Asked and Answered: Prime Medicine CEO on First Prime Editing Patient Data

Earlier this month, Prime Medicine researchers hit a precision gene editing milestone when they published a peer-reviewed article reporting the first demonstration of prime editing to treat human patients. In this study, two patients with chronic granulomatous disease (CGD) were treated with PM359, an autologous hematopoietic stem-cell (HSC) therapy that aims to correct a disease-causing mutation with prime editing to restore immune function without double-strand DNA breaks or donor transplantation. The results have been promising, as both patients remained free of new CGD-related complications during the first few months of follow-up.

However, questions remain as to the future of this program. In his first year as Prime Medicine CEO, Allan Reine, MD, guided the company to pause active recruitment of the PM359 trial due to the CGD market is too small to sustain the company and has prioritized the advancement of programs targeting liver and lung diseases and immune-system cancers, with its Wilson’s disease program leading the pipeline. The company aims to leverage the modularity of prime editing to expand into a broad range of genetic, immunologic, infectious, and common diseases affecting millions.

In this interview, Reine dives into this monumental prime editing report, explaining how the clinical results affect the company’s position on its drug development pipeline, including the CGD program. The Prime Medicine CEO also shares the near-term goals that he has set the company’s sights on and how the company continues to innovate in close collaboration with David Liu, PhD, scientific co-founder of Prime Medicine and the precision gene editing pioneer behind prime editing.

IPM: Does the recent NEJM article reporting the first-ever clinical results for prime editing have an impact on Prime Medicine’s CGD program?

Reine: What we’ve said publicly is that we plan to engage with regulatory authorities, and what we’ve updated that to say is that we are continuing to engage with regulatory authorities. We’d really like to figure out a path forward.  

I do think all CGD patients can really benefit from this treatment. Using this approach in younger CGD patients over allotransplant is a huge win. But if you just think about the patients that we treated in our trial, those are patients that likely aren’t eligible to get an allogeneic transplant—they have no alternative therapy. This is life-changing for them in many ways, both from morbidity and mortality, through curing their disease. So, we’re going to continue to engage and hopefully we get to a point where we think there is a way that makes sense for us to get this to those patients in need. 

IPM: Is the CGD program compatible with gene editing “umbrella” clinical trial designs, whereby all components (with the possible exception of the guide RNA) are kept constant and tested in different environments?

Reine: What Kiran Musunuru at CHOP did was an in vivo therapy, so it’s a little bit different. If you think about what he’s thinking about doing in terms of treating multiple urea cycle disorders (UCDs) under one umbrella study, I think that could be relevant to us when it comes to in vivo.

There are areas where that may be relevant ex vivo. We are evaluating whether there are platform opportunities for ex vivo therapy. Can we cobble together a number of programs that could all fit under one umbrella? We’re doing some of that analysis because it can be really cost-effective to do this and patients can benefit and there’s a low-resource way to get there. We need to answer the question if this is an attractive opportunity to allocate our resources towards. 

When it comes to in vivo, we believe there is significant leverage going from liver program to liver program. Not only is there an opportunity going from mutation to mutation in Wilson disease, but also leveraging manufacturing, toxicology studies, and clinical data when we go from disease to disease in the liver. Each subsequent program should be cheaper and move a lot faster. 

IPM: You took the helm of Prime Medicine in May 2025. As you approach your one-year anniversary with the company, what do you see as the most significant milestones?

Reine: When it comes to CGD, I hope we can solidify a path forward there. I really do. That would be a fantastic place to be for those patients in need. In addition, to have two in vivo programs, either enrolling or soon-to-be-enrolling patients, to me, that’s the real game-changer. To see what we can do for these patients that have Wilson disease, I’ve talked to these patients directly. I know how big of a difference a therapy like this can make in, frankly, thousands of patients’ lives if we’re successful. So just being able to show that you can safely and effectively treat Wilson Disease and Alpha-1 antitrypsin deficiency would be an amazing accomplishment for Prime.

What we’ve done in CGD is truly life-changing for the two patients that were treated in the clinical study. Again, we hope we find a path to treat the other CGD patients in need. Looking past a year, it’s exploring opportunities beyond CGD and in Wilson and Alpha-1 Anti-trypsin Deficiency (AATD) and cystic fibrosis. What excites me about Prime Medicine, what gets me up excited everyday, is there are endless opportunities for this technology.

We obviously have finite resources to do that with. So, how do we use those finite resources to get as much reach as we can with this technology? To develop Prime Editing for more diseases that could ultimately reach more patients. Part of our strategy is to do more collaborations to go after more disease areas, and how we plan to build the company once we’re successful in Wilson disease and AATD, what are the additional opportunities?

As I get to a year in this position, the vision as to how we do that will not be completely constructed, but it will be laid out in a way that we can execute and continue to refine our strategy, and we’ll be a very different company a year from then, once we demonstrate proof-of-concept data for our first two liver-directed programs. 

IPM: What are Prime Medicine’s plans for future clinical programs? Is Prime Medicine moving in step with David Liu’s lab, such as the work on prime editing-mediated readthrough of premature termination codons?

Reine: Prime editing-mediated readthrough of premature termination codons (PERT) is an incredible opportunity to go after a lot of different diseases with one or a few prime editors. This is a recent example of a Prime Editing advancement out of David Liu’s lab. The science continues to progress. David Liu is not one to stand still. We’re not standing still either. We continue to make advancements across the platform. It comes back to my strong belief: this is the best genetic technology that exists. It’s why others are copycatting us and trying to do it, even though we have a broad intellectual property estate. 

There are so many places we can take this technology.  We get together as a team and when we do big blue-sky thinking, there’s almost no limitation because of what the technology can do, so we focus our energy on the best way to allocate our capital and resources to maximize the potential for patients.