PM647 by Prime Medicine: status and timeline

PM647

Prime editing therapy targets the E342K (Pi*Z) mutation in SERPINA1 to restore alpha-1 antitrypsin production in liver cells. Delivered via liver-targeted lipid nanoparticle.

PilotStage 3 of 5

Development candidate for AATD; IND/CTA filing Q3 2026, first data 2027.

Updated 6 Jul 2026Checked 10 Oct0 updates this week

Milestones

Next · IND/CTA application filing

PM647 selected as development candidateAug 2025Complete.
IND/CTA application filingTarget Q3 2026Current milestone.
Initial clinical data from first-in-human trialTarget 2027Not yet reached.

Most important updates

Upcoming

Q3 2026IND/CTA application filing (next)
2027Initial clinical data from first-in-human trial

Current obstacles

In vivo editing efficiencyAchieving high gene-correction rates in living liver tissue is harder than in cell culture; insufficient efficiency means persistent disease.
Immune activation from lipid nanoparticlesRepeated or high doses of LNP can trigger innate immune responses; balancing therapeutic efficacy with safety margins remains challenging.
Patient population stratificationAlpha-1 deficiency has multiple variants; PM647 targets Pi*Z. Combination approaches for other variants are needed.

Physics limits

Hepatocyte turnoverLiver cells turn over slowly (life span of years to decades); correcting only a fraction of them may require repeated dosing or combination therapy to maintain normal alpha-1 levels.
Off-target prime editingPrime editors can occasionally write at unintended genomic sites; the frequency and clinical consequences are still being characterized in long-term safety studies.

How it works

3 parts

Prime editing

Single-letter DNA correction

Prime editor nicks one strand and rewrites DNA without cutting both, reducing off-target changes.

Liver targeting

Hepatocyte-specific delivery

Lipid nanoparticles with GalNAc ligand deliver the editor directly to hepatocytes.

One-time treatment

Durable correction

Correcting the mutation in liver cells gives a permanent source of healthy alpha-1 antitrypsin; a single infusion may be sufficient for lasting benefit.

Spec sheet

Spec	PM647
Target gene	SERPINA1 (encodes alpha-1 antitrypsin)^R (reported)
Target mutation	E342K (Pi*Z variant)^R (reported)
Indication	Alpha-1 Antitrypsin Deficiency (AATD)^R (reported)
Delivery vehicle	Liver-targeted lipid nanoparticle with GalNAc ligand^R (reported)
Preclinical result	72% gene correction in mouse hepatocytes^R (reported)

^R reported by the company

Update log

2 updates

Mon 6 Jul

Major: Prime Medicine wins arbitration with Beam Therapeutics over PM647 development rightsPressOther

Aug 2025

Major: Prime Medicine selects PM647 as development candidate for Alpha-1 Antitrypsin DeficiencyPressResearch

About Prime Medicine

The team behind PM647

Prime Medicine

Prime editing, Wilson disease

Company built on prime editing, invented in David Liu's lab. A prime editor nicks one DNA strand and writes in a new sequence, like find-and-replace, without fully cutting DNA. After first patient data in 2025 it refocused on liver diseases.

May 2025: first-ever prime-editing patient data (PM359) restored immune-cell function; the drug was then shelved for business reasons.
FDA cleared a trial of PM577a for Wilson disease in Jul 2026; dosing expected in H2 2026.

primemedicine.com (opens primemedicine.com)Company profile →

Founded: 20197 yrs
Headquarters: United States
Status: Public
Listed: PRME (opens google.com)NASDAQ
Valuation: public
Works in: BiotechGene editing & therapy
Coverage: 3 programs · 8 updateslatest 23 Jul 2026checked 25 Sep
People: Allan Reine (opens primemedicine.com)CEOAndrew Anzalone (opens primemedicine.com)Co-founderDavid Liu (opens en.wikipedia.org)Co-founder

Spec

PM647

Target gene

SERPINA1 (encodes alpha-1 antitrypsin)^R (reported)

Target mutation

E342K (Pi*Z variant)^R (reported)

Indication

Alpha-1 Antitrypsin Deficiency (AATD)^R (reported)

Delivery vehicle

Liver-targeted lipid nanoparticle with GalNAc ligand^R (reported)

Preclinical result

72% gene correction in mouse hepatocytes^R (reported)