Prelude Therapeutics Presents Data at the 2025 ASH Annual Meeting from its Myeloproliferative Neoplasm (MPN) Programs
Rhea-AI Summary
Prelude Therapeutics (Nasdaq: PRLD) presented preclinical data at ASH 2025 for two myeloproliferative neoplasm (MPN) programs: a JAK2V617F-selective JH2 inhibitor (PRT12396) and mCALR-targeted degrader antibody conjugates (DACs) carrying a CDK9 degrader payload.
Key points: PRT12396 selectively inhibited JAK2V617F while preserving wild-type JAK2 signaling, showed superior preclinical activity versus ruxolitinib, completed GLP toxicology, and the company anticipates an IND filing and phase 1 start in Q1 2026. The JAK2 program is subject to an exclusive option agreement with Incyte announced November 2025. The mCALR x CDK9 DACs delivered mutant-selective CDK9 degradation, demonstrated deep mutant-selective killing in vitro and in vivo, and spared healthy hematopoietic cells, supporting disease‑modifying potential.
Positive
- GLP toxicology completed for PRT12396 enabling IND filing
- Anticipated IND filing and Phase 1 start in Q1 2026 for PRT12396
- PRT12396 showed mutant-selective inhibition and superior preclinical activity to ruxolitinib
- mCALR x CDK9 DACs demonstrated deep mutant-selective killing and in vivo efficacy
- JAK2 program under an exclusive option with Incyte (announced Nov 2025)
Negative
- Both programs are currently preclinical; no human clinical efficacy or safety data yet
- IND and Phase 1 timing is anticipated (Q1 2026) but not a completed regulatory milestone
Key Figures
Market Reality Check
Peers on Argus
Peers show mixed moves: declines in ANL -18.55% and INKT -6.28%, gains in BYSI +5.29% and OSTX +1.59%, suggesting PRLD’s -5.19% move is stock-specific rather than a broad biotech shift.
Historical Context
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Nov 12 | Earnings and update | Positive | +8.9% | Q3 2025 results, extended cash runway, and pipeline timing updates. |
| Nov 04 | Strategic update | Positive | -55.8% | Incyte option, KAT6A prioritization, SMARCA2 pause, cash runway commentary. |
| Nov 04 | Incyte option deal | Positive | -55.8% | Exclusive JAK2V617F option agreement with Incyte and potential milestones. |
| Nov 03 | ASH abstracts | Positive | +150.3% | Preclinical ASH data for JAK2V617F inhibitors and mCALR-targeted DACs. |
| Oct 17 | Board change | Neutral | -9.2% | Appointment of new director and Audit Committee chair replacing outgoing member. |
News reactions have been volatile and often divergent: large selloffs on partnership news, a sharp spike on ASH abstracts, and mixed responses to corporate updates.
Over the past months, Prelude’s story has centered on financing, strategic focus, and its JAK2V617F and degrader platforms. An Incyte option deal on JAK2V617F and a strategic update on Nov 4 coincided with a sharp selloff despite substantial potential economics. Publication of ASH abstracts on Nov 3 drove a 150.31% move, showing strong sensitivity to MPN data. Q3 results on Nov 12 highlighted improved cash visibility and were followed by an 8.89% gain. Today’s detailed ASH data further develops the same JAK2V617F and mCALR themes.
Market Pulse Summary
This announcement highlights detailed preclinical results for Prelude’s JAK2V617F-selective inhibitor PRT12396 and mCALR-targeted degrader antibody conjugates, both aimed at disease modification in myeloproliferative neoplasms. With an IND planned for early 2026, these programs build on earlier ASH abstracts and the Incyte option agreement. Investors may watch for IND acceptance, initial clinical safety signals, and further updates on mCALR DAC efficacy as key milestones shaping the value of Prelude’s precision oncology pipeline.
Key Terms
myeloproliferative neoplasms medical
AI-generated analysis. Not financial advice.
First disclosure of PRT12396, a JAK2V617F-selective JH2 inhibitor demonstrates disease modifying potential in myeloproliferative neoplasms
PRT12396 has completed GLP toxicology studies and is on track for IND filing in the first quarter 2026
First disclosure of a mutant calreticulin (mCALR) targeted degrader antibody conjugate (DAC) with a novel CDK9 degrader payload
JAK2V617F and mCALR are the two primary driver mutations responsible for disease progression and poor prognosis in the majority of MPN patients
WILMINGTON, Del., Dec. 06, 2025 (GLOBE NEWSWIRE) -- Prelude Therapeutics Incorporated (Nasdaq: PRLD) (“Prelude” or the “Company”), a precision oncology company, presented earlier today the first preclinical data on its JAK2V617F mutant selective JH2 inhibitors and additional preclinical data from its mCALR-targeted degrader antibody conjugate (DAC) discovery program. Both oral presentations took place at the American Society of Hematology (ASH) 67th Annual Meeting in Orlando, FL. These presentations can be found at Publications - Prelude Therapeutics.
“Since JAK2V617F was first identified as a major driver mutation in JAK2 enzyme in myeloproliferative neoplasms two decades ago, our industry has been searching for an inhibitor that can selectively target the mutant JAK2 enzyme without disrupting normal JAK2 function” stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude. “We are proud to have made significant advances in the discovery of such molecules and to share preclinical data demonstrating that our lead candidate meaningfully differentiates between mutant and wild-type JAK2 and potentially overcomes dose-limiting toxicities associated with current therapies. This work underscores the potential for a disease-modifying approach beyond what is achievable with today’s JAK2 inhibitors, and we look forward to advancing this molecule into the clinic in early 2026.”
Continued Vaddi, “Beyond JAK2, mCALR is the other most common driver mutation in MPNs. Clinical data with an mCALR-directed antibody has now demonstrated meaningful therapeutic benefit for patients. Our degrader antibody conjugate (DAC) approach is designed to build on this validation by delivering a disease-relevant payload, such as our highly potent CDK9 degrader, directly to mCALR-positive cells. We believe this innovative strategy offers a differentiated, and potentially even more efficacious approach as we seek to advance the next wave of disease-modifying therapies for MPN patients. We were pleased to share these initial results from both programs today at ASH.”
In the oral presentation, titled “Discovery and preclinical characterization of orally bioavailable JAK2V617F mutant selective JH2 inhibitors with disease modification potential in myeloproliferative neoplasms,” the authors presented data from preclinical studies showing that PRT12396 selectively inhibits JAK2V617F activity in a cellular context while preserving WT JAK2-medited cytokine signaling. Additionally, PRT12396 demonstrated robust preclinical activity in multiple preclinical MPN models, superior to ruxolitinib. PRT12396 also showed selective inhibition of the proliferation of JAK2VF stem and progenitor cells both in vitro and in vivo and was well-tolerated in toxicological studies with minimal effects on hematologic parameters.
The Company has completed GLP toxicology studies and anticipates filing the IND and initiating a phase 1 study in the first quarter of 2026. The Company’s JAK2V617F inhibitor program is subject to an exclusive option agreement with Incyte announced in November 2025.
Additionally, the Company presented data from its mutant calreticulin (mCALR) degrader antibody conjugates (DACs) discovery program. In the oral presentation, titled “Discovery of First-in-Class Calreticulin-targeted Precision Antibody Drug Conjugates Delivering a CDK9 Degrader Payload for the Treatment of CALR-mutated MPNs,” the authors demonstrated that an mCALR x CDK9 degrader antibody conjugate delivers a CDK9 degrader selectively to malignant clones. Through this approach, deep mutant-selective killing across cell lines, HSPCs and primary cultures was shown, highlighting disease modifying potential, supported by compelling in vivo efficacy data. mCALR x CDK9 DACs were also shown to spare healthy hematopoietic cells, indicating potential for a favorable therapeutic index.
About mutant selective JAK2V617F JH2 inhibitor program
JAK2V617F is the primary driver mutation responsible for disease progression in the majority of patients living with myeloproliferative neoplasms (MPNs). The mutation impacts approximately
About mutant calreticulin (mCALR) targeted degrader antibody conjugates (DACs)
Mutant CALR is a neoantigen presented on the cell surface of malignant myeloid cells but not normal cells and is found in approximately 25
About Prelude Therapeutics
Prelude Therapeutics is a leading precision oncology company developing innovative medicines in areas of high unmet need for cancer patients. Our pipeline features highly selective KAT6A degraders and JAK2V617F mutant selective JH2 inhibitors – new approaches to clinically validated targets with transformative potential for patients. We are leveraging our expertise in targeted protein degradation to discover and develop next generation degrader antibody conjugates (DACs) with novel payloads. We are on a mission to extend the promise of precision medicine to every cancer patient in need. Our corporate presentation can be found at Events & Presentations - Prelude Therapeutics. For more information, visit preludetx.com.
Cautionary Note Regarding Forward-Looking Statements
This press release 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, the potential safety, efficacy, benefits and addressable market for Prelude’s product candidates, the expected timeline for clinical trial results for Prelude’s product candidates, and the sufficiency of Prelude’s cash runway. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The words “believes,” “anticipates,” “estimates,” “plans,” “expects,” “intends,” “may,” “could,” “should,” “potential,” “likely,” “projects,” “continue,” “will,” “schedule,” and “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on the Company’s current expectations and projections about future events and various assumptions. Although Prelude believes that the expectations reflected in such forward-looking statements are reasonable, Prelude cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause Prelude's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Prelude's ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, clinical trial sites and our ability to enroll eligible patients, supply chain and manufacturing facilities, Prelude’s ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical and clinical trials, Prelude's ability to fund development activities and achieve development goals, Prelude's ability to protect intellectual property, and other risks and uncertainties described under the heading "Risk Factors" in Prelude’s Annual Report on Form 10-K for the year ended December 31, 2024, its Quarterly Reports on Form 10-Q and other documents that Prelude files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Prelude undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof, except as may be required by law.
Investor Contact:
Robert A. Doody, Jr.
Senior Vice President, Investor Relations
Prelude Therapeutics Incorporated
484.639.7235
rdoody@preludetx.com
FAQ
What did Prelude Therapeutics (PRLD) announce at ASH 2025 on December 6, 2025?
When does Prelude plan to file an IND and start a Phase 1 for PRT12396 (PRLD)?
How did PRT12396 perform versus ruxolitinib in Prelude’s ASH 2025 presentation?
What is the significance of Prelude’s mCALR x CDK9 degrader ADCs presented at ASH 2025?
Does Prelude (PRLD) have any partnerships related to its JAK2 program?
Are Prelude’s ASH 2025 results clinical or preclinical evidence for PRLD investors?
