On May 12, 2026 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported its financial results for the first quarter ended March 31, 2026 and provided an update on its R&D pipeline and other corporate developments.

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"Through this first quarter of 2026, our company has continued to demonstrate focused execution of the strategic priorities we set forth late last year." stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude. "Since the beginning of this year, we’ve advanced PRT12396 into first-in-human studies, presented promising preclinical data from our highly selective KAT6A degrader development candidate, continued to progress towards a development candidate from our mCALR program and importantly, extended our cash runway into the second quarter of 2028."

Program Updates and Upcoming Milestones

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 95% of patients with polycythemia vera (PV), 60% of patients with essential thrombocythemia (ET) and 55% of patients with myelofibrosis (MF). Identifying JAK2 JH2 inhibitors that selectively target V617F+ cells has long been the goal for advancing the treatment of MPNs.

Prelude has designed and identified novel allosteric inhibitors that bind into the JAK2 JH2 "deep pocket" where the V617F mutation resides. These candidates demonstrate mutant specific inhibition in multiple preclinical models of MPNs. Prelude believes this approach may have the potential to reduce mutant allele burden, slow or even reverse disease progression, and transform treatment outcomes for MPN patients.

PRT12396, Prelude’s lead, mutant-selective JAK2V617F inhibitor received IND clearance from the U.S. Food and Drug Administration, as previously announced in February 2026 and recently initiated and commenced enrollment into a Phase 1 study of PRT12396 in patients with PV and MF.

The JAK2V617F inhibitor program is subject to an exclusive option agreement with Incyte announced in November 2025.

Highly selective KAT6A oral degrader program

KAT6 is an emerging and recently validated target in the treatment of ER+ breast cancer. Prelude discovered and is developing first-in-class, highly potent, highly selective and orally bioavailable KAT6A selective degraders. The Company has selected a development candidate, PRT13722 and remains on track to file an IND application in mid-2026, and pending clearance, phase 1 study initiation expected in the 2nd half of 2026. Prelude believes that selectively degrading KAT6A has the potential for improved efficacy, tolerability and combinability with other agents relative to non-selective inhibitors of KAT6A/B.

The Company presented preclinical data supporting this hypothesis at the AACR (Free AACR Whitepaper) Annual Meeting 2026. The presentation can be found at Publications – Prelude Therapeutics.

Degrader payloads for next generation DACs

Prelude is leveraging our expertise in targeted protein degradation to discover and develop novel degrader payloads for use with next generation DACs. We have developed highly potent SMARCA2/4 and CDK9 degrader payloads optimized for efficacy, tolerability and developability when coupled to a wide range of different antibodies. Building on our existing DAC partnership with AbCellera, the Company’s payloads and corresponding payload-linkers are available for licensing to additional partners to expand the reach of this new technology.

We have recently published preclinical data demonstrating that next generation DACs using Prelude degrader payloads have potential for significantly better in vivo efficacy and tolerability compared to traditional cytotoxic ADCs when tested head-to-head in xenograft models. These data can be found at: Publications – Prelude Therapeutics

Mutated calreticulin (mCALR) DAC discovery program

Mutant CALR is a neoantigen presented on the cell surface of malignant myeloid cells but not normal cells and is found in approximately 25-35% of patients with MF and essential thrombocythemia (ET). Recently, a mCALR-targeted monoclonal antibody demonstrated robust clinical activity in high-risk ET patients. Prelude is exploring mCALR-targeted DACs using the Company’s proprietary degrader payloads as a differentiated approach for patients with CALR mutations. This early discovery program is wholly owned and controlled by Prelude.

The Company presented the preclinical data from the program at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress in June and the American Society of Hematology (ASH) (Free ASH Whitepaper) 67th Annual Meeting in December 2025. The presentations can be found at Publications – Prelude Therapeutics.

Corporate Updates

In April 2026, the Company announced the appointment of Charles Morris, M.D. as Chief Medical Officer.

Upcoming Investor Conferences

The Company will participate in the 2026 Jefferies Global Healthcare Conference taking place in New York City. On Wednesday, June 3, 2026 at 12:15 PM ET, Kris Vaddi, Ph.D., Chief Executive Officer, Peggy Scherle, Ph.D., Chief Scientific Officer and Bryant Lim, Chief Financial Officer will participate in a fireside chat.

The Company will also participate in the Goldman Sachs 47th Annual Global Healthcare Conference taking place in Miami, FL. On Wednesday, June 10, 2026 at 11:20 AM ET, Kris Vaddi, Ph.D., Chief Executive Officer, Peggy Scherle, Ph.D., Chief Scientific Officer and Bryant Lim, Chief Financial Officer will participate in a fireside chat.

First Quarter 2026 Financial Results 

Cash, Cash Equivalents, Restricted cash and Marketable securities:

Cash, cash equivalents, restricted cash and marketable securities as of March 31, 2026 were $84.8 million. Subsequent to March 31, 2026, the Company completed an underwritten offering with gross proceeds of approximately $90 million. Based on preliminary estimates, the Company anticipates that its existing cash, cash equivalents, restricted cash and marketable securities will fund Prelude’s operations into the second quarter of 2028.

Research and Development (R&D) Expenses:

For the three months ended March 31, 2026, R&D expense decreased to $13.6 from $28.8 million for the prior year period. Included in the R&D expense for the three months ended March 31, 2026 was $1.1 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $2.3 million for the three months ended March 31, 2025. Along with the decrease in stock-based compensation expense, the decrease was primarily related to lower expense incurred for our SMARCA2 clinical trials which we paused in 2025. Research and development expenses may fluctuate from period to period depending upon the stage of certain projects and the level of preclinical and clinical trial-related activities.

General and Administrative (G&A) Expenses:

For the three months ended March 31, 2026, G&A expenses decreased to $5.2 million from $5.8 million for the prior year period. Included in general and administrative expenses for the threemonths ended March 31, 2026, was $0.9 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $1.6 million for the three months ended March 31, 2025. The decrease in general and administrative expenses was primarily due to a decrease in stock-based compensation along with a decrease in employee-related expenses.

Net Loss:

For the three months ended March 31, 2026, net loss was $10.4 million, or $0.13 per share compared to $32.1 million, or $0.42 per share, for the prior year period. Included in the net loss for the three months ended March 31, 2026, was $2.0 million of non-cash expenses related to the impact of expensing share-based payments, including employee stock options due in part to fewer employees, as compared to $3.8 million for the same period in 2025.

(Press release, Prelude Therapeutics, MAY 12, 2026, View Source [SID1234665555])