Prelude Therapeutics Incorporated (PRLD) reported full-year 2025 results and provided an update on its precision oncology pipeline, highlighting progress across its JAK2V617F mutant-selective inhibitor program and highly selective KAT6 degrader program.
The company said it remains focused on advancing two first-in-class candidates into clinical development in 2026.
For the year ended December 31, 2025, Prelude reported a net loss of $99.5 million, or $1.29 per share compared with a net loss of $127.2 million, or $1.68 per share, in 2024. The improvement was driven by lower research and development expenses following the discontinuation of earlier clinical programs. The company ended 2025 with $106.4 million in cash, cash equivalents, restricted cash and marketable securities, which it expects will fund operations into the second quarter of 2027. Management noted that the strengthened balance sheet supports the transition of two key programs into human studies this year.
Prelude's lead program, PRT12396 is a mutant-selective JAK2V617F inhibitor designed to target the primary driver mutation in myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). The candidate received FDA clearance of its IND application in the first quarter of 2026, and the company expects to initiate a Phase 1 trial in high-risk PV and intermediate-to-high-risk MF patients by the second quarter of 2026.
Prelude believes its allosteric, mutation-selective approach may reduce mutant allele burden and potentially slow or reverse disease progression.
The company is also advancing PRT13722, a highly selective oral KAT6A degrader being developed for ER-positive breast cancer and other malignancies. IND-enabling studies are underway, and Prelude plans to file the IND in mid-2026, with a Phase 1 study expected to begin in the second half of 2026.
KAT6A is an emerging oncology target, and Prelude's degraders are designed to offer improved efficacy and tolerability compared with non-selective KAT6A/B inhibitors.
Beyond its two lead programs, Prelude continues to expand its work in targeted protein degradation through its degrader antibody conjugate (DAC) platform. The company has developed proprietary SMARCA2/4 and CDK9 degrader payloads optimized for next-generation DACs and recently expanded its collaboration with AbCellera to allow broader use of these payloads across additional antibody targets. These payloads are also available for licensing to other partners.
Prelude is additionally advancing an early discovery program targeting mutated calreticulin (mCALR), a neoantigen present in a subset of MF and ET patients. The company is exploring mCALR-directed DACs using its proprietary degrader payloads, with preclinical data presented at major hematology conferences in 2025.
Looking ahead, Prelude expects 2026 to be a pivotal year with PRT12396 and PRT13722 entering clinical development and multiple data catalysts anticipated in 2027.
PRLD has traded between $0.61 and $4.22 over the past year. The stock closed Tuesday's trading session at $3.60, up 16.50%.
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