BY PEOPLE. WITH PEOPLE. FOR PEOPLE. 4SC COMPANY PRESENTATION AMSTERDAM 1 APRIL 2014

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1 BY PEOPLE. WITH PEOPLE. FOR PEOPLE. *Epigenetics: Each and every human cell contains specific genetic information. What happens to a cell is determined by the way this information is processed. Epigenetics is the key to controlling this process. 4SC is one of the pioneers in this field of science. We develop epigenetic anti-cancer drugs. 4SC COMPANY PRESENTATION AMSTERDAM 1

2 FORWARD LOOKING STATEMENTS The information contained in this presentation includes forward-looking statements. Any forward-looking statement applies only on the date of this presentation. By their nature, forward-looking statements are subject to a number of known and unknown risks and uncertainties that may or may not occur in the future and as a result of which the actual results and performance may differ substantially from the expected future results or performance expressed or implied in the forward looking statements. No warranties or representations are made as to the accuracy, achievement or reasonableness of such statements, estimates or projections, and 4SC AG has no obligation to update any such information or to correct any inaccuracies or omission which may become apparent. Neither 4SC nor the management, the directors, employees, agents or advisers of 4SC make any representation or warranty, expressed or implied as to the accuracy or completeness of the information contained in this presentation, and nothing contained herein is, or shall be relied upon as, a promise or representation, whether as to the past or the future. This presentation does not constitute an offer or invitation for the sale of securities of 4SC AG or any interest therein in any jurisdiction and is not intended to provide the basis for any credit, investment or other evaluation or decision. Important information for the United States: This presentation is only being made available to interested parties on the basis that: (A) if they are United States persons, they are accredited investors as defined under Rule 501(a) promulgated under the United States Securities Act of 1933, as amended; or (B) they are outside the United States (all such person collectively being referred to as Relevant Persons ). By accepting this document you represent and warrant that you are such a person. This presentation must not be acted on or relied on, and should be returned to 4SC AG, by persons who are not Relevant Persons. Any investment or investment activity to which this presentation relates is available only to Relevant Persons and will be engaged only with Relevant Persons. 2

3 OUR VISION DEVELOP RESMINOSTAT TOWARDS APPROVAL IN BLOCKBUSTER INDICATION HCC DEADLY DISEASE HIGH NEED: 1 ST & 2 ND LINE TREATMENT No approved 2 nd -line therapy NEXAVAR: ONLY TREATMENT Only one approved 1 st -line therapy for advanced HCC: Sorafenib (Nexavar ) 3 rd leading cause of cancer-related mortality ~700,000 deaths/year MARKET APPROVAL OUR VISION FOR RESMINOSTAT Blockbuster potential in 1 st and 2 nd line HCC (potential peak sales of > 1 billion) Promising Phase IIa efficacy & biomarker data Phase II programme currently in preparation, to be followed by Phase III Phase I/II trial by Yakult in 1 st line HCC in Japan underway (started May 2013) LIVER CANCER (HCC) 3

4 4SC CORPORATE STRUCTURE & BUSINESS MODEL 4SC GROUP CORPORATE STRUCTURE 4SC AG Key focus on developing epigenetic cancer therapies towards the market COMMERCIALISATION & VALUE GENERATION Pharma partnerships: Joint development towards approval Upfront payments Milestone payments Royalties 100% Replenishing 4SC s clinical pipeline Financing contribution through revenues from service collaborations Long-term value generation from early-stage pharma partnerships 4SC Discovery GmbH Commercialising early-stage drug discovery in epigenetics, cancer stem cells and inflammation Discovery Partnerships: Upfront, milestone & royalty payments from early partnering deals Constant revenue from research collaborations 4

5 STRONG FUNDAMENTAL MARKET DRIVERS FOR 4SC HIGH MEDICAL NEED AND LARGE MARKET POTENTIAL CANCER Global oncology market to grow from today US$ 60 bn to US$ 88 bn in 2016 (IMS Health) Blockbuster indication liver cancer (HCC) CHALLENGES FOR BIG PHARMA Urgent need for new drugs to compensate for sales reductions due to patent ends Massive R&D spending cuts offer chances for research-orientied biotechs to fill the gap AUTOIMMUNE DISEASES IBD (Crohn s disease & ulcerative colitis): 4 mn patients are expected by 2016 worldwide. Very limited treatment options available. MEGATREND PERSONALISED MEDICINE Selection and stratification of patients with a particular benefit from a certain therapy, according to certain genes or biomarkers Increasing demand from regulatory authorities, health insurers, and pharma companies MEGATREND EPIGENETICS Epigenetics: linking the genotype with the phenotype GEN (Oct. 15, 2012): Market for epigenetic cancer drugs expected to grow from US$ 800 mn (2011) to US$ 8 bn (2017) * * Source: (Jennifer Cropley, Victor Yang, Cardiac Research Institute) 5

6 (Japan) AN ATTRACTIVE VALUE-FOCUSED CLINICAL PIPELINE Product Indication Research Preclinical Phase I Phase II Phase III Partner Key Focus ONCOLOGY Resminostat Hepatocellular Carcinoma (HCC) (Western) Resminostat HCC (Asia) * 1st line HCC programme in preparation Resminostat Resminostat Hodgkin s Lymphoma (HL) Colorectal Cancer (CRC) Resminostat Solid Tumours * Resminostat 4SC-202 4SC-205 Non-small-cell lung cancer (NSCLC) * Haematological Tumours Solid Tumours Complete Phase I studies, for later partnering / Phase II AUTOIMMUNE AND INFLAMMATION Vidofludimus Inflammatory Bowel Disease (IBD) *) Study performed by Yakult Honsha in Japan Study completed Seek external partner for Phase IIb EARLY-STAGE DRUG DISCOVERY COLLABORATIONS & PARTNERSHIPS BY 4SC DISCOVERY INCLUDING 6

7 :: BY PEOPLE. WITH PEOPLE. FOR PEOPLE RESMINOSTAT A new epigenetic therapeutic option in oncology 7

8 RESMINOSTAT: YAKULT HONSHA DEAL FOR JAPAN Upfront payment of 6m Up to 127m in milestone payments Double-digit royalties linked to product sales RESMINOSTAT Yakult Honsha is a leader in gastro-intestinal oncology in Japan, spearheaded by blockbusters irinotecan and oxaliplatin. Japanese oncology market accounts for c % of global oncology market 8

9 RESMINOSTAT LARGE OPPORTUNITY IN LIVER CANCER (HCC) MARKET 5 th most common cancer disease worldwide 3 rd leading cause of cancer-related mortality (~700,000 deaths/year) High unmet medical need Only 1 approved 1 st line therapy for advanced HCC: Sorafenib (Nexavar ) No approved 2 nd line therapy for advanced HCC Blockbuster indication ESTIMATED NEW LIVER CANCER CASES (TOP 29 w/o Japan) EXPECTED HCC MARKET DEVELOPMENT (w/o China) 606 T 637 T 719 T 809 T 904 T 1000 T The combined value of hepatocellular cancer (HCC) drugs in the US, Japan and five major EU markets will peak at $1.4bn in $1.4bn Source: Globocan Source: Data Monitor 4SC expects peak sales potential of > 1 billion for resminostat in 1 st and 2 nd line HCC 9

10 RESMINOSTAT MODE OF ACTION: MULTIPLE WAYS OF EPIGENETIC HCC TARGETING MONOTHERAPEUTIC EFFECTS Epigenetic (Re)Programming Induction of growth arrest, apoptosis 1 Resminostat HCC cells Inhibition of key tumour signalling pathways (e.g. NOTCH, WNT) Inhibition of EMT, metastasis, tumour progression, stemness 2,3 THERAPEUTIC EFFECTS THROUGH COMBINATION WITH STANDARD CANCER THERAPIES 4 KREBSMEDIKAMENTEN SENSITIVE TOLERANT RESISTENT Epigenetic modifications (reversible) Reversible Standard cancer drugs HDAC inhibition via resminostat Genetic alterations Irreversibel Various Mutations Resminostat targets HCC through inhibition of tumour progression & metastasis 1,2,3 as well as prevention of drug tolerance and resistance 4. 1 Mandl-Weber et al., Br.J.Haematol.2010;149:518-28; 2 van Zijl et al., 2009; 3 van Malenstein et al., 2012; 4 Sharma et al.,

11 RESMINOSTAT: SIGNIFICANT SURVIVAL BENEFIT OVER STANDARD OF CARE IN 2 ND LINE HCC INDICATED Placebo (1st line) 1 Placebo + Best Supportive Care (BSC) 7.9 Months Overall Survival Sorafenib 1st line overall survival benefit +2.7 Months Standard Treatment: Sorafenib (1st line) 1 Sorafenib 10.7 Months Overall Survival BSC Resminostat 2nd line overall survival benefit +2.9 Months Resminostat / Sorafenib Combination (2nd line) months until disease progression under 1st line sorafenib 1 Sorafenib 8.1 months survival after first progression months Resminostat + Sorafenib Cumulated 13.6 Months Overall Survival BSC Resminostat stabilises the disease and prolongs overall survival of second-line HCC patients by approximately 3 months compared to standard of care. 1 SHARP STUDY: Llovet et al., 2008; 2 SHELTER STUDY: Bitzer et al., ILCA

12 TARGETED REPROGRAMMING OF CANCER BY EPIGE- NETIC DISRUPTION OF MAJOR CANCER NETWORKS HEDGEHOG WNT Wnt HH NOTCH Cell membrane Resminostat 4SC-202 GLI 4SC-202 NICD b-catenin TCF/LEF 4SC-202 Nuclear membrane b-catenin TCF/LEF GLI 4SC-202 Resminostat Resminostat ZFP64 Biomarker ZFP64 down regulated by resminostat Several pathways control cell proliferation & migration (EMT), angiogenesis, metastasis, AND cancer stemness 12

13 PERSONALISED MEDICINE: BIOMARKER ZFP64 INDICATIVE OF DOUBLING OVERALL SURVIVAL IN HCC & HL Baseline ZFP64 gene expression split HIGH vs. LOW expression PHASE II SHELTER STUDY IN HCC (n=31) PHASE II SAPHIRE STUDY IN HL (n=30) relative ZFP64 expression low high relative ZFP64 expression low high p = 0.04 p = 0.04 Split: 60% high / 40% low ZFP64 expression Split: 65% high / 35% low ZFP64 expression High baseline ZFP64 expression in blood samples is indicative of doubling overall survival with resminostat. This is a strong signal for a personalised medicine approach with resminostat. 13

14 UPCOMING VALUE INFLECTION POINTS FOCUS ON HCC 1 ST LINE TREATMENT st line HCC Market Approval IND, CMC Phase II 1 st line HCC, placebo controlled, randomized Phase III 1 st line HCC EU and US Active, recruiting Full biomarker validation (ZFP64, DCP) Phase I/II, ~140 pts, TTP Japan, Korea, randomized Phase III, OS Japan/Asia Performing a stepwise HCC 1 st line clinical development offers ideal starting point for risk adjusted phase III with already validated biomarker ZFP64 14

15 RESMINOSTAT: TARGETING CANCER BROADLY GASTRO- ENTEROLOGY Hepatocellular (ZFP64 high) HEMATOLOGY UROLOGY OTHER MAJOR INDICATIONS Hodgkin s Lymphoma (ZFP64 high) Prostate NSCLC Phase IIa completed 1 Phase II/III in preparation 1 Phase I/II (Yakult) 1 Phase IIa completed 3 NHL Bladder Phase I/II (Yakult) 4 Breast Esophagus Stomach Colorectal Phase I completed 2 Scientific rationale and preclincal data support development of resminostat in combination therapy with classical cancer drugs in a broad variety of potential cancer indications. 1 combination with sorafenib; 2 combination with FOLFIRI; 3 monotherapy; 4 combination with docetaxel 15

16 :: BY PEOPLE. WITH PEOPLE. FOR PEOPLE NEXT GENERATION CLINICAL PROGRAMMES 4SC-202: selective HDAC inhibitor targeting WNT & HH 4SC-205: oral EG5 inhibitor Vidofludimus: targeted immune modulator addressing IBD 16

17 4SC-202 NOVEL EPIGENETIC APPROACH TARGETING CANCER STEM CELLS Next generation epigenetic in clinical development Selective inhibitor of LSD1 (KDM1A), HDAC1, 2 and 3 modulating WNT & Hedgehog (HH) pathways Oral available small molecule inhibitor Currently in clinical hematologic phase I TOPAS trial Conventional Chemotherapy / Radiation Cancer stem cells 4SC-202 treatment Long-term clinical benefit and improved OS Treatment of cancer stem cells offer opportunities for all kinds of Combination therapies Adjuvant and neo-adjuvant therapy Attractive clinical potential in various haematological & solid tumours going forward Targeting long-term survival and quality of life of cancer patients 17

18 Patient: male, born 1943, angioimmunoblastic T-cell lymphoma EPIGENETIC CANCER CANDIDATE 4SC-202: COMPLETE RESPONSE SEEN IN CURRENT PHASE I STUDY PATIENT, AT ENTRY PATIENT, AFTER 6 WEEKS OF TREATMENT Promising clinical efficacy signals seen in preliminary Phase I data (complete response in AITL patient) Good PK properties, biomarker response seen already at low doses, safe and well tolerated Data of current Phase I study in haematological tumours expected in H

19 4SC-205 A NOVEL ORAL ANTI-MITOTIC DRUG IN PHASE I PROGRAMME IN SOLID TUMOURS Overview 4SC-205: small molecule Eg5 inhibitor and the only orally administered Eg5 inhibitor in clinical development Potentially a break-through for antimitotic cancer treatments About EG5 a promising cancer target Kinesin Eg5 motor protein is essential for separation of spindle poles during mitosis It is exclusively expressed during mitosis in dividing cells Side efects (e.g. peripheral neuropathies) as seen with other spindle targeting drugs (taxols) not expected for Eg5 inhibition Valentine, Fordyce and Block, Cell Division 1:31 (2006) Current clinical development status Phase I AEGIS study (data expected in mid 2014) Safe and well tolerated to date with excellent PK properties Amended for testing of a new innovative treatment schedule Monoaster formation upon Eg5 inhibition 19

20 VIDOFLUDIMUS: TARGETED IMMUNE MODULATOR IN PHASE IIB PREPARATION IN IBD W/ EXTERNAL PARTNER Oral, once daily tablet Mode of action Targeted therapy strong IL-17 (IL-17A & F) and IFN-gamma cytokine suppression Validated inhibition of DHODH Strong preclinical data in MS, lupus, psoriasis, transplant rejection etc. Strong clinical Phase IIa data in lead indication IBD (Crohn s disease, ulcerative colitis) Clean safety & tolerability Encouraging activity: 88.5% response rate IBD: high market potential & medical need: Market forecast to grow: $ 5.7 bn. by 2019 Patient population forecasted 4 million by 2016 Currently seeking project & financing partner for further external development Planned next step: Start Phase IIb study in Crohn s disease DUAL MODE OF ACTION OF VIDOFLUDIMUS (4SC-101) 20

21 : : BY PEOPLE. WITH PEOPLE. FOR PEOPLE. 4SC DISCOVERY GMBH Commercialisation of early-stage research as a financing contribution and for long-term value creation 21

22 4SC DISCOVERY AT A GLANCE is aiming to be a leading partner of pharmaceutical industry for innovative drug discovery in the fields of epigenetics, cancer stem cells and inflammation. KEY FACTS Fully-owned subsidiary of 4SC AG Start of operations in researchers strategic alliance with CRELUX GmbH, Munich COMMERCIALISE EARLY-STAGE R&D AS A FINANCING CONTRIBUTION TO 4SC GROUP AND FOR LONG-TERM VALUE CREATION Early-stage partnering deals with biotech & pharma for co-development and commercialisation of own discovery assets Research collaborations with biotech & pharma Discovery and optimisation of drug candidates for 4SC s clinical development pipeline ALL CRUCIAL DISCOVERY STEPS IN HOUSE In silico screening In vitro screening X-ray crystallography Computational chemistry Medicinal chemistry Biology Pharmacology 22

23 4SC DISCOVERY: STRONG TRACK RECORD STRONG DISCOVERY AND PARTNERING TRACK RECORD NOVEMBER 2013 Research collaboration with AiCuris JUNE 2013 SEPTEMBER 2013 Partnership with Panoptes for autoimmune uveitis incl. equity stake Research collaboration with UCB APRIL 2012 FEBRUARY 2013 DECEMBER 2012 / JANUARY 2013 Licencing deal with BioNTech in cancer immune therapy ( 2.5m upfront payment, further milestone potential plus royalties) Broad research collaboration in oncology Formed i2c - a strategic partnership for structure based drug discovery with CRELUX Research collaboration with Henkel Exclusive licence option agreement with LEO Pharma for psoriasis ( 1m upfront payment, 95 m milestone potential plus royalties) 23

24 4SC DISCOVERY: LEO PHARMA LICENSE (OPTION) DEAL & RESEARCH COLLABORATION IN PSORIASIS Upfront payment 1m Up to 95m in milestone payments Up to double-digit royalties based on product sales PSORIASIS Leo Pharma S/A (Denmark) is a leading specialty pharma player specialised in dermatology. Both companies will co-develop 4SC discovery s cytokine modulation programme as a novel potential breakthrough therapy in psoriasis. 24

25 : : BY PEOPLE. WITH PEOPLE. FOR PEOPLE. FINANCIAL OVERVIEW 25

26 KEY FINANCIAL FIGURES AND CASH REACH 2013 Revenue increased by 13% year-on-year Costs decreased Operating result considerably improved Cash Burn significantly reduced Funds: 4.9 m (31 Dec. 2013) Average cash burn 2013 reduced by 50% to 0.6 m / month; expected to decrease further in 2014 (not including new clinical trials) Cash reach through the next 12 months secured (as of 26 March 2014)* IN M Revenue Profit/loss for the period Operative Cashburn Funds Balance sheet total *) Based on funds at the end of 2013, the current revenue and expense planning and the convertible note agreement signed with Yorkville in Feb Calculation does not include launch of additional clinical trials. 26

27 SHARE AND SHAREHOLDERS STRUCTURE* Prime Standard Listing (FSE:VSC) No. of shares outstanding: 50,408,654 (26 Mar. 2014) Free Float acc. to Deutsche Börse: 30.3% Backing by family offices and experienced life science investors SHAREHOLDERS in % Ø NUMBER OF SHARES TRADED PER DAY XETRA ALL ** ,050 14, ,307 43, ,434 56, ,179 37, (YTD 21 March 2014) 29,909 65,204 Others: 24.7 Founders & MGMT: 1.2 Roland Oetker: 4.2 Heidelberg Capital: 5.9 Santo Holding: 48.1 FCP: 9.6 DVCG / VCG: 6.1 ANALYSTS DATE TARGET PRICE / RECOMMENDATION Edison equinet (BUY) Kempen (HOLD) 12 Feb 2014: Convertible notes agreement with Yorkville for up to 15 m nominally until 31 Dec * Based on management estimates ** All German exchanges plus Tradegate 27

28 REACHED AND UPCOMING VALUE INFLECTING MILESTONES MILESTONES REACHED 2013 Complete Phase II resminostat HCC Start Japanese resminostat Phase I/II in 1 st line HCC (by Yakult) Start Japanese resminostat 2 nd /3 rd line NSCLC (by Yakult) Complete Phase I resminostat in CRC Detailed biomarker data resminostat HL & HCC 4SC Discovery: service deals & early-stage partnering deals UPCOMING MILESTONES 2014 Complete Phase I 4SC-202 in haematologic tumours Complete Phase I 4SC-205 in solid tumours Complete Phase I resminostat in solid tumours (in Japan by Yakult) Further partnerships of 4SC Discovery ATTRACTIVE GOALS AHEAD Execute further development of resminostat towards the market in 1 st line HCC (discuss planned development plan with authorities; ensure funding; initiate study) Yakult Phase I/II efficacy data with resminostat in 1 st line HCC (Japan) Secure external financing for planned Phase IIb trial with vidofludimus in IBD 28

29 4SC INVESTMENT CASE - STRATEGY TO A MATURING COMPANY CREATING LONG-TERM VALUE FOR INVESTORS Increase Product Value Strengthen Partnering Base Leverage Early-Stage R&D Biomarker-driven development of resminostat towards market approval in advanced HCC Development of remaining 4SC portfolio towards next major clinical value inflection points Establish partnerships for codevelopment & commercialisation of clinical assets Augment deal track record with big pharma/biotech partners Commercialise 4SC Discovery products through collaborative business and licensing deals Provide pharma partners and 4SC AG with development candidates Becoming an established pharma partner for innovative drugs in cancer and immunology 29

30 :: BY PEOPLE. WITH PEOPLE. FOR PEOPLE THANK YOU VERY MUCH! :: CONTACT Enno Spillner, CEO & CFO Jochen Orlowski, Head of CC & IR 30

31 4SC AT A GLANCE CORPORATE FACT SHEET Attractive business model Top technologies, products & markets Discovery & development of novel small molecule drugs for unmet medical needs Growth through clinical stage partnering Attractive deal flow, revenue and value generation though early R&D and discovery collaborations A leader in epigenetic cancer therapies Attractive pipeline with four compounds in clinical Phases I & II Lead compound resminostat in preparation of late stage programme in liver cancer (peak sales potential > 1 bn.) Corporate structure Novel targeted drugs for cancer & autoimmune diseases Finance & Shares Integrated clinical development (4SC AG) and drug discovery (4SC Discovery GmbH) organisation 56 FTEs (31 Dec. 2013) Headquartered in Munich/Germany Founded in 1997 Market cap ~ 69 m (26 March 2014) Prime Standard Listing (FSE:VSC) 50,408,654 shares outstanding (26 March 2014) Convertible note agreement with Yorkville as of 12 Feb for up to 15 m nominally Committed investor base 31

32 4SC - FINANCIAL CALENDAR 2014 Event Date Annual Financial Report March Months Financial Report (Q1) May 2014 Annual General Meeting, Munich (Germany) 9 May 2014 Half-Year Financial Report (Q2) August Months Financial Report (Q3) November 2014 Analyst Conference, German Equity Forum, Frankfurt/Main (Germany) November

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