EDIT - NASDAQ

Good morning and welcome to Editas Medicine’s Second Quarter 2022 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 Ron Moldaver, Investor Relations at Editas Medicine.

Thank you, Paul. Good morning, everyone. And welcome to our second quarter 2022 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate update. A replay of today’s call will be available on the Investors section of our website approximately two hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company’s future expectations, plans and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statement, even if our views change. Now, I will turn the call over to our Executive Chairman, Jim Mullen.

Thank you. Thank you, Gilmore, and good morning. I’m very excited to be speaking with everyone today, and we’ll start off by sharing with drew Editas. Firstly, I was impressed by the quality of the company sign and its leadership in gene editing field. I spent the last several years working in gene therapy and RNA medicine, so I would closely monitor the evolution of genes therapy and new merchants of CRISPR-based in editing. I was triggered by Editas’ work and its unique approach to address disease genetic diseases. Additionally, what inspired me and I think what inspires most people in this industry is the opportunity to create a new medicine to make a difference for people suffering serious diseases. Editas work is highly differentiated from other players in the field and the opportunity to be a part of a gene editing pioneer is why I’m here. Over the course of my career, I have had the privilege to work in all segments of drug development life cycle. I enter pharmaceutical industry as a CMC Scientist over 20 years ago. While working in CMC, I was a leading discovery research team. After transitioning to discovery research, I also had an opportunity to assist in clinical development, which is where I have stayed. I took a leadership role in clinical development with end-to-end responsibility from a first-in-human clinical study to global approval. My experience in CMC and discovery research has been profoundly valuable and has impacted my work in clinical development. In general, I consider myself to be a direct developer at heart and my goal is to help Editas to develop and bring the right medicines through approval for patients who need treatment. I look forward to updating you on our clinical progress on subsequent calls. With that, I will turn the call over to our Chief Scientific Officer, Mark, who will provide an update on our R&D efforts.

Thank you, Baisong. As Gilmore has provided updates on EDIT-101 and EDIT-301, I’d like to begin with EDIT-103 for Row-ADRP. As a reminder, EDIT-103 is highly differentiated from EDIT-101 with a different approach and superior preclinical data. EDIT-103 uses two adeno-associated virus vectors to knock at the mutant rhodopsin in order to correct the toxic gain of function, while simultaneously replacing that aberrant gene with a functional one. The knockout of the gene and the retinal photoreceptor cell can only occur if the components of the replacement gene are also delivered to and active in that same cell. This mutation agnostic approach can potentially address more than 150 gene mutations that cause low ADRP. At the ARVO meeting in May, we presented preclinical data that demonstrated nearly 100% productive editing in nonhuman primates and generated over 30% functional reduction gene replacement, which proved to be therapeutically effective in that NHP study. The data also showed improved photoreceptor organization and improved retinal morphology in the NOCAs and replaced treated group. As we continue to optimize the product, we also think there is potential for further improvement upon that data that we’ve already presented. We also recently received encouraging FDA feedback on EDIT-103 and its expectations as we approach an IND filing. Based on the FDA’s input and our ongoing work on the program, we remain on track to initiate IND-enabling studies later this year. Moving now to our cell therapy program. In June, we announced a collaboration with Immatics related to a strategic research collaboration and licensing agreement, pursuant to which we will apply our gene egging technology to gamma delta T-cell adoptive cell therapy, an area where Immatics has world-class expertise. We believe that this collaboration will give us the opportunity to develop novel T cell-based therapeutics with enhanced tumor recognition. In our cellular therapy collaboration with Bristol-Myers Squibb, we were pleased to announce earlier this morning that BMS was adopted into an eight editing program for alpha-beta T cell therapeutics. This was their fifth opt-in over the last 12 months, and we are collectively optimistic about continuing the momentum of that partnership. CMS has multiple early programs covering both solid and heme tumors that incorporate Editas’ technology and use multiple edits to optimally engineered T cells, both in our target and allogeneic platform. The most advanced program from this collaboration is currently an IND-enabling study. The engineered sales demonstrate improved tumor killing and antitumor efficacy compared to all type cells, both in vitro and in vivo. We believe that these improved pharmacodynamic and phenotypic characteristics in engineered T cells open the door for numerous potential clinical applications. For our in-house cellular therapy programs, we are very pleased with the progress we are making with our iPSC-derived NK cell medicine program for solid tumors, with a focus on EDIT-202 as our lead program in this area and currently in preclinical development. Using our proprietary engineered AsCas12a nuclease and fix technology, we have developed engineered NK cells that have potent antitumor activity and substantially increased persistence in preclinical models, which we believe could lead to lower frequency dosing an important potential advantage for patients compared to many existing NK cell approaches. At the ASGCT Annual Meeting in May, we presented data demonstrating that an in vivo solid tumor model, EDIT-202 in combination with an antibody-induced significant tumor burden reduction, resulting in complete tumor clearance in 40% of mice over the course of the experiment. Further, EDIT-202 dramatically improved mice survival over wild-type INK cells in the same model, such that all mice remained alive at the end of the 120-day study period. These impressive data support the development of EDIT-202 as a potential allogeneic cell-based medicine for treating solid tumors. One of the key differentiators of this program is our use of a feeder cell-free system to expand and differentiate the edited iPSC into mature NK cells. Most approaches that facilitate the differentiation of iPSC into immune cells involve platforms that typically use feeder cells, introducing an inherent risk of exogenous cell segment getting into the final drug product. In contrast, our INK platform is developed using a feeder cell-free system with defined components for GMP INK cell production, and we are currently in the process of scaling the manufacturing. With that, I’ll turn the call over to our Chief Financial Officer, Michelle to review our financial update.

[Operator Instructions] Our first question is from Gena Wang with Barclays. Please proceed with your question.

Thank you. Our next question is from Joon Lee with Truist Securities. Please proceed with your question.

No, I think you answered it. A quick follow-up on the Gamma Delta. What drew you to gamma delta and are you applying your strict method for the Gamma delta program? I might have missed that as I was multitasking. Thank you so much. Mark.

Hey, Joon, it’s Mark here. I can certainly answer that. We really like the opportunity that the gamma delta T cell program with the magic provider. Many of the technologies that we have used to support the DMS program can be equally applied to the Immatics program. As we had indicated in the earlier press release, they have the opportunity to nominate up to a number of targets for that program, and we’re looking forward to getting that initial list from them, but short answer is, yes, we can apply the AsCas12a nuclease technology to that program.

Thank you. Our next question is from Dae Gon Ha with Stifel. Please proceed with your question.

Then I’m happy to answer your question on EDIT-103. The similarities with 101 are really the AAV5 capsid and the FA Cas9 and so we know that with subretinal injection, we can effectively transduce human photoreceptors both with our data as well as from other gene therapy programs, but I think pretty much that’s where the similarities end. With EDIT-103, the reason why we’re using a dual pectosystem is because it’s an autosomal dominant disease with a dominant gain of negative function of the mutated rhodopsin so any therapy has to start by removing that mutant production and then replacing it with a codon-optimized wild-type tumor reduction. The only way you can do that based on the size of the component is with the dual Vexosystem. And as you probably remember, we split the component rationally between the two vectors so that on those photoreceptors, which take up both sectors, which actually, by the way, is probably all of them anyway, but only those photoreceptors who take up both sectors can actually execute the two-step process of knocking down the endogenous and replacing it. And lastly, for this particular, for EDIT-103, we’re targeting Ropotoreceptors as opposed to cone photoreceptors for edit at the moment.

Thank you. Our next question is from Jay Olson with Oppenheimer. Please proceed with your question.

Maybe to add one comment on the adult as you recall, we gave ourselves the option to expand into the mid-and high-dose adults and that used to be a possibility, obviously, it’s reliant upon evaluation of the data in merchant as well. Great.

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

Thank you. Our next question comes from Rick Bienkowski with SVB Securities. Please proceed with your question.

Thank you. Our next question is from Philip Nadeau with Cowen and Company. Please proceed with your question.

That’s very helpful. Then second question on EDIT-103, you’ve disclosed nonhuman primate data that shows 95% editing and about 37% human protein production in the nonhuman primates. What data is there to suggest whether that level of protein production is sufficient to rescue the disease?

Yes. Thanks, Phil. Well, there are two factors that led us to make that statement. One is that in the study itself in the knockout-only arm we were able to demonstrate a lot of photoreceptors that could be corrected with the knockout and replaced approach and so in that particular experiment, that 30-ish percent rhodopsin was sufficient to rescue those cells, which would otherwise be eliminated in that -- from the retina. That’s one. The second is that there’s a well-published dog model from the UPenn Group, Art Cideciyan and William Beltran, where they did a knockout and replace experiment with the shRNA and rhodopsin. In their hands, they showed that about 30% production expression was sufficient to rescue photoreceptors in that model system. Those two pieces of information together, we believe, guide us to an approximate level of reduction expression that will be sufficient. What we’ve also said though is that, that was the level in that particular experiment. There are still some things that we can change in the way that those experiments are conducting to modify the editing versus replacement levels, and that work is ongoing in the lead-up to the IMD&A case study.

Thank you. Our next question is from Joel Beatty with Baird. Please proceed with your question.

Thank you. Our next question comes from Yanan

Yes, Yanan. Early in the program, the preclinical team conducted to the direct comparisons of the different editing mechanisms whether the HPG promoter region or the BC11A itself and the promoter region editing gave slightly higher HDF levels, at least in a preclinical model, but also importantly, that we maintain the fidelity of the lineages derived from those cells, whereas with the TCL11A approach, there was some line queuing. I think efficacy-wise, we believe there could be an advantage and then long-term, safety-wise, also we have some concerns with BC11A on editing and transcription factor, which has more than one function, but at this point in time, the differentiation will be determined by the clinical data and that is the data that’s emerging.

Thank you. Our next question is from Steven Seedhouse with Raymond James. Please proceed with your question.

Thank you. Our next question comes from Madhu Kumar with Goldman Sachs. Please proceed with your question.