7:30 am Morning Registration & Networking Coffee

8:20 am Chair’s Opening Remarks

An Overview of the Landscape for RAS-Targeted Drugs Including Recent Successes

8:30 am The Journey Continues: Widening the Range of Targetable Indications to Expand the Therapeutic Breadth of RAS Inhibition

Synopsis

  • How to target rarer mutations beyond G12C such as G12V to broaden the types of cancers we can treat
  • Advancing the understanding of histotypes and comparing various indications to inform drug discovery
  • Combining mutational and histotype analysis to rationally design precision oncology therapies

9:00 am Adagrasib“ing” the Opportunity: Latest Updates from the G12C Inhibitor for Combatting NSCLC & Other Cancers

  • Debra Ryan Director - Medical Strategy, Mirati Therapeutics

Synopsis

  • Studying the single agent effect of Adagrasib to understand its potential and allow researchers to develop more effective cancer therapies
  • Describing various combinations in the clinic and comparing their performance to enable tailored cancer therapy
  • Evaluating in-market considerations and future directions for Adagrasib to expand standard of cancer care, and improve patients’ access to cutting-edge treatments

9:30 am Leveraging ENCER Cancer Models to Predict Clinical Trial Outcomes of Novel Mono & Combination Therapies

Synopsis

  • Our proprietary ENCER (ENvironmental CEllular Reprogramming) cancer models can predict clinical trial outcomes before the clinic.
  • We capture multi-omic data longitudinally over months, aiding in identifying novel biomarkers and targets which can be used in mono or combination therapy. 
  • ENCER can identify the most effective modality for drugging your target of interest with fewer off-target effect

10:00 am Morning Break & Speed Networking

Synopsis

Our speed networking is the ideal opportunity to get face-to-face time with many of the brightest minds working to target oncogenic RAS. Introduce yourself to the attendees that you would like to have more in-depth conversations with, benchmark against industry leaders to establish meaningful business relationships, that you can, pursue for the rest of the conference and beyond.


Track A: Drug Discovery & Pre-Clinical Development

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

The RAS Toolbox: Showcasing Novel Drugs to Fight RAS-Addicted Cancers

11:00 am Introducing BBO-8520: A First-in-Class Direct Inhibitor of KRASG12C(ON) that Drives Potent & Deep Anti-Tumor Activity in Cancer Models

Synopsis

  • Understanding how BBO-8520 directly, potently and completely modifies GTP-bound KRASG12C for powerful anti-tumor effects
  • Examining how direct KRASG12C engagement correlates with inhibition of pERK in KRASG12C mutant models leading to comprehensive inhibition of the RAS pathway
  • Showcasing how BBO-8520 overcomes growth factor driven resistance and slows the emergence of resistance in KRASG12C mutant models enabling a more effective treatment options for patients

11:30 am Exploring Novel Vulnerabilities for Type II RAF Inhibitors in Living Cells With NanoBRET

Synopsis

  • New NanoBRET assay technology to quantify type II RAF inhibitor occupancy at individual protomers within RAS/RAF complexes
  • Compared to BRAF and CRAF, clinical-stage drugs escape ARAF inhibition in cells
  • Additional application of NanoBRET technology to study conformation-selective DFG-OUT inhibitors across the broader kinome

12:00 pm Drugging RAS: Elucidating Three Different Mechanisms of Action to Target RAS for Effective Anti-Cancer Therapy

Synopsis

  • Reviewing Warp Drive Bio’s discovery platform and how the RAS drugs it discovered are combatting cancer today
  • Elucidating how LifeMine’s platform is algorithmically discovering GEMs in the genomic space to provide a novel strategy against RAS
  • Utilizing alpha helices to develop Helicon™ polypeptides that can exhibit multi-RAS inhibition

Track B: Translation & Clinical Development

Chair: Frank McCormick, Professor & Leader of NCI RAS Initiative, UCSF

Addressing Resistance & Toxicity to Transform Progression-Free Survival into Disease-Free Survival

11:00 am Overcoming Resistance to the First Generation of G12C Inhibitors to Increase Patient Response Rates

Synopsis

  • Assessing the observed resistance mechanisms against G12C inhibitors in the clinic and beyond
  • Creating actionable insights to overcome resistance and increase the effectiveness of RAS therapies
  • Devising strategies from the current learnings to improve patient response to RAS drugs in future trials

11:30 am Reserved for Tempus

Synopsis

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12:00 pm An Overview of the Resistance Mechanisms Against RAS-Targeted Drugs Beyond G12C

Synopsis

  • Understanding the resistance profiles of different KRAS mutants to effectively target each mutation
  • Differentiating resistance based on mechanism of action to devise the most effective treatment regimen and potential lines of treatment
  • Combining the resistance profiles with histotype analysis of associated cancers for each mutation to create a holistic resistance profile
  • Exploring feasibility of combination therapies based on validated molecular resistance mechanisms

12:30 pm Lunch Break & Networking


1:30 pm NST-628 is a Potent, Fully Brain-Penetrant, Best-in-Class MAPK Pathway Molecular Glue that Inhibits RAS- and RAF-Driven Cancers

Synopsis

  • NST-628 overcomes the limitations of traditional RAS-MAPK pathway inhibitors by stabilizing all RAF-MEK complexes in a conformation that sequesters these nodes from dynamic signaling processes that promote RAF-mediated bypass signaling.
  • Analysis of endogenous ternary complexes demonstrates that NST-628 prevents RAF paralog heterodimerization and completely inhibits MEK, ERK, and RSK phosphorylation in RAS-driven cells.
  • NST-628 has a well-balanced metabolic profile and demonstrates broad anti-tumor responses across cell line and patient-derived in vivo tumor models harboring NF1, KRAS, BRAF Class II/III, and NRAS mutations at well tolerated doses.
  • NST-628 has high CNS permeability and demonstrates anti-tumor and PD activity in orthotopic models of intracranial tumors.

2:00 pm Introducing ADT-007: A Novel PAN-RAS Inhibitor with a Unique Mechanism of Action to Treat Pancreatic Cancer

  • Gary Piazza Chief Scientist, ADT Pharmaceutical LLC & Director, Cancer Research Center, Auburn University

Synopsis

  • Utilizing ultra-high potency and selectivity for killing cancer cells with activated RAS that acts independent of the mutation or isozyme
  • Achieving low potential for intrinsic or acquired resistance and off-target effects to effect a robust response
  • Showcasing antitumor activity in mouse tumor models with target engagement at well tolerated dosages
  • Developing an orally bioavailable prodrug to treat pancreatic cancer

Evaluating Degradation-Based Approaches Targeting RAS & Associated Molecules

2:30 pm Targeting PDAC Through a First-in-Class DOCK5 Degrader to Inhibit the RAS Pathway

Synopsis

  • Showcasing the discovery of a highly selective and potent DOCK5 degrader to target a top dependency of KRAS mt Pancreatic cancer cell lines
  • Displaying how targeted protein degradation of DOCK5 demonstrates anti-tumor activity in KRAS mt PDAC models in vitro and in vivo offering a promising new therapy
  • Exploring how combining a DOCK5deg with direct KRAS-targeting agents reveals superior efficacy in in vitro systems enabling a multi-target approach

3:00 pm Targeting KRAS-Mutant Solid Tumors With First-In-Class Oral SOS1 Bifunctional Degraders

Synopsis

  • Using our PRODEGY platform, Biotheryx have designed orally bioavailable bifunctional degraders of SOS1 – the guanine exchange factor catalysing the exchange of GDP to GTP in KRAS – as a mutation agnostic strategy to target KRAS mutant solid tumors.
  • Understand how the preclinical data shows rapid degradation of SOS1 in a Cereblon mediated proteasomal event and significant inhibition of a range of mutant KRAS tumor cell lines including those harbouring G12C, G12V, G12S and G13D mutations.
  • Showcasing how the SOS1 bifunctional degraders strongly synergize with inhibitors of KRAS, MEK and EGFR yielding a potent antitumor response relative to individual agents themselves.

1:30 pm How to Address Resistance Mechanisms Against RAS Therapies Observed in Colorectal Cancer

Synopsis

  • Understanding resistance mechanisms dynamics in CRC and their implications to develop more effective therapies
  • An overview of the consequences of resistance mechanisms in CRC patients to improve patient outcomes and QoL
  • Developing strategies to overcome acquired resistance to RAS inhibition in CRC beyond targeting the RAS pathway

All is Not Quiet on the Non-G12C Front: Updates & Insights to Better Target Other Mutations & Domains

2:00 pm RMC-9805, a First-in-Class, Mutant-Selective Covalent and Orally Bioavailable KRASG12D(ON) Inhibitor that Induces Apoptosis and Drives Tumor Regression in Preclinical Models of KRASG12D Cancers

Synopsis

  • RMC-9805 is a first-in-class, orally bioavailable, and mutant-selective covalent inhibitor of the GTP-bound and active RAS(ON) form of KRASG12D, and drove durable regressions in preclinical KRASG12D cancer models across indications.
  • RMC-9805 is a CNS-penetrant inhibitor and demonstrated significant anti-tumor activity in both orthotopic and intracranial xenograft models of human KRASG12D cancers.
  • RMC-9805 promotes cancer-associated neoantigen recognition and synergizes with immunotherapy in KRASG12D preclinical models.
  • RMC-9805 in combination with SOC or other RAS companion inhibitors further improves bothBdepth and durability of response compared to single agents.

2:30 pm Developing TCR-Engineered T Cell Therapies Targeting Mutated KRAS

  • Hue Lam Vice President of Preclinical Development, Affini-T Therapeutics

Synopsis

  • Showcasing how Affini-T Therapeutics’ TCR discovery platform has identified a library of TCRs with high functional avidity, including those targeting KRAS G12V and G12D
  • Understanding how through the application of gene editing and synthetic biology, engineered TCR-T cells can be enhanced with improved fitness and durability to overcome the immunosuppressive tumor microenvironment.
  • Presenting how with robust preclinical data and manufacturing, KRAS-targeted TCR-T cell programs are poised for clinical investigation in populations with high unmet medical need

3:00 pm Maximizing Anti-Tumor Response: Targeting the RAS/MAPK Pathway Using a RASAgnostic Approach

Synopsis

  • Targeting the RAS binding domain with Rigosertib to inhibit binding of multiple downstream proteins in the RAS/MAPK pathway leads to effective cancer treatment
  • Transforming cold tumors to hot tumors with Rigosertib by upregulating neoantigen presentation increases immune system involvement and results in a better anti-cancer response
  • Exploring combinations with Immune Checkpoint Inhibitors (ICIs) offers the potential for a moreveffective response to cancer

3:30 pm Afternoon Networking Break & Poster Session

Synopsis

As the research, discovery, and development into RAS-targeted therapies continues to progress from strength to strength, it is more important than ever, to collaborate and learn with your peers, as we continue to advance

these therapies to patients in need. Join our dedicated session to share your latest data, and have the first look on what your peers are working on!

Beyond KRAS4a & G12C: Targeting Other Mutations & Splice Variants to Widen the Therapeutic Scope of RAS Drugs

4:15 pm Introducing SOS-Independent Inhibition of KRAS G13D with a Switch-2 Inhibitor to Unlock Targeting Codon 13 Mutations

Synopsis

  • Revealing how KRAS G13D is expected to be hard to target with switch-2 inhibitors due to its high intrinsic exchange rate, which makes it less dependent on SOS for activation in cells.
  • Showcasing how a switch-2 inhibitor can not only blocks SOS exchange but also reduces intrinsic exchange rates of KRAS G13D to levels comparable to WT KRAS.
  • Demonstrating how our molecule is able to achieve deeper pathway inhibition than SOS inhibitors in KRAS G13D driven cell lines.

4:45 pm RMC-0708: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASQ61H Cancers

  • Ida Aronchik Senior Director - Translational Sciences, Revolution Medicines Inc.

Synopsis

  • KRASQ61H mutant cancers represent an unmet medical need and include common solid tumor histotypes such NSCLC, PDAC, and CRC.
  • RMC-0708 is a first-in-class, orally bioavailable, mutant-selective, and non-covalent inhibitor of KRASQ61H(ON).
  • RMC-0708 potently suppresses p-ERK and proliferation in KRASQ61H mutant cancer cells while displaying selectivity against wildtype KRAS.
  • RMC-0708 demonstrates anti-tumor activity in various preclinical models of human KRASQ61H tumors.

5:15 pm Distinctive Properties of KRAS4a and KRAS4b Splice Variants & Therapeutic Considerations

  • Dhirendra Simanshu Principal Scientist & Group Lead - Structural Biology, Frederick National Laboratory for Cancer Research

Synopsis

  • KRAS4a shows high transcriptional activity in bile ducts, liver, and stomach, approaching KRAS4b levels in the colon and rectum.
  • Comparative analysis of KRAS4a and KRAS4b revealed distinct structural properties and thermal stability.
  • Functional disparities in full-length KRAS splice variants highlight HVR variations' impact on interactions with trafficking proteins and downstream effectors.

5:45 pm Introducing TCR-T Therapies Targeted at G12D & G12V KRAS-Mutated Solid Tumors to Utilize the Immune Response to Combat Cancer

  • Hugh Salter Chief Scientific Officer & Vice President - Strategy & Translation, Anocca AB

Synopsis

  • Presenting the characterization of TCR properties to improve T-cell therapies and enable more precise and effective targeting of cancer
  • Showcasing the development of a comprehensive high-precision platform for TCRs as clinical assets, to accelerate the development of new therapies
  • Understanding how the identification of candidates for KRAS G12 variants like G12D and G12V can expand the pool of potential treatment options

6:15 pm Chair’s Closing Remarks & End of Day One