4SC-202: The new dimension in immunooncology 4SC AG February

4SC AG Company Presentation June 2016

© 4SC AG, June 2016

Disclaimer

2

Information set forth in this presentation contains forward-looking

statements, which involve a number of risks and uncertainties. The

forward-looking statements contained herein represent the judgement of

4SC as of the date of this presentation. Such forward-looking statements

are neither promises nor guarantees, but are subject to a variety of risks

and uncertainties, many of which are beyond 4SC’s control, and which

could cause actual results to differ materially from those contemplated in

these forward-looking statements. 4SC expressly disclaims any

obligation or undertaking to release any updates or revisions to any such

statements to reflect any change in its expectations or any change in

events, conditions or circumstances on which any such statement is

based.


4SC at a Glance

3

Well-established partnerships

(e.g. Yakult Honsha, Menarini, Link Health)

Attractive oncology pipeline with

3 compounds in clinical Phase I & II

Focus on cutting-edge

epigenetic cancer therapies • Founded in 1997

• Munich / Germany

• 50 employees*

• Prime standard

listing (FSE: VSC)

4SC - EpiScience for Life

* As of 1 May 2016, corresponds to 43 full-time equivalents


Epigenetics – 3 Key Strategic Goals

4 CTCL: cutaneous T-cell lymphoma; HH: cellular signaling pathway via hedgehog protein

EpiScience for Life –

Epigenetic Therapies

4SC-202

Resminostat Bring resminostat towards

approval in EU in CTCL

Establish 4SC as a global leader in

epigenetic therapies

Develop 4SC-202 in HH-related

diseases and immuno-oncology

combinations


Epigenetic Therapy – Controlling Gene Transcription

5

• Epigenetics

o Regulation of genetic activity

o Independent from DNA sequence

o determines which genes are turned on or off

• Varied influence on genetic activity in

o Particular cell types

o Response to physiological stimuli

o Different diseases states *

* Genetically identical mice yet obviously different epigenetic regulation; Jennifer Cropley, Victor Yang, Cardiac Research Institute


Epigenetic Reprogramming of Cancer Cells – Unique Potential of Resminostat & 4SC-202

6

Resminostat /

4SC-202

Tumor

cell

Gene

regulation

Targeting cancer stem cells

Immuno-sensitization

Combination therapy

Monotherapy


Clinical Oncology Pipeline

7

Completed or ongoing In preparation or planned

* Studies performed by Yakult Honsha in Japan ** Study initiation subject to partnering or financing arrangement

*** Further studies out-licensed to Link Health for Greater China

Phase I Phase II Pivotal

Resminostat Cutaneous T-cell lymphoma (CTCL)

Liver cancer (HCC), second-line treatment

Hodgkin’s lymphoma (HL)

Colorectal cancer (CRC)

Liver Cancer (HCC), first-line treatment*

Non-small-cell lung cancer (NSCLC)*

Pancreatic cancer / biliary tract cancer*

4SC-202 Hematological tumors**

Immune infiltration**

Small-cell lung cancer (SCLC)**

4SC-205 Cancer***


Epigenetic Product Strategy

8

Resminostat

• Mode-of-action of HDAC inhibitors in CTCL proofed

• Orphan disease, no competitors in EU

• Fast-to-EU-market opportunity in 2019 possible

4SC-202

• Phase II development by partnering

or financing

Resminostat – in HCC

• Detailed analysis of promising subgroup data from

Japanese HCC Phase II study

• Continued potential for pivotal HCC studies

4SC-202

• proof-of-concept in solid (e.g. SCLC) cancers

demonstrated

Immuno-sensitization

• 4SC-202 and resminostat sensitize immune system

in solid cancer patients

• Development of 4SC-202 in combination

with checkpoint inhibitors

Near

term goal

Mid term

value option

Substantial

upside

CTCL: cutaneous T-cell lymphoma; HDAC: histone deacetylase, epigenetic active enzyme; HCC: hepatocellular carcinoma (liver

cancer); NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; AML: acute myeloid leukemia


4SC-205 Partnership with Link Health

• 4SC-205

o Cancer compound inhibiting the kinesin spindle protein Eg5

o Only Eg5 inhibitor available as a tablet

o Has shown to be safe and well-tolerated in different dosing schemes

• Link Health

o Chinese pharmaceutical company focused on licensing, registration,

clinical study and regulatory consulting services

o Since May 2016exclusive rights for further development and marketing

of 4SC-205 in Greater China*

* China, Hong Kong, Taiwan and Macao

Undisclosed

upfront

payment

Upfront & milestone

payments of up to

€ 76 m

Double digit royalties

linked to product

sales in China

9


Epigenetics – Innovation with Huge Market Potential

10

• Unique and novel approach by switching on or off cancer-

associated genes

• High potential to become an important player as next

generation cancer treatment

• Many possible combinations with immunotherapies in

oncology and other indications

• Epigenetics market valued at 2.9 billion USD in 2012 is

expected to show very high growth and to become a 12

billion USD market by 2018 showing a CAGR >25%*

With resminostat and 4SC-202, 4SC holds high potential drug

candidates for epigenetic therapies in various indications

* Mordor Intelligence; Global Epigenetics Market Growth, Trends and Forecasts 2014-2020 (published May 2015)


Market cap: $ 681 m*

Epigenetic companies obtain high market valuations

Market cap: $ 143 m*

Epigenetics – Attractive Market Environment

Market cap: $ 44 m* Market cap: € 121 m*

Market cap: $ 213 m* Market cap: $ 227 m*

11

* Market cap as of 15 June 2016

© 4SC AG, June 2016 © 4SC AG, June 2016

Resminostat

12

• New epigenetic therapeutic option in oncology

with broad applicability

• Near term goal: “fast-to-market” option in the EU

as first HDAC inhibitor in CTCL

CTCL: cutaneous T-cell lymphoma; HDAC: histone deacetylase, epigenetic active enzyme


Strong Partnerships for Resminostat

13

• Yakult Honsha is responsible for development,

approval and marketing of resminostat in Japan

• Phase II study in 1st line HCC completed

• Phase II study in 2nd/3rd line NSCLC expected in 2016

• Further study in pancreatic & biliary tract cancers initiated in 2015

• Menarini covers development, approval, marketing in Asia/Pacific ex Japan

• with 75% of all HCC cases occurring in Asia/Pacific, 50% of all cases in China

• Menarini with established sales force in the Asia/Pacific region & strategic focus on oncology

• Currently evaluating next clinical development steps

Upfront payment

of € 6 m

Up to € 127 m in

milestone payments


linked to product sales

Undisclosed

upfront payment

Upfront & milestone

payments of up to

€ 95 m


linked to product sales

HCC: hepatocellular carcinoma (liver cancer); NSCLC: non-small cell lung cancer


Resminostat – Good Clinical Safety

14 GI: gastrointestinal

In general well tolerated

No significant effect on the cardiovascular system

Majority of adverse events: mild to moderate, manageable and reversible

Most frequent adverse events:

GI disorders (nausea, vomiting, diarrhea), fatigue, thrombocytopenia

Safety tested in >300 patients

(5 completed and 3 ongoing clinical studies)


Resminostat: Clinical Phase II Efficacy in Hodgkin Lymphoma

15

-100

-50

0

50

100

% C

ha

ng

e in

Ta

rge

t L

esio

n S

ize

Individual Patients

• Tumor target lesion reduction in 69% of patients

• 1 complete remission,11 partial responders

Note: For each patient the best response observed during the study is plotted. Efficacy Analysis Set (n= 35), but one

patient was not evaluable. Data include partial metabolic responder.


CTCL – Orphan Indication with Commercial Potential for Resminostat (I)

16

• CTCL is one of the most common forms

of T-cell lymphoma

• Orphan disease

o EU incidence: ~5,000 per year*

o EU prevalence: <50,000*

• High medical need for patients with

advanced CTCL

o No cure available

o Median over-all survival <5 years**

* Estimates are based on recent Western world studies and the SEER (Surveillance, Epidemiology, and End Results) database of the

National Cancer Institute in the US; ** Agar et al, JCO, 28, 4730-4739, 2010; *** Peak sales estimation of 4SC based on a calculation

using various public sources and internal assumptions by 4SC. Peak sales is defined as the amount of sales generated by a

pharmaceutical product in the year with the highest sales volume during the product’s life cycle. CTCL: cutaneous T-cell lymphoma;

HDAC: histone deacetylase, epigenetic active enzyme; PTCL: peripheral T-cell lymphoma; EMA: European Medicines Agency

Wobser et al. ARCH DERMATOL, VOL 146 (NO. 7), 805-806, 2010

• Global HDAC inhibitor market for CTCL and PTCL together reached $ 223 m in 2012

and was estimated at $ 362 m for 2013, up >60% (BBC Research)

• Peak sales*** potential for 1st approved HDAC inhibitor in Europe estimated up to

€ 140 m per year


CTCL – Orphan Indication with Commercial Potential for Resminostat (II)

17

• In the US, 2 HDAC inhibitors approved (*) for CTCL,

but none so far in Europe

• CTCL – limited treatment options:

Local PUVA, corticosteroids PUVA, corticosteroids

Systemic 1st line interferon alpha, bexarotene interferon alpha, bexarotene

Systemic 2nd line 4SC‘s Goal: Resminostat

after systemic therapy vorinostat*, romidepsin*

CTCL: cutaneous T-cell lymphoma; HDAC: histone deacetylase, epigenetic active enzyme;

PUVA: psoralen + photodynamic therapy by UVA exposure; EMA: European Medicines Agency

Initiation of pivotal Phase II study for resminostat in CTCL in Europe

Study design in accordance with formal scientific advice from EMA

In case of promising data, immediate filing for conditional approval in the EU anticipated


Ra

nd

om

iza

tion

Maintenance treatment

Primary endpoint: PFS

Key secondary endpoint: TTSW (itching)

Patients

RESMAIN: A Clinical Phase II Study

18

Design

Secondary endpoints:

ORR, PFS2, safety, etc.

• Cutaneous T-cell lymphoma (CTCL)*

• Disease control after prior systemic therapy

Resminostat Roll Over

Follow up

Follow up

PD

PD

Placebo N=75

Resminostat N=75

1:1

A

B PD

*Mycosis fungoides (Stage IIB – IV) and Sézary Syndrome; PD: progressive disease; PFS: progression free survival;

TTSW: time to symptom worsening; ORR: overall response rate


Resminostat: Combining Epigenetic Therapies with Immuno-oncology

19

*

**

***

* American Association for Cancer Research; 15.09.2015; ** Immuno-Oncology News; 17.09.2015; Patricia Inacio;

*** Immuno-Oncology Overview; 21.05.2015


Potential for Resminostat as Booster of Immuno-therapies

20

• Increase response rate to tumor vaccines by enhancing tumor cell

recognition and reducing immuno-suppression

• Increase the rate of durable remissions in patients with limited anti-

tumoral response by combination of resminostat and immune checkpoint

inhibitors

• Broaden the spectrum of indications to render non-immunogenic

tumors more responsive by combination of resminostat and immune

checkpoint inhibitors

• Intended treatment strategy:

Diagnosis Immunomodulation

by resminostat Immuno-therapy Response


4SC-202

21

• Selective LSD1 & HDAC1,2,3 inhibitor targeting

WNT & HH signalling in cells

• Strengthens endogenous immune response to

cancer tissue

LSD1: lysine-specific demethylase 1; HDAC: histone deacetylase, epigenetic active enzyme; WNT: cellular signaling

pathway via WNT protein; HH: cellular signaling pathway via hedgehog protein


4SC-202: Key Features

22

• Immunomodulator – epi-sensitization of checkpoint inhibitors

• Regulating a number of pharmacologically important pathways,

such as WNT or HH

• Promising clinical Phase I data – safe and well tolerated

Ready for clinical Phase II

Small molecule epigenetic regulator

Versatile compound with unique features

Robust, broad and long lasting IP protection

WNT: cellular signaling pathway via WNT protein; HH: cellular signaling pathway via hedgehog protein


4SC-202: Clinical Phase I Study

• 24 patients

• 4SC-202 was well tolerated and safe

o Most frequent adverse events

• Fatigue and diarrhea (21% of patients)

• Elevated levels of liver enzymes AST or

ALT (17% of patients, in the highest dose

level only)

o Adverse events were mainly mild to

moderate, manageable and reversible

• Long-term stabilization (>100 days) in

50% of patients

• 1 complete response for 28 months

• 1 partial responder for 8 months

at entry at week 6

Patient, male, age 69, T-cell lymphoma stage IV,

3 prior treatments

23


4SC-202 Synergizes with PD-1 Therapy

24

0.003 0.008

0.074

Vehicle anti-PD1 4SC-202 4SC-202

+ anti-PD1

• 4SC-202 or anti-PD1 antibody in

monotherapy

o At clinically relevant doses

o Reduced tumor burden

• Combination treatment

of 4SC-202 and anti-PD1 antibody

o Highly synergistic effects

o Significantly reduced tumor burden

o 4 out of 10 animals almost tumor

free

p value

p value

p value

*Renca model: Renal cell carcinoma = renal cancer cell line in immune-competent mouse model*

PD1: target molecule for tumor therapy


4SC-202: Immuno-Oncology Concept

25

Preclinical data on T-cell infiltration and PD1 inhibitor synergy

Phase I/II clinical trial in skin cancer patients

Histological analysis of immune infiltration, gene regulation

Compare mono/combination therapy

of PD-1 inhibitor and 4SC-202

Identify best phase II setting

Randomized phase II

Phase I/II

study

2016/2017

Phase I – Single agent safety demonstrated in hematological cancer patients

Next steps:


4SC-202: Major Potential in Area with High Medical Need

26

4SC-202 combines important and unique therapeutic features addressing

oncology

• SCLC – single agent and PD1/PDL1

combination

• Hematological cancers, such as AML

• GLI-related cancers including TNBC,

la/mBCC, Sarcoma

• Immune checkpoint inhibitors

• Targeted therapies, in particular kinase

inhibitors

• Other epigenetic response modifiers

e.g. DNMT inhibitors

Single agent use In combination with

DNMT: DNA methyl transferase, epigenetic active enzyme; PD1/PDL1: target molecules for tumor therapy; AML: acute

myeloid leukemia; GLI: cellular signaling molecule; TNBC: triple-negative breast cancer; la/mBCC: locally

advanced/metastatic basal cell carcinoma (skin cancer)


Financials & Outlook

27

• Solid financial basis

• Clear go to market strategy for resminostat in CTCL

• Important milestones and data ahead

CTCL: cutaneous T-cell lymphoma


Development of Cash Funds in Q1 2016

28

• Cash balance/funds at € 17.1 m at the end of March 2016

down from € 22.8 m at the end of 2015

o Monthly average operational cash

burn of € 1.2 m on plan and up from

€ 1.0 m in Q4 2015, mainly driven by

higher development costs for

preparing planned Phase II trial of

resminostat in CTCL

o Repayment in full of EUR 1.5 million

shareholder loan from Santo Holding

plus payment of interest on this loan

• Outlook

o Estimated cash reach until 2018

o Expected cash burn for FY 2016: stable at € 1.2 m / month

o Convertible notes agreement in place for up to further € 14 m nominally until YE 2016

CTCL: cutaneous T-cell lymphoma


Shareholders‘ Structure

29

Others:

33.7

Founders &

Management:

0.6

Santo Holding:

47.8

Roland Oetker:

3.9

Wellington Partners:

6.6

FCP:

7.4

Supported by family offices and experienced (international) life science investors

● 18.966.646 shares

● “Free Float“ according to Deutsche Börse: 38,2 %

● No major changes in shareholders‘ structure since cash capital increase inJuly 2015

As of 15 June 2016*

• Since capital increase in July 2015,

Wellington Partners as substantial

new investor

• Several other renowned international

investors on board

* Estimated


Share price development since shareholders‘ meeting

on 27 July 2015

Ø number of shares

traded per day** Xetra all *

2014 7,216 16,721

2015 14,992 30,071

2016 (31.05.2016) 16,749 37,184

Analysts Date Target price

Edison 13.06.2016 € 5.50

equinet 02.06.2016 € 3.50

EQUI.TS 16.12.2016 -

Key information

WKN/ISIN A14KL7/DE000A14KL72

Ticker symbol VSC

Type of shares Bearer shares

Market segment Prime Standard

First day of

trading 15 December 2005

Market cap € 44 m (15 June 2016)

4SC

DAX Subsector Biotechnology Index

Nasdaq Biotechnology Index

30

Share

100

120

80

60

Indexed, 24 July 2015 = 100 Development until 15 June 2016

Aug15 Sep15 Oct15 Nov15 Dec15 Jan16 Feb16 Mar16 Apr16 May16 Jun16

-46%

-30%

-16%

* All German exchanges plus Tradegate; ** Based on adjustments of nominal share price and reduced number of

converted shares after capital reduction in April 2015 (first day of trading: 27 April 2015)


Focusing on Epigenetic Products – Sale of 4SC Discovery Operations to BioNTech

31

• Incorporation of BioNTech Small Molecules on 1 May 2016

o Wholly-owned subsidiary of BioNTech AG, Mainz, Germany

o Transfer of key operating assets

including 22 employees from 4SC Discovery

• 4SC keeps epigenetic compounds and underlying intellectual property

o In addition keeping further advanced preclinical projects for out-licensing

o Reduced personnel expenses compensating increased costs for RESMAIN

study (resminostat in CTCL) due to planned recruitment of 150 instead of

120 patients (EMA advice)

CTCL: cutaneous T-cell lymphoma; EMA: European Medicines Agency


Upcoming Operating Milestones

32

• By mid-year 2016: Start of pivotal phase II CTCL study

o Study design in alignment with comprehensive EMA advice

o Initial results could be available at the end of 2018

• Priming for immune response: clinical concept for

demonstrating 4SC-202’s immune priming capacity

o Unique epigenetic mode of action

o Preclinical testing indicates immono-modulatory activity

• Data from detailed analysis of Yakult-Honsha’s Japanese liver

cancer phase II trial

o Identification of possible subgroups for stratified phase II/III

development in HCC

o Detailed data to be presented by Yakult-Honsha at scientific

congress

CTCL: cutaneous T-cell lymphoma; EMA: European Medicines Agency


4SC AG

Am Klopferspitz 19a

82152 Planegg-Martinsried

Germany

+49 89 700763-0

[email protected]

www.4sc.com

Contact

Dr Daniel Vitt

CSO / CDO

[email protected]

Wolfgang Güssgen

Head of Corporate

Communications & IR

[email protected]

33


Backup

34


Key Financial Figures FY 2015

35

EUR million FY 2015 FY 2014

Revenue 3,266 7,055

Cost of sales -1,763 -4,080

Gross profit 1,503 2,975

Research and development costs -7,255 -8,504

Other costs (admin & distribution) -3,347 -3,966

Other income 0,184 0,058

Operating profit / loss -8,915 -9,437

Net finance income / loss -0,273 -0,189

Income tax expense -0,040 -0,070

Net profit/loss -9,228 -9,696

Monthly average operational cash burn -0,767 -0,706

Cash balance/funds at period-end 22,794 3,202


Recent Market Approvals Boosted Interest for New HDAC Inhibitors and Epigenetic Therapies

36

Compound Mode of

Action Company Approved Indication

Main Approval Geography

(as reported by Cortelis®)

Vorinostat

(Zolinza)

Pan-

HDAC Merck

CTCL

(based on open label single-

arm Phase II study)

US (2006), Canada, Taiwan,

Japan, Australia

EU filing withdrawn in 2009

(EMA concern)

Romidepsin

(Istodax)

Class-1

selective Celgene

CTCL and relapsed /

refractory PTCL

(based on open label single-

arm Phase II study)

US (2009 CTCL, 2011 PTCL),

Canada, Australia (PTCL)

Never filed for EU approval

Belinostat

(Beleodaq)

Pan-

HDAC

Spectrum

(Onxeo) relapsed / refractory PTCL US (2014)

Panobinostat

(Faridak)

Pan-

HDAC Novartis

relapsed / refractory Multiple

Myeloma (3rd line; in combi-

nation with bortezomid +

dexamethasone)

US (2015)

Europe (2015)

Resminostat HDAC1-3

& 6 4SC

GOAL: CTCL (randomized,

placebo-controlled, two-arm)

GOAL: First HDAC inhibitor in

Europe in CTCL


Drug Mode of Action Administration Stage Modus Company Pts. Location Timelines

Mogamulizumab CCR4 mAb

(homing receptor)

Systemic, iv Phase III 2nd line vs

Vorinostat

Kyowa 317 pts WW 13/12/2012

01/02/2017

SGX-301 Hypericin

photodynamic

therapy

Topical Phase III 1st line with light

irradiation

Soligenix 120 pts US 14/12/2015

01/12/2016

Brentuximab ADC vs CD30+

tumor cells

Systemic, iv Phase III 1st line vs

bexarotene

SeattleGenetics 132 pts WW 07/05/2012

01/05/2016

Selinexor Inhibitor of CRM1

(nuclear

transporter)

Oral Phase II 2nd line or more Karyopharm 60 pts US

NM-IL-12 IL 12 cytocine (?) iv Phase II Combined with Total

Skin Electron Beam

Therapy (TSEBT)

Neuromedicines 10 pts Australia 01/11/2015

01/05/2017

SHP-141 HDAC inh Topical Phase II Early stages Tetralogic 60 pts US 18/12/2014

01/05/2016

IL-12 plasmid Immunostimulatory iv Phase II Plasmid insertion

stimulated by

electroporation

Oncosec Medical 34 pts US 09/07/2012

01/12/2015

A-dmDT390

Resimmune

iv Phase II mAb+Diphteria Toxin Angimmune Sep 2015

IPH4102 mAb anti-KIR3DL2

to activate NK cells

iv Phase I 3rd line

Innate 60 pts EU/US Oct 2015-

Dec 2018

Pembrolizumab Anti PD-1 iv Phase I 2nd line NCI 24 pts US Oct 2014-?

37

Current Clinical Studies in CTCL with Innovative Therapies


Resminostat – Safety Profile

38

0 20 40 60 80 100

Abdominal pain…

Fever

Asthenia

Neutropenia

Dysgeusia

Anaemia

Thrombocytopenia

Decreased appetite

Diarrhoea

Fatigue

Vomiting

Nausea

Grade 1,2

Grade > 3

% patients

Grade 1, 2

Grade > 3

AEs related to resminostat observed in > 7.5% of patients*

* Western patient population; AE: adverse event

© 4SC AG, June 2016 39

Solid

tumors1

Solid

tumors2§

Hodgkin‘s

Lymphoma

(HL)

Colorectal

Cancer

(CRC)

Liver

Cancer

2nd line3

Liver

Cancer

1st line§

Lung

Cancer

(NSCLC)§

Pancreatic/

Bilary tract

carcinoma§

Ph I

(FIM)

Ph I Ph I/II Ph I Ph II Ph I/II Ph I/II Ph I

N=19 N=12 N=37 N=17 N=57 N=86/163 N=53/107 N=14*

mono mono mono FOLFIRI sorafenib sorafenib docetaxel S1

Europe Japan Europe Europe Europe Japan,

Korea

Japan Japan

3+3 3+3 Single arm 3+3 Two arm RCT RCT 3+3

✔ ✔ ✔ ✔ ✔ ✔ ongoing recruiting

Monotherapy Combination Therapies

1 Brunetto et al, Cln Cancer Res 19, 5494-5504, 2013; 2 Kitazono et al, Cancer Chemother Pharmacol 75, 1155-1161,

2015; 3 Bitzer et al, J Hepatol xx, 2016; § sponsored and conducted by Yakult Honsha; * as of February 2016

Resminostat – Exposure in Clinical Studies


Resminostat Enhances NK Cell Recognition

40

• NK cells recognize tumor cells by expression of NKG2D ligands (MICA/B, ULBP1-3)

• Increased expression of NKG2D ligands on tumor cells enhances recognition and killing

of tumor cells by NK cells

• Resminostat up-regulates expression of NKG2D ligands on various tumor cells

0 µM 0.5 µM 1 µM 2 µM 4 µM

ULB

P3 (

fold

induction)

0

20

40

60

80

100

120

140

Resminostat

NKG2D

ligands

A549*

(lung)

HepG2*

(liver)

K562*

(CML)

U2OS*

(sarcoma)

Huh7*

(liver)

MICA

MICB n.d.

ULBP1

ULBP2

ULBP3

* Different cancer cell lines; NK cells: natural killer cells of the immune system; NKG2D: activating receptor on NK cells;

MICA/B, ULBP1-3: ligands binding to NKG2D; CML: chronic myeloid leukemia


Resminostat Enhances Killing by NK Cells

41

Increased expression of NKG2D

ligands enhances recognition and

killing of tumor cells by NK cells

Resminostat strongly boosts NK cell mediated killing of tumor cells

Resminostat

0 µM 1 µM 2 µM

specific

lysis

of

pre

-tre

ate

d K

562

cells

0

10

20

30

40

50

60

2.1x

2.6x

* cancer cell line; NK cells: natural killer cells of the immune system; NKG2D: activating receptor on NK cells

*


Summary: Resminostat as Combination Partner for Cancer Immunotherapy

NK cell T cell

Tumor

cell 3934

up

3273

down

IDO / ARG

NKG2D

Ligands TAA pre-

sentation

Killing Killing

42

Resminostat

Resminostat enhances NK cell recognition and killing, TAA expression and presentation,

and reduces unspecific immunosuppressive mechanisms

NK- /T cells: subtypes of immune cells; NKG2D: activating receptor on NK cells; IDO / ARG: indoleamine 2,3-dioxygenase /

arginase, enzymes destroying essential factors for immune cells; TAA: tumor associated antigen


4SC-202 as an Immune Priming Agent II

43

• 4SC-202 is able to “prompt” the immune system for its job to attack

cancer

o By not attacking the immune cells

o In contrast to HDAC-only inhibitors, 4SC-202 does not exert any toxicity to

activated immune cells and thus prompts anti-tumor immune response

NK cells CD4+ T cells CD4+ memory T

cells

CD8+ T cells

4SC-202 6.4 Not toxic Not toxic Not toxic

entinostat 0.8 4 1.6 1.0

vorinostat 0.6 0.6 1.1 0.6

T-cells were stimulated with CD3/28 beads

Different subpopulations were isolated using appropriate Miltenyi kits according to manufacturers instructions; cells were then treated with indicated compounds for

48 h with or without stimulus; viability was determined using Vialight Kit (Lonza); IC50 .


4SC AG

Am Klopferspitz 19a

82152 Planegg-Martinsried

Germany

+49 89 700763-0

[email protected]

www.4sc.com

Contact

Dr Daniel Vitt

CSO / CDO

[email protected]

Wolfgang Güssgen

Head of Corporate

Communications & IR

[email protected]

44

Documents

4SC-202: The new dimension in immunooncology 4SC AG February