WILMINGTON, Del., Feb. 03, 2026 (GLOBE NEWSWIRE) -- Prelude Therapeutics Incorporated (Nasdaq: PRLD), a precision oncology company, today announced that the U.S. Food and Drug Administration (FDA) cleared the Company to proceed with a Phase 1 study under its Investigational New Drug Application (IND) for PRT12396, a mutant-selective JAK2V617F inhibitor being developed for the treatment of patients with certain myeloproliferative neoplasms (MPNs). The Company anticipates dosing the first patient by Q2 of 202 ...

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]

Core Viewpoint - The Schall Law Firm is investigating Prelude Therapeutics for potential violations of securities laws following a significant drop in share price after the company paused its SMARCA2 degrader program [1][2]. Group 1: Investigation Details - The investigation centers on whether Prelude issued false or misleading statements or failed to disclose important information to investors [2]. - Prelude announced the pause of its SMARCA2 degrader program on November 4, 2025, citing a comprehensive review of clinical data and resource allocation considerations [2]. - Following the announcement, Prelude's shares fell by approximately 55.8% on the same day [2]. Group 2: Company Information - Prelude Therapeutics is listed on NASDAQ under the ticker PRLD [1]. - The Schall Law Firm specializes in securities class action lawsuits and shareholder rights litigation, representing investors globally [3].

Financial Data and Key Metrics Changes - The company has enhanced its financial position, providing additional cash runway to advance lead programs into clinical development [4] - An exclusive option agreement with Incyte includes an upfront fee of $35 million and a purchase of $25 million in non-voting common stock, totaling $60 million [20][22] - The deal could deliver up to $910 million in cash payments and future milestones to the company [22] Business Line Data and Key Metrics Changes - The primary focus will be on advancing two development candidates: a JAK2 V617F selective inhibitor for myeloproliferative neoplasms and a KAT6A selective degrader for ER-positive breast cancer, both expected to enter the clinic in 2026 [4][5] - The JAK2 V617F selective inhibitor targets over 200,000 MPN patients in the US alone, with a significant market opportunity [11] Market Data and Key Metrics Changes - The target patient population for the JAK2 program includes over 95% of PV patients and 50%-60% of MF and ET patients that are V617F positive [11] - The KAT6A selective degrader program aims to address the unmet need in ER-positive breast cancer, where resistance to current therapies is common [13][14] Company Strategy and Development Direction - The company is focused on optimizing capital allocation and aligning its business strategy with programs that offer the highest probability of success [4] - The strategy includes enhancing R&D focus and advancing next-generation ADCs called degrader antibody conjugates [5][20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of their lead programs to transform treatment options for cancer patients [4] - The company is energized to enter 2026 with a strong team and financial means to support execution into 2027 [24] Other Important Information - The company plans to file an IND for the JAK2 program in the first quarter of 2026 and expects to initiate phase one trials in the first half of 2026 [11][43] - The KAT6A program is on track for an IND filing in mid-2026, with a phase one start expected in the second half of 2026 [19][43] Q&A Session Summary Question: Can you talk about the clinical development of both the mutant CALR and the KAT6A programs? - The company plans to focus on V617F-positive MPNs, with myelofibrosis as a potential initial study indication [27] - For the KAT6A program, the focus will be on ER-positive breast cancer, with plans to rapidly advance to fulvestrant combinations [30] Question: How do you differentiate the degrader approach versus previous programs? - The company learned from the SMARCA2 program to build in potency, selectivity, and important PK properties into the KAT6A program [42] Question: How does the current mutation testing for V617F perform clinically? - V617F testing has become a standard diagnostic for MPNs, especially in PV patients [39] Question: How did the deal with Incyte come about? - The deal was seen as the best option to bring in capital and leverage Incyte's expertise in the MPN space [56]

Financial Performance - The company reported a net loss of $83.0 million for the nine months ended September 30, 2025, compared to a net loss of $98.4 million for the same period in 2024, indicating a reduction in losses of $15.4 million[112]. - Revenue for the three months ended September 30, 2025, was $6.5 million, an increase of $3.5 million from $3.0 million in the same period of 2024[124]. - Total operating expenses decreased to $26.9 million in Q3 2025 from $37.4 million in Q3 2024, a reduction of $10.5 million[124]. - Net loss for the nine months ended September 30, 2025 was $83.0 million, compared to a net loss of $98.4 million for the same period in 2024, reflecting an improvement of $15.4 million[133]. - Net cash used in operating activities for the nine months ended September 30, 2025 was $79.4 million, slightly lower than $82.1 million in the same period of 2024[153][154]. - Net cash provided by investing activities for the nine months ended September 30, 2025 was $113.8 million, compared to a net cash used of $68.1 million in 2024[156]. Research and Development - Research and development expenses for the three months ended September 30, 2025, were $21.7 million, down from $29.5 million in the same period of 2024, a decrease of $7.7 million[124]. - Research and development expenses decreased from $29.5 million in Q3 2024 to $21.7 million in Q3 2025, a reduction of approximately 26.5%[127][129]. - Research and development expenses for the nine months ended September 30, 2025 totaled $76.3 million, down from $86.4 million in 2024, a decrease of approximately 11.7%[136][138]. - The company has paused the clinical development of its SMARCA2 degrader program to focus resources on the JAK2 and KAT6A programs[110]. - The company plans to file an IND for a KAT6A selective degrader candidate in mid-2026[106]. Cash and Financing - Cash, cash equivalents, restricted cash, and marketable securities totaled $58.2 million as of September 30, 2025[142]. - The company received $6 million from an expanded collaborative agreement with AbCellera in October 2025 and $60 million from Incyte Corporation in November 2025[142]. - The company plans to raise substantial additional capital to support ongoing operations and growth strategy, indicating potential dilution of ownership interests[145][152]. - For the nine months ended September 30, 2025, net cash used in financing activities was primarily for principal payments on finance lease[157]. Compliance and Reporting - The company regained compliance with Nasdaq's minimum bid price requirement on September 18, 2025[111]. - The company has elected to take advantage of exemptions from complying with new or revised accounting standards as an emerging growth company[159]. - The company anticipates no longer being an emerging growth company as of December 31, 2025, which will affect its reporting obligations[160]. - The market value of the company's stock held by non-affiliates is less than $700 million, qualifying it as a smaller reporting company[161]. - The company may continue to rely on exemptions from certain disclosure requirements if it remains a smaller reporting company after ceasing to be an emerging growth company[161]. - The company is not required to provide quantitative and qualitative disclosures about market risk for the period ending September 30, 2025, due to its status as a smaller reporting company[162]. Strategic Agreements - The company has entered into an exclusive option agreement with Incyte Corporation, which could yield up to $910 million in total potential cash payments, excluding royalties[105].

Financial Performance - Prelude Therapeutics reported a net loss of $19.7 million, or $0.26 per share, for Q3 2025, compared to a net loss of $32.3 million, or $0.43 per share, in Q3 2024[19][26]. - Total revenue for Q3 2025 was $6.5 million, up from $3.0 million in the same period last year, representing a 116.7% increase[26]. - Research and Development (R&D) expenses decreased to $21.7 million in Q3 2025 from $29.5 million in Q3 2024, a reduction of 26.6%[16][26]. - General and Administrative (G&A) expenses decreased to $5.2 million in Q3 2025 from $7.7 million in Q3 2024, a decline of 32.5%[17][26]. Cash and Liquidity - Prelude has cash, cash equivalents, restricted cash, and marketable securities totaling $58.2 million as of September 30, 2025, with an expected cash runway into 2027[15]. - The company anticipates that its existing cash resources will support operations into 2027, following recent license payments from partners[15][22]. - Cash and cash equivalents increased significantly from $12,474,000 to $47,532,000, representing a growth of about 280.5%[28]. Assets and Liabilities - Total current assets decreased from $135,895,000 on December 31, 2024, to $58,330,000 on September 30, 2025, a decline of approximately 57.0%[28]. - Total liabilities decreased from $44,056,000 to $36,221,000, a reduction of approximately 17.5%[28]. - Total stockholders' equity decreased from $131,459,000 to $58,534,000, a decline of about 55.5%[28]. - Total assets decreased from $175,515,000 to $94,755,000, a decline of approximately 46.0%[28]. Marketable Securities and Other Assets - Marketable securities dropped significantly from $121,140,000 to $7,425,000, a decrease of approximately 93.9%[28]. - Accounts payable decreased from $7,732,000 to $2,533,000, a reduction of about 67.3%[28]. - Prepaid expenses and other current assets increased from $2,281,000 to $3,373,000, an increase of approximately 47.9%[28]. - Operating lease right-of-use asset slightly decreased from $28,699,000 to $27,549,000, a decline of about 4.0%[28]. Research and Development Updates - The lead candidate from the mutant selective JAK2V617F JH2 inhibitor program is expected to file an IND in Q1 2026, targeting a significant patient population[1][6]. - The KAT6A selective degrader program is on track for an IND filing in mid-2026, with a phase 1 dose escalation study planned for the second half of 2026[9][8]. - Prelude's collaboration with AbCellera has been expanded to include additional undisclosed antibody targets, enhancing its development capabilities[11]. - Preclinical data from both the JAK2V617F and CALR-targeted degrader antibody conjugate programs have been accepted for oral presentations at the ASH 67th Annual Meeting in December 2025[1][6]. Accumulated Deficit - Accumulated deficit increased from $(583,563,000) to $(666,604,000), indicating a worsening of approximately 14.2%[28].

Core Insights - Prelude Therapeutics is advancing two promising drug programs targeting significant unmet needs in oncology, specifically the JAK2V617F inhibitor and KAT6A degrader programs [3][4][19] - The company expects to file Investigational New Drug (IND) applications for both programs in 2026, with the JAK2V617F program anticipated in the first quarter and the KAT6A program in mid-2026 [5][8] Pipeline Programs - **JAK2V617F Inhibitor Program**: This program targets the JAK2V617F mutation, which is prevalent in myeloproliferative neoplasms (MPNs), affecting approximately 95% of polycythemia vera patients, 60% of essential thrombocythemia patients, and 55% of myelofibrosis patients. Prelude has developed novel allosteric inhibitors that selectively target V617F+ cells, showing potential to reduce mutant allele burden and improve treatment outcomes [4][6] - **KAT6A Degrader Program**: This program focuses on KAT6A, a target in ER+ breast cancer. Prelude is developing first-in-class, highly selective oral KAT6A degraders, which may offer improved efficacy and tolerability compared to non-selective inhibitors. Preclinical data supporting this approach has been presented at relevant conferences [7][8] Financial Overview - As of September 30, 2025, Prelude had cash, cash equivalents, restricted cash, and marketable securities totaling $58.2 million. The company anticipates that this funding will support operations into 2027 [14] - Research and Development (R&D) expenses for Q3 2025 decreased to $21.7 million from $29.5 million in the prior year, while General and Administrative (G&A) expenses also saw a decline to $5.2 million from $7.7 million [15][16] - The net loss for Q3 2025 was reported at $19.7 million, or $0.26 per share, compared to a net loss of $32.3 million, or $0.43 per share, for the same period in 2024 [17][21]

Core Viewpoint - Prelude Therapeutics Incorporated is under investigation by the Schall Law Firm for potential violations of securities laws, particularly regarding misleading statements and failure to disclose critical information to investors [1][2]. Company Summary - The investigation centers on Prelude's announcement to pause the clinical development of its SMARCA2 degrader program, which was made on November 4, 2025. This decision was based on a thorough review of clinical data and an assessment of resource allocation compared to other programs [2]. - Following the announcement, Prelude's shares experienced a significant decline, falling by approximately 55.8% on the same day [2]. Legal Context - The Schall Law Firm is encouraging shareholders who have suffered losses to participate in the investigation and is offering free consultations regarding their rights [3].

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