syntarga - vincent de groot 24112011
TRANSCRIPT
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