Editas Medicine, Inc. (EDIT) Bank of America Global Healthcare Conference Call Transcript
Editas Medicine, Inc. (NASDAQ:EDIT) Bank of America Global Healthcare Conference Call May 9, 2023 8:00 PM ET
Gilmore O’Neill – President, CEO & Director
Conference Call Participants
Gregory Harrison – Bank of America Merrill Lynch
Final session of the first day of the Bank of America Healthcare Conference. I’m Greg Harrison, one of the biotech analysts here at BofA. And this afternoon, we have Editas Medicine with us represented by Gilmore O’Neill, Chief Executive Officer. Thanks for joining us.
Thanks very much, Greg.
Maybe we could start off with some opening remarks and then jump into the Q&A.
Sure. Thanks very much for the opportunity, Greg, and thanks to BofA for hosting a wonderful meeting. We’ve had some really great interactions today. Editas is a very exciting place at this moment. I joined just 10 months ago. And in that time, I hired a new CMO, focusing on driving execution. We read out clinical data, made some critical decisions and then, very importantly, redid our strategy based on 3 pillars where, based on our clinical readouts, we doubled down and reassigned capital to accelerating our 301 program for the treatment of sickle cell disease and thalassemia with an investment in both clinical execution as well as on CMC capacity.
In addition, we refined our portfolio to sharpen the focus on in vivo editing going forward and essentially stopped any new cell-based or stand-alone cell-based therapy discovery. The second pillar was to strengthen research by dividing it into a technology group and a therapeutics discovery group. And the key focuses of the technology group were on growing our editing toolbox to span — or broaden the span of therapeutic indications that we can address as well as to look at targeted delivery in support of our new found focus on in vivo editing, which ultimately is the way to truly unlock the true power of CRISPR in a way that would truly transform and, frankly, disrupt health care.
And then on the therapeutics discovery side, really set up a new set of target selection criteria where the convergence of a deep understanding of biology with the technology would maximize the probability of technical success and then ultimately drive probability at a high level for translational and clinical success, regulatory and commercial success, with sort of the overweening or guiding principle being that we would only invest in targets where we could, with our technology truly differentiate from the standard of care.
And then the third pillar has been a focus on business development, not just licensing out our deep IP portfolio but actually also being much more aggressive and open to the idea of bringing in new technologies or capabilities that would complement our own in delivering on that in vivo strategy. And so we actually rolled that out just 3 months ago. And since that time, I’m happy to report that the company has actually really embraced that, has embraced those changes and, very importantly, we can see concrete delivery on that strategy with an execution in our 301 with a substantial uptake in enrollment, editing. And we’re looking forward to sharing data middle of this year — actually, next month.
Q – Gregory Harrison
Great. That’s a great intro. Yes. Let’s jump into 301 discussion. With other cell therapies out there in development for sickle cell, how could EDIT-301 be differentiated? Or how could it stand out from the pack in terms of the underlying technology and that translating into clinical data?
Yes. So that’s a very critical question. Let me just preface by saying that I have a lot of experience in the rare disease space, and indeed a competitive product alone can actually play a role in a rare disease space, and we believe there’s room for more than 1 player in delivering therapies to patients with sickle cell and thalassemia.
Notwithstanding that opening remark, there was a very intentional design mindset brought to the creation of the 301 strategy. This is an ex vivo edited hematopoietic stem cell therapeutic for patients with sickle cell disease and transfusion-dependent thalassemia. The design approach was created or selected to maximize both expression of fetal hemoglobin to replace the abnormal beta-globin that occurs with thalassemia mutations or sickle cell mutations but also to maximize red cell health. And that design essentially looked at editing the gamma-globin promoter rather than a BCL11a suppressor molecule.
In addition, it combines that with our unique and proprietary engineered AsCas12a enzyme, which is a high efficiency, high fidelity CRISPR enzyme. And that design intent really was validated by the nonclinical data which demonstrated, as expected, a superior output of red cells production from the bone marrow, post-transplant and indeed more durable and healthier red cells. And in the data from 301 from our RUBY study of sickle cell patients, the first patient we presented last December indeed was very — should I say, it was gratifying to see that the data from this patient who is actually very consistent with the nonclinical data in that not only did we see robust fetal hemoglobin expression but we actually saw an early and robust correction of their anemia to the point that this patient actually had a normal hemoglobin.
Now how does that translate — sorry, forgive me, Greg, I was on a roll. And I apologize for not getting you a word in, but you’d ask me, how does that translate? What does that mean going forward? Well, we’re looking to see that consistent both confirmation of fetal hemoglobin expression in the additional patients. We’re presenting 4 patients in June at EHA. The abstract is coming out on Thursday, but there will be additional data presented over and above that because the data cut for the abstract, obviously, was a little time ago, the data cut for EHA will be closer to next month.
But what does that mean from a clinical point of view? Where you have normal hemoglobin, it’s important to note that, that has an enormous impact on the complications of both thalassemia and sickle cell disease. Indeed, when I was in medical school, sickle cell disease I was told was called sickle cell anemia because sickle cell disease is characterized not only by sickling but by anemia and by hemolysis. And anemia — or degrees or severity of anemia actually has a direct correlation to the risk of complications, including long-term or irreversible damage to organ systems, the first.
The second thing it does is it has an adverse impact on exercise tolerance. I think any of you who’s been anemic know what that means. Any of you who has never been anemic, if you get off a plane in Colorado, having come from sea level and you start trying to run around or climb a set of stairs, you suddenly feel very different. That’s what anemia feels like. So just correcting sickling without correcting anemia leave some value on the table for the patient.
And I think the third thing is beyond just end organ health and exercise tolerance, it has an impact on the quality of life. And so we actually have in our clinical trials an important focus on collecting patient reported outcomes, in addition to looking at hematologic parameters.
Okay. Great. Yes, where I was going to go is, basically, are these parameters the next step beyond measuring VOCs, right, because that’s going to be essentially 0? And so for you to have a kind of different profile, I think some of these other parameters, organ health, et cetera, could become important.
Yes. So I completely agree, Greg, I think you put it very nicely. We are looking at those parameters. I would be looking at more parameters as we evolve our development plan, obviously, engage with regulators just to help us refine and agree on what that looks like. I think the key thing is we’ll have hematologic parameters. We’ll have VOCs. And then as we look beyond, we want to actually work out the optimal timing and so on. But what I would actually say is we could look at hematologic parameters and VOCs in the near term. And then in the sort of the medium term, we could anticipate that additional clinical parameters that will differentiate or help drive that differentiation.
Got it. And we talked a little bit earlier about enrollment in the RUBY trial. I think you’re going to have 20 patients dosed by year-end is the target. Where does that put you with respect to potentially having a RUBY registrational trial?
Well, if you look actually at the guidance from FDA when it comes to cell and gene therapies, the recommendation and the aspiration is that, even that first patient dosed is actually able to — is generating data for a registration package. In fact, we’re actually in a good position. We’re very happy to be able to say that with our engagement with the agency, FDA, around our INDs, we got agreement around our potency assay matrix, which enables us to use all the data from all the patients in the RUBY study for a registration package. And indeed, while the RUBY study is a Phase I/II, we are actually obviously adjusting it to actually make sure that it can be or can serve as a pivotal registration study. Obviously, what that finally looks like, will depend on agreement and negotiation with the FDA.
I might just say one thing about the 20 patients dosed, we’re very confident that we are on track for that, and that’s actually why we shared that we had dosed — or rather recruited, excuse me, 19 patients, which actually reflects a doubling of recruitment just over the last 3 months. And I think that’s sort of a testament to the importance of our work in refocusing our efforts, narrowing all our efforts and deploying capital to places where we can actually see we can generate real value for patients and obviously for our investors and employees.
Great. Maybe let’s touch on the in vivo approach. Where are you at with these early-stage efforts? And what do you think makes your approach different to some of the other approaches out there?
Yes. So I think where we are is, obviously, it’s early days. We rolled out the strategy just in early January. We are actually making early progress on these. The one thing that we did share rather openly was that we were interested in particularly targeting HSCs, or hematopoietic stem cells, for in vivo editing. Why? Because you have 3 problems to solve for in vivo editing, and we believe we have certainly solved 2, or largely solved to 2. You need an effector molecular enzyme. We have our AsCas12a. By the way, we believe that is a substantially differentiated — or certainly different enzyme, and it’s differentiated because of its fidelity, a substantial reduction in off target. We see that comparison to other CRISPR enzymes or Cas9 enzymes, both in our hands and the hands of others. So that’s one piece. And it’s been validated in humans in our 301 program.
The second piece is your target. We have the guide and we have a robust target in the sequence we’re hitting or editing in the gamma-globin promoter. So that’s been validated in humans. We have our RUBY data.
The third is the targeted delivery. Now that is the area where we’re actually really focusing our efforts. And as I say, with our focus to saying where is the best technology, rather do we have to build it ourselves. That’s something where we actually are very open the idea of combining or selecting other technology capability, combining with our own, to ultimately deliver an optimal in vivo HSC. So I’m actually happy, even though it’s very early on.
With regard to details of disclosure, we would want to really have a very clear path to the clinic to talk about. And when that happens is we believe it will be the appropriate time to talk in more detail about that. And we’re actually also looking beyond HSCs to other tissues as well.
Got it. So was that kind of an intentional strategic decision to pursue in vivo as opposed to gentler conditioning regimen, so you can also leapfrog what some other companies are doing?
I will answer that in the affirmative, with a qualification which is indeed it was a very intentional strategic decision in general for the company. And then with regard to the focus on HSCs, that certainly does have the opportunity to leapfrog milder conditioning. We do have a focus on milder conditioning, but that’s 1 very much where we have sort of looked very hard into the biology, frankly, the kinetics and pharmacology. It’s a challenging space. And one of the things we have to decide is how much effort do you deploy on one versus the other, particularly when in vivo HSC editing could actually not only eliminate the need for severe conditioning or even milder conditioning, but it actually also eliminate the need for pheresis or cell collection and ex vivo editing and all the complications, the burdens and the costs associated with that.
Great. Just a few seconds left, but I wanted to make sure and give you the opportunity to touch on the latest in the IP situation and where you stand there.
Yes. I think one of the things we’ve talked about the IP is really to make sure that people recognized the value. We believe it’s under-recognized, particularly when we look at the valuations given to other gene and cell therapy IP. Notwithstanding that, the market opportunity is large because there are many Cas9 human therapeutics in development. The key point is that we have a large IP portfolio of both IP we’ve developed but also IP we have licensed with the Broad and Harvard.
One of the things that’s caused some confusion is I think everyone has assumed that all that IP is subject to interference. Only some of that IP is subject to interference. Other IP, which is also relevant to Cas9 human therapeutics and to those therapeutics in development, is not subject to an interference. Why does that matter? I think a lot of people have been looking at the IP situation through the lens of, well, it’s a conditional valuation. When does the circuit — or sorry, when does the Court of Appeals of the Federal Circuit make a ruling, which probably is early Q1 of ’24 or maybe Q2. That conditional mindset is probably not accurate because there’s other IP not subject to interference.
And why does that matter? Well, there’s a lot work and development ongoing for Cas9-based human therapeutics, and we are very happy to get those licenses and look forward to have that opportunity, both to help people deliver that technology to patients, but actually also to realize the value that we believe really sits there.
Great. Well, with that, we’re out of time. Thank you, Gil. Appreciate it. I know we’re all looking forward to the EHA abstract coming. And thanks again for joining, and thanks everyone out there for listening.
Thanks very much.