Editas Medicine Inc
NASDAQ:EDIT
Editas Medicine Inc
NASDAQ:EDIT
Price:
5.67 USD
0.89%
Market Closed
Updated:
May 6, 2024
Section:
Earnings Call Analysis
Summary
Q3-2023
Q3-2023
Editas Advances EDIT-301 Trials, Solid Financial Footing
Editas Medicine made significant strides in their EDIT-301 clinical program, enrolling patients across trials for severe sickle cell disease and transfusion-dependent thalassemia, with positive preliminary results and anticipated crucial data presentations. The company highlighted EDIT-301's potential, hinging on its proprietary technology, which could differentiate its therapy in terms of sustained normal hemoglobin levels, impacting quality of life. Financially, Editas is poised with $446 million in reserves funding operations into Q3 2025, and a robust scientific and intellectual property portfolio backing its advanced gene editing endeavors.
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Good morning, and welcome to Editas Medicine's Third Quarter Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Christi Barnett, Corporate Communications and Investor Relations at Editas Medicine.
Thank you, Rob. Good morning, everyone, and welcome to our third 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.
Thanks, Cristi, and good morning, everyone. Thank you for joining us today on Editas Medicine's Third Quarter Earnings Call. I'm joined today by 4 other members of the Editas executive team, Baisong Mei, our Chief Medical Officer; Erick Lucera, our Chief Financial Officer; Linda Burkly, our Chief Scientific Officer; and Karen Deardorf, our new Chief Commercial and Strategy Officer. We are pleased with Editas' momentum and progress in the third quarter, and I look forward to sharing these details. Before that, however, let's take a quick step back to provide perspective. . Editas' goal is to deliver life-changing medicines to patients with previously untreatable or untreated diseases. I joined Editas in June 2022 to help realize this goal tasked with guiding the company's evolution from a platform development company to a commercial therapeutics company. As many of you know, in January of this year, we shared Editas' decision and strategy to position Editas as a leader in programmable gene editing. As a reminder, 3 pillars underpin our strategy. First, to accelerate the clinical development of EDIT-301, our autologous ex vivo gene-edited medicine for severe sickle cell disease and transfusion-dependent beta-thalassemia and drive it towards approval and launch.
Second, to sharpen our discovery focus to 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. At the start of 2023, we outlined the following 2023 objectives. For EDIT-301, to provide a clinical update from the EDIT-301 RUBY trial for severe sickle cell disease or SCD, by the end of 2023. To provide a clinical data update for MDD-301 to trial for transfusion-dependent based thalassemia or TDT by the end of 2023. And to have dosed 20 total patients in the RUBY trial by the end of 2023.
For in vivo medicine development, to hire a new Chief Scientific Officer with specific expertise aligns to our vision and to advance the discovery of in vivo editing of hematopoietic stem cells or HSCs and other tissues. And for business development, to leverage our robust IP portfolio and business development capabilities to drive value and to complement our core gene editing technology capabilities. So how have we executed against this strategy and these objectives in the third quarter.
Let's start with EDIT-301. First, on clinical data. We will present a company-sponsored webinar in tandem with a poster presentation at ASH, both on December 11. That is next month. We plan to share clinical data from 11 sickle cell patients in the RUBI trial and 6 beta thalassemia patients in the Edatel trial. Pason will share more details about our presentation later on the call.
Second, on enrollment. We have enrolled 27 sickle cell and 8 beta-thalassemia patients into our Ruby and EDITHAL studies, respectively, and screening continues at a good pace. Third, on dosing, we now expect to dose the 20th patient in the RUBY trial in the January 2024 time frame due to individual patient schedules. And finally, for 2024 data disclosures, we remain on track to present a substantial clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024 based on will share further details regarding our December data readout and clinical progress of headed 301 in his remarks.
On the regulatory front, we are also pleased at just 2 weeks ago, the FDA recently or granted us their Regenerative Medicine Advanced Therapy or RMAT designation to EDIT-301 for the treatment of severe sickle cell disease. Advantages of the RMAT designation include all the benefits of the Fast Track and baked through therapy designation programs, including, but not limited to, intensive FDA guidance on efficient and expedited drug development possible rolling review and priority review of the BLA. With respect to commercial plans, as we previously shared, we made another important hire as we continue to gain momentum in pursuing a leadership position in hematopoietic stem cell medicines for hemoglobinopathies.
In late September, we announced that Karen Deardorf a highly experienced and successful therapeutics commercial leader has joined Editas as our new Chief Commercial and Strategy Officer. Karen has a proven ability to translate early discovery and clinical assets into robust business strategies with disciplined portfolio prioritization and value creation. Additionally, she has led multiple successful U.S. and global product launches. Karen's expertise and track record make her the ideal leader to help Editas reach this goal for patients. To further enable commercialization, as previously shared in July, we will increase our clean room capacity when we move our CMC team into the new [indiscernible] facility in early 2024.
With this increased capacity, we ensure our ability to scale EDIT-301 manufacturing, both for clinical supply for our Ruby and EDITHAL trials as well as to prepare for commercial readiness. In a step forward for the gene editing industry and patients alike, we were delighted to see the recent XXL AdCom. The very focused review by FDA and the ADCOM confirmed our confidence in the robust nature of our own off-target assessments. The patient testimonies in addition were incredibly moving and powerful and demonstrate the significant need for new and transformative medicines for the treatment of sickle cell disease.
Turning now to in vivo and our pipeline development. As stated earlier this year, our Drug Discovery Group began lead discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues. And in July, we hired Linda Berkley as our Chief Scientific Officer to Spirit head these efforts. Linda looks forward to sharing more at the appropriate time. As a reminder, under our new target selection criteria, we will select therapeutic targets that will 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.
Now let's turn to business development. In August, we shared that we entered into an agreement with VorBio, providing a nonexclusive license for ex vivo Cas9 gene HSC therapies for the treatment and/or prevention of hematological malignancies. Under this agreement, Editas received an upfront payment and will be eligible for future development, regulatory and commercial milestone payments as well as royalties on medicines utilizing the related intellectual property. 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 and the Broad Institute Cas9 patent state covering Cas9 use in developing human medicines. Only a small fraction of these patents are involved in the ongoing U.S. PTO interference proceedings. As the exclusive licensee we are uniquely positioned to issue exclusive and nonexclusive sublicenses for Cas9 to any company seeking to use these enzymes to make human medicines, including in vivo and ex vivo users.
Our recently announced licensing deal with MoBio further bolsters our confidence that our IP portfolio provides meaningful value now and in the future. To conclude my remarks, we are energized by the promising efficacy and safety data we shared in June, taking 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 in the long term, specifically driving early and robust correction of anemia and sustained increases in fetal limoglobal. 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. I will now turn the call over to Baisong, our Chief Medical Officer.
Thank you, Gilmore. Good morning, everyone. Let's start with AD-301 in development of severe sector disease and transfusion dependent [indiscernible]. As Gilmore mentioned in his remarks, we continue to enroll and dose patients in the UBI trial for severe sickle cell disease and in the edit trial for transfusion-dependent barefacemia. As of today, in the RUBY trial, we have enrolled 27 patients and the 20 patients in the RUBY trial is expected to be dosed in the January 2024 time frame.
In the EDITHAL trial for transfusion-dependent [indiscernible] to date, we have enrolled 8 patients. As I shared earlier this year, I have been visiting and continue to visit our Ruby and EDITHAL clinical trial sites, continuously speaking with our investigators, and I appreciate the enthusiasm and the support from the investigator at study sites. I'm pleased with the momentum of EDIT-301 in patient recruitment, [indiscernible], editing and dosing in both studies. I'm excited to hear from the investigators that patients dosed with EDIT-301 have already seen positive changes in their lives. As we have previously shared, we will engage with the FDA in the second half of the year.
On a related note, we found the recent [indiscernible] AdCom recycle, and it has reaffirmed the power and potential of this gene editing technology. As a physician, I'm excited for patients living with serious diseases that gene editing has the potential to transform the treatment of the diseases and ultimately, patient lives. As a drug developer, I'm eager to see the first medicine approved and swiftly followed by more medicine from other companies, including Editas. More importantly, I'm excited to announce that we will share Ruby and EDITHAL clinical data in a poster presentation at ASH as well as in the company-sponsored webinar both on Monday, December 11.
So what we will show. The Ruby data set, we're including clinical data from 11 patients. We will present efficacy data, including total hemoglobin, [indiscernible] hemoglobin and vessel crucibanks [indiscernible] BOE and safety data, including neutrophil and platelet engraftment. The follow-up period of these 11 patients includes 2 patients with at least 12 months follow-up and an additional 4 patients with at least 5 months follow-up. The other patients will have a 1- to 4-month follow-up period. The EDITHAL set will include clinical data from 6 patients. We will present efficacy data including total hemoglobin and feedmiglobin and safety data, including neutrophil and platelet investments. The full up period after EDIT-301 treatment includes at least 5 months data from the first 2 patients treated. The other patient will have 1 to 4 months follow-up period.
As a reminder, this past 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, we also presented possible initial data from the first patient treated in the [indiscernible] trial. The Ruby dataset covers safety and efficacy data from the first 4 patients including 10 month data from the first patient treated and 6-month data from the second patient treated, including total hemoglobin and [indiscernible] hemoglobin, demonstrating EDIT-301 drives early robust correction of anemia to a normal physiological range of total hemoglobin in as early as 4 months after EDIT-301 treatment. EDIT-301 drives robust sustained increase in fetal hemoglobin in excess of 40%. All 4 of those Ruby sickle cell patients remained free of vessel [indiscernible] since EDIT-301 treatment.
Additionally, [indiscernible] including 4 Ruby patients and 1 elite patient to a successful engraftment within 1 month of dosing and has stopped red blood cell transfusion. EDIT-301 was well tolerated by patients, and the safety profile for A31 was consistent with the mobility of stocking conditioning and autologous peasall transplant. And the trajectory of correction of anemia and expression of fetal hemoglobin was consistent across EDIT-301 [indiscernible] patient and [indiscernible] patients at the same follow-up time [indiscernible]. We continue to believe that EDIT-301 can potentially provide robust clinical benefit to patients with severe sickle cell disease and transfusion-dependent thalassemia, potentially provide clinical differentiation in the long term.
We look forward to our presentation of additional clinical data and a longer follow-up in December. As we have previously stated, the choice of CRISPR enzyme and the target to edit to switch on fetal hemoglobin expression matters. EDIT-301 used our proprietary ASK1 enzyme to added HPG12 promoter. ASA increases the efficiency of editing and significantly reduce off-target editing when compared to other critical enzyme including [indiscernible]. Editing HBG1 promoter [indiscernible] HPG 12 promoted in human CD34 post cells, resulting in greater red blood cell production and normal proliferative capacity and improve replan sales health when compared to anything of BCL11A.
We look at the differentiation in 3 categories of endpoints in clinical trials. Hematological parameters and function and patient reported outcome quality of life. Based on the clinical data so far, we believe that sustained normal level of hemoglobin could be a potential point of differentiation for EDIT-301. As a reminder, a sustained normal total hemoglobin level is an important clinical outcome for patients. as the correction of anemia can significantly improve quality of life and ameliorate the end organ damage. We look forward to sharing additional data including Ruby and EDITHAL clinical data next month.
Now I will turn the call over to Erick, our Chief Financial Officer.
Thank you, Baisong, and, good morning, everyone. I'm happy to be speaking with you today and with 1 quarter under my belt at Editas, I'm even more impressed by the quality of our science, our leadership in the gene editing field, the strong intellectual property portfolio and our highly differentiated work from other players in the field. I was excited to join this summer, and I continue to be impressed with what I see. With that, I'd like to refer you to our press release issued earlier today for a summary of our financial results for the third quarter 2023, and I'll take this opportunity to briefly review a few items. Our cash, cash equivalents and marketable securities as of September 30 were $446 million compared to $480 million at June 30, 2023. We expect our existing cash, cash equivalents and marketable equity securities to fund our operating expenses and capital expenditures into the third quarter of 2025. Revenue for the third quarter of 2023 was $5.3 million, which primarily relates to the upfront payment under the nonexclusive Cas9 license to Bora Bio in August 2023. R&D expenses this quarter were $41 million, essentially flat from the third quarter of 2022, which reflects various offsetting expenses, including decreases in R&D spend related to our reprioritization and targeted focus on our EDIT-301 program, offset by increased spending in precommercialization efforts, including medical affairs and patient advocacy. G&A expenses for the third quarter of 2023 were $15 million, which decreased from $16 million for the third quarter of 2022. The decrease in expense is primarily attributable to decreased head count expenses, including stock compensation and reduced legal costs. Overall, Editas remains in strong financial position, bolstered by our sharpened discovery focus, June capital raise recent out-licensing deal. Our cash runway into the third quarter of 2025 provides ample resources to support our continued progress in the Ruby and EDITHAL trials of EDIT-301 and continued commercial manufacturing preparation and advance our discovery and research efforts. As I've shared before, I'm a former buy-side investor, and I know the value of buy-side and sell-side knowledge. I look forward to hearing from our shareholders as we work to advance our gene editing medicine. We value your feedback. And with that, I'll hand the call back to Gilmore. .
Thank you, Erick. As we continue our momentum and the execution of our goals, it remains an exciting year for Editas. We look forward to continuing our transformation and sharing our progress with you. As always, it must be said that we could not achieve our objectives without the support of our patients, caregivers, investigators, employees, corporate partners and you, investment community. Thanks very much for your interest in Editas, and we're happy to answer questions. Thank you.
[Operator Instructions] Our first question comes from the line of Brian Chan with JPMorgan.
[indiscernible].
Brian, thanks very much. I'm afraid it was incredibly difficult to hear you with the background noise, and I know you're suffering from some connection problems there. I think I heard you talk about all targeting. So I'm assuming you're referring to [indiscernible]. Yes. And so let me just go with that and then we can follow if it's incorrect. But I think you referred to the outcome. I have to say is that the AdCom represents an incredibly and drove a great excitement for this week. It was a great day for sickle cell warriors, where patients now can think about not battling a disease, but actually living a life, it was a significant milestone for CRISPR genome editing as that AdCom represents almost a countable step towards approval for the first CRISPR-based medicine. . What struck us in the very focused discussion of the outcome was the positive tone. But actually also, as we listen to the commentary, it really substantially strengthened our confidence in the very robust data package that we've generated about off-target [indiscernible]. I hope I've answered your question because [indiscernible] what I heard. I think the only other thing I want to emphasize, of course, is that we have chosen to advance our proprietary-owned ASK1 enzyme, which indeed has higher fidelity and a significant reduction in off-target edits when compared to Cas9.
I'm just wondering if there were a lot of focus specifically on off-target effects. So I'm just wondering if here is any work that you're doing now that is different than the gene editors players that are in the market that are different to make sure that the regulators will be happy with the way that you're monitoring these off-target effects.
I mean without going into details, I don't think it's appropriate this time to go into details. we are doing more than was discussed at the AdCom. And that's where our confidence about the robustness of our data package comes from. I hope that was the question.
Our next question comes from the line of Samantha Semenkow with Citi.
Just a follow up on the last question, Gilmore, and you sort of touched on this, the difference between Cas12a and Cas9. Can you just talk a little bit more in detail about what you're seeing as the different off-target risk? And how you'd be able to show that to regulators when you get to that step?
Indeed happy to. Let me just preface again with the sort of high-level labs in published data. We have and others have shown a substantial reduction in off-target editing when comparing [indiscernible] Cas12a versus the Cas9 enzyme. With regard to the data package that we have generated and continue to generate off targets, it is substantial. I'm not sure that we are in place to share more details. I don't know, Linda, if you have anything to add. .
Yes, I would just add -- this is Linda Burkly, CFO. Yes, I would just add and echo what Gilmore just said that we're using multiple orthogonal methods additional method as compared -- additional methods as compared to what we heard at the AdCom. And -- and so we're very confident in our package as we proceed in our path to the [indiscernible] and yes, we -- in our preclinical data, we are not seeing more target editing in our preclinical experiments. So we're very confident in our package going forward.
The next question is from the line of Joon Lee with Tui Securities.
Thanks for the update. Based on all that's been presented during the AdCom, where do you see room for clinical differentiation? And is that something that we can expect to see at ASH. Specifically, can you comment on your platelet engraftment reticulocyte count and markers hemolysis?
So I think the key thing is that we are very excited already, the clinical data that we have presented and what we see as a competitive fast follower with potential for differentiation and what we've seen to date was a consistent highest level correction of anemia to the normal physiological range, which is by design in our choosing of AS Cas12a to edit and [indiscernible] global promoter. I'm going to ask Baisong just to tell you a little more about what we can about what we're going to share at ASH on December 11.
Thanks for the question, Joon. So -- as I mentioned that in the ASH presentation, we'll have data from 11 RUBY patients and 6 EDITHAL patients, and we will have a longer follow-up period with 2 patients in the RUBY trial with at least 12 months, and then we have additional data from 5 months for RUBY trial. And go back to your question also on the ADCOM in there. And we are very actually pleased to see, as -- given mentioned, the very successful outcome and reaffirm, I believe, the technology and also the MOA of using fetal hemoglobin as a target to treat sickle disease and betasemia. And we -- for differentiation, we are confident that we are a fast follower, we differentiate molecule -- and we are very pleased to see that we presented data that we'll be able to correct the anemia. And in our case, the normal total hemoglobin for female with 12 to 16 gram per deciliter and for male is 13.8 to 18-gram per deciliter, and we're pleased to see our patients going to the normal range and we are pleased to share more data during the ASH and web [indiscernible].
I think the only other thing is it's -- we do note that we've had very successful engraftment time lines. It's too early to say more than that in the space. And I think we're also very happy with where our hemolytic markers are.
Our next question is from the line of Greg Harrison with Bank of America. .
Just thinking when should we expect an update on the in vivo editing efforts? And how do you think the commercial opportunity is there relative to ex vivo in sickle cell and then what other indications or tissues do you think are attractive candidates for your in vivo technology?
Thanks very much, Greg. With regard to future updates, this is a company who philosophically wants to make promises and make discussions that we believe that we can absolutely deliver on. We have been doing work over the last year. Linda has already been here about 3 months. We want to ensure that she has the time to, again, engaging with our medical and commercial team now led by our new Chief Commercial and Strategic Officer, the ability to make sure that we choose and progress against high conviction targets based on our selection criteria. With regard to your second question, let's just remind me again targeted tissues. Yes, forgive me. So we have actually advanced [indiscernible] Linda. I might have to talk about target tissues.
Yes. Yes, thank you for the question. So of course, we're very excited to to develop an in vivo HSC program based on the success of the -- our targeting approach for sickle cell disease and [indiscernible] and so moving the targeting of the HPG 12 locus to an in vivo approach and so we're very well positioned for that, considering the emerging success that we're seeing in the clinic that Baisong has described. And so we're working very hard to come up with the delivery strategy for in vivo HSC and we're doing that both internally and through potential external partners. And so that's -- we're very excited about that avenue. And then in terms of other tissues of interest, we'll be talking about those in the future. We are interested in the liver, but I'll be talking about other tissues as well in the future.
Thanks very much, Linda. And then with regard to the third part of your question, you asked about the commercial opportunity for in vivo. Essentially, what you can actually see is a strategy that we're driving, which progressively expands the number of patients and the fraction or proportion of the patient population that can actually use the tissue or use these treatments. Allogeneic opened the door to therapeutics, but the substantial issue there was finding matched donors. We're about only about 11 patients can find a matched donor by going to autologous ex vivo, we've increased that tenfold. By going to in vivo and thus eliminating the risks and burdens of conditioning, we can actually further expand the patient population and address the unmet need that extends into patients who are not described as severe, it's worth remembering that the median survival for this disease in a developed healthcare system like that of the United States is about 45 to 50 as again, was impressed upon us at the ADCOM by those incredibly moving testimonies from patients and their parents and family members. And indeed, in economies with no healthcare system it's an 80% mortality about 5 years of age. So there is a substantial unmet need and in vivo will massively increase the commercial -- the eligible patient population.
Great. That's helpful. Looking forward to the update. .
Our next question is from the line of Huidong Wang with Barclays.
I think a lot of questions asked about the differentiating profile for your the EDIT-301. So maybe I wanted to ask, in a way, actually, there was surprising, we saw VOE events happened so early during [indiscernible] AdCom. I'm wondering what is your thoughts there? And then for your efficacy clinical profile, what kind of the factors you can pay attention to in order to monitor these events and try to develop differentiated profile versus Xcel.
Thank you very much, [indiscernible]. So doesn't want to just recapitulate your questions, be sure I get it all. You want to talk about the differentiation of our EDIT-301 product for as we're focusing on severe sickle cell disease, you were interested in or surprised to see VOEs reported in some patients post treatment at the AdCom. And I think you [indiscernible] understanding what are the elements that we're monitoring for, for differentiation in our efficacy profile. Well, I will start and then pass -- I can start and then I'll have Baisong comment on the differentiation of our efficacy profile.
With regard to the BOEs, I think understanding a full explanation will be hard for us at this point. There were many elements of the data that were not presented, which is not surprising in a very truncated presentation. But obviously, looking at the correlation of [indiscernible] expression, the other factors that can drive VOEs, et cetera, is something that we obviously look forward to get with more data being able to understand. I think what does stand and remains true is that the upregulation of fetal hemoglobin actually has a substantive impact on controlling VOEs. Now as we look to differentiation for EDIT-301, we're looking beyond not just the control of VOEs, but actually correcting other elements of the disease. And with that and with a particular focus on the correction of anemia physiologic range and its impact, I ask Baisong to talk more about that.
Yes. Thanks, Gilmore. Absolutely, we are still very confident that we believe that EDIT-301 is a differentiated molecule. Given that what we've seen so far, we have to see that we can actually correction of [indiscernible] to physiological range of total temglobian. And with that, we look into that not only hematological parameters, end organ function and as well as patient reported outcome. So we continue to be that direction will allow us to demonstrate differentiation.
One key thing I think it's worth highlighting when we talk about patient reported outcomes is that fatigue is a significant complaint. In fact, again, we heard of the patient testimonials. Lack of energy, fatigue, not just the hospitalizations and pain, but fatigue and loss of energy. And so these are important elements or specific subdomains of the patient for outcomes that we're paying attention to. .
Our next question comes from the line of Jack Allen with Baird.
Congratulations to the team on the progress made throughout the quarter. I wanted to ask a little bit about the RMAT discussions. To what degree was the differentiation on total hemoglobin discussed in RMAT? And then during the prepared remarks, you mentioned a more substantial data set expected in mid '24. During the RMAT discussions, did you have any conversations around what could be viewed to the pivotal data set here and about to hear any thoughts if so?
Thanks very much, Jack, for your question. I think the first thing is it's premature to go into the details of discussions about the FDA. However, I am glad that you highlighted RMAT because indeed, the FDA does and did review clinical data, including hematologic parameters, which as you quite correctly pointed out, include the correction of anemia. And as we said, we also included the nonclinical package to demonstrate how that happened by design. I think the other point about the RMAT, obviously, as we said in the prepared remarks, is that it essentially increases our confidence in the timeless review through the various mechanisms that are available to us, both with high-frequency engagement with the agency going forward as well as the possibility of our priority review and rolling submission. . You asked about the substantive data set. And I think what I would say is that if you look to excel as a benchmark, we've actually seen that the original XL BLA accepted by the FDA included an efficacy data set of 20 patients with [indiscernible] follow-up. An additional efficacy set of 10 patients was added to that during the review period. What that actually tells us when you look at our being on track to dose our 20th patient by January -- in the January '24 time frame and the continuing robust enrollment that we're seeing in a Ruby study, it really validates our line of sight to creating or generating and present -- being able to present in the middle of 2024 a substantive data set with robust follow-up around a period that shows the correction of anemia and fetal hemoglobin expression and validates line of sight to a BLA into 2025.
Our next question is from the line of Dae Gon Ha with Stifel.
Maybe, I'll briefly go back to the off-target editing and then [indiscernible] for Karen. On the off-target editing, I guess, Gilmore, you talked a lot about the differentiation of AsCas12a versus the Cas9 BUs. Just curious, does that, in your view, I think you need a little bit more characterization work on the molecular side given that Cas9 is being a little bit more prevalently used on the CRISPR-Cas based medicine field. And maybe as an offshoot of that, I think there were also discussions around how [indiscernible] ran all these analyses in a more theoretical manner, but didn't really test the treated patients, blood samples pre and post. So can you confirm if you guys are doing the pre and post testing of the blood samples to see if soft target editing is actually happening or not? And then a question for Karen, to an earlier question about [indiscernible] expansion opportunity, you talked about the in vivo HSD delivery, but I don't know if that was intentional or not, but I didn't hear you talk about nongenotoxic conditioning. So I don't know if you can comment on a little bit more on that. Do you see that as part of your armamentarium going forward? Perhaps from a Gentex view [indiscernible] to that.
So thanks very much, Dae Gon. With regard to the AsCas12a versus Cas9, I think the first takeaway is that we have published -- we have published data from ourselves and other labs showing that there is a differentiated significant reduction in off targets with AsCas12a. Secondly, we have a very -- we don't actually believe that the prevalence of CAS9 would change the requirements for off-target data package generation. Third, our data package that we've generated to date is very robust. And as Linda said, we're using multiple orthogonal both in silico and in vitro evaluations also including, by the way, our nonclinical tox in vivo, but at evaluations that go beyond what we saw presented and discussed at the adcom. So again, all of that adds to our confidence. And then finally, we are actually testing the drug product. So that's kind of the old target.
If I could then turn to your question around or nongenotoxic conditioning. This is an area that remains of interest to us. We have done internal work. We're also monitoring the external landscape. One of the things, one of the additional benefits of having Karen join us is that she knows, as you quite correctly pointed out, that stays very well. So Karen, I can do it a further commentary.
Yes. Thank you. Thanks for the question. And I just want to comment how excited I am to be here with the Editas team to help move these therapies forward. Now you bring up a really important point, something that's important to all of us and will absolutely be part of the evolution of this market space and treatment modality. I think the benefit today is that the risk benefit for severe sickle cell and TDT does remain very strong with the current offering, but we take it very seriously, and we're doing a lot of important work to try to make sure we are part of moving forward to evolve this to be an overall better treatment. .
I just wanted to add to what Gilmore had said, like to affirm that we do test -- we have tested drug product lots from a larger number of sickle cell disease patients to confirm the -- and have not detected off-target editing in that larger number of sickle cell disease patients with samples.
Our next question is from the line of Phil Nadeau with TD Cowen.
Congrats on progress -- And thanks for taking our questions. 2 from us. First, in terms of continued recruitment in the clinical trials. Do you assume any change in the rate that you'll be able to recruit patients following what seems likely to be the approvals of the first 2 genomic medicines for sickle cell disease by the end of the year? That's the first question. And then second, a follow-up on differentiation. How long a follow-up do you think you'll need to determine whether fatigue or the hemoglobin levels are truly differentiated. Is that something that you'll know kind of relatively quickly? Or will that take months if not years of follow-up to determine?
Thanks very much, Phil. With regard to recruitment, no, we do not expect any change. We believe that our enrollment will continue to robust. I'll pass that to Baisong, who can tell you about his personal experience and conversations with sites and investigator.
Thanks, Phil, for your question. Really that -- have been continuously visiting study site as we really very strong momentum and feedback about it. And we actually have many patients on our list for this trial. So we actually do not see the impact. So we continue to see the possible momentum. And not only now, but we'll see it for next year, and we will continue to see the momentum on that.
So indeed, the investigator said that notwithstanding approvals, this is still an area that they are particularly [indiscernible] with regard to our therapy and the trials. You asked another question about differentiation and with regard to the time to actually see differences in total hemoglobin. And then some of the more downstream clinical impacts would be around fatigue or other outcomes. And I've got to ask Baisong to talk about that. .
Yes, yes. Yes. So this is actually a very important question. We are looking into that as we -- as I mentioned, we're looking to 3 categories of clinical end points for the differentiation. Certainly, that for hematological parameter, you will be taking shorter time to see. And for the patient reported outcome, for example, you specifically mentioned the fatigue usually, based on my experience in other studies that when you kind of -- when you kind of see this patient recorded outcome usually takes 6 months and for the CBDs something that usually takes 1 year, you see some kind of improvement. But you more longer, you will see much more impact for compared to the baseline. . So we are very optimistic and confident that we'll be able to see something in that direction for patient reported outcome on that. And the other category I mentioned is also for the end organ damage, and we actually look into the cardiac, pulmonary, liver, and CNS and as well as the kidney. So we'll also see that looking forward to see the improvement. These areas are quite relatively new, but there are publications for allogeneic bone marrow transplant for sickle cell patients, for example, in the brand, blood vessel or plus the vascular system in brands and also the in cardiac system. There are some reports relatively limited, see that allogeneic transplant for sico-cell patients could potentially actually improve the improve organ function. So we're looking forward to that direction.
Yes. And Phil, one of the things I would say is that Bacon and I have been around the block long enough as drug developers to know that when you are start applying new outcomes measures in clinical trials using potent new medicines that have sort of have an unprecedented potency in disease, you're ability to absolutely firmly predict the absolute time point, the number of patients, et cetera, are needed to actually demonstrate that benefit can be an vary and require additional work. So while we are very enthusiastic about the work that we're doing here, we also are pragmatic and experienced enough to know that we will see hematologic parameters quickly. We may see an organ functional physiologic parameters in a slightly longer term. And then with regard to other outcomes, that will be, as I say, we're optimistic, but we have to just temper that with the realism that it may take somewhat longer.
Our next question is from the line of Yanan Zhu with Wells Fargo.
Thanks for taking my questions. So I was wondering, a focus at the AdCom was the adequacy of the number of patient samples tested for off target and whether that's enough to prioritize the risk in certain patients with genetic variants. I think I was wondering in your off-target analysis work, are you targeting, again, single-digit sample numbers? Or are you targeting a number significantly higher than that. The next question is about percent fetal-hemoglobin as a differentiator. I think you talked a lot about total hemoglobin. But I was wondering, based on your -- on the data you have reported so far and also in abstract at ASH -- it seems like you had 3 patients of your first 4 patients who had greater than 50% fetal hemoglobin. I was wondering about your confidence of that being replicated in additional patients and also that being a differentiator. And lastly, I was wondering about your thoughts on whether there is a correlation between total hemoglobin and hemolytic markers and whether you can comment on your thoughts there, i.e. higher maybe at a patient level, whether a higher total hemoglobin is correlated with better hemolytic marker [indiscernible].
Thanks very much, Yanan. So I'm going to try and cariograph a set of answers to a complex set of questions, if you will, or quite diversity question. So -- with regard to the adequate sample, I think the first thing we should do is just remind ourselves that the discussion -- the very -- so what I would say, the informed discussion at the AdCom demonstrated that a robust evaluation of at risk really shows that from an off-target point of view, the risk management, even with the data set presented to the AdCom was actually very good. I will say that we are using additional animotopisity or organal in silico and vitro, and I need some in vivo, that's on the iconic in silico and in vitro assessments which go well beyond what was shown at the ADCOM in our data package.
I'm not going to go into the specifics of the numbers of patients, just to say it's more. And obviously, we'll share more detail about that in -- at an appropriate time in the future. I think the other thing about the variance, again, I just want to reaffirm that I thought actually that the discussion by the geneticists at the AdCom was very illuminating. I thought both parties, the experts on the panel as well as in the sponsor really articulated very clearly how the nature of variation, the nature of common ancestry for all humanity and how we can really manage and identify variants and the risks associated with that. I think it was a very robust discussion. And again, it gave us great confidence in our management of risk and the data package that we're generating there. Linda, I don't know if you want to add to that.
No, I think that was a very good summary. I think that there was -- yes, I think that was a very good summary [indiscernible] .
Thanks very much, Linda. With regards to the percentage of fetal hemoglobin is a different, obviously, very excited about the data we show. It's early days yet. And what is clear from the experience described for people who have coincident inheritance of hereditary persistence of fetal hemoglobin with sickle cell disease or indeed thalassemia that the higher the level of fetal hemoglobin percentage or fracturing feed hemoglobin, the greater the band certainly for sickle cell disease. I'd say it's early days for us. But Baisong, do you want to add to that?
Yes. Yes. Thank you, , for this question. As Jim mentioned, we are very pleased to see the [indiscernible] data, as you referred to, [indiscernible] patients over 50%. And this is -- we are excited on that. It's also because this is a rational design approach for EDIT-301. We compare that this approach of targeting the HBG12 promoter with HBG1 promoter versus BCL11A, we found that we have better feeds and global expression. But we are in the early stage. We actually want to see more data to disease, and we're looking forward to see more [indiscernible] on that.
Thanks very much, Baisong. I think your final question was around the correlation between total hemoglobin and hemolytic markers. I think that, that is an interesting question before handing to Baisong, I'll just remind 1 thing. While hemolytic hemo is a critical part of sickle cell disease. The key driver we believe for driving total hemoglobin by design is enhanced erythroid production. Baisong, I don't know if you want to add anything .
Yes, that's exactly right, Gilmore, -- that's what we're going to say. I think what I want to mention that we are very positive about our mastic market data on that. Then the -- so the total hemoglobin level is related to aspects of that. One is hemolysis, one is [indiscernible]. So we -- I think in our design, we designed to have this molecule have high hemoglobin expression. And also with the targeting of the HPG [indiscernible] promoter we have better process and better value protoproduction. So we are looking forward to see more data on that, but we are very pleased with our hemolytic biomarkers. .
Our next question is from the line of Eric Schmidt with Cantor Fitzgerald.
Congrats on the progress. Maybe the first, the HBF production levels are obviously quite impressive. Is there a total hemoglobin above which you start to grow concerned in sickle cell disease that patients have too much hemoglobin? And if so, what might be -- and then maybe a follow-up for Karen. We saw a couple of large pharma gene editing deals this week. Perhaps you could comment on the overall level of interest in potential platform-type collaborations.
Thanks very much, Eric. With regard to the total hemoglobin, we believe that correcting and that's what we've seen, hemoglobin physiologic range is of substantial benefit. I think it's -- we haven't -- we're not going to -- it's hard to speculate about a level that is too high. Indeed, there has been an experience in general with polycythemia in sort of a broader patient population with some conflicting data about the risks of same. But as I say, we feel very confident about the data we're getting in regard to our total hemoglobal. -- and the way that we are correcting it to normal physiological ranges. I think you asked a question about some recent gene editing deals just this week. -- that are announced. What I would say is that what is striking about it is it is great to see pharma, I say big pharma now in a period where we've seen some dirt up deals leaning in and increasing their excitement around the genome editing space. In other words, what I would say is this has been a very good week for CRISPR genome editing space with both that sort of critical near the final step towards approval for our first CRISPR-based therapy and to see now pharma actually looking essentially to the ends of substantial derisking of their view of the value of genome editing as they look to grow their portfolios. .
Yes. Thanks, Eric. It's Karen. What I would add is I think Editas is so well positioned right now, having refocused the portfolio. We are in a great place to be able to move our own programs forward and are very excited by the continued interest, and it opens the door for partnering, should that be the right path for us.
Our next question comes from the line of Steve Seedhouse with Raymond James.
Two quick ones. First, our lymphocyte and neutrophil counts at baseline and post transplant, something that you are going to share United poster or the associated presentation at ASH. And then separately, is your intent [indiscernible] to commercialize EDIT-301 on your own? .
Thanks very much for that question. With regard to neutrophil engraftment data, that is something that we actually did present at our -- and it would comprise or could be summarized in our presentations at the end of the year because it's actually a measure of -- engraftment is part of the safety monitoring that we do in our studies. And then with regard to your second question, which was around commercializing 301 on our own. Well, we actually look to commercializing 301. We're actually building towards that because that we believe that's important. We have indicated previously that we're interested in an ex U.S. partner with a large footprint. Obviously, the details of any such partnership and how that might expand would really depend very much in those negotiations. It was something that we would share upon any kind of agreement, but only then. .
Gilmore, just to clarify, I was asking about lymphocyte and neutrophil counts like longitudinally post transplant, just because in the [indiscernible] data, they don't recover to baseline. So I'm just curious if that's something you plan to share and it'd be interesting to know whether it's different or the same given the different genomic target and different editor.
So well, we have not seen -- we've been actually very happy with our accounts. We're actually very happy with our accounts to date, but what I can follow up on that. .
Our next question is from the line of Luca Issi with RBC .
Great. Two quick ones here. Maybe based on -- it sounds like you're obviously on track in those 20 patients by January 2024. Are you enrolling any adolescent -- just trying to understand if there is a scenario where your initial label will just include adults versus some of your peers who also get a broad label that also include adolescent -- so again, any color there, much appreciated. And maybe a second one, quick 1 for Linda here. I think during the AdCom earlier this week acquired a potential suggestion to further characterize off-target editing risk was to actually do whole genome sequencing in 20 patients before and after the genetic manipulation. So I just wonder if that's something that you're contemplating to do. Thanks so much.
Yes. Thank you for your question. I'll take your first question, and I'll pass that. I think we we have a plan to dosing [indiscernible]. And also for the general clinical program, we are intending to go to all patients with all ages -- so that's kind of -- because this disease is essentially starting with genetic disease from very young age we intend to actually be able to have this model benefit patient from all ages to that kind of intention. I mean, all those things, of course, the label you mentioned will have further discussion and alignment with FDA.
Yes. Thank you for your question. Yes, that was a very interesting conversation at the AdCom. One of our orthogonal methods and this also came up at the AdCom was the method of using a biochemical method applied to make DNA. And this is a method -- one of the methods that we use, which is unbiased method in which the naked DNA is taken from selves and subjected to cutting with your [indiscernible] -- and then you do a whole genome sequencing basically to look for off-target editing. And so this is called Digenome. And so this is one of our methods that we use and look at with our drug product before putting the drug product to patients. So -- so I think this is one of the robust criteria that we -- one of the robust methods that we use in our approach. So I think that's basically one of the reasons that we are confident in our approach to -- in addition to the other methods that we use in silico and Guide that were described I guess that's basically what I'm prepared to share at this moment, but there are many other aspects to our approach that were also make us very confident to -- about our approach to the off-target editing package that we're preparing.
Our next question is from the line of Jay Olson with Oppenheimer.
Congrats on the progress. Maybe just another question on read across from the Excel AdCom since there was some discussion about long-term monitoring and surveillance of these patients. Can you just share your thoughts and plans to follow EDIT-301 patients long term in a post-approval setting?
Thanks for the question, Jay. So -- we certainly will have a long-term fallout for patients. And so that study is designed to actually pull the patient up to 15 years for anybody who actually dosed with EDIT-301 and that's also consistent with the regulatory requirements. So that's absolutely our plan. .
The next question is from the line of Liisa Bayko with Evercore ISI.
This is Julien on for Lisa. So we have 3 questions. First, we know that CEC has filed an appeal to the Court of Appeals -- when do you expect to hear the decision for that? And then second, as I know you mentioned that more substantial data set for sickle cell coming in the middle of 2024. I'm just wondering when should we expect more substantial dataset for the TDP patients? And then the third is you mentioned that in the second half, you plan to engage with the FDA to seek alignment or regulatory path for 301. We're wondering will you inform the Street on the results of the discussion? And if so, what's the timing for that?
This is Eric. Just with respect to any courses in front of -- court cases in front of the CVC or anything like that. We don't really want to comment on those until the final decision is actually rendered. So we'll we'll just be anxiously awaiting for all of that just like you.
Yes. So based on -- for your second question about the mid of next year for the program. And as part of that, one is, as we just shared that we will have 20 patients dosed by a January time frame next year. Then by middle of next year, we will have substantial follow-up for those 20 patients, and we also have continued dosing patients over the course. So we have a lot of data over the middle of next year for sickle cell disease. Yes. Regarding. Yes, absolutely. Yes, because I saw your question probably cover both, but I'd just make sure that we cover on that. And the -- we actually have a very strong momentum for EDITHAL study also and that we just shared, we actually already have 8 patients enrolled, and we continue to enroll in dosing patients. And but we have not shared what is the goal for next year, how many patients -- EDITHAL patient with dose. We will share that in an appropriate time. . And your third part of your question is about FDA engagement and outcome. And so we're well engaged with the FDA, and we continue to have engagement with the FDA as we just mentioned that we actually have these unmet designation allows us a lot more frac prevent interaction with the agency, including senior management of the agency. But we have not shared -- have a time line to share the outcome yet. We'll share that in appropriate time.
Our next question is from the line of Mani Foroohar with Leerink.
This is [indiscernible] on line for Mani. I just wanted to ask if you could potentially give us an update on the progress of the manufacturing scaling for 301, both for clinical development and for potential commercialization. And then on the other side, second question, in terms of the package for BLA. So with the timing, I think you had mentioned potential package readiness by 2025, but then we might have a post-marketing data from potentially to gene therapy program. I was wondering if you -- and how you would see that impacting potential pivotal design? .
This is Eric. I'll take the first question with respect to the manufacturing scaling and timing. As a reminder, we're very confident in what we're doing and making the investments in manufacturing for the commercial launch. We haven't specifically commented on the scale or timing, but just reiterate our confidence in everything we're doing on a manufacturing standpoint.
This is Baisong. Your second part of your question. As we shared that we will have 20 patients dosed by January time from next year and by middle of next middle of next -- middle of 2025, then we will have substantial data packages probably equivalent to the access BOA volume, which is accepted by by FDA, which have like 20 patients in the efficacy data cohort. So they subsequently added additional 10 patients in the addendum with 4 months additional 4 months data upwards. So we expect that we will be able to file the FDA equipment package to -- we will have equivalent data package by the middle of next year. . But what exactly the exactly Boat package when you align with the FDA so that we are -- that will have the agreement with the FDA on that, too. And you mentioned about post marketing or the commercialization of these 2 molecules. And as I shared earlier that we do not see that recruitment momentum perspective, and you mentioned about data package -- and we're actually very excited about the AdCom discussion. And we feel that this AdCom have further validation of CRISPR technology, further validation of the fetal hemoglobin as a mechanism of action to treat sickle cell [indiscernible]. So we actually see all those work have a positive impact to EDIT-301.
Our final question comes from the line of Terence Flynn with Morgan Stanley.
This is [indiscernible] for Terence Flynn. So looking to the future a bit, can you expand on your approach to target selection, how we should think about your pipeline evolving going forward? Also, as you think about tissue-specific delivery for your future in vivo programs, how are you thinking about the advantages and disadvantages to investing in AAV and/or LNP?
Yes. Thank you very much for your question. So as far as target selection, our approach is really to apply criteria so that we are well differentiated from standard of care. Very important that we're delivering medicines that are meeting needs that the patients have that are not already met by existing therapeutic. And so we are going to look for targets in which we have high conviction as well as targets that have high profitability for technical as well as clinical and commercial success. And so I'm excited here to have Karen having joined so that I can partner with her as well as Baisong and triangulating this to very much select our targets. I think we're really well positioned now to be selecting these where, as I said before, I think we're very excited about the in vivo sickle cell disease [indiscernible] target. Because we already have emerging data supporting that target and getting to your question about delivery.
Where our strategy, which Gilmore described in January is nonviral delivery. And so we are prioritizing LNP delivery amongst the nonviral deliveries and working internally as well as through external partners to drive an approach for in vivo HSC targeting for our HPG12 promoter with an LNP strategy. As far as other targets and tissues, of course, LNPs are validated for delivery [indiscernible] so we're interested in that. And I think we're well positioned there as well with our technology and especially with the recent deal that we saw announced and just showing the interest -- continuing interest [indiscernible] in this space. And -- but we're also interested in other tissues. And so there are many targets out there amenable to [indiscernible] technology, and we're excited to to move forward, and we'll certainly be sharing information with you as we -- as it emerges in the future at an appropriate time. Thank you.
Thank you, everyone. This will conclude today's conference. You may disconnect your lines at this time. We thank you for your participation.