Prime Medicine Announces The New England Journal of Medicine Publication of PM359 Clinical Data for the Treatment of Chronic Granulomatous Disease

Rhea-AI Summary

Prime Medicine (Nasdaq: PRME) announced publication in the New England Journal of Medicine of Phase 1/2 data for PM359, its investigational autologous HSC product for p47phox chronic granulomatous disease (CGD), with results also presented at the 67th ASH Annual Meeting (Dec 6-9, 2025).

Two patients showed rapid neutrophil and platelet engraftment, achieving 69% and 83% DHR+ neutrophils by Day 30 (above a 20% clinical threshold), durable NADPH oxidase activity, early clinical benefit (cessation of mesalamine in Patient 1; marked fecal calprotectin reduction and symptom improvement in Patient 2), and no clinically significant adverse events attributed to PM359; observed toxicities were consistent with busulfan-based conditioning.

Positive

• Day 30 DHR+ neutrophils at 69%
• Day 30 DHR+ neutrophils at 83%
• Durable restoration of NADPH oxidase activity
• No clinically significant AEs attributed to PM359
• Patient 1 stopped mesalamine without CAC flare
• Patient 2 showed large fecal calprotectin reduction

Negative

• Clinical data limited to two patients
• Observed toxicities consistent with busulfan conditioning

Key Figures

Patients treated 2 patients Phase 1/2 PM359 trial initial NEJM report

DHR+ neutrophils Patient 1 69% Day 30 dihydrorhodamine-positive neutrophils vs 20% benefit threshold

DHR+ neutrophils Patient 2 83% Day 30 dihydrorhodamine-positive neutrophils vs 20% benefit threshold

Clinical benefit threshold 20% Projected minimum DHR+ neutrophil level for clinical benefit

ASH Annual Meeting December 6-9, 2025 Poster presentation of PM359 Phase 1/2 data

Market Reality Check

$3.75 Last Close

Volume Volume 2,660,854 is below the 20-day average of 4,074,571 (relative volume 0.65x). low

Technical Shares at $3.749, trading above the 200-day MA of $3.17 after a -2.86% pre-news session.

Peers on Argus 1 Up

Select biotech peers showed mixed moves, with VIR -4.34% and IMTX -7.12% while PRAX +2.90% and AVBP +0.86%, suggesting stock-specific rather than broad sector drivers for PRME.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 25	Conference appearance	Neutral	-1.9%	Announcement of participation in Evercore healthcare conference webcast.
Nov 11	Conference appearance	Neutral	+11.2%	Jefferies healthcare conference fireside chat announcement and webcast details.
Nov 07	Earnings and updates	Neutral	-8.8%	Q3 2025 financials plus pipeline timing updates and CBO appointment.
Nov 07	Earnings and updates	Neutral	-8.8%	Q3 report with cash runway into 2027 and IND/CTA timelines.
Nov 03	Executive appointment	Positive	-7.7%	New Chief Business Officer to lead corporate and BD strategy.

Pattern Detected

Recent news flow often coincided with negative price reactions, even around operational updates and leadership changes.

Recent Company History

Over the last few months, Prime Medicine has focused on investor outreach, quarterly updates, and leadership strengthening. Events included conference appearances on Nov 11 and Nov 25, 2025, Q3 earnings and business updates on Nov 7, 2025, and appointment of a new Chief Business Officer on Nov 3, 2025. Despite these developments, share reactions skewed negative after most items. Today’s NEJM PM359 data extend earlier clinical communications and further establish the company’s Prime Editing platform story.

Market Pulse Summary

This announcement highlights first-in-human Phase 1/2 PM359 data in CGD, with two patients showing rapid engraftment and DHR+ neutrophil levels of 69% and 83%, far above the 20% benefit threshold, and no PM359-attributed safety events. It builds on a prior 2025-05-19 clinical update and supports Prime Editing as a potential therapeutic platform. Investors may track further patient enrollment, durability of NADPH oxidase restoration, regulatory milestones, and how management balances PM359 with its broader in vivo liver pipeline.

Key Terms

autologous hematopoietic stem cell medical

"investigational autologous hematopoietic stem cell product for p47phox"

Autologous hematopoietic stem cells are a patient’s own blood-forming stem cells collected and later returned to the same person to restore their immune and blood systems, like replanting seeds taken from a garden back into that same plot. Investors care because using a patient’s own cells reduces rejection risk and regulatory hurdles but raises costs and logistical complexity tied to personalized manufacturing, affecting therapy pricing and commercialization potential.

AI-generated analysis. Not financial advice.

CAMBRIDGE, Mass., Dec. 07, 2025 (GLOBE NEWSWIRE) -- Prime Medicine, Inc. (Nasdaq: PRME), a biotechnology company committed to delivering a new class of differentiated one-time curative genetic therapies, today announced the publication of Phase 1/2 clinical data with PM359, the Company’s investigational autologous hematopoietic stem cell product for p47^phox chronic granulomatous disease (CGD) in the New England Journal of Medicine (NEJM). The data will also be presented in a poster session at the 67^th American Society of Hematology (ASH) Annual Meeting, December 6-9, 2025 in Orlando, Florida.

The publication, titled “Prime Editing for p47-phox Chronic Granulomatous Disease,” reports initial data for two patients treated in the Phase 1/2 trial of PM359, which was designed to assess safety, biological activity and preliminary efficacy in adult and pediatric study participants. Both patients experienced rapid neutrophil and platelet engraftment, as well as durable restoration of NADPH oxidase activity and early clinical benefit, without any safety concerns. Together, these results provide the first-in-human demonstration of the safety and efficacy of Prime Editing, and support the potential for PM359 as a precise therapeutic strategy for CGD:

• Both patients enrolled in the study had a history of prior CGD-defining complications, including CGD-associated colitis (CAC), and skin and soft tissue infections, and both were maintained on long-term prophylactic therapy.
• Both patients experienced rapid neutrophil engraftment, achieving 69% and 83% dihydrorhodamine-positive (DHR+) neutrophils by Day 30, respectively, far in excess of the 20% projected minimum threshold for clinical benefit. DHR activity remained stable over time in both patients, suggesting that gene correction occurred in the long-term repopulating hematopoietic stem cells (HSCs) of the bone marrow.
• Both patients remain free of new CGD-related complications or significant intercurrent illnesses post-infusion; additionally, Patient 1 stopped his mesalamine treatment and has not experienced a flare of CAC, and Patient 2’s levels of fecal calprotectin have decreased substantially, and his chronic CAC symptoms have abated.
• No clinically significant adverse events attributable to PM359 occurred in either patient, and all observed toxicities were consistent with busulfan-based conditioning.

“Publication of these first-in-human data highlights Prime Editing’s promise as a next-generation therapeutic platform, which is capable of delivering meaningful benefits to patients and which can be manufactured and delivered at clinical scale,” said Mohammed Asmal, M.D., Ph.D., Chief Medical Officer of Prime Medicine. “Beyond demonstrating early clinical efficacy, these results offer important insights into Prime Editing’s safety profile and potential advantages over other gene editing technologies. As described in the NEJM publication, we observed high recovery rates of viable corrected cells after a single mobilization cycle, as well as the rapid reconstitution of the hematopoietic system after infusion. Both support our belief that the mechanism of Prime Editing, which does not induce double-strand breaks, may be better tolerated by HSCs and other cell types – and therefore safer for patients – than other approaches.”

About Prime Medicine
Prime Medicine is a leading biotechnology company dedicated to creating and delivering the next generation of gene editing therapies to patients. The Company is deploying its proprietary Prime Editing platform, a versatile, precise and efficient gene editing technology, to develop a new class of differentiated one-time curative genetic therapies. Designed to make only the right edit at the right position within a gene while minimizing unwanted DNA modifications, Prime Editors have the potential to repair almost all types of genetic mutations and work in many different tissues, organs and cell types. Taken together, Prime Editing’s versatile gene editing capabilities could unlock opportunities across thousands of potential indications.

Prime Medicine is currently progressing a diversified portfolio of investigational therapeutic programs organized around our core areas of focus: liver, lung, and immunology and oncology. Across each core area, Prime Medicine is focused initially on a set of high value programs, each targeting a disease with well-understood biology and a clearly defined clinical development and regulatory path, and each expected to provide the foundation for expansion into additional opportunities. Over time, the Company intends to maximize Prime Editing’s broad and versatile therapeutic potential, as well as the modularity of the Prime Editing platform, to rapidly and efficiently expand beyond the diseases in its current pipeline, potentially including additional genetic diseases, immunological diseases, cancers, infectious diseases, and targeting genetic risk factors in common diseases, which collectively impact millions of people. For more information, please visit www.primemedicine.com.

© 2025 Prime Medicine, Inc. All rights reserved. PRIME MEDICINE, the Prime Medicine logos, and PASSIGE are trademarks of Prime Medicine, Inc. All other trademarks referred to herein are the property of their respective owners.

Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Prime Medicine’s beliefs and expectations regarding: the significance of data from its Phase 1/2 trial of PM359; the potential for PM359 to be a precise and safe therapeutic strategy for CGD;; the safety and efficacy of Prime Editing, including in comparison to other approaches; the potential of Prime Editing to correct the causative mutations of, and to cure, diseases; its strategic plans for its business, programs, and technology; and the potential of Prime Editing to unlock opportunities across thousands of potential indications.

Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: uncertainties related to Prime Medicine’s product candidates entering clinical trials; the authorization, initiation, and conduct of preclinical and IND-enabling studies and other development requirements for potential product candidates, including uncertainties related to opening INDs and obtaining regulatory approvals; risks related to the development and optimization of new technologies, the results of preclinical studies, or clinical studies not being predictive of future results in connection with future studies; the scope of protection Prime Medicine is able to establish and maintain for intellectual property rights covering its Prime Editing technology; Prime Medicine’s ability to identify and enter into future license agreements and collaborations; Prime Medicine’s expectations regarding the anticipated timeline of its cash runway and future financial performance; and general economic, industry and market conditions. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Prime Medicine’s most recent Annual Report on Form 10-K, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Prime Medicine’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Prime Medicine explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.

Investor and Media Contacts
Gregory Dearborn
Prime Medicine
857-209-0696
gdearborn@primemedicine.com 

Hannah Deresiewicz
Precision AQ
212-362-1200
hannah.deresiewicz@precisionaq.com

FAQ

What did Prime Medicine announce about PM359 in the NEJM on December 7, 2025?

Publication of Phase 1/2 data showing rapid engraftment and 69% and 83% DHR+ neutrophils by Day 30 in two patients treated with PM359.

How did PM359 perform on safety in the NEJM report for PRME?

No clinically significant adverse events were attributed to PM359; observed toxicities were reported as consistent with busulfan-based conditioning.

What clinical benefits were reported for PM359-treated patients in the PRME study?

Both patients had durable NADPH oxidase activity, no new CGD complications; Patient 1 stopped mesalamine and Patient 2 had reduced fecal calprotectin and symptom improvement.

What does the reported 69% and 83% DHR+ by Day 30 mean for PM359’s efficacy in PRME’s NEJM paper?

Those DHR+ levels exceed the 20% projected minimum threshold for clinical benefit, indicating early biological activity consistent with gene correction.

When and where were the PM359 results presented besides the NEJM publication?

Results were presented in a poster session at the 67th ASH Annual Meeting, held December 6-9, 2025 in Orlando, Florida.