Syntarga: van onderzoek tot onderneming tot overnameonderneming tot overname

November 24, 2011Vincent de Groot

Valorisation

2Synthon

Syntarga: Inception to Exit - Historical Summary

1997 – 2001: Ph.D. Research Vincent de Groot yielded SpaceLinktechnology

2001 – 2002: Foundation of Syntarga BV (with Patrick Beusker)

2002: grant STIGON/Biopartnerg p

2005: Series A financing by VCs Aglaia & BioPartner Ventures

2008 2010: Loans and PPM Oost steps in2008 – 2010: Loans and PPM Oost steps in

2011: Acquisition by Synthon BV

………………………….2011: Gear up for preclinical toxicology

2013/2014: Start of clinical trials

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2013/2014: Start of clinical trials

Technology count by development stage, 2011

30

35

25

15

20

5

10

0Marketed Approved Phase III Phase II Phase I Preclinical

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Antibody drug conjugate Bispecific Nanobody DAb Fc-engineered Trifunctional

The Synthon Technology

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Synthon - Biopharmaceuticals DevelopmentH i s t o r y & F o c u s

• Biopharmaceutical activities initiated in 2007

• First cGMP DS and DP batch produced in 2011

• First clinical study started in 2011

• Acquisition of Syntarga in June 2011

Focus: MS and oncology

• Monoclonal Antibodies

Bi i il d NBE• Biosimilars and NBEs

• Antibody Drug Conjugates

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Synthon has completed new world class biopharmaceutical labsLocated at Synthon Headquarters in Nijmegen, Netherlands

New Labs since April 1, 2011• 6850m2 gross area

131 ki l• 131 working places

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2000: SpaceLink: Differentiating Releasable Linker Technology

++cleavage

spontaneouscleavage

Inactive drug

Releasable linker

Cleavable moiety

Linker (non-releasable)Antibody Duocarmycin

- Cleavage triggers spontaneous release of the active drug

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2006: Duocarmycins & Mechanism of Action

Molecular target: DNANatural derivatives Binding to DNA

40-100 pM40 100 pM

6 pM

- DNA alkylating agents; binding in minor groove increases drug's reactivity

DNA binding unit in red DNA alkylating unit in blue

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- DNA-binding unit in red, DNA-alkylating unit in blue

- Synthon derivatives: fully synthetic, picomolar activity

Synthon ADC technology exploits the chemistry of duocarmycin’s crucial hydroxy groupChemistries of SpaceLink and the Duocarmycin drug class are uniquely complementary

Cl

NH

R2

H Cleavablepeptide

DeactivatedCytotoxicAgent

N

OH

R1 O

NH Agent

SpaceLinkOH

• OH group must be liberated from the linker to yield precursor moleculeS Li k i li k h i t t

Releasable Linker

• SpaceLink: unique linker chemistry to link drugs via their OH group

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2006 – 2011: Syntarga Potent Payload Technology

Novel, Highly Potent Drugs

Novel, Highly Stable Linkers

- Potent Payload Technology: novel, proprietary Linker-Drug combinationsPotent Payload Technology: novel, proprietary Linker Drug combinations

- Fully synthetic Linker-Drugs (L-D's)

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2011: Synthon ADC products

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ADC Single Dose Potency - Optimized Linker-Drugs

1400Mean Tumor Burden

VehicleTrastuzumab (12 mg/kg, IV)ADC5 (12 mg/kg, IV)ADC10 (12 mg/kg, IV)

1000

1200

)

ADC25 (12 mg/kg, IV)ADC28 (12 mg/kg, IV)ADC29 (12 mg/kg, IV)ADC30 (12 mg/kg, IV)

600

800

or v

olum

e (m

m3 ) Pos Ctrl ADC (12 mg/kg, IV)

- N87 (gastric) xenograft

- Female nu/nu mice

400

Tum

- ADCs based on optimized LDs have long-lasting

- 6 Animals/ADC group

0

200

0 20 40 60 80 100

LDs have long lasting efficacy and lead to high cure rates

DAR 2: 12 mpk of ADC =

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0 20 40 60 80 100Days after start of treatment

- DAR 2: 12 mpk of ADC = 0.16 µmol drug/kg

1 animal found dead (day 18) for ADC28(non-treatment related; no signs of toxicity)

Strategy

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Creating Value

• It is all about science……

• …or…?

• Financing/venture capital

• Objectivesj

• Strategy & Corporate development

• Projects (products)

• IP

• Team – find the right people

• Business model• Business model

• Licensing & business development (& networking)

• Negotiation & dealmaking

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• Alliance management

• Valuation