Editas Medicine, Inc. (NASDAQ:EDIT) Q2 2022 Earnings Conference Call August 3, 2022 8:00 AM ET
Company Participants
Ron Moldaver – Investor Relations
Jim Mullen – Executive Chairman
Gilmore O’Neill – Chief Executive Officer
Mark Shearman – Chief Scientific Officer
Michelle Robertson – Chief Financial Officer
Baisong Mei – Chief Medical Officer
Conference Call Participants
Gena Wang – Barclays
Joon Lee – Truist Securities
Dae Gon Ha – Stifel
Jay Olson – Oppenheimer
Luca Issi – RBC Capital Markets
Rick Bienkowski – SVB Securities
Philip Nadeau – Cowen and Company
Joel Beatty – Robert W. Baird
Yanan Zhu – Wells Fargo Securities
Ryan Deschner – Raymond James
Operator
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.
Ron Moldaver
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.
Jim Mullen
Thanks, Ron, and good morning, everyone. I am joined today by several members of the Editas executive team, including Gilmore O’Neill, our Chief Executive Officer; Mark Shearman, our Chief Scientific Officer; Michelle Robertson, our Chief Financial Officer; and Baisong Mei, who I’m thrilled to welcome as our new Chief Medical Officer.
As you know on June 1, Gilmore assumed the role of CEO and I became Executive Chairman of the Board. Over the past two months, I’ve partnered closely with Gilmore and the executive team to ensure the seamless changeover of the CEO role. We are very fortunate to appoint a leader of Gilmore’s caliber as CEO. During his nearly 20 years of experience in genetic medicine and clinical development including senior leadership positions at Sarepta and Biogen, he has led some of biotech’s most successful clinical programs. Gilmore’s drug development experience, proven leadership, passion for genetic medicine and focus on patients are exactly the right skill set and experience to lever the foundation we’ve built over the past several years and lead the company towards commercialization. If his first few months are any indication of his leadership abilities, Editas’ next few years are undoubtedly poised for success.
With that, I’m very pleased to turn the call over to our new CEO, Gilmore O’Neill.
Gilmore O’Neill
Thank you, Jim. And good morning, everyone. Let me first say that I am delighted to be here today. As you know, Editas is a forerunner in the development of CRISPR gene editing technology and I am very happy to have the opportunity to lead the company to create potentially life changing medicine. I also want to thank Jim for continuing to strengthen the Editas leadership team over the past few years and I’m honored to work alongside such a talented and dedicated group of people. With the addition of our new Chief Medical Officer, we now have a complete and even stronger leadership team in place.
Let me start off by giving you my initial two month assessment. The company’s technology is what drew me to Editas. What I have seen since my arrival has reinforced my enthusiasm and given me even more confidence in the company’s potential. Editas is transforming from a technology platform company into a therapeutics company that will continue to create develop and will commercialize new therapeutic assets to treat previously untreatable serious diseases. Editas has a numerous areas of differentiation including distinct expertise in nucleate enhancements and bioinformatics to drive lead discovery. These enhanced enzymes, then coupled with proprietary RNA chemistry do make efficient high precision edits. And overall the foundational science that has led the current pipeline of potential product is impressive.
In addition, I have found a very creative team of innovators in our discovery group, strong CMC expertise, and posing clinical assets supported by a robust R&D pipeline. With these pieces in place to support our therapeutic pipeline, we now have to focus on clinical execution, which is why I’m so happy to welcome Dr. Baisong Mei as our new Chief Medical Officer to Editas Medicine.
Based on bringing substantial, translational, and registrational trial experiences across several therapeutic areas, including hematology, where specifically, he oversold the global approval of 2 drugs for non-malignant blood disorders. He has extensive and more importantly, a proven track record of both incentive and advancing therapeutics from the bench through clinical development also leading to multiple global drug approval. Baisong joined us from Sanofi, where he served as senior global project head in rare disease and rare blood disorders. Prior to Sanofi, Baisong on work at Biogen, where I had the privilege of working with him, and I can personally attest to his breadth of knowledge and effective leadership skills. He’s officially started about two weeks ago, and we very much look forward to his contribution to the months and years ahead.
Now I would like to provide my initial thoughts on our lead pipeline product starting with our EDIT-301 autologous program for sickle cell disease and transfusion-dependent data thalassemia. As many of you know, EDIT-301 utilizes a unique mechanism of action that edits the promoter of the gamma-globin gene to disrupt binding of the BCL11A suppressor. In turn, this provides high and durable levels of fetal hemoglobin or HBF, in a manner that is independent of a rethread resulting in reduced sickling and vasoactive events in sickle cell patients and resolving anemia, and transfusion dependence in patio thalassemia patients. In addition, this is the first time that an autologous ex vivo drug product has been edited using our high-fidelity AS Cas12a engineered nuclease. We have continued to build momentum with EDIT-301 in the past quarter. We dosed the first patient in the RUBY trial for sickle cell disease, and that patient has successfully engrafted. The partial clinical hold was lifted by the FDA, which will allow us to include efficacy data from all prefer patients in a future registration package, and we have successfully collected and edited cells of additional sickle cell disease patients. We continue to expand trial sites to help create a steady cadence of patient enrollment, and we remain on track to provide top-line clinical data before year-end. Additionally, we received orphan drug designation for base thalassemia in May, and we remain on track to dose the first TDT patient by year-end.
Moving now to our lead in vivo program, EDIT-101 for LCA10, which is a devastating inherited retinal dystrophy caused by autosomal recessive CEP290 mutation. Our ongoing Phase 1 BRILLIANCE study has been designed to achieve several objectives to identify a dose that optimizes the benefit and risk balance of EDIT-101 and that can advance to registration. To identify a segment of LCA10 patients most likely to benefit from therapy in a registrational study using baseline clinical and physiologic characteristics and to identify the optimal endpoint for use in the registration study. The safety profile has thus far been very encouraging and has allowed us to move up into our high dose and into pediatric patients. The efficacy data generated to date support proof of concept that gene editing is occurring in retinal photoreceptors. This morning, we announced that we have dosed two pediatric patients in the mid-dose cohort. As of today, we remain on track to provide a clinical update on the BRILLIANCE trial later this year, which we expect to include safety and efficacy assessments on all patients who have had at least six months of follow-up evaluation. These data will help identify the most relevant and sensitive endpoints to support registrational trial development.
Beyond developing a trip for LC and the EDIT-101 program lays the foundation for subsequent popular drug development programs within our in vivo platform. The proven safety of the capsid, success administration of the editing machinery through subretinal injection, and the delivery of the CRISPR/Cas9nzyme to the photoreceptors have demonstrated that we can effectively edit retinal cells in vivo. For example, our EDIT-103 program for redoxin autosomal-dominant RP leverages all of these elements and in addition, has demonstrated much higher preclinical editing efficiency than EDIT-101 with nearly 100% easing. So even though both the EDIT-101 and EV-103 programs use the same AAV vector and Cas9 enzyme, the editing efficiency of the EDIT-103 program is substantially greater.
Moving to our intellectual property portfolio, as a reminder, Rod patents covering Cas9 are exclusively licensed to Editas for therapeutic development. Earlier this year, the Broad Institute prevailed for the third time against the University of California, along with the co-owners collectively referred to as CDC in protecting these patents when the patent trial and appeal board or PTAB ruled in the Broad’s favor. As anticipated, CDC filed an appeal with the Federal Circuit, and we remain confident growth and by extension, Editas will once again prevail. If that is indeed the case, Editas will retain the sole rights to issue either exclusively or nonexclusively, licenses for Broads, CRISPR/Cas9 IP for human therapeutics in the United States, which is the dominant market for innovative medicines. As a reminder, both our Ex-vivo at cell circuit group platforms use our proprietary ASCs12A enzyme, which is not encumbered by any intellectual property to. We believe this strong IT position, coupled with our exclusive right to grant future IP licenses to companies’ desire to commercialize CRISPR/Cas9 medicine is a significant value driver for our stakeholders.
With that, I will turn over to our new Chief Medical Officer, Baisong Mei.
Baisong Mei
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.
Mark Shearman
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.
Michelle Robertson
Thank you, Mark, and good morning, everyone. I’d like to refer you to our press release issued earlier today for a summary of our financial results for the second quarter of 2022. I’ll take this opportunity to briefly review a few items. Our cash, cash equivalents, and marketable securities on June 30 were $528 million compared to $556 million in the prior quarter. We continue to be disciplined with our expense management and our cash runway is expected to extend into 2024. Revenue for the first half of the year was $13 million compared to $7 million for the same period last year, the increase was primarily attributable to an additional program licensed under our collaboration with BMS.
G&A expenses for the first half of the year were $36 million compared to $43 million for the same period in 2021. The decrease was primarily driven by performance awards granted in 2021 that were recognized in the second quarter of 2021. R&D expenses for the first half of the year were $82 million compared to $76 million for the same period last year. This increase was primarily driven by increased manufacturing and clinical investments, and employee-related expenses.
And lastly, as Mark mentioned, we recently announced a collaboration with Immatics. As part of this collaboration, Editas received an upfront cash payment and is eligible for additional payments based on development, regulatory and commercial milestones. Editas will also receive royalties on future net sales on any products that may result in this collaboration. Overall, Editas remains in strong financial position, and we continue to advance our programs.
With that, I’ll turn the call back to Gilmore.
Gilmore O’Neill
Thank you, Michelle. Again, I want to reiterate how excited I am for the future of Editas. While we have exponentially enhanced our technology capabilities, we are no longer simply a technology platform company. Over the past several years, we have focused on building out our operations and manufacturing teams and have our sights on the end go, which is commercialization of life-changing medicines for our patients, and through very thoughtful clinical development, we are rapidly transitioning to a therapeutics company while remaining on the cutting edge of innovation. Underpinning this transition of further advancements to our innovative technologies, thus there’s our proprietary sleep knock-in gene-edit platform. We also continue to be active with business development activity and look forward to advancing discussions related to our foundational intellectual property.
Moving forward, we will prioritize assets that maximize the possibility of technical, regulatory, and commercial success. This includes current and future programs in our pipeline. Spot is in store for the rest of this year. On the in vivo side, we will be providing a more comprehensive clinical update on our BRILLIANCE trial of EDIT-101 later this year. That update will focus on safety data, additional POC data for CEP290 editing in the retinal photoreceptors, and the identification of the optimal patient segment and functional visual outcomes for use in the future registrational study. Following feedback from the FDA, we plan on initiating IND-enabling studies for EDIT-103 for row ADR later this year. Moving to ex-vivo, we expect to have initial top-line clinical data for our RUBI study in sickle cell disease later this year, which will include data from the first patient and potentially second patient.
Finally, we have begun screening base thalassemia patients for the Editas study of EDIT-301 for beta-thalassemia and anticipate apheresis editing of product as first patient dosing all before the end of the year.
We thank all of you for your interest and support Editas. And with that, we are ready to open up the call for Q&A.
Question-and-Answer Session
Operator
[Operator Instructions] Our first question is from Gena Wang with Barclays. Please proceed with your question.
Unidentified Analyst
Thank you for taking our question. This is Tom for Gena. I have two questions on the — I think third patient and [indiscernible]. So first, I understand it might be earlier, but do you have a rough estimate of the required following period and trial size for both indications, given the FDA’s experience with other more advanced products? Secondly, on the trial enrollment side, would you be able now to dose the next few patients in parallel? Or when would you be able to do that?
Gilmore O’Neill
Thank you. I’m afraid I couldn’t catch your name, but I propose the size of the study, we are closely monitoring while the FDA and other regulatory authorities are guiding to us and to our peers in this space, but we have designed a study to enable us to recruit the patients necessary and we have the manufacturing capacity to ensure that cumulative supply will be available for those numbers. With regards to enrollment, we have in our current protocol a set of criteria for the first couple of patients where when we follow them for approximately 40 days, or rather specifically 40 days, and hold an independent data monitoring review of safety data to initiate the second and third patient. After that, our intention is to move as quickly as is feasible and this is one of the reasons why I’m so happy that we have our new Chief Medical Officer, Baisong Mei with his experience in this space to help us really double down on clinical execution.
Operator
Thank you. Our next question is from Joon Lee with Truist Securities. Please proceed with your question.
Joon Lee
Right. Thanks for the update and taking our questions and looking forward to the progress with the new additions to the management. I have two questions. On EDIT-301, are you able to disclose how quickly the cells engrafted? Also, I presume bypassing the need for biologic EDIT-301 with Promoter edits could lead to better et compared to using enhancer edit? Do you think that will show up as a clinical benefit? Or is that more of a manufacturing consideration? And lastly, how are you looking to differentiate from EXO-Cell? And I have a quick follow-up.
Gilmore O’Neill
Thank you very much, Joon. So we have not — we will be planning to disclose our clinical data at the end of the year when we will actually be able to give outcomes around engraftment as well as hematological parameters. With regard to the differentiation, we believe that as you say, editing the promoter of the gamma-globin actually does increase the durability expression of fetal hemoglobin. That may be displayed in the hematological parameters over time, but I think as we have said in previous discussions, we anticipate that the clinical benefit of which we believe there will be important world, we’ll declare themselves over a longer-term follow-up for patients. I actually could not hear your third question, I’m afraid.
Joon Lee
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.
Mark Shearman
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.
Operator
Thank you. Our next question is from Dae Gon Ha with Stifel. Please proceed with your question.
Dae Gon Ha
Great. Good morning. Thanks for taking our questions and congrats on all the progress and welcome on board Gilmore nice to speak to you again. Two questions from us. I just wanted to follow up on June’s question about differentiation. Gilmore, when you’re talking about differentiation between EDIT-301 and CTX001 potentially declaring itself over the longer term. I guess how long of a follow-up would we anticipate before we differentiate or see that differentiation play out given that the market dynamics at that point would be presumably CTX001 being marketed? Then secondly, on EDIT-301, Mark, just looking back at the strategy you have here using the dual vector, I guess can you walk us through sort of the idea of why it would be superior compared to a single vector utilizing EDIT-101 and perhaps as we anticipate the second half update from BRILLIANCE, is there anything that you would be looking to that could be potentially seen as a read-through to EDIT-301 as the IND enabling studies get underway? Thanks so much.
Gilmore O’Neill
Thanks very much, Dae Gon. Good to talk again. Let me address the first question around 301 differentiation and the read-through on the clinic. That would be something that we will actually have to determine over the long term. However, we do see the potential here of persistent and durable feet homologation is something that we could see based on hematological parameters in the near term. In the medium to long term, we could see and would anticipate reading those through on the clinical side to maintaining hemoglobin levels at a very favorable level to ensure long-term benefits to patients with regard to end organ health. We would see that reading through in both sickle cell and beta-thalassemia in the long term. I will say you address market dynamics. I think I’d like to address that, too. while CTX001 may actually be first to market, based on our experience and observation of recent gene therapeutics or so-called one-on-one therapy launches, we anticipate that the pull-through from that CTX001 approval will not actually lead to a large number of treated patients here a large number of untreated patients remain at the time of our launch and commercialization because of the challenges around site capacity, and again, this is what we’ve seen with other gene or one-on-one therapies as well as the challenges around negotiating access and reimbursement. For those reasons, we do believe that market is there for our product and then with our differentiation of 301, we believe that this could be the treatment of choice.
Mark Shearman
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.
Operator
Thank you. Our next question is from Jay Olson with Oppenheimer. Please proceed with your question.
Jay Olson
Hey, everybody. I want to also welcome the new management team, thank you for the introduction, and thanks for taking the questions. Maybe just on EDIT-101, can you just comment on the pace of enrollment in the pediatric cohort and any color you can provide there in terms of when you expect to complete dosing in the mid-dose cohort. And when is the next IDMC safety review and also any color you can provide on the dosing on expanded cohort, how many patients, and when we should expect to see data or a clinical update in the second half of the year? Thank you.
Gilmore O’Neill
Thanks very much, Jay. So let me start at the end and just say that we will be on track to provide clinical data update at the end of the year or before the end of the year. Prior guidance has been around the October-November time frame and in that data set, we will provide efficacy data from the completed mid- and high adult dose cohort from an efficacy point of view. For safety, we will actually have a data cut from all those patients as would be good practice. With regard to the IDMC, the IDMC is scheduled to meet mature that is the independent data monitoring committee is scheduled to meet later this quarter, at which point it will evaluate data, including the two pediatric mid-dose patients, and that meeting would be given a decision to enable us to start enrolling in the high-dose cohort. Then with regard to the timing of pediatric enrollment, the approach we initially used was slower than we expected. One of the reasons that I’m here and that Baisong has joined us, is to really double down our efforts on clinical execution. We have amended and are actively amending the approach and anticipate that we will be enrolling faster. I do have to say that I don’t have a complete line of sight yet, but we’ll share that with you in the near future.
Mark Shearman
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.
Operator
Our next question is from Luca Issi with RBC Capital Markets. Please proceed with your question.
Luca Issi
Hi, this is Reena Patel on for Luca Issi, thank you for taking my question. I just wanted to ask Mr. O’Neill, given this is your first earnings call, can you talk about the top three reasons why you decided to join the organization and maybe what was the biggest hesitation or concern? And just another on sickle cell, assuming Vertex and CRISPR and possibly blue get approved ahead of you. How are you thinking about the likelihood of getting approved on a single-arm trial? Can the FDA ask you to run a head-to-head trial?
Gilmore O’Neill
Sorry, Reena, thanks for your question. This is Gilmore here. I just want to clarify. I am the one who has just joined the company and based on just the company, Michell, I’m happy to say, has been with the company for some time as a Chief Financial. So forgive me, I just want to be sure that maybe you’re addressing the question to me and what I would say is that what drew me to the company were a number of things, not just the fact and the history of its foundational CRISPR technology, but very importantly, the strength of the science that I saw here and particularly the differentiated core expertise in nuclease design and engineering, one nice example of the AsCas12a evolution, which is a high fidelity, high-efficiency enzyme that we have actually now have in the clinic.
In addition, the guide RNA, there is a substantial expertise in both chemistry and design for guide RNA. Other important capabilities also sit within our discovery group, particularly around our quantitative biology, which aids us in our design of a guide RNA. Finally, the CMC capabilities, which are actually impressive with both scale and quality And you’re more important the concrete examples that we have clinical supply, both for delivery of AAV as well as autologous edited cells. I did see finally about CMC, but there are other things that drew me as well. The fact that the technology is in the clinic using two platforms, and quite frankly, the cash position, which Michelle described as strong and was actually importantly in joining.
Then the other question was around Vertex and CRISPR and what the impact of those approvals might have on our design. How we talk to the FDA and the outcomes are discussed with the FDA are some things that I would not want to speculate on, but I will tell you that our trial currently is designed in a way that enables us to look at both hematological parameters as well as clinical pants, both for the sickle cell patient population that we are treating or in recruiting as well as the beta cell patient population. And the precedent that we’re seeing gives us some confidence about our approach and obviously, as the field evolves, we will be more confident, but I think currently, we are very well positioned in our design approach to developing 301. The other thing I do actually want to remind everyone of is that our partial clinical hold was removed by the FDA. Why does that matter? It matters because it enables us to use all the efficacy data in the ongoing trials as part of a marketing application.
Operator
Thank you. Our next question comes from Rick Bienkowski with SVB Securities. Please proceed with your question.
Rick Bienkowski
Hey, good morning. Congrats on the progress and thanks for taking our questions. There are two from us. My first question is regarding the development of EDIT-301 and beta-thal. Given that there is an upcoming PDUFA date for a competing gene therapy candidate for beta-thal in the US, can you speak to the opportunity along with some of the challenges in starting Phase 1 trials in a treatment setting with an approved gene therapy product? For my second question, both the alpha beta and gamma delta T cell programs have license agreements with outside partners and the INK thal program is currently being developed in-house. I was hoping to get your thoughts on the rationale for keeping this program fully owned and what the right stage of the development would be for thinking about whether or not a partnership here would make sense.
Gilmore O’Neill
Thanks very much, Rick. So with regard to EDIT-301, the opportunity for beta-thalassemia and indeed sickle cell remains strong, we believe. We believe that it has value on its own right, we believe it’s a differentiated product, but actually, very important, we believe that at the time that we both initiate or whether as we continue to recruit patients into our ongoing trials and when we look at the commercial space when we would launch, we believe that going to a number of the challenges I’ve outlined, the uptake and the number of treated patients will actually be relatively slow, certainly for that first approval because of challenges around access and reimbursement. We’re actually confident that there is value to this program for those reasons and also that we will be able to execute and enrolled in our ongoing Edita as well as RUBY studies.
With regard to the partnering, you pointed out our partnerships in some immuno-oncology spaces. As Mark has said, the INK program has moved well. We are always interested in factoring or looking at the potential for partnerships. One of the great opportunities and challenges that I have seen with Editas is the broad applicability of its technology and I think I said when I joined the organization and maintained a position that one very good way to maximize the value of that technology for patients as well as for our other stakeholders is to maximize and broaden our bandwidth for execution through partnerships and so we are open to looking at partnerships and have said before that we are open to partnerships across a number of our platforms, including the INK platform.
Operator
Thank you. Our next question is from Philip Nadeau with Cowen and Company. Please proceed with your question.
Philip Nadeau
Morning thanks for taking our questions. A couple on the ocular programs from us. First, on EDIT-101, I think you’re guiding to defining the registrational trial design by the end of the year. It seems to us like you only have a pretty modest experience with the pediatric high dose by that time. So how can you design the registrational trial without that high dose data? When that high dose data provide important information on the dose necessary patients and possibly the efficacy endpoints?
Gilmore O’Neill
We have not guided to defining a final registration study by end of the year for the very simple reason that one would have to do that in discussions with regulatory authorities, including the FDA. I should say, by the way, Phil, thank you for your question. Good to meet you, but we have not given that guidance. What we anticipate doing is looking at that data, we will have a large data set from our mid- and high-dose adult patients and will be able to look at a segment of the patient population because we have seen proof concept in the adult subjects, and we will be also looking at and evaluating and selecting potential endpoints, and we will bring that entire data set to our regulatory engagement. It is important to note that we also have a natural history data set that we’ll be looking at that actually also helps us in selecting, designing, and understanding performance and interaction of those good endpoints with a broad population that spans the pediatric and adult population.
Philip Nadeau
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?
Mark Shearman
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.
Operator
Thank you. Our next question is from Joel Beatty with Baird. Please proceed with your question.
Joel Beatty
Thanks for taking the question. On EDIT-101, have you gotten any FDA feedback on the thought of the use of the natural history cohort as opposed to using a control arm in a registrational trial?
Gilmore O’Neill
Thanks very much, Joel. Clearly, the fact that we have a natural history cohort has been a very important point in our discussions within internally around our strategy of clinical development. We have not yet had such discussions with the regulatory authorities, but we will be using both our clinical interventional experience in the BRILLIANCE trial as well as a natural history study as we consider the optimal design and prepare for those discussions with the authorities and through the FDA.
Operator
Thank you. Our next question comes from Yanan Zhu with Wells Fargo Securities. Please proceed with your question.
Yanan Zhu
Hi, thanks for taking my question and I wanted to add my congratulations to Gilmore and Baisong for your new appointment. First question is related to 301 million I think you touched upon the differentiation from CTX001 earlier in the call. I just want to follow up more specifically whether you expect to see greater methemoglobin induction with your promoter editing approach compared with CTX001. Also, when you review currently available clinical data for CTX001, where do you see the potential unmet need in those data set and perhaps your perhaps 301 could further improve in those areas? Also on 301, how many patients have you freezed and/or manufacture the product for in the RUBY study, and how at the year-end data update, should we expect just the first patient data, or could we expect more patients data at year-end? Thank you.
Gilmore O’Neill
Thanks very much, Yanan, and nice to meet you. Let me start at the end and I’ll work back and also site and ask Mark to address some of the preclinical data. We are expecting to and planning to share clinical data from one and possibly two patients at the end of this year. That patient data will include safety as well as engraftment and hematological parameters. With regard to the unmet need, we believe that the differentiation given by our product, and there are two elements of the differentiation. I’ve highlighted the fact that we anticipate durable, a very durable expression of fetal hemoglobin owing to the promoter of the Gammaglobin genes that we’ve targeted, but in addition, we’re using a high fidelity, highly efficient editing nuclease in the form AsCas12a, and what we believe is that, that durable benefit is actually — has the potential to be an important differentiator, simply because it is independent. It drives expression independent of CRISPR vitro cohesive, which is something that could actually become increasingly mitigated over time and so it would be important to maintain that durable expression of fetal hemoglobin and doing it independently of CRISPR cohesive, confers a significant differentiated advantage in the long term. Then with regard to our confidence around the expression of fetal hemoglobin, going to ask Mark just to talk a little bit our preclinical data.
Mark Shearman
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.
Operator
Thank you. Our next question is from Steven Seedhouse with Raymond James. Please proceed with your question.
Ryan Deschner
Good morning. This is Ryan Deschner on for Steve. I wanted to ask, what is your general expectation for neutrophil and platelet engraftment for patients in the sickle cell study, and have there been any SAEs of note in particular associated with the cell product? Thank you.
Gilmore O’Neill
Thanks, Brian. Good to meet you. Our expectation for engraftment of places and neutrophils, we actually designed our protocol to capture around day 30 to 40. Obviously, it varies across patients, and that has been the experience for both autologous and our generic experience in general, but we will be able to share more specifics of that near the end of the year and as the program progresses. The Second question is we’ve not actually seen SAEs in this experience to date, but obviously, we are aware that the procedure itself beyond the editing, but in general, for engraftment does carry identified risks and obviously, we monitor that very closely, but I think very importantly, we have not seen SAEs at all and more specifically, have not seen adverse events that would give us concern about the product.
Operator
Thank you. Our next question comes from Madhu Kumar with Goldman Sachs. Please proceed with your question.
Unidentified Analyst
This is Amay on for Madhu. For my first question, could you give us a sense of what kind of efficacy profile do you need to see at a given 101 dose to pursue a registrational trial, and then what value do you present update at a medical meeting or separately?
Gilmore O’Neill
With regard to our success criteria, what we would want to see is an extension of the POD that we’ve seen with stability and potentially improvement in some of the adult patients. I think the other determinants of success for the study will be identifying a segment of the patient population that maximizes or has a maximum probability of responding to the therapy and also interacting with a select set of endpoints that will actually also be determined by the Phase 1 study and our interaction or our analysis of that with co-analysis of the natural history study. And with regard to selection of the dose, the Phase 1 study will actually obviously be part of selecting that dose. And as you say, the success criteria for selected dose will be determined by being maintained stability and improvement in a segment of patients. And we are currently evaluating where we would share that data, but anticipate that it’s likely to be at a webinar later this year.
Operator
Thank you. There are no further questions at this time. This does conclude today’s conference call. Thank you for your participation. You may now disconnect.
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