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

8:00 am Registration Opens & Chair’s Opening Remarks

Keynote Plenary Sessions

8:30 am Progress in Targeting RAS

  • Frank McCormick Professor, Leader NCI Ras Initiative, University of California, San Francisco and Frederick National Laboratory for Cancer Research/Leidos Biomedical Research, Inc.

Synopsis

  • Targeting KRAS, G12C has significant clinical value: combinations may increase efficacy
  • Progress is being made in targeting other alleles, and KRAS specifically
  • Targeting the interface between RAS and its effectors is an attractive strategy

8:55 am Impact of G12C KRAS Inhibitory Drugs on the Tumor Microenvironment

  • Julian Downward Senior Group Leader and Associate Research Director, Francis Crick Institute

Synopsis

  • KRAS G12C inhibitors have proved effective on many G12C KRAS mutant tumours in vitro, in vivo and in clinical trials, but acquired and pre-existing resistance is a fundamental limitation to the clinical efficacy of these drugs
  • Several approaches have been taken to establish how best to combine these drugs for more effective treatment of KRAS G12C mutant cancers and minimisation of resistance, but those reported to date largely delay rather than eliminate the development of resistance
  • The response of KRAS G12C mutant lung tumours with these inhibitors profoundly alters the tumour immune microenvironment, allowing ingression of various effector immune cells: studying the phenotype of these cells suggests optimal combinations between KRAS G12C inhibitors and immunotherapies and suggests approaches to preventing the acquisition of therapy resistance

9:20 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

9:45 am Live Panel Q&A – Ask Speakers Your Burning Questions

  • Frank McCormick Professor, Leader NCI Ras Initiative, University of California, San Francisco and Frederick National Laboratory for Cancer Research/Leidos Biomedical Research, Inc.
  • Julian Downward Senior Group Leader and Associate Research Director, Francis Crick Institute
  • Namratha Sastry Manager Medical Affairs, Biodesix

10:00 am Morning Break & Speed Networking

Synopsis

Reinventing the face-to-face networking in the virtual world. We will pair you up with fellow attendees to break the ice and make new and lasting connections with other RAS experts from industry and academia

Accelerating Discovery & Emerging Strategies

Harnessing Synthetic Lethality to Disrupt KRAS Based Protein-Protein Interactions

11:00 am Synthetic Lethality Revisited: Using PROTEINi to Uncover Novel RAS Targets

Synopsis

  • PROTEINi is a transformative new target ID technology which simultaneously delivers the means to inactivate undruggable targets
  • Targeting RAS mutations in oncology is a crucial therapeutic objective
  • We have used PROTEINi to discover a new and unanticipated synthetic lethal target for mutant RAS and deployed our SITEBLOCK platform to develop new small molecule lead compounds

11:25 am STX200 Disrupts the RAS-RAF1 Interaction: A New Synthetic Lethality Strategy for Selectively Killing Oncogenic RAS Driven Cancer Cells

Synopsis

  • Using our PPI-disruption identifying platform, ToRPPIDO, we have discovered several new compounds that disrupt the KRAS(G12D/V)-Raf1 interaction
  • One set of compounds exerts its disruptive effect allosterically by binding Raf1 in a new pocket distal to its RAS Binding Domain
  • STX200, a cell-permeable member of this set, exhibits potent and selective killing activity against a variety of mutant RAS cancer lines but not against mutant BRAFdriven or WT RAS lines
  • Mechanistic characterization suggests that this cytotoxic activity of STX200 is independent of the kinase activity of Raf1

11:50 am Live Panel Q&A – Ask Speakers Your Burning Questions

Validating Robust Combination Strategies

Successes in Combinations – Lessons Learnt & Future Directions

11:00 am Dual RAF/MEK Inhibitor VS-6766 as a Backbone of Therapy for RAS Pathway-Driven Cancers

Synopsis

  • Low grade serous ovarian cancer: combination with defactinib
  • Distinct combinations for KRAS G12V and G12C mutant NSCLC
  • New combinations for additional cancer indications

11:25 am Session Details to be Confirmed

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

11:50 am Live Panel Q&A – Ask Speakers Your Burning Questions

Advancing Translation & Clinical Development

Exploring the Treatment Landscape Beyond Cancer

11:00 am Targeting RAS in Pediatric Solid Tumors & RASopathies

  • Marielle Yohe Tenure Track Investigator, National Cancer Institute

Synopsis

  • In addition to identifying therapeutics for RAS-driven pediatric malignancies and RASopathies, studying RAS in these diseases allows us to:
  • Evaluate the impact of mutant RAS on cellular differentiation of embryonal tumors and developing organs
  • Understand the biology of RAS isoforms and RAS variants uncommonly mutated in adult malignancies
  • Identify biomarkers of response to RAS-targeted agents in systems with fewer confounding additional mutations

11:25 am Advancing RASopathies Therapies (ART): An NCI Intramural-Extramural Collaboration

  • Andrea Gross Assistant Research Physician, Pediatric Oncology Branch, National Cancer Institute

Synopsis

  • Review the NIH/POB experience with the RASopathy Neurofibromatosis
  • Type 1 and how studying the natural history of the disease has contributed towards the development of an FDA approved treatment option
  • Provide an overview of the Advancing RASopathy Therapy program
  • Update on the status of the NCI RASopathy Natural History Study

11:50 am Live Panel Q&A – Ask Speakers Your Burning Questions

  • Marielle Yohe Tenure Track Investigator, National Cancer Institute
  • Andrea Gross Assistant Research Physician, Pediatric Oncology Branch, National Cancer Institute

12:00 pm Networking & Lunch Break

Improving Selectivity & Effectivity for RAS Targeting

1:00 pm PANEL DISCUSSION: Exploring Chemistry Between Mutations – How to Exploit Mutations for Selective Targeting

Synopsis

There is a wealth of evidence demonstrating how mutations of RAS exist with varying chemistry and interactions. Despite successes with targeting the common G12C mutation, other KRAS mutant variants exist as high-value targets for successful intervention to treat RAS driven cancers beyond lung. In order to produce an effective and selective RAS therapy, this panel will consider optimal methods to exploit RAS mutations to develop covalent inhibitors to target KRAS beyond the G12C mutant, as we discuss:

  • How we can exploit the differences between the various RAS oncogenic alleles
  • What the major bottlenecks preventing non-G12C inhibitors are
  • Advantages of potential non-G12C covalent inhibitors compared to non-covalent compounds
  • Methods and approaches which could allow us to discover selective G12D and G12V drugs

Clinical Perspectives to Anti-RAS Drugs

1:00 pm The Clinician Hour – Patient Perspectives & Clinical Insights

  • Kathryn C. Arbour MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center
  • Michael Kim Assistant Professor, UT MD Anderson Cancer Center
  • David Hong Professor, Deputy Chair of the Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center
  • Bob Li Medical Oncologist, Co-Director, Thoracic Liquid Biopsy Program, Memorial Sloan Kettering Cancer Center

Synopsis

As the number of RAS targeted therapies within the clinic reaches record high, it is essential that we reflect, learn and act on the results we receive. With this, this session will bring together clinicians from across the globe working first-hand with patients and clinical candidates, as they share experiences, thoughts, and reflections to ultimately drive progression and success in future RAS combination therapies

2:45 pm Afternoon Break & Poster Session – Present, Learn & Collaborate

Synopsis

Aiming to stimulate discussion in the oncology community about ongoing work and to promote collaboration between peers, we bring to you the RAS Poster Session, back for the third year. As the viability of targeting RAS as an effective therapeutic application against RAS driven cancers is closer than ever to approval, it is more important than ever to collaborate and learn with your peers as we continue to advance RAS targeted therapies through discovery and development. Join our dedicated session to share your latest data and have a first-look at what your peers are working on!

Exploring Novel Therapeutics & Emerging Strategies Targeting RAS

3:15 pm Derived from a First-In-Class Platform of Therapeutic Molecular Clusters (TMC), Ag5 is a Differentiated Molecule That Promises to be Efficacious in Hard-To-Treat Solid Cancers

Synopsis

  • TMCs are individually unique entities with highly specific physical, chemical, and biological properties and represent a totally new therapeutic modality
  • Ag5 will preferentially kill cancer cells, but will spare normal cells due to their REDOX homeostasis, leading to efficacy in the most difficult to treat cancers along with minimal off-target effects
  • We are investigating biomarkers that allow us to identify cancers with the highest levels of ROS, and therefore the most sensitivity to Ag5. This includes oncogenic drivers such as KRAS

3:40 pm TCR-Based Immunotherapies Targeting KRAS Mutations

Synopsis

  • Non-viral gene transfer such as the Sleeping Beauty system can be used to express KRAS neoantigen-specific TCRs
  • T cells can be engineered to target public neoantigens shared between tumors
  • T cells can be engineered to target patients with solid tumors carrying hotspot KRAS mutations

4:05 pm PANEL DISCUSSION: On the Horizon – Discussing the Post-Approval Landscape for Successful RAS Drugs Beyond AMG510

  • Steve Kelsey President R&D, Revolution Medicines
  • David Hong Professor, Deputy Chair of the Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center
  • Lusong Luo Senior Vice President, External Innovation, BeiGene
  • Martin Treder Chief Scientific Officer, Arjuna Therapeutics
  • Raffaele Baffa Chief Medical Officer, Ziopharm Oncology

Synopsis

As this industry progresses from the first-in-class approval for an anti-RAS therapy, the landscape of RAS targeting is more exciting than ever and there is a clear roadmap toward future clinical success. This panel discussion will consider what is next for the RAS community, what will be the next emerging strategy to reach the patient and what the landscape of regulatory approval and commercialization look like beyond the US

5:00 pm Chair’s Closing Remarks

5:15 pm End of the 3rd RAS Targeted Drug Development Summit