*All agenda timings below are displayed in EDT. For PDT, please download the full program here*

8:30 am Online Registration & Opening Remarks

9:00 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

9:30 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

10:00 am Session Details to be Confirmed

  • Ryan Corcoran Associate Professor of Medicine, Harvard Medical School

10:30 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

11:00 am Virtual Speed Networking & Morning Break

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!

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

Exploring Techniques Beyond Small Molecules Towards Enhanced RAS Targeting

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

12.00am 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

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

12.30pm 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

12.00pm Session Details to be Confirmed

Piro Lito, Medical Oncologist, Memorial Sloan Kettering Cancer Centre

1.00pm 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

1.00pm 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

1:30 pm Networking Lunch & Roundtable Discussions

Room A: Direct Versus Indirect Targeting of Oncogenic RAS Proteins

  • What are the pros and cons of direct targeting vs indirect targeting?
  • Critically review the successes and failures of modulating RAS via direct and indirect binding
  • How can we enhance RAS targeted success through what we know about indirect and direct RAS modulation?

Matt Meyer, Senior Director & Head of In Vivo Biology, Bristol Myers Squibb

Room B: How to Optimize Robust Translation from Pre-Clinical to Clinical Development

  • How can we improve PK/PD, robust in vivo target engagement & antitumor efficacy
  • Overcoming translational challenges, response rates, drug resistance and safety considerations in order to design optimal next generation small molecules against undruggable RAS targets

Ida Aronchik, Principal Scientist, Celgene

Exploring Techniques Beyond Small Molecules Towards Enhanced RAS Targeting

Leveraging RAS Associated Targets to Optimize Combination Therapies

2.30pm Outlining the Structural Model for the RASRAF 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

2.30pm 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

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 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 Beilhartz, Senior Research Associate,
Hospital for Sick Children

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 Virtual Networking Break & Poster Session

Synopsis

Take a break, grab a coffee and immerse yourself in our virtual poster session! Showcasing the latest advancements and recent updates from the RAS community, take this opportunity to connect with your peers and forge new and existing relationships

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