Prime Medicine Announces U.S. FDA Clearance of Investigational New Drug Application for PM647 in Alpha-1 Antitrypsin Deficiency

The study will begin with adults who have lung-only disease before any expansion to a liver-disease cohort.

Rhea-AI Summary

Prime Medicine (PRME) received U.S. FDA clearance for PM647's investigational new drug application on September 24, 2026. The clearance allows clinical study to proceed initially in the United States. PM647 is an investigational in vivo Prime Editor designed to correct the PiZZ genotype in alpha-1 antitrypsin deficiency (AATD). Approximately 100,000 people in the United States carry that genotype.

The planned global Phase 1/2 study is a first-in-human, single-arm, open-label trial assessing safety, tolerability and preliminary clinical efficacy across ascending doses of a one-time intravenous infusion. Enrollment will start with adults who have lung-only AATD. A separate cohort with significant liver disease, with or without lung manifestations, will be added after tolerability is demonstrated in the lung-only group. Prime Medicine expects initial clinical data in 2027.

Positive

• FDA clearance permits PM647 clinical study to proceed initially in the United States.

Negative

• None.

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Details

Market move: PRME +11.08% vs previous close. PM647 IND clearance

$3.00 $3.57 Day Range

$618.55M Market Cap

On Sep 24, the day this news came out, the latest delayed price for PRME is 11.08% above the previous close. Our momentum scanner has recorded 21 alerts for this stock so far that day. The latest delayed price is $3.41.

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Market Context

On Sep 24, the day this news came out, the latest delayed price for the stock is 13.7% above the pre...

Analysis

On Sep 24, the day this news came out, the latest delayed price for the stock is 13.7% above the previous close. On July 8, 2026, an arbitration ruling confirmed PM647 fell within Prime Medicine’s contractual field; the FDA IND clearance advances the same candidate from planned filing to clinical study, linking a prior rights milestone to this development step.

Key Figures

PiZZ genotype population: approximately 100,000 people Trial phase: Phase 1/2 Initial clinical data: 2027 +1 more

PiZZ genotype population

approximately 100,000 people

U.S. population carrying the genotype PM647 is designed to correct

Trial phase

Phase 1/2

PM647 clinical trial

Initial clinical data

2027

Expected timing

Treatment administration

one-time intravenous infusion

PM647 trial treatment

Key Terms

investigational new drug (ind), aatd, in vivo, single-arm, +2 more

6 terms

investigational new drug (ind) regulatory

"Investigational New Drug (IND) application for PM647"

An investigational new drug (IND) is a drug or biologic that is being tested but has not yet been approved for general use; it is the application and formal status that allows a company to begin human clinical trials under regulator oversight. Investors care because an IND marks the transition from lab work to human testing — like getting a permit to run real-world experiments — which creates important milestones, costs, timelines and regulatory risk that drive a development-stage company's value.

aatd medical

"adults with AATD"

Alpha-1 antitrypsin deficiency (AATD) is a inherited condition in which the body makes too little of a protein that protects the lungs and liver, leaving those organs vulnerable to damage over time. For investors, AATD matters because it creates a defined patient group and clear clinical needs—like a broken brake in a car—so diagnostics, replacement therapies, or gene treatments targeting AATD can represent focused markets, regulatory pathways, and long-term revenue potential.

in vivo medical

"an investigational in vivo Prime Editor"

In vivo describes tests or experiments performed inside a living organism, such as an animal or human, to observe how a drug, device or biological process behaves in a real, functioning body. Investors care because in vivo results reveal safety, effectiveness and possible side effects that lab tests cannot, much like road-testing a prototype car in traffic rather than only on a bench — outcomes can strongly influence regulatory approval, clinical success and a company’s valuation.

single-arm medical

"global, single-arm, open-label, first-in-human study"

A single-arm study is a clinical trial that gives all participants the same treatment and does not include a separate comparison group or placebo. Think of it like testing a new recipe by serving it to diners without offering a control dish — you can see how people respond, but you can’t directly compare results to another option. For investors, single-arm trials can speed development and reduce cost but leave more uncertainty about how a treatment stacks up against existing therapies and how regulators will view the evidence.

open-label medical

"global, single-arm, open-label, first-in-human study"

Open-label describes a situation where everyone involved in a study or process knows the full details, such as who is receiving a treatment or intervention. For investors, understanding whether a project or product is open-label helps gauge the level of transparency and potential biases, influencing trust and decision-making. It’s like knowing whether a test or experiment is conducted openly or behind closed doors.

intravenous infusion medical

"a one-time intravenous infusion of PM647"

Intravenous infusion is the delivery of fluids, medications or nutrients directly into a vein over a controlled period using tubing and often a pump—like giving a plant a slow, steady watering instead of one big splash. It matters to investors because many hospital treatments and advanced drugs must be made, tested and billed for this form of use; that affects production complexity, clinical trial design, regulatory approval and potential revenue.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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-- Clearance highlights continued execution, modularity and momentum across Prime Medicine’s liver franchise, building on recent regulatory clearances for PM577a --

-- Initial clinical data expected in 2027 --

CAMBRIDGE, Mass., Sept. 24, 2026 (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 that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for PM647, an investigational in vivo Prime Editor for Alpha-1 Antitrypsin Deficiency (AATD). The clearance enables PM647 to proceed to clinical study initially in the United States, where approximately 100,000 people carry the PiZZ genotype that PM647 is designed to correct.

“FDA clearance of the PM647 IND is an important milestone for Prime Medicine, marking continued momentum across our liver franchise,” said Allan Reine, M.D., Chief Executive Officer of Prime Medicine. “PM647 has the potential to change how AATD is treated, offering a Prime Editing-based approach that moves beyond protein replacement and targets the root cause of disease. By correcting the underlying mutation and restoring production of fully functional AAT, PM647 may simultaneously address both lung and liver manifestations of AATD and provide a differentiated, one-time treatment approach for patients. Beyond its therapeutic potential, PM647 demonstrates the repeatability and productivity of Prime Medicine’s platform. Just months after regulatory clearances for PM577a, the advancement of PM647 into clinical development also reinforces how Prime Medicine's modular platform and universal liver LNP can support the rapid progression of multiple programs.”

Phase 1/2 Clinical Trial

The Phase 1/2 clinical trial will be a global, single-arm, open-label, first-in-human study designed to evaluate the safety, tolerability and preliminary clinical efficacy of ascending doses of a one-time intravenous infusion of PM647 in adults with AATD. The study will initially enroll adult participants with lung-only manifestations of AATD. Upon demonstration of tolerability in lung-only participants, the study will expand to include a separate cohort enrolling adults with significant liver disease, with or without concurrent lung manifestations of AATD.

About PM647

PM647 is an investigational, one-time in vivo Prime Editor designed to correct the E342K (Pi*Z) mutation in the SERPINA1 gene, the most common cause of AATD. By correcting the mutation at its source, PM647 is designed to restore production of functional M-AAT and address both the liver and lung manifestations of the disease. In fully humanized mouse models, PM647 achieved high editing efficiency and restored corrected M-AAT protein into the healthy human range at clinically relevant doses with a single infusion. PM647 uses the same liver-directed lipid nanoparticle (LNP) as PM577a, Prime Medicine's investigational program for Wilson disease.

About Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency is an inherited genetic disorder caused by variants in the SERPINA1 gene. In people with severe disease, insufficient functional alpha-1 antitrypsin can lead to progressive lung damage, while accumulation of mutant protein in the liver can cause progressive liver disease. Patients have no approved curative treatment that addresses the underlying genetic cause of both manifestations of the disease. Approximately 200,000 people are estimated to carry the PiZZ genotype across United States and Europe.

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 its 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.

© 2026 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 potential of PM647 to correct the causative mutations of, and to treat, AATD; the Phase 1/2 clinical trial of PM647, including the trial design, global reach of the trial and the anticipated timing of initial clinical data in 2027; the continued development and advancement of the Company’s AATD and Wilson disease programs; the modularity of the Prime Editing platform and universal liver LNP and the benefits thereof; 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

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What does FDA clearance of Prime Medicine's PM647 application allow?

It allows PM647 to proceed to clinical study initially in the United States. The clearance is for an investigational new drug application, not approval of PM647 as a treatment.

When does Prime Medicine expect initial PM647 clinical data?

Prime Medicine expects initial clinical data in 2027 from the planned Phase 1/2 study.