Amplia Therapeutics Ltd. · ASX:ATX
Amplia Therapeutics — 2nd Next Generation Kinase Inhibitors Summit (February 2023)
23 slides from Amplia Therapeutics's conference presentation, Feb 23, 2023
Slide 1: US Conference Presentation (ASX Release)
ASX RELEASE 23 February, 2023 US CONFERENCE PRESENTATION For personal use only • Amplia’s FAK inhibitor program to be presented at Next Generation Kinase Inhibitors Summit in Boston, USA Melbourne, Australia: Amplia Therapeutics Limited (ASX: ATX), (“Amplia” or the “Company”), a company developing n
Slide 2: Targeting Focal Adhesion Kinase (FAK) for the treatment of cancer and fibrotic diseases
For personal use only Targeting Focal Adhesion Kinase (FAK) for the treatment of cancer and fibrotic diseases Terrie-Anne Cock PhD Amplia Therapeutics, Melbourne, Australia Amplia Therapeutics Limited
Slide 3: Focal Adhesion Kinase
Focal Adhesion Kinase For personal use only Promotes fibrosis Shields tumours from chemotherapy Focal Adhesion Fibrotic Fibrotic Tissue Kinase (FAK) tumourmicroenvironment Fibrotic Diseases Solid Cancers 2
Slide 4: FAK association with cancer
FAK association with cancer For personal use only Percentage of tumour samples with increased FAK mRNA: • FAK is rarely mutated in cancer, The Cancer Genome Atlas cBioPortal for Cancer Genomics) most frequently occurring in cancers arising from the uterus (9.24% of samples), colon (7.25%) and liver
Slide 5: Amplia's Focus
Amplia’s Focus For personal use only Pancreatic Cancer Idiopathic Pulmonary Fibrosis (IPF) • 60,000 new diagnoses and 48,000 deaths from • Affects ~3M people worldwide** pancreatic cancer in the US each year* • Devastating, progressive disease caused by the build • Difficult-to-treat cancer up
Slide 6: AMP945 is a potent and selective FAK inhibitor
AMP945 is a potent and selective FAK inhibitor For personal use only AMP945 Defactinib AMP945 is the most selective FAK inhibitor in clinical development FAKi AMP945 Defactinib IN10018 Company Amplia Verastem InxMed IC50 >1 µM 3 9 4 (468 kinase (468 kinase (262 kinase tested) tested) tested) 5
Slide 7: Amplia's Hypothesis | Enhancing Chemotherapy
Amplia's Hypothesis | Enhancing Chemotherapy For personal use only • Fibrotic shields protect many solid tumours from chemotherapy • Amplia’s FAK inhibitors aim to remove the shield FAK inhibitor Exposed tumour Dead tumour Fibrotic tumour microenvironment 6
Slide 8: AMP945 inhibits collagen cross-linking in vitro
AMP945 inhibits collagen cross-linking in vitro For personal use only Second Harmonic Generation measures only cross-linked collagen AMP945 [ ] Vehicle 5 nM AMP945 10 nM AMP945 20 nM AMP945 50 nM AMP945 100 nM AMP945 7 Timpson Lab (Garvan Inst.)
Slide 9: AMP945 inhibits new collagen deposition in vitro
AMP945 inhibits new collagen deposition in vitro For personal use only Picosirius red staining for total collagen Vehicle 5 nM 10 nM 20 nM 50 nM 100 nM Take home messages: • Fibroblasts remodel collagen and also lay down new collagen • AMP945 causes less new collagen to be deposited by the fibroblas
Slide 10: AMP945 priming enhances cleaved caspase and Ki67 response to chemotherapy
AMP945 ‘priming’ enhances cleaved caspase 3 and Ki67 response to standard of care Gemcitabine + Abraxane treatment (Day 6) For personal use only KPC mouse model is a clinically relevant Tumors analysed 24 hrs post model of pancreatic ductal Gem/Abraxane administration adenocarcinoma AMP945 Gem/Abrax
Slide 11: FAK – a drug target for multiple cancers and fibrotic diseases
FAK – a drug target for multiple cancers and fibrotic diseases For personal use only Growth Murphy, J. M., et al. (2020). Experimental & molecular medicine, 52(6), 877–886. 10 Wu, Y., et al. (2021). Discover. Oncology, 12(1), 52.
Slide 12: Priming with FAKi AMP945 in the subcutaneous KPC mouse model
Priming with FAKi AMP945 in the subcutaneous KPC mouse model of pancreatic cancer For personal use only 11
Slide 13: AMP945 enhances survival to gemcitabine and Abraxane in mouse model
AMP945 enhances survival to gemcitabine and Abraxane in an aggressive mouse model of pancreatic cancer For personal use only * P ≤ 0.05 *** p ≤ 0.005 12
Slide 14: Priming is more effective than continuous daily dosing
Priming is more effective than continuous daily dosing For personal use only Daily dosing AMP945 for each cycle Priming for first 4 days of each cycle Vehicle Vehicle ✱ ✱ Vehicle/Gem/nab-Pac Vehicle/Gem/nab-Pac ✱✱ ✱✱✱ AMP945/Gem/nab-Pac AMP945/Gem/nab-Pac 100 100 Probability of Survival Probability
Slide 15: AMP945 Improves Survival in PDX Pancreatic Cancer Model
AMP945 Improves Survival in PDX Pancreatic Cancer Model Treatment with AMP945 or vehicle, twice daily, AM and PM For personal use only Treatment with Gemcitabine/Abraxane or vehicle Day 1 Orthotopic AM AM AM PM PM PM Day 7 Day 10 cell injection ….. ≥ 7 days of Tumour Repeat up to 20 cycles or until
Slide 16: Phase 1 trial of AMP945 in healthy volunteers
A phase 1 trial of AMP945, a potent and selective focal adhesion kinase inhibitor, in healthy volunteers For personal use only 15
Slide 17: Results – plasma pharmacokinetics of AMP945
Results – plasma pharmacokinetics of AMP945 For personal use only 16
Slide 18: Results – Pharmacodynamics and safety
Results – Pharmacodynamics and safety For personal use only • No serious or severe TEAEs, nor any TEAEs leading to study withdrawal (majority of TEAEs reported were mild) • There were no dose-related trends observed in the reporting of TEAEs • No TEAEs were considered probably or definitely related
Slide 19: Conclusions - Phase 1 trial of AMP945
Conclusions - Phase 1 trial of AMP945 For personal use only • AMP945, a selective FAK inhibitor, was safe and well tolerated across SAD (15 to 125 mg) and MAD (25 to 100 mg) cohorts in healthy volunteers • No serious adverse events or withdrawals • No trends observed in AE reporting, no shifts in cl
Slide 20: Phase 2 pancreatic cancer clinical trial "ACCENT"
Phase 2 pancreatic cancer clinical trial "ACCENT" For personal use only • First-line therapy - Largest patient cohort - Healthier patients - Aims to position AMP945 as a first-line treatment option Phase 2 pancreatic cancer clinical • Patients with non-resectable or metastatic pancreatic cancer
Slide 21: ACCENT Priming Dose Regimen
ACCENT Priming Dose Regimen For personal use only • Amplia’s Phase 1b/2a clinical trial AMP945-PC-201 (ACCENT, NCT05355298) will assess a pulse dosing regimen of AMP945 in combination with gemcitabine and nab-paclitaxel as first-line therapy in patients with unresectable or metastatic pancreatic can
Slide 22: ACCENT Clinical Trial Summary
ACCENT Clinical Trial Summary For personal use only • Patients with Stage III or IV pancreatic cancer • First line therapy Population • ECOG status ≤ 1 • Life expectancy of >3 month • Phase 1b/2a open label, single arm study to Design evaluate safety, PK, PD and efficacy of AMP945 in combination
Slide 23: Acknowledgements
Acknowledgements For personal use only • Patients, families and caregivers Amplia Team: involved in trials Garvan Institute: • Christopher Burns • Paul Timpson • Rhiannon Jones • Amplia (ASX: ATX) Investors • Kendelle Murphy • Charlotte Mulder • David Herrmann • Funding bodies: NHMRC, ARC, Cancer •
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