Summary of Prelude Therapeutics (PRLD) FY Conference Call - June 11, 2025 Company Overview - **Company**: Prelude Therapeutics (PRLD) - **Focus**: Development of targeted therapies, specifically SMARCA2 and CAT6 degraders for cancer treatment Key Points on SMARCA2 Degraders - **Agents in Development**: Two SMARCA2 degraders are in the clinic, one oral and one intravenous (IV) [2][3] - **IV Agent**: The IV agent has shown proof of concept for the novel pathway, with ongoing dose escalation and a maximum dose selected at 500 mg/m² [6][12] - **Efficacy Data**: An objective response rate of approximately 23% was reported for the IV agent, significantly higher than the expected 5-10% for the patient population [10][11] - **Patient Population**: Focus on upper gastrointestinal (GI) and non-small cell lung cancer (NSCLC) patients, particularly those with SMARCA4 mutations [8][9] - **Next Steps**: Full data set expected by the end of the year, with plans for a combination study with docetaxel [12][13] Key Points on Oral Degrader - **Development Status**: The oral agent is in dose escalation at 60 mg, with expectations to select a dose by the end of the year [23] - **Advantages**: Oral administration is preferred by patients for convenience and continuous dosing, potentially increasing therapeutic activity [16][17] - **Safety Profile**: Both agents have shown a clean safety profile with no dose-limiting toxicities (DLTs) reported [25][26] CAT6 Degrader Insights - **Target**: CAT6 is an epigenetic target with a focus on ER-positive breast cancer due to observed amplifications [34][37] - **Mechanism of Action**: The company is developing selective degraders for CAT6, aiming to reduce toxicities associated with existing therapies [38][39] - **Development Plans**: Plans to advance CAT6 into IND (Investigational New Drug) application next year, depending on capital allocation [45] Combination Strategies - **Potential Combinations**: Preclinical studies indicate potential synergies with immunotherapies like pembrolizumab and chemotherapy [28][29] - **Target Patient Populations**: Focus on frontline NSCLC patients, as they have limited treatment options and poor progression-free survival [30][31] Financial Overview - **Cash Position**: As of the latest report, the company has $103 million in cash, expected to last into Q2 2026, covering ongoing projects including SMARCA4, oral agents, and CAT6 [51] Additional Considerations - **ADC Pipeline**: The company is exploring antibody-drug conjugates (ADCs) to deliver degraders directly to tumors, enhancing treatment specificity [46][48] - **Strategic Collaborations**: Collaboration with Absella for antibody development is underway, aiming to expand treatment options for aggressive cancers [50] This summary encapsulates the critical insights and developments discussed during the conference call, highlighting Prelude Therapeutics' strategic focus on innovative cancer therapies and their ongoing clinical programs.