Pre-Conference Workshop Day

Tuesday, September 26, 2023


09:00am
Workshop A

RAS 101: Understanding the RAS Pathway & Its Oncogenic Mutations to Improve Drug Discovery & Design

  • Channing Der Sarah Graham Kenan Distinguished Professor, UNC Chapel Hill
  • Said Sebti Co-Founder, Prescient Therapeutics & Associate Director of Basic Research, VCU Massey Cancer Center
  • Frank McCormick Professor & Leader of NCI RAS Initiative, UCSF

Synopsis

The RAS/MAPK pathway is an extremely important signalling cascade that plays a major role in

driving oncogenesis. It stretches from receptors on the cell membrane to transcription factors in

the nucleus and is naturally robust to prevent disruption. Hence, to effectively target RAS and its

surrounding molecules for effective cancer therapy, it is important to understand the basic biology

of Wild-Type RAS, as well as the idiosyncrasies of its various mutations.

This workshop will:

  • Provide an in-depth understanding of the basic biology of the RAS/MAPK Pathway to highlight
  • targetable nodes
  • Present a complete overview of the various oncogenic mutations that occur to understand RAS’
  • role in oncogenesis
  • Take a deeper look at protein prenylation in the RAS pathway as a targetable node

09:00am
Workshop D

How to Address Resistance Mechanisms to Increase Response Rates & Durability to Prevent Cancer Recurrence

  • Chiara Ambrogio Associate Professor, University of Turin
  • Mark Awad Medical Oncologist, Lowe Center for Thoracic Oncology

Synopsis

RAS. Therefore, RAS-targeted drugs apply a strong selective force on cancer, leading to the

evolution of resistance.

Hence, understanding the mechanisms of resistance, as well as, pre-empting new ones for

different RAS therapies, and subsequently, developing strategies to counter them, is vital achieve

disease free survival of patients.

This workshop will:

  • Review existing literature to compile an actionable list of resistance mechanisms
  • Utilize previous learnings to predict resistance mechanisms for newer modalities to address challenges early on
  • Develop strategies to deal with resistance, such as evolutionary medicine approaches, combination therapy, and many more

11.00am Morning Break & Networking


12:00am
Workshop B

Exploring Mechanisms of Action & Non-Canonical Approaches Against the RAS Pathway to Identify Promising Therapies

Synopsis

The classic “undruggability” of RAS was overcome with the approval of Sotorasib, and now

again with the approval of Adagrasib. The push for new RAS inhibitors has been followed by the

emergence of many novel targeting approaches, such as degradation, protein modulation, and

nanoparticles. Hence, it is vital to bring together various experts to examine the RAS-targeting

landscape and tease out promising new modalities and targets.

This workshop will:

  • Showcase various modalities to compile a list of our arsenal against mutant RAS
  • Address the benefits and pitfalls of each approach to create a data-led landscape of the arsenal
  • Benchmark the modalities to determine the most promising directions to target RAS

12:00am
Workshop E

Assessing Biomarkers & Genomic Data to Inform Patient Selection & Stratification in Clinical Trials

  • Mark Awad Medical Oncologist, Lowe Center for Thoracic Oncology
  • Ida Aronchik Senior Director - Translational Sciences, Revolution Medicines Inc.
  • Antreas Hindoyan Director - Clinical Biomarkers & Diagnostics, Amgen Inc.

Synopsis

As with any trial, understanding patient profiles to create classification and stratification criteria

is extremely important for successful clinical design. Even more so, for RAS, pre-empting patient

reactions to drugs, possible resistance mechanisms, and then accurately assessing the drug’s

activity in each patient, is essential. Biomarkers and genomic data are some of the most reliable

tools to achieve this.

This workshop will:

  • Showcase how biomarkers and genomic data can be assessed to reliably predict patient response and resistance
  • Apply insights from biomarker and genomic analysis to select, classify and stratify patients
  • Compile the most important biomarkers to conduct effective PK/PD during clinical trials for accurately measuring patient response

2.00pm Lunch Break & Networking


03:00pm
Workshop C

Make it a Combo Meal: Exploring Combination Therapies that Assist RAS-Targeted Drugs in Ensuring Cancer Free Survival

  • Ida Aronchik Senior Director - Translational Sciences, Revolution Medicines Inc.
  • Emily Chan Medical Director, Clinical Research, Amgen Inc.
  • Poulikos Poulikakos Associate Professor, Icahn School of Medicine at Mount Sinai

Synopsis

Given the RAS pathway’s importance to normal cell homeostasis, it has evolved to be a naturally

robust pathway that is difficult to disrupt. For a few years now, it has become clear that RAStargeted

drugs work more effectively when combined with other therapies, such as inhibitors up/

downstream of RAS, immune checkpoint inhibitors and various IO strategies among others.

However, optimal combinations are complicated to construct as they are affected by drug design,

the cancer histotype and patient profile to name just a few factors. Hence, it is important to assess

the results from various combinations to create effective frontline RAS therapies for cancer.

This workshop will:

  • Evaluate various combination therapy possibilities to elucidate the range of treatment options for RAS addicted cancers
  • Examine pre-clinical and clinical data on combination therapies to tease out the patterns in efficacy
  • Leverage strategies to effectively apply the patterns to support designing combination therapy regimens

03:00pm
Workshop F

From Conception to Accessible: Making Strategic Decisions About the Development, Adoption & Promotion of RAS-Targeted Therapies

Synopsis

With two approved therapies (Sotorasib and Adagrasib), the field has certainly achieved the

monumental task of validating RAS as a “druggable” target. However, the landscape of RAS drugs

stretches from conception to phase 3 clinical trials. Making the right decisions to develop your

drug before approval, and then make it accessible to patients after approval can be a complicated

process, and so requires a collaborative push from many organizations and stakeholders to

achieve this. Hence, it is vital to bring together a panel of key experts together to discuss how a

RAS-targeted therapy can be strategically developed to get better drugs to patients faster.

This workshop will utilize the expertise of large pharma speakers to:

  • Review the RAS landscape including trends, challenges, and opportunities to give you the best starting point for your RAS pipeline
  • Elucidate approaches to accelerate early and pre-clinical drug development in order to reach the clinic faster
  • Evaluate market strategies to ensure proper reimbursement, easy patient access and effective promotion of RAS drugs

5.00pm End of the Pre-Conference Day