*All agenda timings below are displayed in EDT. For PDT, please download the full program here*

8:30 am Opening Remarks & Virtual Coffee Networking

  • Piro Lito Assistant Member, Memorial Sloan Kettering Center

9:00 am Approaches to Inhibiting RAS Driven Tumors Beyond KRAS G12C

Synopsis

  • Targeting the ON form of KRAS G12C
  • Targeting mutant form of RAS beyond G12C
  • Relevant combinations to achieve synergy in KRAS mutant cancers

9:30 am Exploration of Synergistic Effects: RAF Dimer Inhibitor Lifirafenib (BGB- 283) & MEK Inhibitor Mirdametinib (PD-0325901)

  • Lusong Luo Senior Vice President, External Innovation, Beigene

Synopsis

  • How can inhibiting RAF dependent MEK reactivation suppress the proliferation of KRAS mutated cancer cells?
  • Discuss methodologies of inhibiting tumor growths in KRAS mutant xenograft models
  • Deconstruct the pharmacodynamic analysis of synergistic phospho-ERK blockade to confirm the antitumor activity in the KRAS mutant models
  • Explore the decision to support a vertical inhibition strategy

10:00 am Combination Therapies with SHP2 Inhibitors to Treat KRAS Mutant Cancers

Synopsis

• Exploring the potential of SHP2i & G12Ci combination for KRAS G12C mutant cancers
• Benchmarking the effectivity of combining SHP2i & MAPKi to target KRAS mutant cancers
• Adopting CDK4/6i within combination for effective KRAS therapy combination approach for effective KRAS therapy

10:30 am Real-World Data: Importance of Monitoring KRAS Mutations in Blood

Synopsis

  • Why is it important to monitor KRAS in blood with ddPCR?
  • Analytical, clinical and real-world data for KRAS G12C mutations in NSCLC
  • Bringing blood-based diagnostics from initial discovery to the clinic

11:00 am Morning Break & Virtual Networking

Early Discovery & Mechanism of Action

Translation & Clinical Development Considerations

Leveraging Small Molecules & Structural
Mechanisms to Aid Effective RAS
Targeting

The Promising Nature of RAS Combination
Therapies – The Future of Oncology
Treatment

12.00am A Novel Approach to Pan-RAS Inhibition

  • Discovery and current development of our novel small molecule pan-RAS inhibitors
  • Downstream signalling through RAF and PI3K pathways, initiate cell-cycle arrest and induce apoptosis
  • Stimulate anti-tumor T-cell mediated immune mechanisms

Frank Haluska, President & Chief Executive Officer, Anchiana Therapeutics

12.00am Clinical Combinations: RAF/MEK Inhibitor with the FAK inhibitor to Treat KRAS Mutant Cancers

  • Clinical activity of defactinib in KRAS mutant NSCLC
  • Clinical activity of CH5126766 in KRAS and BRAF mutant
    cancers
  • Combination of defactinib and CH5126766 in patients
    with KRAS mutant cancers

Jonathan Pachter, Chief Scientific Officer, Verastem Oncology

12.30am Revealing New RAS Vulnerabilities Utilizing a Protein Interference Technology

  • Discussing how PROTEINi tecnology has identified undiscovered targets which are synthetic lethal with RAS
  • Through harnessing an effective toolkit, the SITESEEKER platform provides key pharmacophoric information about how to drug the undruggable

Grahame McKenzie, Chief Scientific Officer, PhoreMost

12.30am Rigosertib as a Unique Small Molecule RAS Antagonist: Scientific & Clinical Studies

  • Rigosertib targets RAS through mimetic interaction with effector proteins
  • An update on the role of genetic and RAS pathway mutations in MDS RAS in the clinic

Steven Frutchman, Chief Executive Officer, Onconava

1.00pm Interrogating T50 Substitutions in KRAS Oligomerization & Function

  • Discussing how PROTEINi tecnology has identified undiscovered targets which are synthetic lethal with RAS
  • Through harnessing an effective toolkit, the SITESEEKER platform provides key pharmacophoric information about how to drug the undruggable

Pan-Yu Chen, Postdoctoral Fellow, University of California

1.00pm A Curative Therapy for Pancreatic Cancer

  • Problems that need to be overcome with late stage pancreatic cance
  • A general strategy for bringing late stage pancreatic cancer patients to remission and preventing relapse
  • Optimizing the utilization of oncogenic KRAS inhibitors in combination therapy

Nicholas Heimann, Chief Executive Officer & Cancer Biologist, Nicholas Pharmaceuticals LLC

1:30 pm Networking Lunch & Roundtable Discussions

Room A: Outlining & Overcoming Disadvantages of Combination Strategies

  • How can we overcome & account for the co-toxicity effect of the combined strategies?
  • How to ensure that combination strategies add efficacy and not toxicity
  • Exploring the regulatory considerations for monotherapies and combination strategies against RAS

Shiva Malek, Senior Director & Head of Discovery Oncology, Genentech

Room B: Overcoming Lack of Predictability of RAS Animal Models

  • Do we have the right animal models to investigate RAS?
  • How can we improve the lack of predictability of animal
    models to ensure robust translation?
  • How can we overcome the lack of comparability and
    reproducibility of results obtained?

Chiara Ambrogio, Assistant Professor, University of Turin

Advancing Target Validation Through
Optimizing Mechanisms of Action &
Resistance

Exploring & Prioritizing KRAS Specific Combination Strategies

2.30pm Synergistic Combinations with the Dual RAF/MEK Inhibitor VS-6766 to Overcome Resistance Mechanisms

  • Unique mechanism of action of RAF/MEKi VS-6766 and relevance to overcoming resistance of RAS-driven tumors
  • Synergistic combination with FAK inhibitor defactinib preclinically and clinically
  • Synergistic combination with KRAS-G12C inhibitors

Jonathan Pachter, Chief Scientific Officer, Verastem Oncology

2.30pm Leveraging Synthetic Lethality of KRAS & PLK1 in Metastatic CRC Patients

  • Second-line treatments for KRAS mutant mCRC patients is an unmet need and PLK1 is a promising therapeutic target for KRAS mutant CRC patients
  • Onvansertib has significant anti-tumor activity in KRAS mutated CRC preclinical models
  • Onvansertib in combination with FOLFIRI & bevacizumab in second-line KRAS mutant mCRC patients demonstrates safety and efficacy

Mark Erlander, Chief Scientific Officer, TrovaGene

3.00pm Mitochondrial Mediated Mechanisms of Resistance

  • Understanding common mechanisms of resistance to targeted therapies
  • Exploring mechanisms of reversing resistance to targeted therapies
  • Highlight the role of the mitochondrial enzyme Sirt3 in RAS signalling

Jack Arbiser, Thomas Lawley Professor of Dermatology, Emory School of Medicine

3.00pm Leveraging Combination Approaches for Effective Use of G12C KRAS Inhibitors

  • Understanding why pre-existing resistance to KRAS G12C inhibitors prevents their effectivity in clinical trials
  • Discuss the different combination approaches which can ensure effective treatment of KRAS G12C mutant cancers and minimise resistance
  • How studying the phenotype of effect or immune cells can highlight the most optimal combinations of KRAS G12C inhibitors and immunotherapies

Miriam Molina-Arcas, Senior Laboratory Research Scientist, Francis Crick Institute

3:30 pm Afternoon Break & Virtual Networking

4:00 pm Opportunities & Lessons for targeting KRAS

  • Marie Evangelista Senior Scientist & Project Team Lead, Discovery Oncology, Genentech

Synopsis

  • Novel technologies to enable KRAS translational research and drug development
  • Insights into tumor evolution following treatment with G12C covalent molecules

4:30 pm Panel Discussion: Empowering Combination Strategies to Target RAS Mutant Cancers: The Future of Oncology Therapy

  • Steven Fruchtman President & Chief Executive Officer, Onconova Therpaeutics
  • Jonathan Pachter Chief Scientific Officer, Verastem Oncology
  • Martin McMahon Presidential Chair of Cancer Biology, Huntsman Cancer Institute of University of Utah
  • Jan Smith Vice President Biology, Revolution Medicines
  • Peter Hammerman Global Head of Translational Oncology, Novartis

Synopsis

  • What are the key factors to consider ensuring successful translation from discovery to clinic?
  • The importance of moving beyond G12C – with the abundance of research surrounding G12C mutation, how and why should we be pushing for new avenues to explore?
  • Technology, platforms & collaborations – what does the RAS community need in order to progress and produce effective, quality and safe RAS mutant cancer therapies?

5:15 pm Translating Rational Combinations Targeting RAS into the Clinic

  • Scott Kopetz Distinguished Professor, MD Anderson Cancer Centre

Synopsis

  • Discussing tumor specific observations from clinical trials
  • Provide perspectives and rational for novel combinations currently in or entering the clinic
  • Review barriers to durable responses based on clinical and preclinical data

5:45 pm Closing Remarks & End of the Digital 2nd RAS- Targeted Drug Development Summit

  • Piro Lito Assistant Member, Memorial Sloan Kettering Center