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Syntarga: van onderzoek totonderneming tot overnameNovember 24, 2011Vincent de Groot
ValorisationSynthon            2
Syntarga: Inception to Exit - Historical Summary          1997 – 2001: Ph.D. Research Vincent de Groot yielded SpaceLink  ...
Technology count by development stage, 2011353025201510 5 0          Marketed       Approved         Phase III      Phase ...
The Synthon TechnologySynthon                            5
Synthon - Biopharmaceuticals Development  History & Focus          • Biopharmaceutical activities initiated in 2007       ...
Synthon has completed new world class  biopharmaceutical labs  Located at Synthon Headquarters in Nijmegen, Netherlands   ...
2000: SpaceLink: Differentiating Releasable Linker Technology                            cleavage                         ...
2006: Duocarmycins & Mechanism of Action      Natural derivatives               Molecular target: DNA        Binding to DN...
Synthon ADC technology exploits the chemistry of  duocarmycin’s crucial hydroxy group  Chemistries of SpaceLink and the Du...
2006 – 2011: Syntarga Potent Payload Technology                                 Novel, Highly Potent Drugs                ...
2011: Synthon ADC productsSynthon                        12
ADC Single Dose Potency - Optimized Linker-Drugs                                                                          ...
StrategySynthon              14
Creating Value          • It is all about science……          • …or…?          • Financing/venture capital              j  ...
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Syntarga - vincent de groot 24112011

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Syntarga - vincent de groot 24112011

  1. 1. Syntarga: van onderzoek totonderneming tot overnameNovember 24, 2011Vincent de Groot
  2. 2. ValorisationSynthon 2
  3. 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 trialsSynthon 3
  4. 4. Technology count by development stage, 2011353025201510 5 0 Marketed Approved Phase III Phase II Phase I Preclinical Antibody drug conjugate Bispecific Nanobody DAb Fc-engineered TrifunctionalSynthon 4
  5. 5. The Synthon TechnologySynthon 5
  6. 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 ConjugatesSynthon 6
  7. 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 lSynthon 7
  8. 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 drugSynthon 8
  9. 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 drugs reactivity - DNA-binding DNA binding unit in red, DNA-alkylating unit in blue red DNA alkylating - Synthon derivatives: fully synthetic, picomolar activitySynthon 9
  10. 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 groupSynthon 10
  11. 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-Ds)Synthon 11
  12. 12. 2011: Synthon ADC productsSynthon 12
  13. 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) Synthon 13
  14. 14. StrategySynthon 14
  15. 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 • ValuationSynthon 15

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