7:30 am Morning Networking Coffee

8:20 am Chair’s Opening Remarks

Revealing Phase I-III Clinical Data for Drugs Shaping the Clinical Landscape of RAS Therapies

8:30 am The Story of Sotorasib: The First Clinical Journey of the First Approved RAS-Targeted Drug

  • Emily Chan Medical Director, Clinical Research, Amgen Inc.


  • Sotorasib: From first in human to first accelerated approval in under 3 years – A case-study for drug approval
  • A look back: Lessons learned from the journey of Sotorasib into the clinic and beyond
  • A look forward: Latest clinical development updates

9:00 am RMC-6236, a Novel, First in Class, Tricomplex RASMULTI(ON) Inhibitor: Preliminary Clinical Results & Learnings

  • Brian Wolpin Robert T. & Judith B. Hale Chair in Pancreatic Cancer & Professor of Medicine, Dana-Farber Cancer Institute & Harvard Medical School


  • Basis of inhibiting the RAS(ON) form of multiple RAS mutational drivers
  • Initial tolerability profile during phase 1 dose escalation and potential mechanistic explanation
  • Preliminary anti-tumor activity in RASMUT pancreatic cancer and non-small cell lung cancer

9:30 am Revealing Program Updates from LY3537982, a Highly Selective & Potent KRAS G12C Inhibitor

  • Arjun Balar Vice President - Global Clinical Development, Loxo Oncology


  • Discussing the discovery and rational design of LY3537982 its transition from bench to clinic
  • Reviewing recent first-in-human data for LY3537982 in patients with KRAS G12C-Mutant Advanced Solid Tumors, Including NSCLC and CRC
  • Exploring LY3537982 development avenues and promising future directions

10:00 am Advancing RAS-Targeted Therapies with Blood-Based Biomarker Solutions


  • Integrating blood-testing alongside tissue-testing for a comprehensive and robust biomarker strategy.
  • Prevalence of RAS in a study of 3,500+ patients with non-small cell lung cancer monitored over three years.
  • Enabling real-time monitoring of RAS mutations in ctDNA for timely intervention.
  • Overcoming challenges in RAS clinical trial enrollment with Biodesix solutions.

10:30 am Morning Networking Break

Track A: Drug Discovery & Pre-Clinical Development

Chair: Channing Der, Sarah Graham Kenan Distinguished Professor, UNC Chapel Hill

Early Discovery Efforts Expanding the Arsenal to Attack RAS-Addicted Cancers

11:15 am Creating & Targeting Cancer-Specific Neoantigens with Covalent Inhibitors to Combine IO with Traditional Inhibition Approaches

  • Shohei Koide Co-Founder of Aethon Bio & Professor, Grossman School of Medicine, nyu langone health


  • Showcasing how covalent drugs such as KRAS(G12C) inhibitors can be designed to create cancer-specific neoantigens that can be targeted
  • Displaying how antibodies that selectively recognize drug-peptide conjugates presented by multiple MHC types can be engineered to increase immune involvement
  • Understanding how KRAS(G12C) drug resistant cancer cells can be selectively killed with bispecific T-cell engager antibodies
  • Unlocking the potential of targeted and immune therapies by combining them through this “HapImmune” technology

11:45 am Targeting KRAS Mutants with Cell-Penetrating Nano-Antibody (SBT-100) for Mutation Agnostic RAS Therapy


  • Inhibiting KRAS and its mutants using cell and BBB penetrating nano-antibody SBT-100 provides a targeted and effective treatment option
  • Minimizing toxicity to host enables safer targeting of RAS due to non-covalent binding of KRAS by SBT-100
  • Examining how to take a multi-target approach by inhibiting KRAS, KRAS(G12D), and KRAS(G13D) with just one nano-antibody for a more comprehensive therapy option

12:15 pm Identifying & Developing Cyclic Peptide KRAS Inhibitors Through a Novel Screening Platform


  • Showcasing how Curve’s MicrocycleTM drug discovery platform utilizes a genetically-encoded intracellular library of 3.2 x 106 cyclic peptides in combination with mammalian cell-based screening for inhibitor identification
  • Examining how intracellular screening holds several advantages over traditional in vitro screening approaches to drug discovery and has led to the identification of a series of KRAS inhibitors
  • Understanding how these molecules are currently being developed towards the clinic and how the hexameric backbone of MicrocyclesTM allows rapid scaffold-hopping the pharmacophore from a peptide into a small molecule backbone

Track B: Translation & Clinical Development

Chair: Chiara Ambrogio, Associate Professor of Molecular Biology, University of Torino

Evaluating the Novel Pan-RAS & Multi-RAS Approaches to Advance Personalized Cancer Therapy

11:15 am Panel Discussion: Reviewing the Toxicity Concerns with Multi-Inhibitors & Strategies to Pre-Emptively Address Them

  • Andrea Wang-Gillam Chief Medical Officer, Jacobio Pharmaceuticals Inc
  • Brian Wolpin Robert T. & Judith B. Hale Chair in Pancreatic Cancer & Professor of Medicine, Dana-Farber Cancer Institute & Harvard Medical School
  • Greg Verdine President & CEO, LifeMine Therapeutics


  • PAN-RAS inhibitors are known to be mutations and often isofrom agnostic. Due to their unique mechanisms of action, they often target wild-type RAS as well, resulting in normal cell toxicity. Preemptively dealing with these foreseen negative effects is important to ensure that PAN-inhibitors and multi-inhibitors can reach their full potential as personalized cancer treatments.
  • Reviewing the PAN-RAS inhibitors in currently in development to determine their expected toxicity levels
  • Differentiating the expected toxicity concerns based on mechanisms of action to address the unique issues for each modality
  • Developing strategies to deal with expected toxicity levels to increase therapeutic index

11:45 am Exhibiting a Combination of SOS1:KRAS Inhibitor with A MEK Inhibitor Reconfigures the Immune Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinomas & Sensitizes to Immunotherapy


  • Showcasing the efficacy of SOS1i and MEKi as monotherapy and combination in controlling KPCY tumor growth in vitro and in vivo
  • Presenting how the combination of SOS1 and MEK inhibition rewires the immune tumor microenvironment
  • Displaying how CD8+ T cells increase is restricted to the individual tumor site and resulted from both recruitment and intra-tumoral division, suggesting tumor-specific T cell clonal expansion
  • Understanding how a combination of SOS1 and MEK with immunotherapy prolongs tumor regressions and induces memory

12:15 pm Advancing Cancer Therapy Using Natural Compound Derivatives: Mutation Agnostic Targeting of the RAS & MAPK Cascades


  • Assessing novel Pan-RAS inhibitors with a unique MoA and providing updates on the clinical development of a promising new therapeutic
  • Validating targets identified by multi-omics analysis of patient materials to enable personalize precision therapy for patients
  • Elucidating the role of atypical MAPKs in human cancers to explore targeting opportunities for enhanced treatment opportunities

1:00 pm Lunch Break & Networking

Attacking the RAS Pathway Just Right: “Off” Target & Combination Approaches Against RAS Cancers

1:45 pm Vertical Inhibition of RAS, RAF & MEK: Enhancing Antitumor Efficacy of KRAS G12C & G12D Inhibitors with RAF/MEK Clamp Avutometinib (Vs-6766)


  • Examining how Avutometinib, a RAF/MEK clamp, has established clinical activity and safety with oral intermittent dosing, providing a promising new therapy
  • Showcasing how combination with G12C inhibitors yields a deeper pERK blockade for enhanced tumor regression in G12C inhibitor-naïve and -resistant models, indicating potential for improved patient outcomes
  • Understanding how combination with KRAS G12D inhibitors potentiates antitumor efficacy in colorectal and pancreatic cancer models, expanding the scope of therapy to more mutations and indications

2:15 pm Targeting MEK-RAF Complex to Overcome CRAF Mediated Resistance & Drive Superior Anti-Tumor Activity in RAS/RAF Altered Cancers


  • Showcasing how trapping MEK-RAF in an inactive complex blocks CRAF mediated MEK reactivation that limits the efficacy of approved MEK inhibitors in RAS mutant tumors
  • Examining how more complete MAPK pathway inhibition results in potent anti-tumor activity across a broad range of RAS/RAF altered cancer cell lines/models
  • Understanding how intermittent dosing schedules that enable transient drug exposure above IC90 followed by low exposure recovery improve therapeutic window

2:45 pm Demonstrating Fragment-Based Drug Discovery of ASTX029, a Dual Mechanism ERK1/2 Inhibitor


  • Describing the fragment-based drug discovery of ASTX029, a dual-mechanism ERK1/2 (ERK) inhibitor that suppresses both the catalytic activity and phosphorylation of ERK
  • Highlighting the opportunity that ASTX029 offers as a potent inhibitor of MAPK-activated tumor growth in preclinical models
  • Showcasing ASTX029, which is currently undergoing clinical development in a Ph1/2 trial in advanced solid tumors

Phase I-III Clinical Data from Off-Target Drugs to Effectively Target the RAS Pathway as a Whole

1:45 pm Latest Clinical Update on the Geranylygeranyltransferase-1 Inhibitor PTX-100 that Targets Pathway Downstream of RAS

  • Said Sebti Co-Founder, Prescient Therapeutics & Associate Director of Basic Research, VCU Massey Cancer Center


  • Evaluating how inhibition of Geranylgeranyltransferase 1 (GGT1) blocks prenylation of Rho and other GTPases and results in improved patient outcomes
  • Understanding the CAAX peptidomimetic PTX-100’s potent pre-clinical anti-tumor activity
  • Showcasing advancements in clinical trials that have shown promising results in the efficacy of PTX-100 for T-cell lymphomas

2:15 pm Conveying how Tipifarnib Suppresses KRAS G12C Inhibitor-Induced mTOR Reactivation Leading to Superior Antitumor Activity of the Combination


  • Elucidating phase1/2 data for Tipifarnib, a potent, selective inhibitor of farnesyl transferase with alpelisib, a PIK3C alpha inhibitor as a potential therapy for patients with HRAS-overexpressing
  • metastatic head and neck squamous cell carcinoma (The KURRENT-HN Trial)
  • Showcasing how Tipifarnib is a farnesyl transferase inhibitor that blocks compensatory feedback reactivation through inhibition of adaptive mTOR signaling
  • Examining how a combination of tipifarnib with KRASG12C inhibitors drives tumor regression in innately resistant KRAS G12C NSCLC CDX and PDX models

2:45 pm Introducing Rational Combinations of RAF/MEK Clamp Avutometinib: Breakthrough Designation & Beyond


  • Presenting RAF/MEK clamp Avutometinib and FAK inhibitor Defactinib which are in clinical development in RAS/MAPK driven cancers, offering new hope for patients
  • Demonstrating the potential for improved patient outcomes with registration-directed trial design and clinical development progress in low-grade serous ovarian cancer (LGSOC) and other RAS/ MAPK driven cancers
  • Discussing future directions, including clinical trials in new indications and combination treatment approaches to advance cancer treatment and benefit patients

3:15 pm Afternoon Networking Break

Reviewing the Future Outlook & Role of Patient Advocacy in Drug Developement

4:00 pm Leveraging JDQ443 to Face New Challenges & Utilize Opportunities in Treating KRAS G12C Mutant Cancers


  • Elucidating the latest preclinical and clinical data on JDQ443, a promising inhibitor of KRAS G12C mutant cancer cells, resulting in improved therapeutic outcomes
  • Overcoming emerging mechanisms of resistance to KRAS G12C-targeted therapy and how JDQ443 offers a potential solution to overcoming these challenges
  • Advancing combination treatments to explore the opportunities for combining JDQ443 with other cancer drugs to enhance its effectiveness ultimately leading to better patient outcomes

4:30 pm Inclusion of the Person for Personalized Medicine: From Mouse-Hole to Whole-Person

  • Terri Conneran Founder & Lung Cancer Speaker, Advocate, Survivor, KRAS Kickers


  • Assessing why patient engagement is important and how can we increase patient inclusivity in the process
  • Discussing strategies for increasing patient access to RAS therapies as early as possible
  • Celebrating the success of RAS-targeted therapies while also highlighting the work that is yet to be done

5:00 pm Revolutionizing Cancer Treatment: Unleashing the Power of RAS-Targeted Drugs in 2023 & Beyond

  • Channing Der Sarah Graham Kenan Distinguished Professor, UNC Chapel Hill


  • Highlighting past successes and preparing for future challenges in RAS-targeted drug development to keep you up-to-date on the latest trends in cancer treatment
  • Exploring innovative research avenues for targeting oncogenic RAS using emerging approaches, providing insights into cutting-edge techniques for developing more effective treatments
  • Assessing clinical developments and setting actionable goals to rapidly advance RAS-targeted therapies to empower developers to make a positive impact on the future of cancer treatment

5:30 pm Chair’s Closing Remarks & End of the 5th Annual RAS-Targeted Drug Development Summit