© 2013 Ganymed

Ideal Monoclonal Antibodies for the Treatment of Cancer

Dr. Luc St-Onge

BIO Deutschland

Düsseldorf, September 23, 2013

© 2013 Ganymed

Company Overview

10/1/13 2

Focus Development of a new class of anticancer drugs called Ideal Monoclonal Antibodies (IMABs) History Founded in 2001 Spin- off from the Universities of Mainz and Zurich 125.5M EUR of financing raised to date Management Dr. Özlem Türeci, CEO - CMO Dirk Sebastian, CFO - COO Investors ATS (Strüngmann brothers), Future Capital, FCP Biotech Holding, MIG Fonds, private investors

Kaiserslautern

Frankfurt

Ludwigshafen Mannheim

Mainz

Wiesbaden Ingelheim

Darmstadt

r = 25 km

r = 50 km

© 2013 Ganymed

Conventional Anticancer Drugs

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(1)

breast cancer

HER2/neu

Healthy tissue Cancer tissue

Pot

ency

Dose

Narrow therapeutic window

Anticancer activity

Toxicity

Most conventional anticancer drugs targets are often expressed in numerous healthy tissues

  Bind to healthy cells, increasing the risk of side effects

  End up having lower potency to avoid the threat of toxicity

  Have a narrow therapeutic window and can not be used at optimal doses

© 2013 Ganymed

Ideal Monoclonal Antibodies (IMABs)

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IMABs targets are expressed in little or no healthy tissues IMABs are cancer cell selective

(2)

(3)

ovarian cancer

stomach cancer

Healthy tissue Cancer tissue

CLDN18.2 (IMAB362)

GT512 (IMAB027)

Broad therapeutic window

IMAB Dose

Anticancer activity

Toxicity

Pot

ency

  Do not bind to healthy cells, reducing the risk of side effects

  Designed for maximal potency while mitigating the threat of toxicity

  Have a broad therapeutic window and can be used at optimal doses

© 2013 Ganymed

Product Pipeline

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Product Target Validation Lead Selection Preclinical/CMC Phase I Phase IIa Phase IIb

Prod

uct-D

evel

opm

ent IMAB362

(CLDN18.2)

IMAB362 (CLDN18.2)

IMAB027 (GT512)

Ant

ibod

y-D

isco

very

2nd generation anti-CLDN18.2

2nd generation anti-GT512

GT468

GT352

GT353

Gastroesophageal cancer

Pancreatic cancer

Ovarian cancer

Breast cancer

Solid cancers

Solid cancers

Solid cancers

Solid cancers

© 2013 Ganymed

IMAB362 for Gastroesophageal and Pancreatic Cancers

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Healthy Stomach

Healthy pancreas

 Selective and specific for the tight junction protein Claudin-18.2 (CLDN18.2)

 CLDN18.2 only expressed on differentiated cells of the stomach mucosa

 Absent in over 45 healthy tissues analyzed

Stomach cancer

Pancreatic cancer

 Overexpressed in various solid cancers

•  Up to 80% gastric cancers •  Up to 80% esophageal cancers •  Up to 60% pancreatic cancers •  Other solid cancers (lung, ovary, colon,…) •  Primary and metastatic tumors

CLDN18.2 expression

© 2013 Ganymed

Clinical Development Overview

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  IMAB362 obtained orphan drug designation for gastric cancer in EU and US   Obtained orphan drug designation for pancreatic cancer in EU, pending in US   4 clinical studies in gastroesophageal cancer

Phase Study Design # Patients Status

Phase I - Single dose escalation, safety

15 Completed

Phase IIa Mono Single arm, repeated dose, monotherapy study

54 Completion H2/2013

Phase I PILOT Multiple dose, Immunomodulation IMAB362 + zoledronic acid + IL-2

20 Completion H2/2014

Phase IIb FAST 3 arms, repeated dose EOX chemotherapy ± IMAB362

210 Data review H2/2014 Completion H2/2015

© 2013 Ganymed

Phase IIa Study (Mono) Design

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Design Phase II, single arm, open label, repeated dose, monotherapy study Patient population Late-stage patients with refractory, recurrent or metastatic advanced gastroesophageal cancer Only CLDN18.2 positive patients are eligible Treatment 600 mg/m2 IMAB362 every 2 weeks for 5 cycles Patients who benefit could continue treatment at the discretion of the investigator Primary endpoints: Rate of Remission (CR, PR) according RECIST

Secondary endpoints: Safety, Clinical benefit, Progression free survival (PFS), Quality of life, PK, Immunogenecity

Last patient-in: Q3/2012

© 2013 Ganymed

Phase IIa: Efficacy (Preliminary results)

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Best response (RECIST) N %

Full analysis (FAS) 40 100

Partial response (PR) Stable disease (SD) Disease progression (PD)

4 8

28

10.0 20.0 70.0

Per protocol (PP) 21 100

Partial response (PR) Stable disease (SD) Disease progression (PD)

4 6 11

19.5 28.6 52.4

  Overall disease control rate (PR+SD)

30.0 % Full analysis set 48.1 % Per protocol set

Strong evidence for single agent activity of IMAB362

  Patients with clinical benefit to IMAB362 have an extended PFS

0 10 20 30 40 50 0

20

40

60

80

100

weeks

% s

urvi

vals

Progression free survival (PFS) Clinical response

34 wks median PFS Clinical response:

All patients (FAS)

10 wks median PFS All patients in study:

No response

8.5 wks median PFS No response:

© 2013 Ganymed

Phase IIa: Safety (Preliminary results)

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Related AEs by preferred term (N=46). Each AE is counted once

System organ class / Preferred term

Overall N (%)

Gastrointestinal disorders Abdominal pain Diarrhea GI haemorrhage GI mucosal disorder Nausea Salivary hypersecretion Vomiting

6 (13.0) 5 (10.9) 2 (4.3) 3 (6.5) 21 (45.7) 3 (6.5) 22 (47.8)

General disorders Fatigue Edema peripheral

11 (23.9) 5 (10.9)

Immune system disorders Hypersensivity

2 (4.3)

Metabolic disorders Decrease appetite Hypoalbuminaemia

7 (15.2) 1 (2.2)

Musculoskeletal disorders Pain in extremities

1 (2.2)

Respiratory disorders Dyspnea Hiccups

1 (2.2) 1 (2.2)

Skin disorders Erythema

3 (6.5)

Vascular disorders Hypertension

1 (2.2)

IMAB362 safe and well tolerated in study Transient nausea and vomiting were the most frequent related AEs

© 2013 Ganymed

Phase IIb Study (FAST)

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Design Phase II, open-label, first-line, multiple dose, 3-arm randomized, 70 patients per arm, international, multicenter study Patient population Late-stage patients with recurrent or metastatic advanced gastroesophageal cancer Only CLDN18.2 positive patients eligible

Treatment Arm 1: Epirubicin + Oxaliplatin + Capecitabine (EOX) every 3 weeks for 8 cycles Arm 2: 600 mg/m2 IMAB362 + EOX every 3 weeks for 8 cycles Arm 3: 1000 mg/m2 IMAB362 + EOX every 3 weeks for 8 cycles

Primary endpoints: Progression free survival (PFS), Safety with EOX

Secondary endpoints: Survival rate at 12 mths, Overall survival (OS), Time to progression (TTP), Objective tumor response rate (ORR), Disease control rate

Intended drug label: 1st line therapy in combination with chemotherapy

© 2013 Ganymed

In vitro Diagnostic (IVD) Test CLAUDETECT™18.2

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CLAUDETECT™18.2 IVD Test Jointly developed by Ganymed and Theracode GmbH Selectively and exclusively assesses CLDN18.2 expression levels in cancer tissues Semi-quantitative immunohistochemical assay for formalin fixed, paraffin embedded cancer tissues CE marking obtained / ISO13485 manufacturing CLAUDETECT™18.2 used in all ongoing clinical studies to validate the test as a predictive companion diagnostic for IMAB362

© 2013 Ganymed

IMAB362 Strengths and Opportunities

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 First-in-class antibody drug candidate directed against CLDN18.2

 Very restricted expression of CLDN18.2 in healthy tissues reduces risks of side effects by IMAB362

 Targets a large segment of the patient population

•  80% patients with gastroesophageal cancers are CLDN18.2+ •  60% patients with pancreatic cancers are CLDN18.2+

 Companion IVD diagnostic test CLAUDETECT™18.2

•  Predictive biomarker for personalized medicine

© 2013 Ganymed

Product Pipeline

10/1/13 14

Product Target Validation Lead Selection Preclinical/CMC Phase I Phase IIa Phase IIb

Prod

uct-D

evel

opm

ent IMAB362

(CLDN18.2)

IMAB362 (CLDN18.2)

IMAB027 (GT512)

Ant

ibod

y-D

isco

very

2nd generation anti-CLDN18.2

2nd generation anti-GT512

GT468

GT352

GT353

Gastroesophageal cancer

Pancreatic cancer

Ovarian cancer

Breast cancer

Solid cancers

Solid cancers

Solid cancers

Solid cancers

© 2013 Ganymed

IMAB027 for Ovarian Cancer

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GT512 expression

Healthy ovary

Healthy testis

Selective and specific for the surface protein GT512

GT512 is absent from adult tissue

Ovarian carcinoma

Testicular carcinoma

Overexpressed in multiple solid cancers

•  testicular cancers •  ovarian cancers •  uterine cancers •  lung cancers •  other solid tumors (lung, liver, breast,…)

© 2013 Ganymed

IMAB027 for Ovarian Cancer

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Orphan drug designation in Europe and US for ovarian cancer

Phase I/II study in ovarian cancer to be initiated before end of 2013

  IMAB027 does not bind to healthy adult cells

  Targets only cancerous cells

  Reduces risk of toxicity and side effects

Predictive IVD companion test under development

© 2013 Ganymed

Ganymed Highlights

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Key Highlights in Past 12 Months

  Promising efficacy and safety observed with IMAB362 in preliminary analysis of Phase IIa (Mono) in gastroesophageal cancer (GEC)

  Granting of orphan drug status for IMAB362 in gastric cancer

  Initiation of Phase IIb (FAST) study and Phase I immunomodulation (PILOT) study for IMAB362 in GEC

  CE marking of CLAUDETECT™18.2 IVD test for CLDN18.2 expression in cancer tissues

  Granting of orphan drug status of IMAB027 in ovarian cancer

© 2013 Ganymed

Ganymed Highlights

10/1/13 18

Upcoming Highlights

  Completion of analysis of Phase IIa (Mono) of IMAB362 in GEC

  Initiation of Phase I/II of IMAB027 in ovarian cancer

  Granting of orphan drug designation for IMAB362 in pancreatic cancer

  Preliminary analysis of Phase I immunomodulation (PILOT) of IMAB362 in GEC

  Completion of enrollment and data review of Phase IIb (FAST) of IMAB362 in GEC

© 2013 Ganymed 10/1/13 19

Ideal Monoclonal Antibodies for the Treatment of Cancer

Ganymed Pharmaceuticals AG Freiligrathstrasse 12

55131 Mainz Germany

+49 (0) 6131-1440 100 +49 (0) 6131-1440 114

bd@ganymed.ag

www.ganymed-pharmaceuticals.com