Explore the Agenda
8:00 am Registration Opens & Morning Welcome Coffee
8:50 am Chair’s Opening Remarks
Shining a Spotlight on Degraders for Achieving Potent Targeting of RAS Mutations with Greater Durability
9:00 am Discovery of a Novel Molecular Glue Degrader Engaging a New E3 Ligase to Target KRAS Mutants & C-RAF
- Discovery of a novel small-molecule glue degrader with selectivity for KRAS mutants over KRAS WT
- Identification of a new E3 ligase pathway independent of the Cullin-RING system
- Dual degradation of mutant KRAS in complex with C-RAF
9:30 am LZTR1 Interaction with RAS GTPases Provides Insight into RAS Degradation
- LZTR1 targets GDP-bound RAS proteins for degradation via the Cul3 ubiquitin ligase
- Loss of LZTR1 in cancer increases Rit1 and other RAS proteins, sustaining MAPK signaling
- Harnessing LZTR1 offers a potential strategy to degrade oncogenic RAS therapeutically
10:00 am What is the best approach to target KRAS: PROTAC or DAC?
- Introducing Polymed’s optimized development approach to create best-in-class PROTACs and DACs
- Development of Polymed’s PROTAC targeting KRAS G12D optimized for potency, selectivity, bioavailability, and ADME properties
- Creation of a KRAS G12D degrader antibody conjugate: the next frontier of KRAS targeted therapies
10:30 am Morning Networking Break
TRACK A: Drug Discovery & Preclinical Development
TRACK A: Drug Discovery & Preclinical Development
Moving Beyond Small Molecules to Find New Modalities for Effectively Treating RAS-Driven Cancers
11:30 am Amplifying mKRAS-Specific T cell Immunity for Treatment of MRD+ Pancreatic Cancer
- Targeting vaccine immunotherapy to lymph nodes with the AMP technology
- Development of ELI-002, an off-the-shelf therapeutic vaccine targeting mKRAS
- Clinical updates from AMPLIFY-201 and AMPLIFY-7P Phase 1/2 Trials
12:00 pm Advancing mRNA-Based Therapeutics for Targeting RAS Mutations with Enhanced Specificity & Versatility
- Addressing RAS mutation subtypes through mRNA technology
- Enhance specificity, tolerability and versatility of RAS-targeted therapies with mRNA
- Altering and adapting mRNA platforms to address challenges of tumor heterogeneity and evolving mutations
TRACK B: Translation & Clinical Development
TRACK B: Translation & Clinical Development
Enhancing RAS Inhibitor Durability by Understanding & Overcoming Resistance Mechanisms Leading to Improved Longevity of Treatment
11:30 am Analyzing Resistance to RAS Inhibitors to Improve Therapeutic Design for Achieving Greater Durability of Responses
- Showcasing comprehensive profiling of resistance mechanisms which arise from RAS inhibitor treatment
- Generating resistance cell lines to identify acquired resistance mechanisms to KRAS inhibitors
- Evaluating molecular consequences and resistance mechanisms of direct KRAS Q61H-selective inhibitors
12:00 pm Understanding Intrinsic & Extrinsic Resistance to RAS Inhibitors to Improve Depth & Durability of Response
- Understanding how tumor cell-instrinsic and microenvironmental mechanisms limit response of KRAS-mutant lung cancers to RAS inhibitors
- Targeting adaptive vulnerabilities conferred by co-occurring genomic alterations in KRAS-mutant lung cancers
- Improving suppression of KRAS and downstream growth and survival pathways
12:30 pm Lunch & Networking Break
TRACK A: Drug Discovery & Preclinical Development
Deep Diving into Structurally Challenging Mutations for Accelerating Treatment for a Wide Landscape of Cancers
1:30 pm Leveraging Strategies for Selective Targeting of NRAS & Q61 Mutations for Cancer Treatment
- Synthetic binding proteins are powerful tools for examining the feasibility of achieving unprecedented specificity and discovering new druggable sites
- We have developed monobodies, synthetic binding proteins, that show pan-NRAS and Q61Xselective specificity profiles, and defined their structural bases
- A new protein delivery technology enables efficient and selective inhibition of RAS signaling with monobodies, expanding their utility as tool biologics and potential therapeutics
2:00 pm Panel Discussion: Delving into Strategies to Achieve Selective Targeting of NRAS & HRAS Mutations for Successfully Treating a Wide Array of Cancers
- Uncovering preclinical evidence to showcase the potential for NRAS and HRAS-targeting programs
- How to selectively target NRAS or HRAS and minimize off-target effects
- How to develop a successful patient stratification strategy for clinical trials related to NRASmutant and HRAS-mutant cancer
TRACK B: Translation & Clinical Development
Illuminating Clinical Successes within RAS-Targeted Therapeutics to Achieve High Response Rates for a Variety of RAS-Driven Cancers
1:30 pm VS-7375: An Oral, Selective KRAS G12D (ON/OFF) Inhibitor with Potent Preclinical Anti- Tumor Efficacy & Promising Initial Clinical Data
- Characterization as a selective KRAS G12D (ON/OFF) inhibitor and differentiation vs. other RAS inhibitors
- Exploring combinations in preclinical models to define clinical directions
- Clinical update
2:00 pm Phase I/II Study of D3S-001, a New Generation KRAS G12C Inhibitor in Advanced/ Metastatic Solid Tumors with KRAS G12C Mutations
- Favorable Safety Profile: No dose-limiting toxicities (DLTs) or treatment-related deaths were observed. Grade 3 treatment-related adverse events (TRAEs) occurred in about 15% of patients (no Grade 4 or 5), and no discontinuations due to toxicity
- Promising Early Efficacy: D3S-001 demonstrated strong and consistent anti-tumor activity (confirmed ORR 73.5%) across all KRAS G12C-mutated cancers; in addition, promising activities observed in G12Ci refractory NSCLC patients; and in patients with CNS metastases
- Rapid and early ctDNA clearance and positive correlation with clinical responses, supporting novel G12C target inhibition MoA
2:30 pm Afternoon Networking Break
TRACK A: Targeting Alternative RAS Pathways to Enhance Therapeutic Efficacy for Inhibiting Cancer Progression
Targeting Alternative RAS Pathways to Enhance Therapeutic Efficacy for Inhibiting Cancer Progression
3:30 pm Covalent Inhibitors of the RAS Binding Domain of PI3Kα Impair Tumor Growth Driven by RAS & HER2
- VVD designed compounds that covalently bind to cysteine 242 in the RBD of PI3K p110α and block RAS-mediated activation of PI3K activity
- These inhibitors have a profound impact on the growth of RAS-mutant and HER2 overexpressing tumors without causing hyperglycemia
- The combination of VVD compounds with other inhibitors of the RAS/MAPK pathway provides optimal efficacy in RAS-driven cancers
4:00 pm Improving Therapeutic Efficacy by Targeting the MAPK Pathway to Disrupt Tumor Growth & Reduce Oncogenesis
- How to target specific MAPK substrates that are critical for tumor growth without disrupting broader cellular functions
- How does targeting upstream and downstream regulators of RAS signaling enhance drug efficacy?
- Addressing how alternative signaling pathways, particularly the PI3K/AKT pathway, contribute to resistance against MAPK-targeted therapies
TRACK B: Fast-Tracking RAS-Targeted Drugs Towards Approval by Tackling Clinical Bottlenecks & Improving RAS-Targeted Drug Efficacy
Fast-Tracking RAS-Targeted Drugs Towards Approval by Tackling Clinical Bottlenecks & Improving RAS-Targeted Drug Efficacy
3:30 pm Roundtable Discussion: Tackling Clinical Roadblocks & Pharmacokinetic Challenges to Supercharge Translation into the Clinic & Fast-Track Therapeutics to the Patients
- What are the major roadblocks hindering the transition from preclinic into the clinic?
- How to bridge the gap between preclinical testing strategies and clinical settings to achieve more clinical successes
- How to enhance pharmacokinetic profiles of RAS inhibitors for accelerating translation into the clinic
4:00 pm Spotlighting Alternative Clinical Trial Designs to Improve Evaluation of RAS-Targeting Therapies Leading to Accelerated Approvals
- How to create alternative clinical trial designs to better assess efficacy and reduce traditional barriers
- Uncovering lessons from past trials and using them to inform future clinical trials for KRAS inhibitorsÂ
- Highlighting the importance of considering additional mutations beyond KRAS to predict treatment responses