, Cell 2017 Viteri , AACR 2019 21 Tedopi®: Cases of Interest in NSCLC Post-Checkpoint Failure Clinical 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

Viteri et al., AACR 2019 *HLA typing by PCR-SSOP (Luminex) 22 Tedopi®: Cases of Interest in NSCLC Post-Checkpoint Failure Efficacy & 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

Post-injection Cytokine release syndrome x 5; Local Hypothyroidism; Immune–related adverse events No side effects Hyperthyroidism site induration; Post-injection Fever x 2 Hyperthyroidism

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

Viteri et al., AACR 2019 23 Tedopi® For Pancreatic Cancer

3rd MOST DEADLY CANCER 55,440 44,330 In the United States1 NEW CASES IN 2018 DEATHS IN 2018 leading to 44,330 deaths per year

• Worldwide incidence: 337,000 Cases = 330,000 Projected Number of Pancreatic Cancer Patients Cases With Mortality2 Eligible for Treatment in 2018 • The five-year survival with pancreatic cancer rate Diagnosed in 2018: 55,440 is 9% Patients Treated: 34,373 • There is a lack of effective therapies with minimal Receiving 1L Treatment: 27,498 side effects Receiving 2L Treatment: 10,999-13,749

1 American Cancer Society. Facts & Figures 2018. American Cancer Society. Atlanta, Ga. 2018. 2 Globocan 2012 (World Health Organization) 24 Tedopi® Phase 2 Study in Pancreatic Cancer The Potential to Address High Therapeutic Needs Combining Tedopi® with PD-1 CKI Opdivo®

Phase 2 Study To evaluate Tedopi® as a maintenance therapy, alone or in combination with Opdivo® (Nivolumab) and evaluated versus Folfiri (current second-line SoC) Sponsored by GERCOR: HLA-A2 positive patients a cooperative group of with stable disease digestive oncology experts, who received 4 months international recognition of Folforinox Control and supported by (the current SoC) Tedopi® Group Bristol-Myers Squibb Tedopi® + Folfiri alone Opdivo® (standard protocol)

1 American Cancer Society. Facts & Figures 2018. American Cancer Society. Atlanta, Ga. 2018. 2 Globocan 2012 (World Health Organization) 25 First-in-Class Portfolio Immuno-Oncology

Pre-Clinical PROGRAM Indication Phase 1 Phase 2 Phase 3 POC

IMMUNO-ONCOLOGY

BI 765063 Various (OSE-172) Ongoing cancers SIRP⍺ 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 26 A Strategic Partner of Choice For BI 765063 (OSE-172)

Sales over € 16Bn R&D over € 3Bn

“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

COMBINATION POTENTIAL GLOBAL EXECUTION CAPABILITIES

INTERNAL PARTNERSHIPS GLOBAL FOOTPRINT COLLABORATION Anti-PD1 Vira Therapeutics Anti LAG 3 (oncolytic viruses) Europe Sarah Cannon RI SMAC mimetics CureVac Americas (57 sites in the US) IL23-i (mRNA vaccines) Asia

“We are excited to partner with OSE Immunotherapeutics to develop this promising, novel cancer immunotherapy (…)” Jonathon Sedgwick, VP & Global Head, Cancer Immunology Boehringer Ingelheim 27 BI 765063 (OSE-172) Joint Development Agreement

Global Immuno-oncology Partnership to develop BI 765063

€ 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

Boehringer Ingelheim has acquired the rights to develop, register and commercialize BI 765063 and will bear all costs for this product development 28 BI 765063 (OSE-172): Tackles Myeloid Suppressive Cells (MDSC, TAM) Activates Anti-Tumor Macrophages and Dendritic Cells Function

BI 765063

First-In-Class

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 29 BI 765063 (OSE-172) An Original Approach to CD47 Blockade in Humans 30 First-in-Class Portfolio Immuno-Oncology

Pre-Clinical PROGRAM Indication Phase 1 Phase 2 Phase 3 POC

IMMUNO-ONCOLOGY

OSE-703 Various cancers 2020 First-in-class product

OSE-703: Cytotoxic targeted mAb IL-7R, in collaboration with MSKCC 31 OSE-703: Targeting the Interleukin-7 Receptor Research Collaboration with MSKCC, NY

OSE-703: cytotoxic monoclonal antibody against the alpha chain of Interleukin-7 Receptor (IL-7R) • IL-7R is aberrantly expressed on tumor cells • OSE-703 has an engineered IgG1 Fc-tail that helps to improve binding to FcgR (e.g. CD16) and thus increases three types of antibody mediated cytotoxicity: • Antibody Dependent Cell-mediated Cytotoxicity (ADCC) • Antibody-Dependent Cellular Phagocytosis (ADCP) • Complement-Dependent Cytotoxicity (CDC)

The antibody induced dose-dependent killing of tumor cells according to IL7Ra expression level, for example on acute T-cell leukemia or mesothelioma cells.

*Kei Suzuki et al.; J Clin Oncol 31:490-498. ©, 2012 *Tumoral IL-7 Receptor is a Potential Target for Lung Adenocarcinoma Immunotherapy Ming-Ching Lee et al. ; WORLD CONFERENCE ON LUNG CANCER 2017 32 BiCKI® Platform Novel 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 Priming , activation, homeostasis, expansion

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

• Synergistically potentiates TCR signaling

• Expands TEFF but not TREG • Inhibits T functions REG BiCKI®IL-7 BiCKI®IL-7 Mucosal Migration • Promotes mucosal T cell migration Reinvigorates TEX Prevents clonal deletion

• Restores TEX proliferation and functions • Prevents T cell apoptosis & clonal deletion BiCKI®IL-7

Disarms TREG function 33 First-in-Class Portfolio Auto-Immune Diseases

Pre-Clinical PROGRAM Indication Phase 1 Phase 2 Phase 3 POC AUTOIMMUNE DISEASES Autoimmune FR104 Phase 2 planning diseases & CD28 ongoing Transplantation

First-in-class product

• 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 34 FR104 is a Selective CD28 Antagonist 34

Original Control of Immune Synapses: TEFF Controlled and TREG Potentiated CD28, CTLA-4 and PD-L1 ligands on T cells binding to CD80/CD86 on human APCs Antigen-presenting Cell-APCs

ICOS-L

Immune checkpoint

TREG function

PDL-1 (abatacept)

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 35 35 FR104: Phase I Clinical Trial Data Placebo-controlled, Randomized, Double-blind - Single and Multiple IV Doses of FR104 in 65 Subjects

• FR104 demonstrated a good safety profile No clinical or biological events - FR104 did not alter Selective CD28 antagonist FR104 induces persistent total lymphocyte counts or lymphocyte subsets No elevation of cytokines observed in the serum of any

expression of anti-KLH Abs ) 1

subjects y

P la c e b o a P la c e b o

2 0 0 0 0 0 5 0 0 0

) D

l 0 .0 2 m g /K g 0 .0 2 m g /K g

0 .2 m g /K g • FR104 shows efficacy in human to control0 .2 m g /K g

m m

/ 0 .5 m g /K g 0 .5 m g /K g

o U r 4 0anti0 0 -KLH (IgG) responses 1 .5 m g /K g

( 1 .5 m g /K g

1 5 0 0 0 0

(

A • 3 0At0 0 1.5mg/kg the anti-KLH antibodies (IgG) was

H 1 0 0 0 0 0 suppressed at long term until Day 57

K 2 0 0 0

t n K • FR104 controls T follicular helper (Tfh) and

5 0 0 0 0 -

i A

t 1 0thereby0 0 IgG responses n

A Tfh cells ( CD4+ Cell subset) are correlated with

0 0disease activity and autoantibody production in D 1 D 1 5 D 2 9 D 5 7 D 8 5 D 1 1 3 variousD 1 humanD 1 5 autoimmuneD 2 9 D 5 7 diseasesD 8 5 D 1 1 3 T im e T im e • Recommended Phase 2 doses based on KLH responses : 0.5 mg/kg and 1.5 mg/kg

Poirier et al J of Immunology 2016 First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28 36 First-in-Class Portfolio Auto-Immune Diseases

Pre-Clinical PROGRAM Indication Phase 1 Phase 2 Phase 3 POC AUTO-IMMUNE DISEASES Ulcerative Colitis Positive Phase 1 OSE-127 2020 IL-7R Sjögren syndrome Results Q4 2019 First-in-class product

• 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 37 OSE-127: Differentiated MoA as Full IL-7 Receptor Antagonist License Option to Servier after Phase 2

• 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 OSE-127

€ 30m Two-step option fee € 10.25m upfront Phase 2 completion UC & Sjögren’s Total potential € 272m Including € 10m paid upon exercise of Milestone payments and December 2016 first option step (February 2019) royalties on sales 38 OSE-127: Positive results of First-in-Human Dose-Escalation Phase 1 Clinical Trial A Breakthrough Approach for the Treatment of Inflammatory Autoimmune Diseases*

Positive Phase 1 results First-in-human dose-escalation, • Good safety and tolerability profile for randomized, double-blind, To evaluate the safety OSE-127 placebo-controlled clinical and tolerability of single- • Consistent PK & PD parameters, dose- trial in 63 healthy and multiple-ascending proportionality across the several dose- volunteers intravenous and levels up to 10 mg/kg subcutaneous doses First subjects dosed of OSE-127 Two planned Phase 2 trials in Phase 1 • In Ulcerative Colitis (OSE sponsor) and December 2018 in Sjögren’s syndrome (Servier sponsor) • Both trial initiations expected in 2020

* Belarif, L. et al.IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation. Nature communications, 26 October 2018 39 Current Academic & Public Partnerships Financing and Innovation

OSE-127 BI 765063 (OSE-172) TEDOPI® OSE-703 EFFIMab EFFI-CLIN

Objective: Objective: Objective: Objective: Clinical development Clinical development Phase 2 in pancreatic cancer Product efficacy profile and until Phase 2 until Phase 2 in combo with Opdivo® development strategy Partners: Partners: Partners: Partner:

Next step: Next step: Next step: Next step: Phase 2 clinical trial in UC Phase 1 clinical trial Phase 2 clinical trial Development strategy in ongoing in premier ongoing solid tumors expected to start in 2020 European cancer centers Potential CAR-T 40 Key Figures in H1 2019

First Half 2019 Results

Turnover of € 16m • Net profit of € 0.5m

• R&D expenses: - € 9.2m representing 84% of total operating expenses

Cash available of € 26.5m (€ 23.6m in cash & cash equivalents and € 2.9m in current financial assets) Cash-in H1 2019 • Exercise of option 1 by Servier (OSE-127) : + € 10m • BI milestone after CTA and dosing of 1st patient (BI 765063): + € 15m Experienced Management Team 41 From Discovery to Market

Dominique Costantini, M.D., Immunology, Maryvonne Hiance, Vice Chairman Chairman & Director of Development & Director of Public Affairs • Roussel-HMR-Sanofi • SangStat Atlantic, DrugAbuse Sciences • Founder & CEO BioAlliance Pharma (Onxeo) • Founder & CEO Effimune • Founder & CEO OSE Pharma • Vice Chairman of France Biotech Association

Alexis Peyroles, CEO Anne-Laure Autret-Cornet, CFO • Finance & BD, Sanofi Japan & Eastern countries • Auditor, Deloitte • GM, Guerbet Latin America (Brazil) • Finance & Administration, Effimune

Claudia Fromond, Ph.D., Director of Preclinical & Translational Development • Ablynx-Sanofi, Pfizer • Inventiva Pharma, • Track record of success in pharma and biotech / immunology & oncology Experienced Management Team 42 42 From Discovery to Market

Bérangère Vasseur, M.D., CMO IO Frédérique Corallo, M.D., CMO AIDs • Broad experience in oncology development • Specializing in immunology • At Roche and at several biotechnology • Janssen Cilag, Roussel-HMR-Sanofi companies • Biogen, Medical Director

Nicolas Poirier, Ph.D., CSO Emilienne Soma, PharmD, Ph.D., • Ph.D. Immunology Director of Pharma Program Development • CRTI - Center for Research in Transplantation • Experience in R&D management and Immunology, Nantes • And in alliances in several biotechnology companies

Jean-Pascal Conduzorgues, PharmD, Qualified Person (QP) • Expertise in pharmaceutical development and drug management for clinical trials • Experience in pharmaceutical strategy and implementation in biotech companies 43 Our International Network Scientific Advisors and Collaborators

Leslie Kean Giuseppe Giaccone Prasad Adusumilli Tom Mc Donald Katryn Wood Bert‘t Hart Masayuki Miyasaka C.H. - Seattle NIH - Washington MSKCC – New York Queen Mary – London NDS – Oxford BPRC – Rijswijk Suita – Osaka

Luis Rizzo Richard Pierson Régis Josien Gilles Blancho – Benjamin Besse Christophe Louvet A. Einstein - Sao Paulo SOM - Baltimore INSERM – Nantes Nantes IGR – Paris IMM/GERCOR – Paris 44 OSE Immunotherapeutics Investor Highlights

Alexis Peyroles, CEO [email protected] Head Office +33 6 11 51 19 77 22, boulevard Bénoni Goullin 44200 Nantes, France Dominique Costantini, Chairman, Director of Development Paris Office [email protected] 100, avenue de Suffren +33 6 13 20 77 49 75015 Paris, France

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