1) Syntarga was founded in 2001 to develop antibody-drug conjugate (ADC) technology using a novel releasable linker called SpaceLink. 2) In 2011, Syntarga was acquired by Synthon BV, a pharmaceutical company focused on biosimilars, monoclonal antibodies, and ADCs for oncology and multiple sclerosis. 3) Synthon has advanced Syntarga's ADC technology, completing new biopharmaceutical laboratories and developing optimized linker-drug combinations that show potent anti-tumor activity in preclinical models of cancer.

1. Syntarga: van onderzoek tot
onderneming tot overname
November 24, 2011
Vincent de Groot

2. Valorisation
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3. Syntarga: Inception to Exit - Historical Summary
1997 – 2001: Ph.D. Research Vincent de Groot yielded SpaceLink
technology
2001 – 2002: Foundation of Syntarga BV (with Patrick Beusker)
2002: grant STIGON/Biopartner
g p
2005: Series A financing by VCs Aglaia & BioPartner Ventures
2008 – 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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4. Technology count by development stage, 2011
35
30
25
20
15
10
5
0
Marketed Approved Phase III Phase II Phase I Preclinical
Antibody drug conjugate Bispecific Nanobody DAb Fc-engineered Trifunctional
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5. The Synthon Technology
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6. Synthon - Biopharmaceuticals Development
History & Focus
• 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
Biosimilars and NBE
d NBEs
• Antibody Drug Conjugates
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7. Synthon has completed new world class
biopharmaceutical labs
Located at Synthon Headquarters in Nijmegen, Netherlands
New Labs since April 1, 2011
• 6850m2 gross area
• 131 working places
ki l
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8. 2000: SpaceLink: Differentiating Releasable Linker Technology
cleavage spontaneous
+ +
cleavage
Inactive drug Cleavable moiety
Antibody Duocarmycin
Releasable linker Linker (non-releasable)
- Cleavage triggers spontaneous release of the active drug
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9. 2006: Duocarmycins & Mechanism of Action
Natural derivatives Molecular target: DNA Binding to DNA
40 100
40-100 pM
6 pM
- DNA alkylating agents; binding in minor groove increases drug's reactivity
- DNA-binding
DNA binding unit in red, DNA-alkylating unit in blue
red DNA alkylating
- Synthon derivatives: fully synthetic, picomolar activity
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10. Synthon ADC technology exploits the chemistry of
duocarmycin’s crucial hydroxy group
Chemistries of SpaceLink and the Duocarmycin drug class are uniquely
complementary
R2
Cl
H Deactivated
Cleavable
peptide Cytotoxic
NH Agent
N
R1 O
SpaceLink
OH
Releasable
Linker
• OH group must be liberated from the
linker to yield precursor molecule
• S
SpaceLink: unique li k chemistry t
Li k i linker h i t to
link drugs via their OH group
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11. 2006 – 2011: Syntarga Potent Payload Technology
Novel, Highly Potent Drugs
Novel, Highly Stable Linkers
- Potent Payload Technology: novel, proprietary Linker-Drug combinations
Linker Drug
- Fully synthetic Linker-Drugs (L-D's)
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12. 2011: Synthon ADC products
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13. ADC Single Dose Potency - Optimized Linker-Drugs
Vehicle
Mean Tumor Burden
1400 Trastuzumab (12 mg/kg, IV)
ADC5 (12 mg/kg, IV)
ADC10 (12 mg/kg, IV)
1200 ADC25 (12 mg/kg, IV)
ADC28 (12 mg/kg, IV)
ADC29 (12 mg/kg, IV)
1000
ADC30 (12 mg/kg, IV)
Tumor volume (mm3)
Pos Ctrl ADC (12 mg/kg, IV)
800
- N87 (gastric) xenograft
600 - Female nu/nu mice
- 6 Animals/ADC group
400
- ADCs based on optimized
LDs have long lasting
long-lasting
200 efficacy and lead to high
cure rates
0
0 20 40 60 80 -100 DAR 2: 12 mpk of ADC =
Days after start of treatment
0.16 µmol drug/kg
1 animal found dead (day 18) for ADC28
(non-treatment related; no signs of toxicity)
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14. Strategy
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15. Creating Value
• It is all about science……
• …or…?
• Financing/venture capital
j
• Objectives
• Strategy & Corporate development
• Projects (products)
• IP
• Team – find the right people
• Business model
• Licensing & business development (& networking)
• Negotiation & dealmaking
• Alliance management
• Valuation
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