26th April 2016, BioTrinity - London Innovative Drug Discovery The EUD-GK-91 Program: Targeting Oncogenic Kinases & Drug Resistance Mutations Mauro Angiolini, PhD 26th April 2016, BioTrinity - London

Kinase Inhibitors: Scenario Several human cancers are triggered by a family of dysregulated proteins: the kinases Kinase inhibitors are showing remarkable clinical impact and market success in cancer therapy Challenging issue: drug resistance due to mutations of kinase target causing failure of therapy Urgent need of a novel generation of kinase inhibitors effective against target mutations

Eudendron: Drug Discovery Strategy Craft highly engineered orally available kinase inhibitors based on internally developed molecular designs addressing: - drug resistance mutations - modulation of selectivity profile across large panel of kinases Provide better therapies for kinase-driven diseases with high medical need

EUD-GK-91: a Lead Compound First result of developed molecular design is EUD-GK-91, a selective lead compound successfully targeting kinases and resistance mutations clinically relevant for Lung Cancer Therapy

EUD-GK-91: a Breakthrough Molecule Potent inhibitor of 5 kinases associated to oncogene addiction in several human cancers: ALK, DDR2, RET, TRK, ROS1 High selectivity in a 300 protein kinases panel Outstanding activity in cells across drug resistance mutations Crucial role of inhibited targets in lung cancer development EUD-GK-91 might potentially provide an answer to that 20% of all lung cancer patients with currently no effective treatment

EUD-GK-91 vs Resistance Mutations EUD-GK-91 displays impressive data in cells expressing ALK mutations causing therapy failure of Crizotinib (Pfizer), 1st line treatment for lung cancer In addition EUD-GK-91 displays in cells superior potency against mutations compared to newly approved drugs Ceritinib (Novartis) and Alectinib (Roche)

EUD-GK-91: the Chemical Series Several synthesized analogues defined a novel developable chemical series having a clear Structure Activity Relationship Different analogues show potent antiproliferative activity with low nanomolar IC50 values against clinically relevant mutations IP: full positive International Search Report obtained

EUD-GK-91 Series: Development Collaborations with groups in UK, Italy and Netherlands have been started with research focus on inhibited targets Strategic advantages: increased efficacy by anticipating target mutations responsible for drug resistance, improved tox profile by increasing selectivity against other kinases

EUD-GK-91 Series: Medical Needs The unique inhibition profile of EUD-GK-91 provides opportunity to address cancer indications aiming at First / Best in Class inhibitors for the following needs

EUD-GK-91 Program: Investment Proposition Total capital need: 2M£ Use of funds: identification of Pre-Clinical Drug Candidate Timescale: 2 years ROI strategy: out-licensing EUD-GK-91 program or acquisition

Eudendron: Achievements & Future Step Eudendron has developed drug resistance/selectivity solutions applicable to many chemotypes within the whole protein kinases family identified selective EUD-GK-91 lead compound and chemical series successfully targeting kinases and drug resistance mutations relevant for cancer therapy Eudendron is looking for funding and collaboration opportunities to develop the EUD-GK-91 program and build a sustainable pipeline

Eudendron: the Team Several years’ experience in Pharmaceutical Drug Discovery Multi-million € preclinical/clinical deals Founders Advisors Mauro Angiolini, PhD Past positions: Pharmacia, Pfizer, NMS Silvano Spinelli Former CEO EOS, NovusPharma Fabio Zuccotto, PhD Past positions: GSK, Inpharmatica, NMS Kevin Read, PhD Drug Discovery Unit, Dundee

Eudendron: Contact Details Mauro Angiolini mauro.angiolini@eudendron.com +41 76 675 15 89 Fabio Zuccotto fabio.zuccotto@eudendron.com +44 7918 92 84 62 info@eudendron.com www.eudendron.com