8:20 am Chair’s Opening Remarks

  • Piro Lito Assistant Member, Memorial Sloan Kettering Center

8:30 am Exploring the Continual Progression & Efforts to Target RAS

  • Frank McCormick Professor & Leader NCI RAS Initiative, Frederick National Laboratory for Cancer Research

Synopsis

  • Discuss the clinical value for KRAS mutant cancers through targeting the specific isoform G12C
  • Highlight the importance of targeting other alleles such as G12D
  • Emphasise the feedback responses gained from Inhibiting RAS and the targeting potential for future therapies

9:00 am Highlighting the Successes of Targeting KRAS in Pancreatic Cancer

  • Channing Der Sarah Graham Kenan Distinguished Professor, University of North Caroline at Chapel Hill

Synopsis

  • Exploring why the ERK MAPK cascade is the key effector driving KRAS-dependent pancreatic cancer growth
  • Understanding how the MYC oncoprotein and transcription factor is a key ERK target for ERK-dependent pancreatic cancer growth
  • Driving altered metabolic processes that support pancreatic cancer growth via the MYC Oncoprotein

9:30 am Session Details to be Confirmed

  • Ryan Corcoran Associate Professor of Medicine, Harvard Medical School

10:00 am Reaffirming the Functional & Mechanistic Characteristics of KRAS & KRAS Mutants

  • Richard Somberg Director of Pharma, Biotech & Strategic Collaborations Manager, Promega

Synopsis

  • Ensuring intracellular target engagement through KRAS G12C Analyzing the interactions between KRAS/BRAF & KRAS/CRAF via live cell kinetic inhibition assays
  • Benchmarking HiBiT CRISPR KRAS wildtype and mutant reporter cell lines within clinically relevant backgrounds

10:30 am Speed Networking & Morning Break

Early Discovery & Mechanism of Action Confirmed Chair: Matt Meyer, Senior Director & Head of In Vivo Biology, Bristol Meyers Squibb

Translation & Clinical Development
Considerations Confirmed Chair: Ida Aronchik, Principal Scientist, Celgene

Harnessing Internal Structural Biology of Oncogene Mutations for Effective RAS Targeting

Unlocking Therapeutic Potentials of Targeting RAS Mutations Through Utilizing RAS-Specific Chemistry

11.30am Outlining the Structural Model for the RAS-RAF Signalosome

  • KRAS signaling is centered on the the large formation of KRAS & RAF assemblies
  • How can we harness the RAS-RAF signalosome for experimental structural modeling
  • Inhibiting the signalosome formation for the efficacy of drugs targeting KRAS or RAF proteins

Yibing Shan, Senior Scientist, D. E. Shaw Research

11.30am Exploiting Apoptotic Vulnerabilities of KRAS Mutant Lung Cancer

  • Understanding and characterizing diversity of co-occurring mutations in KRAS mutant lung cancers
  • How loss of the suppressor LKB1 may alter apoptotic dependencies and confer sensitivity to targeted therapy combinations

Aaron Hata, Assistant Professor of Medicine, Harvard Medical School

12.00pm The Crucial Role of Farnesylation in RAS Mutant Rhabdomyosarcoma

  • Outlining common RAS mutations fusion-negative subtype of rhabdomyosarcoma
  • Explaining how the farnesyl transferase inhibitor tipifarnib inhibits HRAS membrane localization as opposed to membrane localization of NRAS or KRAS
  • Harnessing Tipifarnib as an effective therapeutic strategy for pediatric patients with HRAS mutant solid tumors

Christine Pratilas, Associate Professor of Oncology & Pediatrics, The Johns Hopkins University School of Medicine

12.00pm Session Details to be Confirmed

Piro Lito, Medical Oncologist, Memorial Sloan Kettering Cancer Centre

12.30pm Direct Targeting of RAS by Engineered Chimeric Toxins

  • Bacterial enzymes can rapidly and efficiently cleave all RAS isoforms and oncogenic mutants
  • Discuss how enzymes can be delivered efficiently into cells expressing specific surface receptors using engineered bacterial toxins
  • How will such toxin chimeras show reduction of tumor growth in vivo?

Greg Beilharts, Senior Research Associate, Hospital for Sick Children

12.30pm Combined Targeting of RAF, MEK & ERK Signalling & Autophagy Treatment of RAS Driven Cancers

  • Inhibition of RAF, MEK & ERK signalling in RAS driven cancers cells elicit an increase in autophagy
  • Synergistic anti-proliferative effects in vitro and promotion of regression of established tumours in preclinical models
  • Elevated expression of c-MYC as a marker and a mediator of resistance to combined targeting

Martin McMahon, Presidential Chair of Cancer Biology, University of Utah

1:00 pm Networking Lunch

Exploring Techniques Beyond Small Molecules Towards Enhanced RAS Targeting

Leveraging RAS Associated Targets to Optimize Combination Therapies

2.00pm Targeting the Lymph Nodes to Enhance Mutant KRAS Specific Vaccine Responses

  • Review of Elicio’s Lymph Node targeting AMP vaccination platform
  • Data showing AMP vaccine-induction of potent mKRAS specific T cell responses
  • Review of Elicio’s mKRAS clinical development program

Peter DeMuth, Vice President of Research, Elicio Therapeutics

2.00pm Combination Therapies with SHP2 Inhibitors to Treat KRAS Mutant Cancers

  • Exploring the potential of SHP2i and G12Ci combination for KRAS G12C mutant cancers
  • Benchmarking the effectivity of combining SHP2i and MAPKi to target KRAS mutant cancers
  • Adopting CDK4/6i within combination for effective KRAS therapy

Huaixing Hao , Principal Scientist, Novartis

2.30pm Generation & Characterization of Antibodies Targeting Mutant KRAS Proteins

  • How can we generate selective antibodies for modeling purposes?
  • Biochemical characterization is essential for effective KRAS targeting
  • Functional characterization in wild type and mutant cancer cell lines

Sreesha Srinivasa, Senior Vice President, Oblique Therapeutics

2.30pm SOS1 Inhibition & Combination Strategies for Targeting KRAS-Mutant Cancer

  • Discussion into preclinical data for SOS1 & KRAS inhibitors

Marco Hofmann , Senior Principal Scientist & Research Project Leader, Boehringer Ingelheim

3.00pm Silencing KRAS with a Centyrin Guided siRNA Conjugate

  • Introduction to centyrins and a description of their ability to deliver siRNA into tumor cells
  • Discuss effects of centyrin delivered siRNA on knockdown of KRAS mutants in various cells
  • Explore the potential therapeutic applications of centyrin siRNA conjugates in KRAS mediated cancer

Steven Nadler, Vice President of Research, Aro Biotherapeutics

3.00pm Preclinical Studies of ULK Kinase Inhibitor Designed to Inhibit Autophagy

  • RAS mutant cancers have high levels of autophagy
  • Inhibitors of the MAPK pathway lead to increased autophagy in RAS mutant cancers in preclinical studies to allow for cell survival
  • Combination of inhibitors of the MAPK pathway and an inhibitor of autophagy allows for greater efficacy in vitro and in vivo

Bryan Smith, Vice President of Biological Sciences, Deciphera Oncology

3:30 pm Networking Break & Poster Session

4:30 pm

Unleashing the Full Potential of Degrading RAS with PROTACs

Maximizing Translational & Predictive
Efforts - Selective Targeting During Combination Therapies

4.30pm PROTAC Mediated Degradation of KRAS

  • How ligands bind novel ligases aiding their PROTAC to degrade previously undruggable targets
  • Ubiquitylation patterns and types of poly-ubiquitin chains responsible for degradation
  • How the application of E3 ligases to degrades undruggable targets and provides an opportunity for breakthrough therapies

Tauseef Butt, Chief Executive Officer, Progenr

4.30pm Single Agent & Combination Activity of Tipifarnib in HRAS Dependent HNSCC

  • Discuss the potent and selective farnesyltransferase activity of Tipifarnib
  • Explore preclinical models of HRAS mutant cancer and pivotal testing in HRAS mutant HNSCC patients
  • Benchmarking the translational efforts, focused on exploring tipifarnib anchored combination

Francis Burrows, Vice President of Translational Research, Kura Oncology

5.00pm Identification & Targeting of KRAS-Driven Vulnerabilities Using Degradation Strategies

  • Applications of targeted protein degradation
  • Case studies highlighting functional evaluation of cancer dependencies including KRAS using the dTAG system
  • Development of strategies targeting dependencies in KRAS-driven cancers

Benham Nabet, Katherine Loker Pinard Fellow, Dana- Farber Cancer Institute

5.00pm Adopting a Polyvalent Approach to Aid Development of Vaccines Against Mutant RAS

  • Update on phase I/II clinical response data in pancreatic cancer
  • Use of mutant RAS cfDNA tracking as a predictive tool
  • Next steps in combination treatment and new mutant

RAS vaccination strategies Erik Digman Wicklund, Chief Business Officer, Targovax

5:30 pm Chairs Closing Remarks & End of Conference Day One

  • Piro Lito Assistant Member, Memorial Sloan Kettering Center

5:40 pm Drinks Reception & Poster Session