*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 Clinical Development of Sotorasib, The First Three Years

  • Gregory Friberg Vice President Global Development & Oncology Therapeutic Area Head, Amgen

Synopsis

  • Sotorasib entered the clinic in Summer 2018 and in the past three years it has reached over 700 patients across 5 continents
  • Phase 1 and 2 datasets clearly demonstrate deep and durable responses in KRAS G12C tumors with sotorasib once daily dosing
  • Key insights from clinical studies have provided clues as to where future deployment of sotorasib may be most beneficial in patients with KRAS G12C mutations

8:55 am Targeting Tumors with KRAS-G12C Mutations with Adagrasib (MRTX849): Current Status & Future Questions

  • Susan Yang Adagrasib Medical Lead, Mirati Therapeutics

Synopsis

  • History of targeting KRAS in the clinic & recent advancements to directly target KRAS G12C
  • Clinical progress of KRAS G12C inhibitors (eg, adagrasib) in the clinic
  • Future questions and directions for targeting KRAS G12C, including biomarkers and combination strategies

9:20 am Staying One Step Ahead of KRAS

  • Marco Hofmann Scientific Director & Group Leader, Boehringer Ingelheim

Synopsis

  • BI’s approaches to selectively drugging KRAS mutants, discussing mutant selective KRASG12Ci, KRASG12Di & combination opportunities
  • BI’s approaches to discovering pan-KRAS medicines, addressing broad KRAS mutation driven patient populations with high medical need, including KRAS G12D, G12V, G13D in NSCLC, CRC and PDAC
  • Rationale for positioning in KRAS wild-type cancer e.g. NF1-LoF and combination opportunities
  • Future implications of initial insights into KRAS inhibitor resistance

9:45 am Demonstrating Reversible Switch-2 Pocket Engagement Across KRAS Hotspot Mutants in Cells

Synopsis

  • Target occupancy can be observed at selected protomers within RAS/MAPK complexes using a novel BRET method
  • In the presence of oncogenic KRAS, RAF protomer selectivity drives drug escape mechanism
  • S2P engagement can be quantified at RAS dimers in live cells
  • KRAS G12, G13, and Q61 alleles are vulnerable to S2P engagement

10:10 am Live Panel Q&A – Ask Speakers Your Burning Questions

10:30 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

Discussing Potent KRAS Degraders for Tumor Specific Targeting

11:30 am PROTAC Mediated Degradation of RAS

Synopsis

  • RAS PROTACs that employ novel ubiquitin ligase and degrades different RAS proteins will be the subject of this talk
  • Current methods for PROTAC discovery are inefficient and not amenable to HTS. PROTAC mediated in vitro ubiquitination can expedite discovery of novel PROTACs
  • Me too ligases, VHL or cereblon do not offer novelty or IP Relationship between in vitro and in vivo ubiquitination and PROTAC mediated degradation will be discussed

11:55 am RAS Targeting Using Armed Biologics

  • Terry Rabbitts Professor of Molecular Immunology, Institute of Cancer Research London

Synopsis

  • Intracellular antibodies are biologics that can be armed with warheads to degrade target proteins
  • Biologics can be engineered to specifically interact with RAS isoforms
  • Biologics combine the flexibility of molecular biology with the potency of chemical binding
  • Introducing biologics to cells as drug per se (macrodrugs) is a major challenge and progress to this goal will be presented

12:20 pm Discovery of Cell Active Macrocyclic Peptides with On-Target Inhibition of KRAS Signaling

  • Nicole Boo Associate Principal Scientist, Merck Sharp & Dohme

Synopsis

  • Explore how peptides provide new opportunities to inhibit KRAS on epitopes that are distinct from the Switch II pocket
  • Insights on how to optimize a non-cell active peptide into a cell permeable, stable and functionally active molecule that inhibits KRAS with low nanomolar binding affinity
  • Explore how KRAS peptide ligands may provide novel mechanisms for achieving KRAS inhibition
  • Discuss the opportunities and challenges faced by KRAS peptide ligands and their potential application as Pan-KRAS inhibitors to treat cancers beyond KRASG12C

12:45 pm Live Panel Q&A – Ask Speakers Your Burning Questions

12:45 pm Redefining Visualization and Collaboration through Virtual Reality

Synopsis

  • Virtual reality provides a novel interface for collaboration across skillsets
  • Enhanced visualization offers key insights to structural problems and elucidates drug interactions
  • Nanome integrates of computational workflows and applications to evaluate contexts and expand discovery opportunities

Validating Robust Combination Strategies

Harnessing Vertical Pathway Inhibition for Optimal Anti-RAS Effects

11:30 am Rational Drug Combinations to Inhibit the MAPK Pathway

  • Rene Bernards Professor of Molecular Carcinogenesis, Netherlands Cancer Institute

Synopsis

  • Rational drug combinations identified through functional genomic approaches are more likely to deliver clinical benefit than trial and error approaches to drug combination therapy
  • Multiple drugs used at low dose may deliver more lasting clinical benefit that single agents used at high concentration
  • Exploiting senescence for cancer therapy represents an attractive new treatment option

11:55 am Autophagy Inhibition Sensitizes LKB1- deficient KRAS-Driven Lung Tumor to MEK Inhibitor

Synopsis

  • Autophagy compensates for Lkb1 loss for KRAS-driven lung tumorigenesis
  • A combination of autophagy inhibitor and MEK inhibitor displays a synergistic anti-tumor effect on Lkb1- deficient, but not Lkb1-wild type, KRAS-driven lung tumor
  • A combination of autophagy and MEK inhibition can be a novel therapeutic strategy to specifically treat LKB1-deficient KRAS-driven NSCLC

12:20 pm Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition

  • Ryan Corcoran Associate Professor of Medicine, Harvard Medical School

12:45 pm Quantitative Analysis of Ras/MAPK Signaling Pathway Proteins Using a Novel Targeted Mass Spectrometry (MS) Workflow

  • Bhavin Patel Senior Staff Scientist, Thermo Fisher Scientific

Synopsis

-A major limitation in the quantitation of RAS pathway proteins is the lack of rigorously validated methods/reagents and a reliance on semi-quantitative methods.

-Thermo ScientificTM SureQuantTM targeted assays can quantitate multiple signaling pathway proteins in a single MS analysis, which creates new possibilities for cancer therapy and precision medicine.

-Accurate and precise quantitation of multiple total and phosphorylated RAS/MAPK and AKT/mTOR pathway proteins by multiplex IP to targeted MS assays and comparison to Western blot technique

1:00 pm Live Panel Q&A – Ask Speakers Your Burning Questions

  • Rene Bernards Professor of Molecular Carcinogenesis, Netherlands Cancer Institute
  • Jessie Yanxiang Guo Associate Professor, Rutgers Cancer Institute of New Jersey
  • Ryan Corcoran Associate Professor of Medicine, Harvard Medical School
  • Bhavin Patel Senior Staff Scientist, Thermo Fisher Scientific

Advancing Translation & Clinical Development

Evaluating the Landscape of Clinical Trials – Successes, Insights & Learnings

11:30 am Phase 1 Clinical Trial Updates for Oral Rigosertib & PD-1 Inhibitor in KRAS-mutated NSCLC

  • Rajwanth Veluswamy Assistant Professor, Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai

Synopsis

  • Discussing phase 1 study of rigosertib and nivolumab in KRAS and NSCLCC
  • Outlining future progression into Phase 2 dose for oral rigosertib in KRAS-mutated non-small cell lung cancer

11:55 am Targeting KRASG12C(ON) & Potential Application to Overcoming Drug Resistance in RASAddicted Tumors

  • Bob Nichols Project Team Lead, RMC-6291, Revolution Medicines

Synopsis

  • RMC-6291 is a potent, selective, covalent tri-complex inhibitor of KRASG12C(ON)
  • Inhibition of the (ON) state of oncogenic RAS offers advantages over inhibition of the (OFF) state
  • The tricomplex inhibitor mechanism of action facilitates re-sensitization of some cells with acquired resistance to KRASG12C(OFF) inhibitors

12:20 pm Prognostic Impact of KRAS Mutation Status for Patients with Stage IV Adenocarcinoma of The Lung Treated with First-Line Pembrolizumab Monotherapy

Synopsis

  • KRAS NSCLC in the Netherlands
  • The survival of KRAS mutated versus KRAS wild-type lung adenocarcinoma patients
  • The survival of KRAS mutated versus KRAS wild-type lung adenocarcinoma patients treated with first line pembrolizumab monotherapy

1:00 pm Live Panel Q&A – Ask Speakers Your Burning Questions

  • Rajwanth Veluswamy Assistant Professor, Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
  • Bob Nichols Project Team Lead, RMC-6291, Revolution Medicines
  • Wouter Van Geffen Consultant Respiratory Physician, Medical Center Leeuwarden

1:00 pm Networking & Lunch Break

Targeting Effector Proteins & Genetic Drivers to Reduce KRAS Activity

2:00 pm Targeting Genetic Drivers in Pancreatic Cancer

  • Michael Kim Assistant Professor, UT MD Anderson Cancer Center

Synopsis

  • Oncogenic KRAS enables mutant p53 gain of metastatic function
  • Oncogenic transcriptional networks downstream of mutant KRAS are amplified by mutant p53
  • CREB1 is an effector of oncogenic KRAS activity and is a therapeutic target in pancreatic cancer

2:25 pm Voruciclib, a CDK9 inhibitor, Downregulates MYC & Inhibits Proliferation of KRAS Mutant Cancers in Preclinical Models

Synopsis

  • Voruciclib, a potent inhibitor of CDKs 9/4/6/1, inhibits MYC transcription and phosphorylation of MYC protein on Ser62, leading to a reduction in total MYC protein.
  • In in vitro and in vivo preclinical models, voruciclib demonstrated single agent efficacy against KRAS mutant cancer cell lines harboring various G12, G13, and Q61 mutations.
  • Voruciclib acted synergistically with KRAS G12C inhibitors in killing KRAS G12C mutant cancer cell lines, both in vitro and in vivo

2:50 pm RAS-Effector Interaction Interface: Looking Beyond the Switch-I Region

  • Dhirendra Simanshu Team Lead, RAS Initiative Frederick National Laboratory for Cancer Research

Synopsis

  • Inhibiting KRAS-effector interaction remains a promising therapeutic approach to target RAS-driven cancers
  • Structural studies done so far have suggested that RAS effector interactions are mainly limited to the switch-I region of RAS
  • Our recent results suggest that other regions of RAS also play an important role in RAS-effector interaction

3:15 pm Live Panel Q&A – Ask Speakers Your Burning Questions

  • Michael Kim Assistant Professor, UT MD Anderson Cancer Center
  • Sandra Wiley Senior Medical Scientist, MEI Pharma, Inc
  • Dhirendra Simanshu Team Lead, RAS Initiative Frederick National Laboratory for Cancer Research

Combination Strategies to Overcome Resistance to KRAS Targeted Therapies

2:00 pm Combination Strategies to Defeat RASAddicted Cancers

  • Jan Smith Senior Vice President, Head of Biology, Revolution Medicines

2:50 pm Live Q&A & PANEL DISCUSSION: Reviewing the Landscape of Combination Therapies – What Combinations are Best? As the landscape potential

  • Jan Smith Senior Vice President, Head of Biology, Revolution Medicines
  • Jessie Yanxiang Guo Associate Professor, Rutgers Cancer Institute of New Jersey
  • Eric Haura Associate Center Director for Clinical Science, H. Lee Moffitt Cancer Center

Synopsis

As the landscape potential combination therapies continues to rapidly expand, the important question remains as to which combination therapy will be the first to reach the patient. This panel will consider the landscape of successful combination therapies, explore limitations, and discuss which combination of therapies will prove most viable in clinical trials

Adopting Precision Medicine & Personalised Cancer Therapies to Optimize Patient Outcome

2:00 pm Inclusion & Diversity: Pathway Towards Sustainability in Clinical Trials

  • Maha Maglinao Life Sciences and Healthcare Management Consultant, Moderna

Synopsis

  • Lessons learned in sustainable clinical trial design and operations thus far which can aid the development and future success of anti-RAS cancers
  • Inclusion and diversity in clinical trial design
  • Key elements and considerations to effectively incorporate inclusion and diversity to optimize sustainable and successful clinical trials

2:25 pm Development of Vaccines Targeting KRAS

Synopsis

  • Design of K-RAS specific vaccine cassettes
  • Preclinical assessment of K-RAS specific vaccines
  • Clinical assessment of K-RAS specific vaccines

2:50 pm KRAS-LODER to Target Pancreatic Cancer: Ongoing Clinical Results From Phase 2

Synopsis

  • LODER is a drug delivery product for regional delivery of RNAi-based drug
  • KRAS-LODER shows encouraging clinical results in pancreatic cancer
  • Utilization of KRAS-LODER to target NSCLC is in development

3:15 pm Live Panel Q&A – Ask Speakers Your Burning Questions

3:30 pm Networking Break

Evidence of KRAS Expression & Resistance from Tumor & Tissue Models

4:00 pm KRAS Inhibition vs KRAS Ablation: Lessons from Mouse Tumor Models

  • Mariano Barbacid AXA-CNIO Professor of Molecular Oncologym, Spanish National Cancer Research Center (CNIO)

Synopsis

  • Comparison of results in terms of tumor regression of treating KRAS/P53 mutant lung mouse tumors with AMG510 versus eliminating KRAS expression
  • Presentation of available data on the mechanisms of tumor resistance in both instances

4:25 pm Reducing Cancer Risk by Modulating Tissue Landscapes

  • James DeGregori Professor, Dept of Biochemistry and Molecular Genetics; Deputy Director, University of Colorado Cancer Center, University of Colorado Anschutz Medical Center

Synopsis

  • We show that aging and inflammatory insults result in changes in tissue microenvironments that promote selection for adaptive oncogenic mutations, including in RAS genes.
  • Reversing aging-associated inflammation can greatly reduce oncogenesis, with partial restoration of more youthful tissue microenvironments.
  • We suggest that an alternative or complement to oncogene targeted therapies (or prevention strategies) could be interventions that sculpt tissue landscapes so that they no longer favor cells with oncogenic mutations such as in RAS genes

4:50 pm Live Panel Q&A – Ask Speakers Your Burning Questions

  • Mariano Barbacid AXA-CNIO Professor of Molecular Oncologym, Spanish National Cancer Research Center (CNIO)
  • James DeGregori Professor, Dept of Biochemistry and Molecular Genetics; Deputy Director, University of Colorado Cancer Center, University of Colorado Anschutz Medical Center

Identification & Selection of Optimal KRAS Combination Therapies

4:00 pm Integration of Drug Repurposing & Dual Screening Unveils Combinatorial Therapies for Mutant KRAS Lung Cancer

  • Silve Vicent Associate Professor, Center for Applied Medical Research (CIMA-University of Navarra)

Synopsis

  • The distal gene expression output elicited by oncogenic KRAS can be used for the prediction of the potential efficacy of drugs entering combinatorial strategies
  • A drug combination consisting of MEK1/2 and FLT3 inhibitors is identified as a therapeutic opportunity for mutant KRAS lung cancer using in vitro (2D and 3D) and in vivo models
  • The covalent KRAS inhibitor Sotorasib can replace the MEK1/2 inhibitor with similar antitumor activity in KRAS G12C lung cancer

4:25 pm Mass Spectrometry Based Phosphoproteomics Provides an Unbiased Approach to Identifying Mechanisms of Signaling Adaption to KRAS Inhibition in KRASG12C Mutant Lung Cancer Cells

  • Eric Haura Associate Center Director for Clinical Science, H. Lee Moffitt Cancer Center

Synopsis

  • ERBB2/3 signaling compensates for repressed ERK and AKT signaling following KRASG12C inhibition in epithelial cell types, while both high basal and feedback activation of FGFR or AXL signaling were identified in mesenchymal cells
  • In human lung cancer tissues with KRASG12C, we observed high basal ERBB2/3 associated with epithelial gene signatures, while higher basal FGFR1 and AXL were observed in tumors with mesenchymal gene signatures
  • Our group is developing proximity ligation assays that detect RTK and RAS signaling associated protein complexes that could provide additional insights into RAS signaling in human cancer biopsies

4:50 pm Live Panel Q&A – Ask Speakers Your Burning Questions

  • Silve Vicent Associate Professor, Center for Applied Medical Research (CIMA-University of Navarra)
  • Eric Haura Associate Center Director for Clinical Science, H. Lee Moffitt Cancer Center

The Clinical Trial Review

4:00 pm Clinical Trials in Progress – What to Expect for 2021 & Beyond

Synopsis

This dedicated session will provide drug developers and academic leaders the opportunity to share insights into their ongoing and future clinical trials with this community. With quick fire 10 minute back-to-back presentations, this is an important session keeping you up to date on what data you can expect to see through 2021 and beyond.

4:50 pm Live Panel Q&A – Ask Speakers Your Burning Questions

5:00 pm Chair’s Closing Remarks

5:15 pm End of Conference Day One