EDIT - NASDAQ

Good morning, and welcome to the Editas Medicine First Quarter 2024 Conference Call. [Operator Instructions] 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 talk about reni-cel, which is on the clinical development for severe sickle cell disease and transfusion-dependent beta thalassemia. As Gilmore shared, we are pleased that we have completed enrollment in the adult cohort of the Phase I/II/III RUBY trial and the dosing continues. In the adolescent cohort of the RUBY study, we have enrolled in multiple patients and the several more patients in screening. The interest and demand are high. I'm very pleased about how quickly we have moved in screening and enrollment of liability cohort. I'd like to thank colleagues and editors and our clinical trial partners for the collaboration and hard work. And more importantly, I would like to thank patients, their families, investigators and the study site stock for their trust and support. In the EdiTHAL trial for transfusion-dependent beta-thalassemia, we continue to move forward with enrollment and dosing. We look forward to sharing clinical data in the middle of this year and also at the year-end. As I have shared, I visited and continue to bid our RUBY and EdiTHAL clinical trial sites and speak with the investigators. I appreciate enthusiasm and support from investigators and study size. I'm pleased with the momentum of reni-cel patient recruitment, [indiscernible] and dosing in both studies. I'm excited to hear from the investigators that patients dose to reni-cel, have already seen positive changes in their lives. As we shared on our February earnings call, we aligned with the FDA that RUBY clinical trial is now considered a Phase I/II/III trial for BLA filing. We also have alignment with the FDA on the study design, end points and sample size. We look forward to future discussions with FDA and continued the collaboration. Turning to clinical data. As Gilmore mentioned, we are on track to present a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024 and a further update by year-end 2024. What we will show the RUBY data set were including clinical data from at least 18 sickle cell patients with 2 to 21 month follow-up. And the substantive data set will include clinical data from 7 patients with 4 to 12 months follow-up. We will present efficacy data, including total hemoglobin, fetal hemoglobin and vaso-occlusive event or VOE for sickle cell patients in RUBY study, and red blood cell transfusion for transfusion-dependent beta thalassemia patient in EdiTHAL study and safety data, including [indiscernible] for both studies. As a reminder, in December 2023, we shared safety and efficacy data from 11 RUBY patients and 6 EdiTHAL patients. Once again, the data confirms the observation from our prior clinical results, including reni-cel drove early robust correction of anemia to a normal physiological range of total hemoglobin in sickle cell patients. Reni-cel drove robust and sustained increase in fetal hemoglobin level in excess of 40%. All RUBY sickle cell patients remain free of vaso-occlusive events following reni-cel treatment. Reni-cel treated sickle cell patients and transfusion-dependent beta thalassemia patients have shown successful engraftment, have stopped red blood transfusion. And the safety profile of reni-cel to date is consistent with busulfan and myeloablative conditioning and autologous hematopoietic stem cell transplant. This data reinforce our belief that we have a competitive product and the product potentially differentiated from other treatments, with a rapid correction of anemia. Thanks to the delivery choice of our discovery group have made early in the program. The choice of CRISPR enzyme and the target to edit for increased fetal hemoglobin expression matters. Reni-cel uses our proprietary AsCas12a enzyme to upregulate the HBG1, 2 promoter. Based on the clinical data thus far, we believe that sustained normal levels of total hemoglobin could be a potential point of differentiation for reni-cel. Now I'll turn the call over to Linda, our Chief Scientific Officer.

Thanks, Baisong, and good morning, everyone. I'm happy to be talking to you this morning to share more details about our in vivo strategy and our progress towards building an in vivo pipeline. I would like to take a moment to remind you why we believe in vivo medicines will be a disruptive transformative development in medical history with the potential to address genetically determined diseases with durable and curative outcomes for patients. First, in vivo medicines may reduce the administration burden of delivering editing medicines to patients in need, which will provide the broader access to patients all around the world. Second, off-the-shelf administration may allow for scalable manufacturing and lower cost to produce. Based on these 2 principles, we believe that in vivo gene editing will provide accessible cures for genetic diseases and, therefore, may be the most disruptive development in medical history. So how will Editas position itself? There are many monogenic diseases that can potentially be cured with a gene editing approach. We have said that we will at first target the development of treatments that are clearly differentiated from current standard of care and that will leverage the aspects of CRISPR editing that give it a unique advantage over other therapeutic modalities. Our internal development efforts are differentiated by leveraging the indel CRISPR technology we use to upregulate gamma globin expression through direct editing of the HPG 1, 2 promoter site in our ex vivo reni-cel program. Our in vivo approach is aimed at functional upregulation of gene expression in genetic diseases in rare and orphan patient populations from which we intend to expand to more common diseases. I am also pleased to share several progress updates as we advance our in vivo capabilities towards our long-term vision of being a leader in in vivo programmable gene editing. First and most importantly, as Gilmore mentioned, we remain on track to establish in vivo preclinical proof of concept for an undisclosed indication by the end of the year. Editas is well positioned with established capabilities in the 4 main components of in vivo gene editing medicine, one, guide RNA; two, editing enzyme, three, messenger RNA; and four, delivery technology, and we are currently evaluating lipid nanoparticles for delivery of gene editing cargo into multiple tissue types with multiple companies. Additionally, we are evaluating next-generation delivery technology. Second, our in vivo capabilities with the potential to be used in developing transformative in vivo gene editing medicines are demonstrated by the preclinical data we are presenting at the American Society of Gene and Cell Therapy or ASGCT Annual Meeting in 3 presentations, taking place on Thursday and Friday of this week. On Friday, in an oral presentation, we will share in vivo preclinical data from mouse studies using lipid nanoparticle mediated delivery of an optimized guide RNA and engineered AsCas12a messenger RNA. In poster presentations on Thursday and Friday, we will share preclinical data demonstrating AsCas12a guide RNA modifications that enable high potency gene editing in multiple cell types, including in the liver, and improved gene editing outcomes in vivo, enabling the development of in vivo gene editing medicine and research on identifying potent large serine recombinases, LSRs, as the foundation to develop novel in vivo gene editing technologies for whole gene knock-in, expanding potential in vivo gene editing targets for developing medicines. Third, Editas CRISPR-based in vivo gene editing capability has been clinically validated. Notably in 2020, Editas is the first company ever to treat a human with an in vivo delivered CRISPR-based gene editing medicine EDIT-101. In fact, earlier this week, the New England Journal of Medicine published in manuscript titled Gene Editing for CEP290 Associated Retinal Degeneration, detailing our former lead development candidate EDIT-101 for the treatment of Leber Congenital Amaurosis type 10 or LCA10. Editas established clear in vivo human proof of concept in 2022, and we are pleased that the results from this groundbreaking clinical trial were published by the New England Journal of Medicine. These progress updates demonstrate Editas' execution on our in vivo strategy and our proven in vivo gene editing capabilities, and I look forward to sharing more details about our in vivo development strategy and our progress towards building an in vivo pipeline later this year. Now I will turn the call over to Erick, our Chief Financial Officer.

We will now be conducting a question-and-answer session. [Operator Instructions] Our first question comes from Samantha Semenkow from Citi.

We are looking for proof of concept for high efficiency delivery and editing for our targeted interest in vivo in this preclinical POC that will give us confidence in our ability to target the target of interest. We are going to be sharing more information on this at a future date. Thank you for the question.

Our next question comes from Joon Lee from Truist Securities.

We're excited about the LSR technology that we're disclosing here. We are identifying many different novel LSRs. We're not disclosing at the moment, the size of the integrations that can be accommodated by the large serine recombinases but we have quite a few novel LSRs that we have identified and we further charactering them.

Our next question comes from Mary Kate Davis from Bank of America.

So in this middle year release, we expect to have at least 18 patient data for RUBY study. And within the 18 patients and 4 of them will have 12 longer, 12 to 21 months of exposure, and 7 will have 5 months to 12-month exposure and another 7 with 2 to 5 months exposure. With that, we feel this data is very meaningful to see the direction not only the increase of total hemoglobin normalization of total hemoglobin and increase of fetal hemoglobin, but also the durability of the study and the impact from an efficacy perspective, for example, severe vaso-occlusive events. For the EdiTHAL study, we will have patients from at least 7 of those patients with 4 to 12 months of exposure, which also will be very meaningful. That is compared to the December release we have 11 RUBY patient and 6 EdiTHAL patients. So that substantial more data will help us to understand group in better.

Our next question comes from Jack Allen from Baird.

Yes. For regulatory, as we shared that we have alignment with the FDA that the RUBY study is a Phase I/II/III study for BLA filing. And we also have alignment on the sample size, duration and study design of that. So we continue to have collaboration with FDA on the further discussion about this program.

Our next question comes from Gena Wang from Barclays.

Primary open-angle glaucoma is obviously an area of very high unmet need. And while we conducted those studies because of that, we are not currently pursuing that indication, but we were able through those studies to really demonstrate intensive preclinical POC and showcase our in vivo capabilities with respect to 3 components: our ability to deliver lipid nanoparticles in vivo with our gene editing cargo, our proven capability of our proprietary enzyme, AsCas12a to edit in vivo and our guide modifications to enhance a gene editing potency. So these capabilities really position us well for delivering in vivo gene editing medicines and we're really pleased with the ASGCT disclosures.

I will take up on the question about the VOE relapse for sickle cell patients. First, I would say, I want to congratulate the entire field for the effort of treating sickle cell disease, including the recent approval of the 2 molecules. And so I think what we see is that with the continued effort of all of us, we will continue to improve and transform the treatment for sickle cell disease patients. With reni-cel, and we are still continuing to collect the clinical data. As I mentioned, we expect this is a different -- not only competitive but differentiated molecule and with the normalization of the total hemoglobin correction of anemia. So we're looking forward to see our own data on the VOE as we reported so far, we have seen all those patients dosed with reni-cel is free of VOE event.

Our next question comes from Mani Foroohar from Leerink Partners.

Obviously, as we said in the transcript, we view the future potential royalty monetization and licensing activities as an integral and very important source of nondilutive capital. As you know, these are foundational IP patents in which are applied to just about everybody's projects in Cas9, Cas12. And we expect to have conversations with those folks as soon as we can.

Our next question comes from Brian Cheng from JPMorgan.

Yes. So Brian, as I mentioned, we are very pleased with the data we're going to release in the middle of the year and which is substantive and also give us good direction how much we will get and to have, for example, a data set to have equivalent to the [indiscernible] BLA filing, for example, right? So that's one part of that. We're very happy to see the amount of data and the patient outcome from the data. And then the other thing is about the regulatory engagement. As I mentioned, we already have a line of this Phase III study to support the VOE and then we have continued engagement with FDA. We have not disclosed all the details of the interaction yet. But as a reminder, we have unmet designation and which allow us to have frequent interaction with agency, but also with a high-level interaction with agency. And this, of course, help give us opportunity for potential priority review and rolling submission. So we're very excited on the direction. We'll continue to have engagement and collaboration with FDA.

Our next question comes from Eric Schmidt from Cantor Fitzgerald.

We are very pleased with the momentum by the enrollment in both the EdiTHAL cohort and the adolescent cohort. And for the EdiTHAL cohort, we shared that in February with those, we enrolled 40 patients, now we entrolled slightly more than 40 patients. And therefore, we closed the adult cohort enrollment. And for adolescent cohort, we started at the beginning of this year. We already enrolled multiple patients and have modification experience. We're very pleased with that. Then as I mentioned, I'm on the road all the time to visit our investigators and the study size. And then they really feel that one is actually there, I believe the reni-cel based on the MOA, based on the data we have continued to share on that. I also give credit the entire field been working on that with the 2 gene therapy approved for sickle cell is also increased interest in the direction of the gene therapy for sickle cell disease. So that's how we see over the last year or so, we see really great momentum that for reni-cel enrollment, especially after we release our data.

Our next question comes from Jay Olson from Oppenheimer Company.

With respect to the timing of the renegotiation of the extension, obviously, we put out a press release in the very recent past a week or 2 ago, something like that and that would give you an update on the timing. I'd say with respect to the data, Bristol-Myers, as you know, recently completed a portfolio review, and we are pleased to see that all of the projects that we're working on them are continuing to move forward. I think it -- we would leave discussion of specific programs to them to talk about anything that they're seeing in those programs. I would highlight the fact that at their most recent R&D Day last September, which I think was the first one they've done in several years, they did mention 6 products on their pipeline chart, which we're using our technology. So I would refer you to their R&D disclosures from that meeting to get an update on the work that they're doing with us. But we are very excited about working with them. This has been a partnership that has survived several mergers and several portfolio reviews. So we're very excited about what we're seeing.

Our next question comes from Philip Nadeau from TD Cowen.

We certainly have measurements for the end organ function. We look into the several major organ system to monitor the function improvement. For example, we monitor the liver function, not only with these different lab values. We're looking to pulmonary function to check the respiratory system. And we also have cardio echo and other measures you're talking to measure the cardiovascular system on that too. So we are looking forward to see more data on that and give us more understanding of the end organ function may behave after the treatment. Just a reminder that we also, of course, look into the not only sickle cell but also other areas in terms of the anemia, how that impact function and how that correction of anemia may be able to improve that function of the treatment. And in sickle cell specifically, over the last couple of years, you already see more publications about end organ function given after the allogeneic transplant to treating sickle cell patients, we are very excited on that. But just to be very honest to ourselves, right, this field is still fairly new, and we see some really good publication and direction in this, and we're looking forward to our own study as well as the literature on this field.

Our next question comes from Yanan

Yes. In vivo, our in vivo approach is aimed at functional upregulation of gene expression in genetically determined diseases and this strategy positions us very well to be differentiated from others in terms of our targets and our target editing strategies. And what this means is that we can go after targets that others can't go after. And so from an indication perspective, we can go after indications that perhaps others can't go after, and so we could have a first-in-class strategy. Also within a given indication, we could devise a targeting strategy that would be best in class, if you will. So we can have first-in-class strategies as well as best-in-class opportunities. I hope that answers your question.

Our next question comes from Luca Issi from RBC Capital.

We are very pleased with the interaction with the agency and continued interaction with agency about the reni-cel for the RUBY study as a Phase III study to support BLA and all the front of the Phase III study, we have alignment on that, and we have a continued conversation with FDA on this route. We have not shared the specifics about the date of the BLA or the indication of adult or alone or adolescent. But as we shared, we are very pleased with the enrollment for both EdiTHAL cohort as well as adolescent cohort. So that gives us a great position for this molecule.

Thanks for the question about Middle East and certainly just the populations outside the United States. And there's absolutely a number of geographies where there is a significant population of sickle cell patients and really high unmet need beta thalassemia as well. What I'd say is our continued drive to execute in the U.S. and to move reni-cel forward with differentiation, just continues to support the opportunity for us to partner at the appropriate time, and that's certainly something that we've said we are open to and we'll certainly provide more color in the future as appropriate.

Our next question comes from Steve Seedhouse from Raymond James.

First, we'd say I'd say that I'm really pleased to see some of the initial progress for the other therapies and being able to get patients started. We always anticipated that it would be a dipping many centers starting to dip their toe as they build the infrastructure and they gain the confidence, so to answer your question, absolutely. We've always said that in this kind of market of the complexity of the ex vivo being a fast follower is absolutely an advantage. We also, on our own, have a really strong base of over 20 clinical sites in the U.S. with very strong enrollment, and relationships that we're leveraging and those relationships and the guidance they're giving us will be really pivotal for us as well. But this is a field that will benefit from the increase in education with patients which Baisong mentioned also helps with our enrollment and just building the infrastructure, but we are engaged on the KOL, the patient advocacy as well as on the payer front to ensure that we're prepared. So thanks for the question.

Our next question comes from Jack Allen from Baird.

We have not shared specifics about the number of cycle in apheresis. When I mentioned before was -- since I joined, we actually worked together with our internal as well as apheresis external. We actually have critical management to improve the apheresis cycle and also provide assistance to study side to -- for the press cycle, which is significant because it's reduced the patient burden is a smooth manufacturing process. We are very pleased to see the progress in that front. And just to add on that, we are hoping this clinical experience will be very much helpful for our commercial [indiscernible].

Our next question comes from Mani Foroohar from Leerink Partners.

Yes, happy to -- we are over this process really working together that to get the steady size to optimize this process and that coming from multiple factors. One of the factors just mentioned is bio-apheresis. The other factor is the logistics, and we provide support on that. The third factor is actually patient condition as we know that we are treating the severe sickle cell disease. And before the reni-cel treatment, they can have multiple VOE per year, and that also can impact [indiscernible].

Mani, this is Caren. I would just add that, again, in the fast follower position, one of the things that gives us the opportunity to do is to really understand as the first 2 therapies are commercialized, what's working, what's not working, what they need to see differently and really making sure that Editas sets ourselves up as the partner of choice. And so we're working very hard on that, and we'll certainly talk about that at a later time.