[First of two parts]

With $43 million in Series A financing and a brain trust full of big names, Editas Medicine launched late in 2013, intent on reshaping drug development by pursuing therapies that apply gene editing. It was truly a CRISPR all-star ensemble: Feng Zhang, PhD, and George Church, PhD, co-founded the company along with J. Keith Joung, MD, PhD, David R. Liu, PhD, and Jennifer Doudna, PhD.

Less than a year later, Doudna resigned after clashing in court with Zhang in the bitter legal battle over who invented CRISPR-Cas9 gene editing technology—in which Zhang and the Broad recently withstood a second challenge to their CRISPR-Cas9 patents in the United States. Also in 2014, Editas appointed CEO Katrine Bosley, the second of five executives who will have served as chief executive as of June 1. That’s when Gilmore O’Neill, MB, MMSc, takes office after spending the past four years or so at Sarepta Therapeutics.

At Editas, O’Neill faces several challenges—although he prefers to call them opportunities. The first is shepherding the company’s lead candidate—EDIT-101 for Leber congenital amaurosis-10 (LCA10)—through the rest of its clinical trials towards regulatory approval. Earlier this month, Editas said it achieved the world’s first dosing of a pediatric patient with an in vivo CRISPR gene editing treatment by administering EDIT-101 in the Phase I/II BRILLIANCE trial (NCT03872479). Last November, Editas announced positive initial clinical data for EDIT-101 showing it to be safe, and to have generated “signals” of efficacy in two of three patients in the study’s adult mid-dose cohort. Those preliminary data were not as warmly received by analysts as the initial clinical data published in the New England Journal by fellow CRISPR biotechs, CRISPR Therapeutics and Intellia Therapeutics.

Editas’ second challenge is expanding its pipeline by successfully developing other gene editing therapies. Later this year, Editas expects to report initial findings for its ex vivo CRISPR-Cas12a gene editing cell therapy—EDIT-301 in sickle cell disease—and dose the first patient in a study of EDIT-301 for transfusion-dependent beta thalassemia. Editas is also developing novel engineered induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells—what the company calls iNKs—for the treatment of cancer, based on the company’s AsCas12a gene editing tech, and has reported positive in vitro and in vivo preclinical data.

Editas is among several companies striving to stand out in gene editing therapies. Most notably, Vertex Pharmaceuticals and CRISPR Therapeutics plan regulatory submissions later this year for their CTX001™, being developed for sickle cell disease and beta thalassemia through a multi-billion-dollar partnership with Vertex committing $900 million upfront. Vertex is also pursuing an up-to-$695 million collaboration with Mammoth Biosciences to develop in vivo gene-editing therapies for two undisclosed genetic diseases, while CRISPR Therapeutics and ViaCyte have dosed the first patient in a Phase I trial (NCT05210530) of their gene edited cell therapy VCTX210 for type 1 diabetes.

Kevin Bitterman, PhD, was Editas’ founding CEO when the company was launched; he was then with Polaris Partners, an initial investor, and now with Atlas Venture. Bitterman was followed in 2014 by Bosley, who took the company public two years later before resigning unexpectedly in 2019. She was succeeded by Cynthia Collins. Jim Mullen, the veteran Biogen CEO, stepped into Editas’ CEO role in 2021.

In an exclusive interview with GEN Edge, Gilmore and Mullen discussed Editas’ strengths in technology and R&D, as well as its challenges in developing its pipeline and business opportunities. (This interview has been lightly edited for length and clarity; Part II will appear separately).

GEN Edge: Gilmore, what are your thoughts on the challenge of your new role at Editas, and how have you been gearing up for it?

Gilmore O’Neill, MB, MMSc, who will become President and CEO of Editas Medicine effective June 1

Gilmore O’Neill: I’m incredibly excited, incredibly happy about joining Editas at this moment in its evolution and growth. Over the last few months, I spent a lot of time looking at many opportunities, exciting new technologies, etc. But Editas just leapt off the page at me for a couple of reasons: This speaks to the challenge and the opportunity.

The opportunity I saw was this platform or technology with unlimited potential, and also a core differentiated expertise in nuclease evolution and enhancements in guide RNA and chemistry and design. And frankly, the experience it is developing on various delivery technologies for bringing the mechanism to the many targets that would be necessary to go after in different cells and tissues to treat what are, or have been until the evolution of this technology, previously untreatable diseases.

I was talking about the unlimited opportunity. In many ways, that’s one of the key challenges, to ensure that an organization like Editas is able to focus, while exploiting that full opportunity. What I’ll see, on June 1, when I will hit the ground running as CEO, is really to continue on the foundational strategy that has been built by Editas, particularly focusing on R&D execution, and more specifically on driving programs into and through the clinic.

In addition, I’m going to be focusing on business development partnerships, capital raising, and obviously working with the company and the excellent leadership team to evolve and tweak the strategy as we look out beyond the immediate needs to the intermediate and long term to fully exploit this technology.

My preparation right now is, now that the announcement is out, being able to talk and engage with people throughout the company, and learn more about Editas and the technology. Those conversations have been really interesting.

GEN Edge: What have you learned so far from those conversations?

O’Neill: What I learned, or more importantly I’ve confirmed, is that the quality of the science and the scientists of this organization is very, very strong. I knew that from my initial due diligence but being able to engage and talk with these people has been incredibly exciting.

In addition to their differentiated technical expertise, this is a creative team that is very passionate about turning this science and evolving it into therapeutics that are really going to help people with previously untreatable diseases.

GEN Edge: Is this akin to a listening tour for you?

O’Neill: It’s not akin to a listening tour, because I would think a listening tour would be something from outside. This is where I am able to engage with people—yes, you’re right, listen—but ask probing questions, and not just look at the technology answers but look at the people as well. I’m more excited than I was last week because of the quality of the people that I’m talking to.

GEN Edge: You spoke earlier about the need for focus. As the company executes programs going forward, does that focus include a narrowing down of the technologies it will pursue? Or will Editas continue to pursue a broad menu of different modalities?

O’Neill: I think focus is not necessarily about narrowing like that. It’s really about making sure that one balances one’s capabilities of bandwidth with what you’re doing. One of the things that Jim and I have discussed, even leading up to my joining the organization, is how you can continuously do that with decision making, business development, but obviously maximizing the way in which you most effectively and efficiently drive your pipeline forward.

GEN Edge: You mentioned the technology and pipeline being big draws for you, but how much is it working with Jim Mullen again, as you did years ago at Biogen?

O’Neill: I’ve had huge respect for Jim, and it would actually be wonderful to have the opportunity to work going forward with him. But obviously I’ve had the opportunity to meet the Editas leadership team and others in the company and they are also a huge draw! I’m really excited to be working with them all.

GEN Edge: Jim, what attracted you to working with Gilmore again at Editas?

James C. (Jim) Mullen, Editas’ Chairman, President and CEO, who will become Executive Chairman on June 1

Jim Mullen: I was chairman of the board for three years and then appointed CEO early last year, and I’ve spent quite a bit of time building the team and trying to really evaluate: Where is all this technology going? What are the skills we need in leadership going forward as well? I had pretty much focused after conversations of course with my board colleagues about the leaders we need here, because the speed of the foundational science is moving quite rapidly. And then, we have a couple of products in the clinic we’re advancing more.

But moving these kinds of novel products with this kind of underlying technology through the clinic requires a deep understanding of the science and the clinical medicine. We needed somebody as a complement to the skills we had that really has this deep medical and scientific bent, but also the broad view to sit in the CEOs chair. That was a profile I was looking for.

Along the way, I probably looked at 100 or more CVs, and interviewed a number of people. Quite a few people on that list were people I knew, either worked with or known as people that worked in other companies. It’s a small industry.

Gilmore happened to be one of those. We overlapped when I was CEO of Biogen. We initiated the conversation late last year, and it’s moved forward from there, culminating in the announcement. I couldn’t be more excited because it fits exactly the profile we were looking for. We’ve got a person that’s done very complex drug development successfully in a couple of companies over a number of modalities, so that’s perfect for what we need.

GEN Edge: Gilmore will be Editas’ fourth CEO in less than four years. How will the two of you go about providing the stability that Editas needs in the corner office?

Mullen: The first thing is I’m not going anywhere! So there’s not one person out the door and the next person in. In fact, just looking at this transition, this gives Gilmore a number of weeks, both to wrap up some other obligations [at Sarepta], but also learn the organization, learn the programs, without having to worry about the day-to-day operational pieces.

Once he takes over, I’ll be freed up to focus on more external things, raising capital and business development, using my network of 40 years in this business. The stability also comes from making sure we’ve got somebody as CEO that’s the right profile and has the right runway in front of them. I expect Gilmore to be here for 5–10 years. That’s not a time frame that you can associate with me, because I’m just that much older!

GEN Edge: You mentioned one of the priorities is investor outreach and development. How challenging will that be given the current market climate for biotech?

Mullen: I’ve been through these markets a number of times, so that’s probably an advantage to being one of the old guys in the business now. I know this too shall pass. What’s different in this environment is that there is money out there. You may not like the valuations, but there’s money available that will go to good companies, good technology.

To a certain extent, this is not a bad time to be out there and trying to spend what I’d call non-deal, roadshow time with investors, educating them on the business and the products we have under development, the portfolio and the science. At some point in the next 6-12 months, every emerging biotech will be out looking for money. This is a good time to spend building relationships, educating the analysts and the portfolio managers about what we have, and getting ourselves positioned to be one of those companies to which they allocate capital.

GEN Edge: Given the company’s focus on genome editing technologies, how much have analysts and investors had to be educated on what Editas is up to?

Mullen: We were pretty quiet for a couple of years with investors on both the products we were working on, and the advantages of our own underlying technology. I think there’s a reasonable amount of education [needed].

I just got out of a meeting with Mark Shearman, PhD, our CSO [executive vice president and chief scientific officer]. We were talking about a lot of chatter about off-target effects of gene editing, greatly exaggerated beyond what we actually see in our own hands, because we’ve spent seven years optimizing the technology to increase the efficiency and decrease any of the potential off-target effects. So it’s true, if you give it to some high-school students, you’ll get a bunch of off-targets effects with Cas9 and Cas12. That’s not what we’re doing.

That’s just an example of where we need to bring education with data, like in our programs and our data, our bioinformatics and sophisticated analytics, we don’t see all these off-target effects that people talk about. I’m not trying to say nothing exists there, but that’s an example of some of the education that’s required.

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