Earnings Call Transcript - EDIT Q2 2023

Operator, Operator

Good morning and welcome to Editas Medicine's Second Quarter Conference Call. 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.

Cristi Barnett, Corporate Communications and Investor Relations

Thank you, Maria. Good morning, everyone and welcome to our second quarter 2023 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate updates. A replay of today's call will be available in the Investors section of our website approximately 2 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 the 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 statements, even if our views change. Now, I will turn the call over to our CEO, Gilmore O’Neill.

Gilmore O’Neill, CEO

Thanks, Cristi and good morning, everyone. Thank you for joining us today for Editas' second quarter earnings call. I am joined today by 3 other members of the Editas executive team, our Chief Medical Officer, Baisong Mei; our new Chief Financial Officer, Erick Lucera; and our new Chief Scientific Officer, Linda Burkly. I joined Editas 1 year ago tasked with guiding its evolution from platform development company to commercial therapeutics company. In January of this year, we shared Editas' strategy and a set of objectives for 2023. The strategy, just as a reminder, comprises 3 pillars: first, to accelerate the clinical development of EDIT-301, our autologous ex vivo cell therapy for sickle cell disease and beta thalassemia and drive toward approval and launch. Second, to strengthen our discovery organization by dividing it into an advanced technology group and a translational therapeutics discovery group to sharpen our discovery focus on in vivo editing therapies; and third, expand our business development activities to partner complementary technological capabilities that can advance our in vivo pipeline development in addition to out-licensing our robust IP and know-how to maximize the use of CRISPR-based medicines. Our 2023 objectives include providing a clinical update from the EDIT-301 RUBY trial by the end of 2023, providing a clinical update for EDIT-301 EDIT trial for transfusion-dependent thalassemia by the end of 2023, dosing 20 total patients in our EDIT-301 RUBY trial by year-end, hiring a new Chief Scientific Officer with specific expertise aligned to our vision, advancing discovery of in vivo editing of hematopoietic stem cells and other tissues, and leveraging our robust IP portfolio and business development to drive value and complement our gene editing technology capabilities. So, how have we executed against this strategy and these objectives in the second quarter? On the leadership side, we made 2 important hires to drive our new strategy. Just last week, we announced that Linda Burkly, a respected scientist and highly experienced therapeutic discovery leader, has joined Editas as our new Chief Scientific Officer. Linda has an outstanding track record of inventing or contributing to the foundations of multiple approved medicines and late-stage clinical candidates. We are looking forward to Linda's leadership as we build on the current in vivo editing work in hematopoietic stem cells and other tissues. Also, 8 weeks ago, we announced that Erick Lucera, a highly experienced former biotech buy-side investor, Chief Financial Officer, and Strategic Corporate finance executive had joined Editas as our new Chief Financial Officer. You will hear from him later on this call. As a reminder, under our new target selection criteria, we will select therapeutic targets that allow our genome editing approach to differentiate maximally from the current standard of care for serious diseases. The target selection criteria will work to identify targets that maximize the probability of technical, regulatory, and commercial success. Linda will tell you about these developments at a future date. We remain on track to dose 20 RUBY patients by the end of 2023 and we commenced parallel dosing of patients in our EDIT-301 trial in the second quarter of this year. In June, we presented clinical data from our RUBY trial at the European Hematology Association's Annual Scientific Meeting and data from both our RUBY and EDIT-301 trials at a company-sponsored webinar. We remain on track to provide another clinical trial update by year-end for both trials. We will share a further update on our progress in the coming months. Baisong will share further details regarding the development of 301 in his remarks as well as recapitulate the RUBY and Editas takeaways and clinical data that we provided in June. As we have previously stated, we plan to engage with the FDA in the second half of the year. After EHA and our company-sponsored webinar, we raised approximately $117 million in net proceeds from our follow-on issuance of common stock, extending our cash runway into the third quarter of 2025 as we continue our advancement of EDIT-301 towards BLA, prepare for commercial manufacturing and build our pipeline to transform the treatment of serious diseases. As we progress towards our goal of delivering life-changing medicines to patients, we also continue to expand our footprint to support our manufacturing and quality management for clinical supply and for preparation of commercial launch. We recently increased our cleanroom capacity and are moving to a new AsierDevons facility. This new facility and increased capacity will support the scaling of the EDIT-301 program, manufacturing clinical supply for RUBY and EDIT trials and preparations for commercial readiness. Turning to our intellectual property position, as a reminder, Editas holds a large portfolio of foundational U.S. and international patents and is the exclusive licensee of Harvard University's and Broad Institute's Cas9 patent estate covering Cas9 use in making human medicines. Only a small fraction of these patents are involved in the ongoing U.S. PTO interference proceedings, and we remain confident that our IP portfolio provides meaningful value now and in the future. We are energized by the promising efficacy and safety data that we shared in June, seeing that EDIT-301 may be a clinically differentiated onetime durable medicine that can provide life-changing clinical benefits to patients with sickle cell disease and beta thalassemia long-term, specifically driving early and robust correction of anemia and sustained increases in fetal hemoglobin. With our sharpened strategic focus, our world-class scientists and employees, and our keen drive in execution, we continue to build momentum to progress our strategy to deliver differentiated editing medicines to patients with serious genetic diseases. We look forward to updating you on our progress in executing our new strategy throughout the year. Now, I will turn the call over to Baisong, our Chief Medical Officer.

Baisong Mei, Chief Medical Officer

Thank you, Gilmore. Good morning, everyone. Let's start with the EDIT-301 RUBY trial for sickle cell disease. As Gilmore stated in his remarks, we continue to dose and enroll patients in the RUBY trial. As we have previously shared, we began parallel dosing of patients in the RUBY trial earlier this year and we remain on track to dose a total of 20 patients in the RUBY trial by year-end and to provide additional clinical data by then. We will share further updates on enrollment progress in the coming months. As Gilmore also mentioned, we plan to engage with the FDA in the second half of the year. In the EDIT-301 trial for transfusion-dependent beta thalassemia, or TDT, we continue to dose and enroll patients. We commenced parallel dosing in this trial in the second quarter. We remain on track to provide an additional clinical update from the EDIT-301 trial by year-end. As we have done for the RUBY trial, we are also taking multiple measures to accelerate the development of EDIT-301 for TDT and we have a strong foundation. We have enrolled multiple patients who have been dosed or have completed treatment and have undergone engraftment. Turning to EDIT-301 clinical data, in June, we shared promising RUBY clinical data in an oral presentation at the European Hematology Association Congress, or EHA, followed by our company-sponsored webinar where we also presented positive initial data from the first patient treated in the EDIT-301 trial. The RUBY data from the EHA covered safety and efficacy data from the first 4 patients treated, including 10 months data from the first patient and 6-month data from the second patient, including total hemoglobin and fetal hemoglobin. Excitingly, the data were consistent with the clinical results we shared in last December. I would like to take a few minutes to recap some of the RUBY trial key takeaways from our presentations in June. These include the following: EDIT-301 drives early robust correction of hemoglobin to a normal physiological range in as early as 4 months; it drives robust sustained increase in hemoglobin in excess of 40%, All 4 dosed RUBY patients remain free of vaso-occlusive events (VOE) since EDIT-301 treatment; all dosed RUBY patients and 1 patient showed successful neutrophil engraftment within 1 month of dosing and have stopped regular transfusion; the treatment was well tolerated by patients and the safety profile was consistent with myeloablative busulfan conditioning and autologous hematopoietic stem cell transplant; and the trajectory of changes in fetal hemoglobin and increased expression of fetal hemoglobin was consistent across EDIT-301 treated patients. Looking at the data in more detail, RUBY study patient 1 experienced normalization of total hemoglobin by 5 months after EDIT-301 infusion and these normal levels persisted during the 10 months follow-up. Patient 1's fetal hemoglobin fraction increased to 45.5% 5 months after treatment and persisted during the 10 months follow-up. The increase of total hemoglobin and fetal hemoglobin of RUBY patients 2, 3, and 4 followed the same trajectory as patient 1. For the first patient treated with EDIT-301, they achieved improvements that resembled that of the 4 RUBY patients. This first patient achieved a hematoglobin level of 34.9% or over 4 grams per deciliter in just 1.5 months after EDIT-301 treatment. We continue to believe that EDIT-301 can potentially provide robust clinical benefits to patients, potentially provide clinical differentiation in the long-term. As we have previously stated, the choice of CRISPR enzyme and the gene editing target to switch on fetal hemoglobin expression is critical. We use our proprietary ASKA enzymes to edit the HBG1 and HBG2 promoters. ASKA increases editing efficiency and significantly reduces off-target editing when compared to other CRISPR enzymes, including Cas9. HBG1 editing in human CD34 positive cells resulted in greater red blood cell production, normal morphology, and improved red blood cell health when compared to editing of BCL11A. Based on clinical data so far, we believe that sustained normal levels of total hemoglobin could be a potential point of differentiation. As a reminder, a sustained normal total hemoglobin level is an important clinical outcome for patients as the correction of anemia significantly improves quality of life and ameliorates organ damage. As I shared last quarter, I have been visiting our RUBY clinical trial sites and continuously speaking with investigators. I appreciate the inclusiveness and support when we investigate and study size. I'm pleased with the momentum of EDIT-301 in patient recruitment, editing, and dosing in both studies. I'm excited to hear from the investigators that the patients dosed with EDIT-301 are already seeing positive changes in their lives. We look forward to sharing additional updates as the year progresses, including additional RUBY clinical trial data by year-end. Now, I will turn the call over to Erick, our Chief Financial Officer, to review our financials.

Erick Lucera, Chief Financial Officer

Thank you, Baisong and good morning to everyone. Let me first say that I'm excited to be speaking to you today. I came to Editas because I was impressed by the quality of the company's science, its leadership in the gene editing field, its strong IP portfolio, and its highly differentiated work compared to other players in the field. I was eager to take this opportunity and join Editas at this pivotal time, as we just shared exciting human data for our lead asset and we're preparing our regulatory and commercialization strategy. I look forward to leveraging my experience to help the company execute our vision to bring innovative medicines to patients and drive shareholder returns. With that, 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 2023. In future quarters, I will provide more guidance. And for now, I'll take this opportunity to briefly review a few items. Our cash, cash equivalents, and marketable securities as of June 30 were $480 million compared to $402 million as of March 31, 2023. We expect our existing cash, cash equivalents, and marketable securities to fund our operating expenses and capital expenditures into the third quarter of 2025. Revenue for the second quarter of 2023 was $2.9 million compared to $6.4 million in the same period last year. The decrease is related to a program license opt-in from our collaborator, Bristol-Myers Squibb, that occurred in the second quarter of 2022 that did not occur in the second quarter of 2023. General and Administrative expenses for the quarter were $17.2 million, which remained relatively flat from $16.9 million for the second quarter of 2022. The slight increase in expense is primarily attributable to increased professional services expenses to support business development activities, partially offset by a decrease in stock compensation expense. Research and Development expenses this quarter were $29.8 million, representing a decrease from $43.7 million in the second quarter of 2022. The decrease in expenses reflects the focus on execution following the strategic reprioritization of our portfolio, offset by increased activities to accelerate the development of EDIT-301. Overall, Editas remains in a strong financial position, and our sharpened discovery focus, coupled with our recent capital raise, allows us to concentrate our talent and extend our cash runway further into 2025, which provides ample resources to support our continued progress in the RUBY and EDIT clinical trials of EDIT-301, continued commercial manufacturing preparation, and advancing our discovery efforts. As a former investor, I know the value of buy-side and sell-side knowledge, and I look forward to working with the company and hearing from our shareholders as we work to advance our gene editing medicines. With that, I will hand the call back to Gilmore.

Gilmore O’Neill, CEO

Thank you, Erick. It has been an exciting year for Editas thus far and a fulfilling first full year for me at Editas. We look forward to continuing our transformation and sharing our progress with you as a reminder, our strategic objectives for the year include providing a clinical update from the EDIT-301 RUBY study by end of this year, providing a clinical data update from the EDIT-301 EDIT trial for transfusion-dependent thalassemia by the end of 2023, dosing 20 total patients in our EDIT-301 RUBY study by year-end, advancing discovery of in vivo editing of the hematopoietic stem cells and other tissues, and leveraging our robust IP portfolio and business development to drive value and complement our gene editing technology capabilities. As always, it must be said that we could not achieve our objectives without the support of our patients, investigators, employees, and you. Thanks very much for your interest in Editas. And we're happy to answer questions now. Thank you.

Operator, Operator

At this time, we will be conducting a question-and-answer session. Our first question comes from Terence Flynn with Morgan Stanley.

Terence Flynn, Analyst

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

Gilmore O’Neill, CEO

Thank you very much, Terence, for your questions. Regarding the in vivo program, our focus is on maximizing the chances of technical and commercial success with clear positive differentiation from the standard of care. The work is continuing to progress, and I am particularly pleased to welcome Linda Berkly, whose leadership will help us advance this initiative. We will provide updates on timelines at an appropriate moment once Linda has had time to settle in and make her impact. Concerning the Azure facility, we plan to engage with the FDA during this half of the year and are on track for those discussions. We do not expect significant or major work during the transition; essentially, our existing processes are mostly finalized. We are in communication with the agencies to ensure we are aligned on our readiness for commercialization.

Operator, Operator

Our next question comes from Samantha Semenkow with Citi.

Samantha Semenkow, Analyst

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

Gilmore O’Neill, CEO

Yes. Thanks very much, Samantha, for your question. Linda has just joined, and so I'm going to talk about how she and I are really aligned philosophically on our approach to this. We have made substantial ongoing work and progress in that area. The challenges are to deliver the functional enzyme and guides to the hematopoietic stem cells. The good news is that we feel that we have certainly solved 2 of the 3 challenges. The first being that we have human validation of our Cas12a enzyme thanks to our EDIT-301 program. Additionally, we have validated in our clinical trials the use of our target fetal hemoglobin promoter. The specific targeting and delivering of those mechanisms to the hematopoietic stem cell is something that we're working on currently and we'll be happy to update you more on specifics and progress there at an appropriate time.

Operator, Operator

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

Greg Harrison, Analyst

What feedback have you had from physicians since the recent update at EHA regarding a clinically meaningful data set in sickle cell, especially with respect to hemoglobin response? And what are they looking for from the next update?

Gilmore O’Neill, CEO

Thanks very much, Greg. I'm going to ask Baisong to take that question.

Baisong Mei, Chief Medical Officer

Thanks, Greg, for the question. Absolutely, we received very positive feedback from our investigators as well as the patient community. From investigators, they’re excited to see the consistency of our results and the normalization of the total hemoglobin. I actually specifically asked one of our investigators how they feel about the normalization of hemoglobin and the response was a strong endorsement of its importance. We've also heard from patients who reported significant improvements in their energy levels and overall quality of life due to the treatment. The volume of inquiries from patients increased tenfold after our June presentation. We are very pleased with this growth in interest, covering not only the U.S. but also Canada, and we are assisting interested patients in finding opportunities to join our trials.

Operator, Operator

Our next question comes from Joon Lee from Truist Securities.

Joon Lee, Analyst

Congrats on the progress. Your cash guidance into the third quarter of 2025 is pretty specific. What's baked into that guidance? Specifically, does that include preclinical and IND-enabling studies of in vivo programs and/or BLA and pre-commercial activities for EDIT-301? In fact, is it your intention to commercialize EDIT-301 yourself? Or would you be looking to a partner to help you with the heavy lifting on the commercial side?

Gilmore O’Neill, CEO

So I think, Joon, I'll let Erick start.

Erick Lucera, Chief Financial Officer

Yes, with respect to the specific dollars that are included in the cash runway guidance, we have included all of the BLA activities and everything we need to do to prepare for that within the guidance. With respect to IND-enabling studies, we do have some early preclinical research amount included in that, and we'll assess any reallocations based on Linda's contributions in the future. Regarding commercialization, we see commercialization as a nice upside, particularly for expanding our global footprint. We previously stated that we would definitely want to partner internationally. As we discuss partnerships or potential partners, if the terms align favorably, we could consider co-commercialization in addition to global development and commercialization in the United States.

Operator, Operator

Our next question comes from Gena Wang with Barclays.

Gena Wang, Analyst

Two very quick questions. Regarding the in vivo target, is it fair to say it will be liver targeted with particle delivery? And then regarding the manufacturing, just to follow up. You do have a facility now. What is your plan for commercial manufacturing capacity in the future? Will you plan to wholly conduct it in the U.S. or will you also collaborate with the CDMO for the commercial supply?

Gilmore O’Neill, CEO

Thanks very much, Gena. With regard to the in vivo targets, we've talked about hematopoietic stem cells as an area of particular interest because of our EDIT-301 work and the validation of our ASKA technology. The liver is definitely on our list of potential tissues for targeting, and we are interested in non-AAV technologies and LNPs; this is certainly an area we have been working on. Regarding manufacturing, the Azure deal enables us to build toward our commercial capacity and readiness for launch. More specific elements around capacity and prediction are being worked through, and we will discuss those in the future.

Operator, Operator

Our next question comes from Dae Gon Ha with Stifel.

Dae Gon Ha, Analyst

Two for me as well. One, with regards to Baisong, your remark on total hemoglobin as being a differentiation. At what point do you draw the line in the sand and look at that as a differentiator from potential competitors? And then as a follow-up to that, Vertex announced last night that there will be an AdCom for XL. What are your thoughts on the potential points of contention or discussion as we approach that? How would you see the ASKA targeting the HBG promoter potentially affecting any future approval discussions?

Baisong Mei, Chief Medical Officer

Thanks for the question. Regarding total hemoglobin and related differentiation, we are actively looking at this in our current protocol. We are focused on 3 categories: hematological and other lab values, end organ function, and patient-reported outcomes. For endpoint measures, we monitor key organ functions such as cardiovascular, hormonal, and renal function; we believe that total hemoglobin increase will have a positive impact on quality of life and organ health. Related to patient-reported outcomes, we will actively track factors like fatigue and pain, which are main complaints from sickle cell patients. The normalization of hemoglobin is certainly important and we continue tracking that and will provide updates accordingly. Regarding the AdCom, we are looking forward to learning how the FDA addresses data presented at that meeting; we do not foresee the ASKA targeting HBG promoter raising any additional concerns in that regard.

Operator, Operator

Our next question comes from Phil with Cowen & Company.

Unidentified Analyst, Analyst

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

Baisong Mei, Chief Medical Officer

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

Unidentified Analyst, Analyst

Great. And then second question on the interference proceedings that you referenced in the prepared remarks. Can you remind us where the next steps in those proceedings are and when they could conclude?

Gilmore O’Neill, CEO

Yes. Thanks, Phil. The scheduling of oral presentations is the next step. These presentations have yet to be scheduled. We anticipate a judgment in early to mid-2024. It’s worth stating that we are confident that we will prevail as we have before, both in front of the Federal Circuit Appeals Court as well as with the U.S. PTO.

Operator, Operator

Our next question comes from Yanan Zhu with Wells Fargo.

Yanan Zhu, Analyst

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

Gilmore O’Neill, CEO

Thanks very much, Yanan, for that detailed question. I'll start. Regarding the FDA interactions that we are planning for this half of the year, we will discuss multiple elements, including our CMC, as I've mentioned, as well as engaging on clinical interactions. I'm glad that you highlighted where we see Vertex's BLA acceptance of an efficacy cohort of 17 patients with about 18 months of follow-up data, which I think serves as useful precedent. The upcoming AdCom will also provide valuable insights to aid our discussions with the FDA on what our pivotal path and BLA filing strategy might look like. Concerning differentiation, we are evaluating the regulatory designations, and we are excited about the data we've seen so far and will carefully consider this on our path.

Baisong Mei, Chief Medical Officer

Yes, thanks. Your question about differentiation as it relates to eligibility for breakthrough designation is under careful consideration. We are excited by the data we’ve seen so far and will evaluate our approach accordingly based on feedback and data presented in due course.

Gilmore O’Neill, CEO

The good thing to highlight is that we are on track to dose 20 patients by the end of this year. This number is helpful in aligning with what we see with the BLA acceptance for competitors.

Operator, Operator

Our next question comes from Rick Bienkowski with Cantor Fitzgerald.

Rick Bienkowski, Analyst

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

Gilmore O’Neill, CEO

Thanks very much, Rick. You're quite right in noting that we have this exciting new agreement with Azure as we prepare for BLA and commercial launch. Regarding ex-U.S. manufacturing, we would prefer and expect to partner with a larger entity to help us expand our global footprint. We are keen to collaborate with partners who can assist in ex-U.S. activities.

Rick Bienkowski, Analyst

Right. Got it. And I do have one quick follow-up. One of the areas of development highlighted back in January this year was the exploration of milder conditioning regimens for stem cell transplant. Could you elaborate on how this could be incorporated into clinical trials and what the approval pathway looks like for the use of EDIT-301?

Gilmore O’Neill, CEO

Thanks very much, Rick. By developing milder conditioning, we see an opportunity to increase eligibility for sickle cell disease and TDT patients. The balance between reducing toxicities and maintaining engraftment efficacy is crucial. We see milder conditioning as something transplant sites will likely adopt, allowing for a more extensive application of autologous ex-vivo therapeutics.

Rich Law, Analyst

My congrats to both Erick and Linda for joining the company. Can you provide insight into how the partner programs are progressing, specifically the 11 alpha beta T cell program for BMS and the NK cell program with Shoreline Biosciences? When do you expect these programs to be disclosed in more detail?

Baisong Mei, Chief Medical Officer

Sure. Thanks very much, Rich. Regarding the 11 beta T cell program, we are pleased with the progress. The recent opt-ins suggest advancement, with some now in IND-enabling studies. However, BMS is managing this program, so they’ll provide more specifics. For the Shoreline deal regarding NK oncology, they are making good progress, and any specific updates would come from them.

Gilmore O’Neill, CEO

In regard to your second question about milder conditioning, yes, that could enable outpatient therapy setups, essentially balancing the reduction of risk alongside achieving successful transplant outcomes. Further evaluations in this regard will continue as we determine the best approach for expanding the eligible patient population.

Operator, Operator

Our next question comes from Jack Allen with Baird.

Jack Allen, Analyst

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

Gilmore O’Neill, CEO

Thanks, Jack. I'm going to ask Baisong to take that question.

Baisong Mei, Chief Medical Officer

Yes, Jack, thanks for that question. We definitely intend to expand this study to all age groups and are actively working toward that end. As we gather more data, we become increasingly comfortable evaluating our treatment protocols for younger patients.

Gilmore O’Neill, CEO

On the IP front, you mentioned that the hearings for the interference case have not been scheduled quite yet, but I would love to hear any thoughts you have as it relates to leveraging our IP while some of your competitors advance towards potential approval. Should we think about potentially a settlement coming before approval? Could it come after? How do you think about conversations surrounding that IP and how you're looking to leverage your strong position? I think our key position on our IP is that we want to ensure that it enables therapeutics for multiple patients across disease areas. There's a significant number of Cas9 products in development, and the economic value will vary depending on the disease area and development stage. We’re open to licensing but will protect our IP.

Operator, Operator

Our next question comes from Jay Olson with Oppenheimer.

Jay Olson, Analyst

Can you provide an update on the number of patients enrolled in the sickle cell and thalassemia trials to date? Since you're on track to dose 20 patients in sickle cell by year-end, do you have a similar dosing goal for thalassemia? And if so, how many? Can you also talk about the ex-U.S. opportunity for sickle cell and thalassemia?

Baisong Mei, Chief Medical Officer

So we have experienced great momentum in patient enrollment, and as stated earlier, we are on track to dose 20 patients by year-end. As for thalassemia, we are pleased with the patient enrollment progress but have not disclosed specific dosing goals for that study as of yet. Regarding the ex-U.S. opportunity, we see significant potential in this market and believe partnering with a larger entity will be instrumental in maximizing our global outreach.

Operator, Operator

Our next question comes from Manny with Leerink Partners.

Unidentified Analyst, Analyst

A lot of questions on this call have been around clinical trial execution, enrollment, et cetera. I want to dig into endpoints, if we could. You've discussed earlier on this call, pain and fatigue, some quality of life issues as important areas for potential differentiation. As clinical trial endpoints, these are notoriously variable and have some element of subjectivity. What efforts have you made to ensure comparability between your data on these endpoints and your competitors' data, which could likely present themselves before you do?

Baisong Mei, Chief Medical Officer

Very good question. To address the endpoints, after I joined Editas last year, we adjusted our primary endpoint to focus on complete remission of severe VOE, aligning it with other Phase III clinical trials in similar settings. We will monitor endpoints related to organ function as well as patient-reported outcomes. We are aware of the potential variability and subjectivity within these PROs, and we are taking steps to minimize those differences. Meanwhile, we will continue to inform our direction with our findings, adding to our understanding of where we stand in relation to other programs.

Gilmore O’Neill, CEO

I believe it’s worth reiterating that the biochemical and physiological differences we've already talked about are generating significant excitement within the medical community along with the overall patient population. We have received positive feedback regarding the efficacy data we presented earlier this year.

Operator, Operator

Our next question comes from Luca Issi with RBC.

Luca Issi, Analyst

One more question on manufacturing since you're moving your manufacturing process to a new facility. Is it fair to assume that the FDA will ask you to run a clinical bridging study similar to what we've seen from REGENX? Or do you think that just analytical comparability study will be sufficient? Any color there would be much appreciated. And then on R&D, the material decline in the R&D spend this quarter versus prior quarters. Could you provide additional color on what drove that and how we should model that line going forward? Lastly, any update on partnering LCA10?

Gilmore O’Neill, CEO

On manufacturing, it is important to note that our manufacturing has occurred under the Azure umbrella. We are already running our clinical supply in a separate manufacturing environment. The specifics of what will be required as it pertains to regulatory compliance will be outlined in our discussions with the FDA. Regarding R&D spending, the decrease in expenditures aligns with our sharpened focus on in vivo programs and the strategic reprioritization of our portfolio. Our recent divestiture in NK assets to Shoreline played a role in the adjustments of the spending. I won't discuss partnering on LCA10 until we have news to share. I will say that we've seen some promising signals in patient data and hope that it encourages more interested sponsors.

Liisa Bayko, Analyst

I just had a question to drill down on the gentler conditioning regimen program. What are you working on in that regard, and what do you think are the most promising approaches out there? When might we see something like that come to market, and if someone else developed it, could you fold it into your program? How do you view ownership of such a therapy versus collaborating with another company?

Baisong Mei, Chief Medical Officer

Thank you very much for the question. Milder conditioning is a crucial factor for many therapeutic indications, including oncology. We are monitoring the landscape and keeping active on various approaches out there. My familiarity is still on the rise, but the team’s work is critical in this area. I'll hand it to Gilmore for additional insights.

Gilmore O’Neill, CEO

To respond, the advances in milder conditioning can potentially be applied across various therapeutic areas. We want to ensure that our therapy remains adaptable and accessible, and we would be keen to fold in any promising milder conditioning therapies that other sponsors develop, particularly when it expands patient eligibility.

Operator, Operator

Ladies and gentlemen, we have reached the end of our question-and-answer session which concludes today's call. Thank you once again for your participation. You may now disconnect.