1. 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

2. 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

3. 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

4. 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

5. 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

6. 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)

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. Eudendron: Contact Details
Mauro Angiolini
Fabio Zuccotto