Core Insights - Prelude Therapeutics announced the acceptance of a poster presentation for its oral KAT6A selective degrader (PRT13722) at the AACR Annual Meeting 2026, scheduled for April 17-22 [1] - The company aims to file an IND in mid-2026 and initiate clinical trials in the second half of 2026 for PRT13722, which is expected to improve efficacy and tolerability in treating ER+ breast cancer [2][4] Presentation Details - The poster titled "First-in-class potent and selective oral KAT6A degrader development candidate, PRT13722, drives complete tumor regressions as a monotherapy with an improved pre-clinical hematological safety profile" will be presented on April 21, 2026, from 2:00 PM to 5:00 PM [3] - The presentation will be part of the Experimental and Molecular Therapeutics session, located at Poster Section 15, Board Number 20, Poster Number 5793 [3] Product Development - Prelude is developing a highly selective KAT6A oral degrader, which is believed to offer improved efficacy and tolerability compared to non-selective inhibitors [4] - The company has previously presented initial preclinical data supporting the potential of KAT6A as a target for ER+ breast cancer at the AACR Annual Meeting 2025 [5] Educational Session - On April 18, 2026, Prelude's Director of Biology and Translational Research will present a lecture on "Beyond Conventional Payloads: Unlocking New Therapeutic Landscapes with Targeted Protein Degrader-Antibody Conjugates (DACs)" during an educational session [6] Company Overview - Prelude Therapeutics is focused on developing innovative precision oncology medicines, including KAT6A degraders and JAK2V617F mutant selective inhibitors, targeting areas of high unmet need in cancer treatment [6]

Prelude Therapeutics Conference Call Summary Company Overview - Prelude Therapeutics is a precision oncology company with a differentiated pipeline targeting clinically validated pathways [2][3] - The company announced a strategic shift in its portfolio, pausing the SMARCA2 selective degrader program to focus on JAK2 V617F and KAT6A programs [3][4] Key Programs and Developments JAK2 V617F Program - The JAK2 V617F program has received IND clearance, with plans to initiate clinical trials in 2026 [4] - The program targets myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) [11][12] - The JAK2 mutation is present in over 90% of PV cases and about half of ET and MF cases [11] - Prelude's approach aims to develop a mutant-selective inhibitor that spares normal bone marrow function, addressing limitations of first-generation JAK2 inhibitors [13][14] KAT6A Program - Prelude is developing a KAT6A degrader, which is expected to have a better safety profile by selectively targeting KAT6A while sparing KAT6B [38][40] - The KAT6A degrader aims to provide deeper responses by eliminating the protein rather than just inhibiting it [39] - The IND for the KAT6A program is expected to be filed by mid-2026 [44] Mutant CALR Degrader - Prelude is also working on a mutant CALR degrader, which targets a specific fraction of ET and MF patients [46] - This program aims to utilize a degrader conjugate payload to effectively kill disease-initiating cells with minimal receptor occupancy [46][47] - The company has built expertise in developing these conjugates through a collaboration with AbCellera [48] Strategic Partnerships - Prelude has entered a business development deal with Incyte for the JAK2 V617F program, which includes an option for Incyte to acquire the program [5][29] - This partnership is expected to extend the company's financial runway into the second quarter of 2027, with $106 million in cash reported [53] Financial Position - Prelude reported $106 million in cash, which is projected to last until the second quarter of 2027, not including potential additional funding from Incyte [53] Clinical Development Plans - The clinical development plan for the JAK2 program includes a parallel design for both myelofibrosis and polycythemia vera, allowing for rapid development [23][24] - The company aims to enroll patients who may not be eligible for other JAK2 inhibitors, enhancing the trial's potential for meaningful data [25][26] Competitive Landscape - Prelude's JAK2 inhibitor is differentiated from competitors by its selective targeting of the mutant form of the enzyme, which is expected to improve efficacy and safety [18][21] - The KAT6A degrader is positioned to outperform existing KAT6 inhibitors by offering better efficacy and reduced side effects, particularly neutropenia [42][44] Conclusion - Prelude Therapeutics is strategically focusing on its JAK2 V617F and KAT6A programs while leveraging partnerships to enhance its financial position and clinical development capabilities [3][29][53]

Financial Performance - For the year ended December 31, 2025, the company reported a net loss of $99.5 million, compared to a net loss of $127.2 million for the year ended December 31, 2024[148]. - As of December 31, 2025, the company had an accumulated deficit of $683.1 million and has never generated any revenue from product sales[148][151]. - The company expects to continue incurring operating losses for the foreseeable future, which will adversely affect stockholders' equity and working capital[150][155]. - The company anticipates requiring substantial additional funding to pursue its business objectives and may face challenges in raising capital on favorable terms[156][158]. - The company has incurred substantial losses and does not expect to achieve profitability in the near future, which may limit the use of net operating loss carryforwards[325]. Research and Development - The company expects to incur significant research and development expenses as it advances its product candidates through clinical development and seeks marketing approval[150][156]. - The company is highly dependent on the successful completion of preclinical studies and clinical trials, with many factors influencing the outcome, including safety and efficacy demonstrations[165]. - The company may incur additional costs or experience delays in completing the development and commercialization of product candidates due to regulatory requirements and clinical trial challenges[169]. - The company is pausing the clinical development of its SMARCA2 degrader program, which includes PRT3789 and PRT7732, for strategic reasons, not due to safety or regulatory concerns[187]. - The company may need to conduct additional confirmatory studies, requiring significant time and resources, which could impact its operational efficiency[200]. Regulatory and Compliance Risks - The company has not completed successful late-stage pivotal clinical trials or obtained regulatory approval for any product candidates, which may hinder its ability to generate revenue[146][151]. - The FDA approval process for new drugs is expensive and uncertain, with only a small percentage of drugs successfully completing the regulatory approval process[191]. - The company has not obtained FDA approval for any product, which may impede its ability to secure timely approvals for clinical product candidates[196]. - Regulatory authorities may impose additional requirements or disagree with the company's clinical trial designs, potentially delaying approval[199]. - Non-compliance with safety monitoring and pharmacovigilance regulations may result in significant financial penalties for the company[225]. Market and Competitive Landscape - The company faces substantial competition from major pharmaceutical companies and biotechnology firms, which may impact the development and commercialization of its product candidates[283]. - The oncology market is highly competitive, with various existing drug therapies that may limit the market acceptance of the company's product candidates[290]. - Competitors may develop safer and more effective products, potentially obtaining regulatory approvals faster, which could hinder the company's market entry[291]. - The company may not achieve sufficient market acceptance for its product candidates, which is critical for commercial success[279]. - Pricing regulations and reimbursement practices may adversely affect the commercialization of the company's products, impacting revenue generation[292]. Funding and Capitalization - Cash, cash equivalents, and marketable securities as of December 31, 2025, were $103.2 million, which the company believes will fund operations for at least the next twelve months[149][157]. - If the company raises additional capital through equity offerings, it may cause dilution to existing stockholders and restrict operational flexibility[159][160]. - The company may engage in strategic transactions that could impact liquidity and increase expenses, potentially distracting management from core operations[146][159]. Intellectual Property - The company has filed patent applications in the United States and foreign jurisdictions for its product candidates, which are crucial for protecting its proprietary technologies[329]. - The patent application process is complex and costly, with uncertainties regarding the issuance and enforceability of patents, which could affect the company's competitive position[330]. - The company faces risks related to intellectual property, including potential challenges to patent validity and enforceability, which could allow competitors to commercialize similar products[335]. - The company may become involved in legal disputes to protect its intellectual property, which could be expensive and time-consuming[343]. Operational Risks - The company relies on third-party contractors for clinical trials and research, which may lead to delays or increased costs if these parties fail to meet their obligations[250]. - Manufacturing of pharmaceutical products is complex, and reliance on third-party suppliers increases the risk of insufficient quantities or quality, potentially delaying commercialization efforts[255]. - The company is dependent on sole suppliers for certain components, which increases the risk of delays and additional regulatory submissions if disruptions occur[257]. - Natural disasters and extreme weather conditions could materially disrupt operations, particularly given the concentration of operations on the east coast of the United States[321]. Strategic Transactions - The company may engage in strategic transactions, including acquisitions and partnerships, which could impact liquidity and increase expenses[326]. - The company may enter collaborations with third parties for product development, but failure in these collaborations could hinder the ability to capitalize on market potential[266].

Financial Performance - Prelude Therapeutics reported a net loss of $99.5 million, or $1.29 per share, for the year ended December 31, 2025, compared to a net loss of $127.2 million, or $1.68 per share, for the prior year[19]. - Prelude's total operating expenses for 2025 were $116.7 million, down from $146.7 million in 2024[24]. - Other income for the year was $5.1 million, compared to $12.5 million in the previous year[24]. Research and Development - Research and Development (R&D) expenses decreased to $94.3 million in 2025 from $118.0 million in 2024, reflecting a reduction in stock-based compensation and discontinued clinical trials[16]. - The company received FDA clearance for the Investigational New Drug application (IND) for PRT12396, a mutant-selective JAK2V617F inhibitor, with a Phase 1 study anticipated to start in Q2 2026[1]. - Prelude plans to file an IND for PRT13722, a highly-selective oral KAT6A degrader, in mid-2026, with Phase 1 study initiation expected in the second half of 2026[1]. Financial Position - Prelude had cash, cash equivalents, restricted cash, and marketable securities totaling $106.4 million as of December 31, 2025, expected to fund operations into the second quarter of 2027[15]. - Total assets decreased from $175,515,000 in 2024 to $141,315,000 in 2025, a decline of approximately 19.5%[26]. - Current assets fell from $135,895,000 in 2024 to $105,692,000 in 2025, representing a decrease of about 22.2%[26]. - Cash and cash equivalents increased significantly from $12,474,000 in 2024 to $35,256,000 in 2025, an increase of approximately 182.5%[26]. - Total liabilities rose from $44,056,000 in 2024 to $72,678,000 in 2025, an increase of about 65.1%[26]. - Stockholders' equity decreased from $131,459,000 in 2024 to $68,637,000 in 2025, a decline of approximately 47.9%[26]. - The accumulated deficit increased from $(583,563,000) in 2024 to $(683,061,000) in 2025, reflecting a worsening of approximately 17.1%[26]. - Additional paid-in capital rose from $714,982,000 in 2024 to $751,684,000 in 2025, an increase of about 5.1%[26]. - Total current liabilities increased from $25,641,000 in 2024 to $52,994,000 in 2025, a rise of approximately 106.7%[26]. - The company reported a deferred revenue of $33,734,000 in 2025, compared to none in 2024[26]. - The number of shares issued and outstanding increased from 42,298,859 in 2024 to 48,225,493 in 2025[26]. Collaboration and Market Insights - Prelude is expanding its collaboration with AbCellera Biologics to utilize degrader payloads on additional undisclosed antibody targets[9]. - The JAK2V617F mutation affects approximately 95% of patients with polycythemia vera (PV), 60% of patients with essential thrombocythemia (ET), and 55% of patients with myelofibrosis (MF)[3].

Core Insights - Prelude Therapeutics has received FDA clearance for the Investigational New Drug (IND) application for PRT12396, a mutant-selective JAK2V617F inhibitor, with a Phase 1 study expected to start in Q2 2026 [1][4] - The company is also advancing PRT13722, a highly-selective oral KAT6A degrader, with an IND filing anticipated in mid-2026 and Phase 1 study initiation planned for the second half of 2026 [1][5] - Prelude's current cash runway is projected to last into Q2 2027, with $106 million in cash and equivalents as of December 31, 2025 [1][14] R&D Pipeline Updates - The JAK2V617F mutation is a significant driver in myeloproliferative neoplasms (MPNs), affecting approximately 95% of polycythemia vera patients, 60% of essential thrombocythemia patients, and 55% of myelofibrosis patients [3] - Prelude has developed novel allosteric inhibitors targeting the JAK2 JH2 "deep pocket" where the V617F mutation resides, showing potential to reduce mutant allele burden and improve treatment outcomes for MPN patients [3] - The KAT6A oral degrader program targets ER+ breast cancer, with the potential for improved efficacy and tolerability compared to non-selective inhibitors [5] Financial Performance - For the year ended December 31, 2025, Prelude reported a net loss of $99.5 million, or $1.29 per share, a decrease from a net loss of $127.2 million, or $1.68 per share, in the previous year [17][21] - Research and development expenses decreased to $94.3 million from $118.0 million in the prior year, attributed to reduced stock-based compensation and discontinued clinical trials [15] - General and administrative expenses also decreased to $22.4 million from $28.7 million, primarily due to lower stock-based compensation and employee-related expenses [16] Upcoming Milestones - The Phase 1 study of PRT12396 will be an open-label, multi-center trial focusing on patients with high-risk polycythemia vera and intermediate to high-risk myelofibrosis [4] - Prelude plans to present initial preclinical data for its KAT6A program at upcoming conferences, showcasing its commitment to advancing its R&D pipeline [6][11] - The company will participate in the Citizens Life Sciences Conference on March 10, 2026, where key executives will discuss the company's strategic direction and upcoming milestones [12]

Core Insights - Prelude Therapeutics has received FDA clearance for its Investigational New Drug application (IND) for PRT12396, a mutant-selective JAK2V617F inhibitor, with a Phase 1 study expected to start in Q2 2026 [1][4] - The company is also advancing its KAT6A degrader program, with an IND filing anticipated in mid-2026 and a Phase 1 study initiation planned for the second half of 2026 [1][5] - Prelude's current cash runway is projected to extend into Q2 2027, with $106 million in cash and equivalents as of December 31, 2025 [1][14] R&D Pipeline Updates - The JAK2V617F mutation is prevalent in 95% of polycythemia vera (PV) patients, 60% of essential thrombocythemia (ET) patients, and 55% of myelofibrosis (MF) patients, making it a critical target for treatment [3] - Prelude has developed novel allosteric inhibitors that specifically target V617F+ cells, aiming to reduce mutant allele burden and improve treatment outcomes for patients with myeloproliferative neoplasms (MPNs) [3] - The KAT6A oral degrader program targets ER+ breast cancer, with the potential for improved efficacy and tolerability compared to non-selective inhibitors [5] Financial Performance - For the year ended December 31, 2025, Prelude reported a net loss of $99.5 million, or $1.29 per share, a decrease from a net loss of $127.2 million, or $1.68 per share, in the previous year [17][21] - Research and development expenses decreased to $94.3 million from $118.0 million in the prior year, attributed to reduced stock-based compensation and discontinued clinical trials [15] - General and administrative expenses also saw a decline to $22.4 million from $28.7 million, primarily due to lower stock-based compensation and employee-related expenses [16] Upcoming Milestones - The company is on track to have both PRT12396 and PRT13722 in clinical development in 2026, which may lead to significant data catalysts in 2027 [2] - Prelude will participate in the Citizens Life Sciences Conference on March 10, 2026, where key executives will discuss the company's progress and future plans [12]

Corporate Presentation March 2026 Confidential Forward Looking Statements & Disclaimers This presentation contains "forward-looking" statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated discovery, preclinical and clinical development activities for Prelude's product candidates and milestones, the potential safety, efficacy, benefits and addressable market for Prelude Therapeutic Incorporated's (the " ...

Core Insights - Prelude Therapeutics has received FDA clearance to proceed with a Phase 1 study for PRT12396, a mutant-selective JAK2V617F inhibitor aimed at treating myeloproliferative neoplasms (MPNs) [1][2] - The company plans to begin dosing the first patient by Q2 of 2026, marking a significant milestone in its strategic focus on JAK2 and KAT6 programs [2] Company Developments - The Phase 1 study will be an open-label, multi-center trial assessing safety, efficacy, and pharmacokinetics in patients with high-risk polycythemia vera (PV) and intermediate to high-risk myelofibrosis (MF) [2] - Prelude's JAK2V617F inhibitor program is under an exclusive option agreement with Incyte, which was announced in November 2025 [3] Scientific Background - JAK2V617F is a key mutation affecting approximately 95% of patients with polycythemia vera, 60% of those with essential thrombocythemia, and 55% of myelofibrosis patients [4] - Prelude has developed novel allosteric inhibitors that specifically target V617F+ cells, which may reduce mutant allele burden and improve treatment outcomes for MPN patients [4] Company Overview - Prelude Therapeutics is focused on precision oncology, developing innovative medicines for cancer patients with high unmet needs [5] - The company's pipeline includes selective KAT6A degraders and JAK2V617F inhibitors, aiming to leverage targeted protein degradation for next-generation therapies [5]

Core Insights - Prelude Therapeutics has presented preclinical data on its JAK2V617F-selective JH2 inhibitors and mCALR-targeted degrader antibody conjugates at the American Society of Hematology (ASH) 67 Annual Meeting, highlighting their potential for disease modification in myeloproliferative neoplasms (MPNs) [1][2] JAK2V617F Inhibitor Program - PRT12396, a JAK2V617F-selective JH2 inhibitor, has shown robust preclinical activity, selectively inhibiting JAK2V617F while preserving wild-type JAK2 signaling, and demonstrated superior efficacy compared to ruxolitinib in multiple preclinical MPN models [2][4] - The company has completed GLP toxicology studies and plans to file an Investigational New Drug (IND) application and initiate a Phase 1 study in the first quarter of 2026 [3][4] - JAK2V617F mutation is present in approximately 95% of polycythemia vera (PV) patients, 60% of essential thrombocythemia (ET) patients, and 55% of myelofibrosis (MF) patients, making it a critical target for treatment [5][6] mCALR-targeted Degrader Antibody Conjugates - The company has introduced a novel mCALR-targeted degrader antibody conjugate (DAC) that delivers a CDK9 degrader payload selectively to malignant cells, demonstrating deep mutant-selective killing and sparing healthy hematopoietic cells [4][7] - mCALR is found in approximately 25-35% of patients with MF and ET, and recent clinical data has shown meaningful therapeutic benefits from mCALR-directed antibodies [7][8] Company Overview - Prelude Therapeutics is focused on developing innovative precision oncology medicines, with a pipeline that includes selective KAT6A degraders and JAK2V617F-selective JH2 inhibitors, aiming to address high unmet needs in cancer treatment [8]

Core Insights - Prelude Therapeutics has presented preclinical data on its JAK2V617F-selective JH2 inhibitors and mCALR-targeted degrader antibody conjugates at the American Society of Hematology (ASH) 67th Annual Meeting, highlighting their potential for disease modification in myeloproliferative neoplasms (MPNs) [1][2][4] JAK2V617F Inhibitor Program - PRT12396, a JAK2V617F-selective JH2 inhibitor, has shown robust preclinical activity, selectively inhibiting JAK2V617F while preserving wild-type JAK2 signaling, and demonstrated superior efficacy compared to ruxolitinib in multiple preclinical MPN models [2][3][6] - The company has completed GLP toxicology studies and plans to file an Investigational New Drug (IND) application and initiate a Phase 1 study in the first quarter of 2026 [3][6] - JAK2V617F mutation is present in approximately 95% of polycythemia vera (PV) patients, 60% of essential thrombocythemia (ET) patients, and 55% of myelofibrosis (MF) patients, making it a critical target for treatment [5][6] mCALR Degrader Antibody Conjugate Program - The company has introduced a novel mCALR-targeted degrader antibody conjugate (DAC) that delivers a CDK9 degrader payload selectively to malignant cells, demonstrating deep mutant-selective killing and sparing healthy hematopoietic cells [4][7] - mCALR is found in approximately 25-35% of patients with MF and ET, and recent clinical data has shown meaningful therapeutic benefits from mCALR-directed antibodies [7] Company Overview - Prelude Therapeutics is focused on developing innovative precision oncology medicines, including selective KAT6A degraders and JAK2V617F-selective JH2 inhibitors, aiming to address high unmet needs in cancer treatment [8]