Conference Day Two

8:00 am Coffee & Networking

8:55 am Chairman’s Opening Remarks

Targeting the Major Kinase Signalling Pathway

9:00 am Targeting RAF Kinases to Overcome Adaptive Resistance to RAS Targeted Therapies


  • Clinical and pre-clinical data emphasizes the frequency of on-target and onpathway (ERK-MAPK) adaptive and acquired resistance mechanisms to KRASG12C targeted therapies.
  • CRISPR LoF screens in KRAS-G12C inhibitor resistant cell lines reveal gene subsets whose depletion restores sensitivity to KRASG12C inhibitor treatment. RAF kinases, notably CRAF, was uncovered as one such gene.
  • CRISPR genetic ablation and acute protein destruction methods, including DTAG, provide unique insights into the kinetics of ERK-MAPK pathway modulation by CRAF. These technologies reveal mechanism of action hypotheses and biomarker opportunities for this challenging onco-target.

9:30 am [VIRTUAL] Sourcing the Immune System to Induce Immunogenic Cell Death In Kras-Colorectal Cancer Cells


  • Review how current approaches aimed at inducing immunogenic cell death (ICD) to incite an immune response against cancer neoantigens are based on the use of chemotherapeutics and other agents
  • Results are hampered by issues of efficacy, combinatorial approaches, dosing and toxicity. Here, we adopted a strategy based on the use of an immunomolecule that overcomes pharmachemical limitations.
  • Cytofluorometry, electron microscopy, RT-PCR, western blotting, apotome immunofluorescence, MLR and xenografts

10:10 am Kinetic Profiling of Reversible & Irreversible Kinase Inhibitors : At Scale & Speed

  • Jeremy Hague Chief Business Development Officer, Enzymlogic


  • Why kinetic profiling matters in drug discovery
  • Enzymlogic’s KINETICfinder® and COVALfinder® platforms: optimized for reversible and irreversible inhibitor kinetic profiling in early discovery Case studies that illustrate:
    • How kinetic profiling reinforces drug discovery decision making
    • Kinetic Selectivity is a superior predictor of efficacy compared to Affinity Selectivity
    • How Enzymlogic supports your kinetic investigation

10:25 am Targeting Pantothenate Kinase as an Effective Strategy for Antifungal Drug Development

  • Shalev Gihaz Postdoctoral Researcher, Yale School of Medicine


  • Pantothenate kinase (PanK) activity is the first step in Co-enzyme A (CoA) biosynthesis. In fungi, a single PanK gene, CAB1, encodes this function
  • A high-throughput chemical screen identified fungal PanK inhibitors and the CAB1 3D structure revealed essential residues for catalysis, inhibitor binding, and future SAR studies
  • The fungal PanK were validated as targets for antifungal drug development

10:55 am Morning Networking Break

11:30 am Targeting Oncogenic KRAS-G12D Mutation Employing Engineered Exosomes in Pancreatic Cancer

  • Raghu Kalluri Professor- Cancer Biology, University Texas MD Anderson Center


  • Direct inhibitors do not exist for KRAS-G12D
  • We engineered exosomes to deliver siRNA specific to Kras-G12D (iExosomes). The iExosomes target pancreatic cancer cells to suppress tumor growth and increase the overall survival of mice with PDAC
  • Preclinical studies, GLP-toxicology studies, clinical grade GMP production and FDA IND filing led to a Phase I clinical trial in PDAC

12:00 pm Structural Insights into Emerging Inhibitors Targeting EGFR Mutations

  • David Heppner Assistant Professor - Medicinal Chemistry, University at Buffalo


  • The structure of lazertinib allows for enhanced potency and mutant selectivity against EGFR T790M
  • Next generation mutant EGFR C797S inhibitors bind the kinase domain through H-bonding with conserved catalytic residues
  • Spanning ATP-allosteric EGFR inhibitors can be developed exhibiting unique kinase domain binding and mutant selectivity

12:30 pm Tumor-Selective Targeting of Kinase Conformations For Cancer Therapy


  • Therapeutic effectiveness of targeted cancer therapies is limited by Incomplete inhibition of the target pathway in the tumor caused by various adaptive resistance mechanisms
  • Increased drug dosing or vertical drug combinations to overcome resistance are limited by on-target toxicities in normal tissue and low Therapeutic Index
  • Improved therapies require drugs and drug combinations that target tumor-selective kinase conformations to achieve both potent antitumor efficacy and a high Therapeutic Index

1:00 pm Lunch & Networking

Improving Response Rates Through Well-Tested, Powerful Combination Therapies

2:00 pm Lymphatropic Combination Therapy


  • Targeting MAPK and PI3K/mTOR pathways is critical due to crosstalk
  • Combination therapy strategies have been hampered by dose-limiting toxicities
  • A Lymphatropic single agent orally bioavailable mutikinase inhibitor provides a path forward

2:30 pm [VIRTUAL] Targeting Focal Adhesion Kinase (FAK) for the treatment of cancer and fibrotic diseases

  • Terri-Anne Cock Head of Translational Biology, Amplia Therapeutics Limited


  • Amplia’s opportunity with AMP945 a FAK inhibitor for combination therapies
  • Preclinical data demonstrating FAK’s role modulating the tumour and in the tumour environment 
  • Clinical evidence gathered so-far that supports progression of AMP945 combination therapy in patients with advanced pancreatic cancer 

Targeting Established Pharmacological Mechanisms in Alternative Indications Beyond Oncology to Meet Unmet Needs

3:00 pm Novel Potential Applications of Kinase Activators And Inhibitors In Neurological Conditions


  • The interplay between potassium channels and protein kinases appears to play important roles in physiology and disease
  • otassium channels can lead to activation and/or inhibition of kinases
  • The talk will explore potassium channels-kinases interactions in mouse models of dementia and developmental and epileptic encephalopathies

3:30 pm Chairman’s Closing Remarks

End of Summit