Editas Medicine, Inc. Q2 FY2023 earnings call

• Leadership Hires: Hired Linda Burkly as Chief Scientific Officer and Erick Lucera as Chief Financial Officer.
• Strategy Pillars: Three pillars - accelerate EDIT-301 clinical development, strengthen discovery organization, expand business development.
• Clinical Progress: On track to dose 20 patients in RUBY trial by year-end, commenced parallel dosing in EDITHAL trial, shared clinical data from RUBY trial at EHA and company webinar.
• IP Position: Strong IP portfolio, confident in IP value, only a small fraction of patents involved in interference proceedings.
• Manufacturing: Increased clean room capacity, moving to new facility to support EDIT-301 program scaling.

No detailed product segment financial performance with revenue contribution percentages provided as the transcript focuses on overall operations and specific programs.

• On track to dose 20 patients in RUBY trial by year-end.
• Provide clinical updates from EDIT-301 trials by end of 2023.
• Extend cash runway into third quarter of 2025 with recent capital raise.

• Interference proceedings in U.S. PTO, but confident in prevailing.
• Uncertainties in FDA interactions and regulatory approvals.
• Dependencies on successful execution of clinical trials and commercialization.

Q: Two for me. I was just wondering if you could provide any update on the time lines for your first in vivo program? And then secondly, on the ASR facility, what's going to be required there from an FDA perspective? And do you have to make any changes or do any bridging work to use product from the two facilities in the expanded trials?

A: Thanks very much, Terence, for your questions. APRA in vivo, as I've said, our focus is on maximizing the property of technical and commercial success with clear positive differentiation against the standard of care. The work is continuing to progress. And I'm particularly delighted to welcome Linda Berkley here whose leadership is really going to double down and really help us drive this forward. And we'll update you on time lines at an appropriate time when Linda has had a chance to really settle in and make our mark. With regard to the Asia facility, we anticipate from a regulatory point of view, obviously, we are engaging -- are planning to engage with the FDA in this half of the year and are on track to have those conversations. And we don't anticipate significant or major work in the transition. It's essentially the processes. We have are largely locked down. And as I say, we were engaging with the agencies just to ensure that we're really aligned on our readiness for commercialization there.

Q: Now that you have Linda on the team, could you discuss some of the challenges of in vivo delivery to hematopoietic stem cells and how you're thinking about mitigating these challenges going forward?

A: Yes. Thanks very much, Samantha, for your question. I've got to say, Linda, has to say, has just joined. So I'm going to talk about how -- she and I and lend, if you want to add anything, please feel free. One of the things that Linda and I are really highly aligned philosophically on our approach to this. We have made -- we actually have some ongoing work and work is progressing on that. The challenges, obviously, are to deliver the executive functional enzyme and guides to the hematopoietic stem cells. The good news is that we feel that we have certainly solved 2 of the 3 challenges. The first being that we have human validation of our Cas12a enzyme thanks to our 301 program. And also, we have validated in man in our clinical trials, the use of our targeting fetal hemoglobin promoter, the specific targeting and delivering of those mechanisms to the hematic stem cell is something that they're working on currently and we'll be happy to update you more on specifics and progress there at an appropriate time.

Q: What feedback have you had from physicians since the recent update at EHA, the 301 program. Regarding a clinically meaningful data set in sickle cell, especially with respect to hemoglobin response? And what are they looking for from the net update?

A: Thanks very much, Greg. I'm going to ask Ben to take that question.

Q: Congrats on the progress. Your cash guidance into the third quarter of '20 is pretty specific. What's baked into that guidance? Specifically, does that include preclinical and IND-enabling studies of in vivo programs and/or BLA and pre-commercial activities for EDIT-301. In fact, is it your intention to commercialize E-301 yourself? Or would you be looking to a partner to help you with the heavy lifting on the commercial offer?

A: So I think, Jim, I'll let Eric start.

Q: Two very quick questions. Regarding the in vivo target, is it fair to say it will be a liver targeted and with particle [ph] delivery? And then regarding the manufacturing, just follow-up. So you do have a so facility. And what is your plan for commercial manufacturing capacity in the future? Will you wholly sit in the U.S. try to do a wholly in-house? Or would you plan to also collaborate with the CDMO regarding the manufacturing commercial supply?

A: Thanks very much, Gina. With regard to the in vivo targets, obviously, we've talked about hematopoietic stem cells of an area of particular interest because of our 301 work and the human validation or ASCs 12a and gamma globin promoter. The liver is definitely on our list of potential tissues at [indiscernible] stem cells. And I think you can reasonably infer with the cessation of our activities of AAV that we're interested in non-AAV technologies and LNPs is certainly an area of interest and one that we have been working on in the past and actually talked about working on over the past year plus. With regard to manufacturing, thanks for asking about that. We actually -- with the announcement of our Azure deal, this is essentially enables us to build towards our commercial capacity and readiness for launch. With regard to the more specific elements of around capacity and our prediction, that's something that we are working through and would talk about in the future.

Q: Two for me as well. One, with regards to Bison, your remark on total hemoglobin as being a differentiation. I guess at what point do you kind of draw the line in the sand and look at that as a differentiator from potential competitors? And then as a follow-up to that, Vertex last night announced that there will be an AdCom for XL. I guess what are you kind of thinking about in terms of point of contention or debate or discussion as we approach that? And how would you see the AsCas-12a targeting HPG promoter as potentially raising another ADCOM when you guys go down that line?

A: Thanks for the question. Regarding the total hemoglobin and related differentiation, we are in the current protocol, we're already actively looking to that. And as I outlined previously, we are looking for 3 category of things. One is come from hematological and other lab values. The other one and the second is the end organ function. The third would be patient report outcome and part life. And maybe a few words on the last two. We -- in the current protocol, we monitor key organ functions such as cardiovascular, hormonary and renal function; we have multiple measures to measure the function. So we believe that the total hemoglobin increase would impact the quality of life and organ health. So that's why we focus on the end organ function. And then regarding reported patient reported outcomes, it could be a very important part of that for differentiation. For example, fatigue is the main -- one of the main complaints by sickle cell patients. And that -- and already data to show that fatigue can really relate to the anemia on that, too. And similarly, for pain, that's also another the complaint that the patients have and we also have a close monitoring of those patient reported outcome. -- main other things we can share more on [ph].

Q: Two for me as well. First, in terms of the year-end update on RUBY and EDITHAL, what is your most recent thinking about the number of patients that will be disclosed for both trials and the follow-up for the patients in the disclosures?

A: Yes. Thanks for the question. Yes, we are on track those total of 20 patients by year-end. We are not disclosing the specific data to be released at the year-end but we are on track to provide a clinical update for 4 studies at the year-end.

Q: Two for me as well. First, in terms of the year-end update on RUBY and EDITHAL, what is your most recent thinking about the number of patients that will be disclosed for both trials and the follow-up for the patients in the disclosures?

A: Yes. Thanks for the question. Yes, we are on track those total of 20 patients by year-end. We are not disclosing the specific data to be released at the year-end but we are on track to provide a clinical update for 4 studies at the year-end.

Q: I wanted to ask about your FDA interaction in the second half of the year. What will be the focus there? Do you think you have enough data to inquire about pivotal path? Do you think the kind of treatment afforded to the competitor in terms of 17 patients forming the basis for a pivotal cohort and the length of follow-up could be similarly afforded to your -- to added 301 as well? And also, lastly, do you think you have enough differentiation on the total hemoglobin to request a breakthrough designation?

A: Thanks very much, Yanan, for that detailed question. I'll start. With regard to the FDA interactions that we are planning for this year or this half of the year, we will be talking about multiple elements, including our CMC, as I've said, as well as having a clinical interaction. With regard to the clinical data, I'm glad that you highlighted where we see Vertex's BLA and the acceptance of an efficacy cohort of 17 patients with about 18 months of follow-up data which I think is a helpful precedent and certainly an element of guidance that we can actually use. And then as Basin has said, the AdCom that will be scheduled towards the end of this year by the FDA, I think, will actually also be very illuminating as we continue in our continuous process of aligning with the agency and understanding how we can come to agreement on what will be ultimately our pivotal path and BLA filing strategy. With regard to differentiation, based on, I don't know if you want to add anything.

Q: Hi, everyone. Welcome to Linda and Eric. So I wanted to get some clarification on manufacturing. The expanded agreement with the Azure group seems to be focused on clinical and commercial readiness for U.S. markets given that the footprint is based in Massachusetts. But does the company have any manufacturing capabilities in European markets? Or would any Europe-based manufacturing have to come from another potential partner?

A: Thanks very much, Rick. You're quite right in reminding everyone that we have this exciting new agreement with Azure as we get ready for BLA and commercial launch. With regard to ex U.S., I think we'd be consistent in our messaging that we actually would prefer and actually expect a partner to help us with the ex U.S. from the point of view, expanding our footprint. And obviously, when we talk about that, we talk about in terms of co-development, co-commercialization and all the activities necessary for that.

Q: My congrats to both, Erick and Linda [ph] for joining the company. So the question I have is like can you provide insight to how the partner programs are progressing, so the 11 alpha beta T cell program for BMS and the NK cell with shoreline Biosciences. And when do you expect these programs to be disclosed in more details? And then I have a second follow-up question.

A: Sure. Thanks very much, Rich. With regard to the [indiscernible], we're actually happy with the progress. There have been 11 opt-ins, most recently 5 in 2022; two of those opt-ins have passed DC and the most advanced is in IND-enabling studies. Beyond that, it is BMS that is obviously in the driving seat and would actually provide more specifics on the program. And with regard to Shoreline, we're really delighted to have the opportunity to divest our NK oncology programs to Shoreline. Shoreline is actually happy with where they're going. And I think really any more specific updates would come from Shoreline.

Q: Congratulations to the team on the progress. Maybe first to start on the clinical side; it seems like you made a lot of progress dosing patients with sickle cell disease that are adults. But I was wondering if you had any comments as it relates to your plans to move into younger patients? I know some of your competitors have moved into patients 12 to 18 years old. I love to hear any thoughts there. And then I have one quick follow-up.

A: Thanks, Jack. I'm going to ask Bean to take that question.

Q: Obviously, a lot of questions on this call have been around for clinical trial execution, enrollment, et cetera. I want to dig into endpoints, if we could. You've discussed earlier on this call, pain and other sort of fatigue, some quality of life issues is important area of potential differentiation. As clinical trial endpoints, these are pretty notoriously variable and has some element of subjectivity. What efforts have you made, if any, to ensure comparability between your data on these endpoints and that your competitors who are likely to have an ADCOM approval prior so that we can clearly differentiate -- sorry, clearly demonstrate differentiation, if any.

A: I'm going to ask Baisong to address that.

Q: Great on the progress. Maybe one more manufacturing since you're moving your manufacturing process to a new facility. Is it fair to assume that the FDA will ask you to run a clinical bridging study similar to what we've seen from REGENX? Or do you think that just analytical comparability study will be sufficient. So get any color there much appreciated. And then maybe on R&D, pretty material decline in the R&D spend this quarter versus prior quarters. So I wonder if you could provide any additional color on what drove that and how should we think about modeling that line going forward? And then finally, one last one on BD. Any update on partnering LCA10 A: Yes. Thanks very much, Luca. With regard to manufacturing, I think a couple of key points. One is that we are manufacturing within the Asia space. We're already running our clinical supply in a separate Asia space. With regard to the details and specifics of what will be required. This is a -- would be part of our alignment and meetings with the FDA, as we have outlined. With regard to R&D spend, I will start and then ask Eric if he wants to actually add any additional color to the spend. The key thing about the R&D spend, obviously, was that following the rollout of our new strategy where we sharpened our focus on in vivo and really focused on accelerating our 301 asset. We did actually sharpen and narrow our pipeline. And so that had an impact on spend with the divestiture of our NK assets to Shoreline as well as the cessation of our AAV inherited Redland dystrophy programs. Eric, I don't know if you want to add anything more to that?

Q: This is Nick [ph] on for Steve. We were wondering if and how you're measuring off-target edits or translocations for EDIT-301 and RUBY or EDITHAL and whether or not you plan to share those data.

A: Thanks very much, Nick, for the question. Indeed, we actually have a comprehensive. We have a comprehensive set of assays for looking at off-target edits. We're actually very happy with the data we have seen. Interestingly, we actually saw following our proposed set of assays that controls to the agency that many of those remarks were reflected in the guidance that was published after our submissions. But we're actually very happy we're seeing off-target edits. We believe that it really supports and validates our approach to choose an ASK1 a CRISPR enzyme which, as you know, is differentiated both for its efficiency as well as its specificity and very low indeed, undetectable off-target editing. So, all is actually moving consistently with the selection of that enzyme and its prioritization in our portfolio.