JANUARY 2017

"Safe Harbor" Statement

This presentation contains forward-looking statements, which are based on our current expectations and assumptions. Due to various risks and uncertainties including changes in business, economic competitive conditions, regulatory reforms, foreign exchange rate fluctuations and the availability of financing, actual results, performance or achievements could differ materially from those included in the forwardlooking statements. These and other risk factors are discussed in the Company’s public reports. The company does not assume any obligations to update or revise any of these forward-looking statements, even if new information becomes available in the future.

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Medigene – clinical stage immunotherapies Corporate strategy  World-class immuno-oncology company focused on T-cell directed therapies

 Proprietary pipeline and partnered clinical development programs in oncology including hematological malignancies

Novel technology platforms  Dendritic cell vaccines (DCs), phase I/II in AML

 T-cell receptor-modified T cells (TCRs), late preclinical stage  T-cell-specific antibodies (TABs), preclinical development

Corporate information  Headquarters: Munich Germany, with offices/significant presence in the USA (DC & CA)  New Management Team with significant experience  Strong Balance Sheet with revenues from approved products  Listed on Frankfurt Stock Exchange: MDG1; WKN: A1X3W0; TecDax 3

Immunotherapy ̶ the future of cancer therapy

Cancer Immunotherapies

Newer Treatments

Classical Mainstays Surgery Radiation Chemotherapy

Before 1990

Hormone therapies Small molecule targeted therapies Antibody therapies

1990-2010

Stem cell transplantation Immune response modifiers DC vaccines Latest developments: Adoptive cell therapies CARs and TCRs

From 2010 4

Medigene’s immunotherapy pipeline

PROJECT

INDICATION

PRECLINICAL

PHASE I

DC vaccine

Acute myeloid leukemia (AML)

TCR

Undisclosed

Start H2 2017

TCR

Undisclosed

Start H2 2018

TABs

T cell leukemias + new applications

TCR-IIT *

Multiple myeloma

PHASE II

PHASE III

Start 2017

* Investigator-initiated trial (IIT) of a publicly funded collaboration between MDC, Charité and Medigene.

Additional IITs utilizing Medigene’s DC vaccine technology are ongoing at LMU Munich (Phase I/II in AML) and Oslo University Hospital (Phase II in prostate cancer)

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Medigene’s technology platforms are linked synergistically – to treat different kinds of cancer Medigene’s immunotherapy platforms DC vaccines

TCRs

TABs

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Medigene’s immunotherapies are tailored to address different types and stages of cancer DCs DC vaccines

TCR-modified T cells

high tumor burden

low tumor burden

Legend: tumor

TABs

TCRs

; T cell

; DC vaccine

; TCR-modified T cell

; pathogenic T cell

T-cell-specific mabs

unwanted T cells

; monoclonal antibody

;

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Medigene’s living immunotherapies reinforce immune defense Function

Biology mRNA, peptide

Encoded target

Products mRNA or peptide vaccines

dendritic cells

General

DC vaccines

T cells TCR-modified T-cell products

Soldiers

cancer cell = target

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Medigene’s technology platforms are linked synergistically – to treat different kinds of cancer Medigene’s immunotherapy platforms DC vaccines

TCRs

TABs

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Personalized cancer treatment based on Medigene’s TCR technologies

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Patient

1

Thawing and reinfusion into patient

TCR T-cell product

Leukapheresis & T-cell isolation

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GMP: expansion, freezing and quality tests

2 GMP: activation of T cells and transfer of TCR from TCR pipeline 10

Medigene’s TCR platform provides high versatility to build a pipeline of diverse therapeutic TCRs The Process: DCs are used to stimulate T cells In vitro system using healthy donors mDC

No need for patient blood samples T cell clones specific for diverse HLAs and antigens provide lead TCR candidates The TCR pipeline: therapeutic TCRs to modify patient T cells

Optimal-affinity TCRs without need for mutation Specificity for well characterized target epitopes Extensive screening for safety Transfer of desired functional capacities 11

Medigene has established a robotic platform for high-throughput generation of TCR lead candidates Selection of T cells

Screening of TCR candidates

High-throughput TCR analysis

(Source: www.tecan.com)

DNA sequence of individual TCR candidates

TCR pipeline 12

Medigene’s Immune Monitoring Facility supports the complete value chain  Target validation  Safety  Potency evaluation Immune Monitoring Facility Lead

R&D

Assay development NSG mouse model

Preclinic

Multicolor ELISPOT Cytokine assays Cytotoxicity assay Self-peptide analysis Alanine substitution analysis Expitope (in silico analysis) Nanostring methods Statistical data evaluation Interlaboratory comparison tests

Clinic

GCP/GCLP-compliant immune monitoring FACS sorting Multicolor flow cytometry Cytokine secretion assay

Market

Therapy

Data evaluation Documentation

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Compared to CARs, Medigene’s TCRs target a broader spectrum of tumor targets HER2

CD19

Minor histocompatibility antigens

Differentiation antigens

Mesothelin

Universal antigens

CD38

CARs target surface proteins:  

 

App. 30% of human proteome Limited to cell surface antigens, only tens of options Recognition is MHC*-independent Higher risks of side effects

*MHC: Major Histocompatibility Complex

Cancer-germline antigens

Viral antigens

Mutations

TCRs target intracellular proteins:  

 

App. 70% of human proteome Recognize intracellular targets, with many thousands of options (more addressable targets) Recognition is MHC-restricted (adds specificity) Lower risk for side effects if TCRs are natural, nonmutated structures 14

Medigene’s value creation along the TCR development chain Medigene’s TCR value chain

TCR generation module

TCRs

GMP production module

TCR R&D collaborations

TCR clinical development program

TCR development collaborations Target antigen: MAGE-A1 First TCR study in Germany!

TCR therapies

Medigene’s own TCR product development program Start of first Medigene TCR study in 2017 15

Medigene and bluebird bio establish strategic T-cell receptor (TCR) alliance in cancer immunotherapy Medigene to receive an upfront payment of USD 15 million, R&D funding, potential preclinical, clinical and commercial milestone payments, which together could total over USD 1 billion, in addition to royalties on net sales T cell receptor (TCR) therapeutic candidates against four targets to be generated using Medigene’s proprietary TCR technology platform

Medigene responsible for the generation and delivery of the TCRs to bluebird bio Joint preclinical development of all product candidates bluebird bio responsible for clinical development and commercialization of resulting products

bluebird bio will hold worldwide development and commercial rights and exclusive license for IP covering the TCRs Medigene retains all rights for its proprietary TCR development program and our own TCR pipeline 16

Collaboration with Charité and Max Delbrück Centre: IIT for multiple myeloma First TCR Clinical Trial to be conducted in Germany Grant-funded IIT with Charité and MDC in Berlin (2017): Medigene contributed to TCR characterization: MAGE-A1 and TCR epitope

expression in tumors / Expitope® Regulatory advice meetings held with competent authorities Investigational Medicinal Product Dossier (IMPD) in preparation for filing

Upcoming milestones in the collaboration: Submission of Clinical Trial Application (CTA), which includes the IMPD Official approval of CTA Start of the trial: 2017

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What will Medigene gain from this IIT study? Scientific benefit: Validation of Medigene’s in silico work on selected target antigens Validation of several in vitro functional assays for TCR assessment

Regulatory benefit: Experience on critical regulatory activities and first-hand feedback Advanced templates for IMPD content for our own TCR studies

Economic benefit: First right of negotiation for license of MAGE-A1 TCR for MM Participation at fixed rate if Medigene does not exercise its option and another party acquires the rights

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Status quo of preparations for Medigene’s first company-sponsored TCR study in 2017 Selection of lead TCR candidate

Vector

Manufacturing process development







GMP-process development at CMO

Clinical trial application (CTA)

Start of clinical study

2017

2017

Ongoing

Medigene’s first company-sponsored trial (2017): Viral vector production secured at EUFETS GmbH Commercial manufacturing partner selected Clinical trial sites chosen

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Summary of Medigene’s TCR assets & expertise Established R&D platform to identify, isolate and characterize TCRs across various target classes and HLA allotypes Vector system (SIN-RV) with CMO agreement for manufacturing Upscaling of cGMP process for individualized cells at designated CMO

Immune monitoring platform GCP/GCLP/GMP-compliant facility established at Medigene GCP/GCLP-compliant immune monitoring for future clinical trials in place

Regulatory experience Strong interactions with PEI for pioneering 1st TCR study in Germany Medigene’s history of successful interactions with PEI/EMA/FDA for clinical trials and MAs 20

Medigene’s technology platforms are linked synergistically – to treat different kinds of cancer Medigene’s immunotherapy platforms DC

TCRs

TABs

vaccines

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Our lead indication is acute myeloid leukemia (AML) – High medical need Disease characteristics: Most common type of leukemia in adults About 20,830 cases in USA* Median age at diagnosis: 63 years 5-year survival rate Adults < 65 years of age: 20 – 50% Adults > 65 years of age: 2 – 10%

*Source: NIH, SEER Stat Fact Sheets: Acute Myeloid Leukemia (AML) 22

Personalized cancer treatment with DC vaccines

4

Patient

1 Isolation of DC precursor cells from patient’s blood

Thawing and vaccination

DC vaccine product

3

GMP: freezing of vaccine cells in multiple aliquots and quality testing

2 GMP: generation of DCs and loading with tumor-target antigens 23

Medigene’s “new generation” DC vaccines overcome the weakness of other DC vaccines Medigene’s DC vaccines are high quality, fully characterized with >85% mature polarized DCs The special DC manufacturing process is patient-oriented, time-saving, cost-efficient and logistically simplified: No tumor tissue from patient needed Only one leukapheresis per patient Manufacturing time just three days High quantity yield of dendritic cells for more than 20 vaccinations Over two years shelf-life of frozen cells

Can be administered to the patient as required 24

Investigator-driven studies use Medigene’s DC vaccine technology to treat AML Lead indication AML trials

Sponsor

Status

Clinical Study, Investigator-initiated AML, intermediate and high-risk pts. Phase I/IIa Opened: Q1/2014 Enrollment completed Treatment/observation ongoing

Prof. M. Subklewe Data presented at: Ludwig-Maximilians-University CIMT 5/2016 Munich ASH 12/2016 NCT01734304

Compassionate Use Enrollment completed Treatment/observation ongoing

Prof. G. Kvalheim Dept. of Cellular Therapy Oslo University Hospital

Data presented at: CIMT 5/2016 AACR 4/2016

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Results from IIT* and Compassionate Use** DC vaccine treatment in AML patients (*IIT at Ludwig-Maximilians-University Munich; **CU Patients at Oslo University Hospital)

High success rate for GMP generation of DC vaccines Efficient logistics for DC vaccine delivery Vaccine antigens demonstrate immunogenicity T cell responses as potential biomarkers of DC activity

Excellent safety profile of DC vaccines

Conclusion: Production efficiency & safety profile allow extensive vaccination

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Medigene’s company-sponsored DC trial in AML: Phase II started in April 2016 Trial design: Phase I/II: open-label, prospective, non-randomized trial 20 AML patients: 6 phase I + 14 phase II, complete remission after chemotherapy, not eligible for allo-transplantation Patients selected with AML expressing the vaccine antigens: WT-1 with or without PRAME (expressed on LIC/LSC) Continuous vaccination for 2 years or until progression/death Primary objectives: feasibility and safety Secondary objectives: overall survival (OS), progression free survival (PFS), induction of immune responses; control of minimal residual disease (MRD); clinical response: time to progression (TTP)

ClinicalTrials.gov Identifier: NCT02405338 27

Medigene’s technology platforms are linked synergistically – to treat different kinds of cancer Medigene’s immunotherapy platforms DC vaccines

TCRs

TABs

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TABs – Medigene’s unique T-cell-specific antibodies Full-scope platform for antibody isolation Unique animal models to assess MoA and clinical efficacy Proof-of-principle is established Removal of unwanted T cells: T-cell leukemia

TCR-modified T cells: Ex vivo tracking of T cells In vivo removal of T cells

Status quo: Ongoing studies establish proof-of-concept in preclinical models 29

Management aligned to Medigene’s transformation

Prof. Dolores J. Schendel

Dave Lemus

Dr. Thomas Taapken

CEO/CSO Medigene AG MD Medigene Immunotherapies GmbH

COO Medigene AG CEO Medigene Inc.

CFO Medigene AG

Dr. Kai Pinkernell SVP Medical Affairs Chief Medical Officer

Dr. Dr. Olav Zilian SVP Corporate Development

Dr. Markus Dangl SVP Research & Pre-Clinical Development

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Values from legacy product pipeline realized – allows further focus on core business EndoTAG® sold to SynCore (2015) First payment of € 1m received in Q1-2016 Medigene receives € 5m from SynCore in five annual installments and is eligible for milestone payments and royalties for EndoTAG-1

Medigene spin-off Catherex, Inc. sold to Amgen Inc. (2015): Medigene ownership: approximately 40% of all upfront payments, milestones and net sales payments for Amgen's drug ImlygicTM In Q1-2016, Medigene received its share of the upfront payment and a milestone payment totaling € 4.5m

Rhudex (2014) Phase I compound, developed in Primary Biliary Cirrhosis (PBC) Out-licensed to Dr. Falk Pharma (2014) - eligible for clinical milestones and royalties 32

Remaining legacy product: Veregen®

First FDA-approved botanical therapeutic (2006) Indication: EGW - exposure to HPV Sold in 27 countries around the world Medigene’s Veregen® revenue (2015): € 3m Sold exclusively through global network of various distributors – no sales force on the ground

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Financials 9M-2016

(in €m)

30.09.2016

31.12.2015

7.1m

6.8m

-15.6m

-16.1m

Thereof R&D

-8.0m

-8.5m

Thereof SG&A

-7.6m

-7.6m

-5.7m

-13.0m

Total revenue Operating expenses

Net loss

Cash position at September 30, 2016 of € 43.6m Sold 50% Immunocore stake € 6m Sold Catherex, Inc. to Amgen € 4m

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The share and the shareholder structure QVT

15%

Aviva

Key share information

DJS Montana

Listed on Frankfurt Stock Exchange (Prime Standard) Symbol: MDG1; ISIN: DE000A1X3W00; TecDax

7%

Ridgeback 4%

Number of outstanding shares: 20.1 m Current market cap of approx. € 270m

RTW Master Fund

Freefloat**

4% 3% 68%

> 20% of shares owned by US investors December 2016 Numbers based on last voting right notifications **shareholding below 3%

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Financial guidance 2016

2015

GUIDANCE 2016

Total revenue

€ 6.8m

Stable/increasing

Veregen® total revenue*

€ 3.1m

€ 3 – 4m

R&D expenses Immunotherapies

€ 5.5m

€ 9 – 11m

EBITDA loss

€ 9.5m

€ 10 - 12m

* assuming constant exchange rates

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Clinical outlook and milestones for 2016/17 TCR IIT, Berlin: IMPD submission as part of the clinical trial application and approval/start of IIT TCR study in Berlin Target: MAGE-A1 in multiple myeloma

Medigene’s first TCR trial: GMP process finalization and validation Clinical trial application and approval Study start

DC trial in AML, Oslo: Complete enrollment in 2017

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The Medigene Investment Case Medigene’s immunotherapy programs are deeply rooted in world-class science Established company for biopharmaceutical product development from research to market approval Management team composed of Medigene’s immunotherapies inventors in addition to very experienced executives from the biopharmaceutical industry

Up-scalable technology platforms for fueling continual development of candidates for the pipeline – for Medigene and partners Unique knowledge and speed on TCR discovery and validation Well funded

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For your notes

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Medigene AG Lochhamer Straße 11 82152 Planegg / Martinsried Germany

T +49 - 89 - 20 00 33 - 0 F +49 - 89 - 20 00 33 - 2920 [email protected] www.medigene.com

Listed on Frankfurt Stock Exchange (MDG1, Prime Standard, TecDax)