EDIT - NASDAQ

Good morning, and welcome to Editas Medicine’s First Quarter Conference Call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this call. Please be advised that this call is being recorded at the Company’s request. I would now like to turn the call over to Cristi Barnett, Corporate Communications and Investor Relations at Editas Medicine.

Thank you, Gilmore. Good morning, everyone. Let’s start with EDIT-301 RUBY study for severe sickle cell disease. As Gilmore mentioned, we continue to enroll and dose patients in the RUBY study. We have activated 20 study sites and enrolled 19 patients, almost double the number of patients enrolled from three months ago. As we previously shared, we began parallel dosing of patients earlier this year. We are on track to provide an update on the RUBY clinical data both next month and year-end as well as to dose 22 total patients by year-end. Turning to clinical data. I’m excited that we will present RUBY clinical data as an oral presentation at the European Hematology Association, or EHA Congress, and at our company-sponsored webinar in June. The data set will include safety and efficacy data for multiple patients, including 10 months data from the first patient treated and 6 months data from the second patient treated, including total hemoglobin, fetal hemoglobin. We will also share data on safety, neutrophil and platelet engraftment and vaso-occlusive events or VOE, from the first four patients. As a reminder, last December, we presented initial data from the first two patients treated in the RUBY trial. The first patient who had five months of follow-up after treatment with EDIT-301 showed clinically significant improvements across all hematological parameters and no VOEs. Specifically, that patient had an increase of fetal hemoglobin fraction to 45.4%, five months after EDIT-301 infusion. And the correction of anemia with total hemoglobin level well into the normal range at 16.4 grams per deciliter. These initial clinical data indicated that EDIT-301 provides patients with high and sustained level of fetal hemoglobin and normal level of total hemoglobin. This clinical observation is consistent with preclinical data, which has demonstrated that targeting of gamma globin promoter enables increases of fetal hemoglobin independent of erythropoietic stress. Given the unique gene-editing approach and mechanism of action by EDIT-301, supported by preclinical data and initial clinical data, we continue to believe that EDIT-301 can potentially provide robust clinical benefit to patients with severe sickle cell disease, and potentially provide clinical differentiation in the long-term. As a reminder, a sustained normal total hemoglobin level is an important clinical outcome for patients, as the correction of anemia can significantly improve quality of life and ameliorate an organ damage. We believe sustained normal level of total hemoglobin could be a potential point of differentiation for EDIT-301. Turning to EDIT-301 EDITHAL Phase 1/2 trial for transfusion-dependent beta thalassemia. As Gilmore mentioned earlier, we dosed our first patient in Q1 and the patient has successful neutrophil and platelet engraftment. We remain on track to provide initial clinical data from the EDITHAL trial by year-end. As we have done for the RUBY study, we are also taking multiple measures to accelerate the development of EDIT-301 for TDT and have strong positive momentum. We have enrolled multiple patients who have completed pheresis and have their CD34 positive cells edited or are in the process of pheresis. Recently, I have been traveling around the country visiting our RUBY and EDITHAL clinical trial sites. I very much appreciated the enthusiasm and the support from the investigators and study sites. I’m pleased with the momentum of EDIT-301 in patient recruitment, pheresis, editing and dosing in both studies. I’m excited to hear from investigators that patients dosed with EDIT-301 have already seen positive changes in their lives. We look forward to sharing additional updates as the year progresses, including RUBY study data next month and at year-end, and sharing initial clinical data from EDITHAL study by year-end. Now, I will turn the call over to Michelle, our Chief Financial Officer, to review our financials.

[Operator Instructions] And our first question comes from Joon Lee with Truist Securities.

Joon, I think you are a little breaking down, but let me try. This is Baisong. Let me try and see whether I understand correctly. There is background noise. So I think your question is to say compared to Novartis and do you have a comparison between Cas9 and Cas12a and also the region just Gilmore mentioned. Is that your question?

Yes. No, actually, if you target the same region, either with Cas9 or Cas12a, what differences in outcome you get?

Yes. Let me just kind of take it. We did the comparison, we did -- from a clinical perspective, we scanned a large region -- of the promoter region to identify which areas to do the editing. So, without too many specifics, but we covered a large region of the promoter in the HBG1 and 2. And we find out that related to the region we selected, which Gilmore just mentioned, is consistent to the clinical observation for these HPFH. And then we also compared the Cas9 with Cas12 and we found the difference between Cas9 and Cas12. Does that answer your question?

Yes. No, absolutely. Your impaired data is very good, but just was just curious what was driving that difference. Thank you so much. I’ll hop back in the queue.

Thank you.

Our next question is from Samantha Semenkow with Citi.

It is a normal oral presentation that is expected.

And then I also wanted to clarify, I heard you mention, obviously, we’ll have updated data for the first and second patients. And then, I heard you, I think, say, four patients. So will it be six patients total that will get data on VOE, or is that -- or VOCs, or is it four patients total?

Total will be four patients at the EHA presentation.

And then when you’re making that cutoff for those incremental additional two patients, what level of follow-up was the cut-off there? So I’m just curious, is it a couple of months, is it one month? Any information you can provide would be helpful.

Yes. Thanks, Gilmore. And just kind of also follow-up on that, the abstract will be available on May 11th.

Next question is from Dae Gon Ha with Stifel.

And then second question, I just wanted to follow up on Baisong’s commentary during prepared remarks. So, as you were going into the field and kind of gauging physicians’ take on EDIT-301, you expressed -- or you commented on their high enthusiasm. Wondering if you could comment, I guess, what proportion of those docs you visited are also looking to administer CTX001? And I guess, has there been any kind of gauge or ascertainment from your part as to what their sort of motivation would be in taking CTX001? Like, are they lining up patients right now for CTX001? What kind of sentiment do you have? Are there any reservations on that approach? Any thoughts on that would be helpful. Thanks so much.

Our next question comes from Steve Seedhouse with Raymond James.

My question actually requires a bit of a prelude, so I hope everyone can bear it for a moment. You made a comment on globin locus editing increasing fetal hemoglobin independent of erythropoietic stress. And as you know, ICER -- the recent ICER report on exa-cel uncovered an ongoing phlebotomy, at least one in sickle cell and some of the earlier data releases for that program in thalassemia indicated phlebotomy use there as well, but that just stopped being reported at some moment. So it’s not clear how prevalent phlebotomy use is for exa-cel. And this is all important because there was data at ASH years ago, as I’m sure you also know, indicating BCL11A editing cooperates with phlebotomy and primates to accentuate F cells and ultimately HBF levels probably because of the stress erythropoiesis causes. So all that said, I’m curious if you agree that phlebotomy is potentially confounding fetal hemoglobin data for BCL11A approaches. And if you know what is the impact specifically where your editing approach at the HBG1/2 locus, what has phlebotomy use been like in your study and if you think this is all potentially a competitive advantage for you? Thank you.

Our next question is from Yanan

Maybe to continue the discussion a little bit from the prior question. Gilmore, you mentioned that the total hemoglobin for the first patient is quite robust in the normal range. The percent of fetal hemoglobin appears to be very much in line with competitor gene editing product. So, I was wondering, is the -- greater total hemoglobin reported for that patient, is that due to the total number of red blood cells? Could that potentially be a reason, or could it be related to the baseline level of hemoglobin in that patient? And along that line, to continue a little further and to -- perhaps looking into what we could expect from patient number two at EHA. I was just wondering, could you remind us the baseline hemoglobin for patient number two and what is the normal range for the female patient, which obviously is the second patient? Thank you.

Yes. Maybe just add a little bit nuance on that baseline for sickle cell patient, especially for gene-editing trial. And because the patient -- when they prepare for pheresis and conditioning, they usually have blood transfusion. So, the baseline actually we have is not the lowest level we recorded. We just set at the time of the visit 2 as a baseline. So actually it’s compounded, it could be many different reasons for the baseline on that, too. That’s just a nuance. It’s actually -- it’s lower than -- it’s around a little bit over 10 grams per deciliter when we actually -- on our record for this patient. This is just an example about the baseline, maybe not confusing.

Our next question is from Phil Nadeau with TD Cowen.

Yes. Thanks for your question. So, we certainly have a lot of engagement with FDA. As you see that recently, we have the orphan drug destination. And from the registration perspective, we previously announced that we actually have the alignment on the potency assay with the FDA, which FDA will consider this efficacy data can be supporting registration. And we will have further engagement with the agency to align on the total registration package for the BLA submission, which is also planned. And your second part of the question is about the beta-thal data. So, we are moving really along with the EDITHAL study, and we expect that we will have data by year-end, more than sentinel patient. And so, we’re looking forward to share that data by the year-end.

Our next question comes from Rick Bienkowski with Cantor Fitzgerald.

I guess, I’ll expand a bit on the last question on the path towards registration for EDIT-301. 20 patients is a pretty substantial cohort size in sickle cell disease. So, do you have any sense of how many patients’ worth of data you will need for a registrational filing?

Yes. Thank you for the question. So we certainly think that with the gene editing approach that we have we will be able to generate a substantial amount of data. And the specifics on the number of patients to be able to use for registration, we need to align with the regulatory agencies. So, we are planning to discuss with FDA.

And I just have another quick one. I was hoping for a little bit more granularity on the collaborative revenues for the quarter. Were all of the $9.9 million in revenue attributable to the Shoreline transaction, or are there some other revenues attributable to other partnerships in there?

It’s a combination of both the Shoreline and then some other small sublicense revenues.

Our next question is from Rich Law with Credit Suisse.

Our next question is from Debjit Chattopadhyay with Guggenheim.

Thanks for your question. I can say that we have looked into this milder conditioning in very deep, looking the space as well as internal efforts wise. And there were generally probably two approaches. One is that CD117 antibody and in that direction. And the other one is actually doing the cell modification together with gene editing. So, the latter approach is still -- is in infancy, if I may say, and the previous approach with antibody have many different exercise on that. So I think we are very closely monitoring the space and understand these. And I also want to mention that the milder conditioning, if successful, is not going to be only successful for sickle cell transplant, it’s going to be successful for leukemia and many different gene therapeutic areas. So, we are actually very much looking into this space.

Our next question is from Madhu Kumar with Goldman Sachs.

Yes. So, Rob, I mean, we don’t disclose our annual OpEx -- or our quarterly OpEx, but I can tell you that about half of our spend is in -- on the both the RUBY trial and the TDT trial. So, we don’t expect an enormous increase quarter-over-quarter. But as we do dose more patients, obviously, our R&D spend will go up, but not substantially. And our current, I’ll just say one more, our current cash runway supports our RUBY trials.

Our next question is from Greg Harrison with Bank of America.

This is Mary Keith on for Greg. Thanks for taking our questions. So, with 19 patients enrolled and plans for 20 to be dosed by year-end. Maybe how many sickle cell patients have been currently treated with EDIT-301, and maybe how could we expect to see this represented in the efficacy readout by the year-end update? Thank you.

So, we have 19 patients enrolled. And among those, as we just mentioned, 4 have been dosed, and we actually have -- more patients have been completed pheresis, and have CD34 cells edited and ready to schedule dosing. And then, we have other patients who are in the process of pheresis. And so we are very confident that we will be able to dose 20 patients by year-end.

Our next question is from Luca Issi with RBC Capital Markets.

And maybe just add one more point -- sorry, just add one more point. As Gilmore mentioned about pricing, right? So certainly, we are very early stage, and we are happy to see the community is looking to the value of this gene editing therapy, and we are happy to see that the report recently in this space. So we -- as Gilmore mentioned, this will be evolving, but we are pleased to see that -- the entire community recognize the value of the medicine in this field.

Our next question is from Jay Olson with Oppenheimer.

Our next question is from Joel Beatty with Baird.

Our next question is from Joon Lee with Truist Securities.

So, I had the same question as Steve, but maybe a different way of asking. What percentage of sickle cell patients with hereditary persistence of fetal hemoglobin have mutations along the globin locus versus the BCL11A locus?