Editas Medicine Q4 2023 Earnings Call Transcript

Quartr
Provided by Quartr
February 28, 2024

There are 15 speakers on the call.

Operator

Good morning, and welcome to Editas Medicine's 4th Quarter and Full Year 2023 Conference Call. All participants are now in a listen only mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Christi Barnett, Corporate Communications and Investor Relations at Editas Medicine.

Speaker 1

Thank you, Maria. Good morning, everyone, and welcome to our Q4 and full year 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 and A.

Speaker 1

As a reminder, various remarks that we make during this call about 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 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 ks, 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.

Speaker 1

Thanks, Christy, and good morning, everyone. Thank you for joining us today on

Speaker 2

Editas' 4th quarter and full year 2023 earnings call. I am joined today by 4 other members of the Editas executive team: our Chief Medical Officer, Baisong Mai our Chief Financial Officer, Eric Lucira our Chief Scientific Officer, Linda Berkley and our Chief Commercial and Strategy Officer, Karen Deardorff. We are pleased with Editas' momentum and progress in the Q4 and all of 2023. In early 2023, we shared our vision and the three pillars of our strategy to position Editas as a leader in in vivo program for gene editing and hemoglobinopathies. The first of these pillars to drive reticel formerly known as EDIT-three zero one toward BLA and commercialization.

Speaker 2

The second, to strengthen, reorganize and focus our discovery organization to build an in vivo editing pipeline. And the third, to increase development activities with a particular focus on monetizing our very strong IP. So how did we do last year? Well, we achieved a lot. 1st, we accelerated the clinical development of Ranucel, exceeding our enrollment goal of 20 patients and sharing clinical updates from our RWBY and Edithal studies in June and in December of 2023.

Speaker 2

And those accumulating data have strengthened our belief that retinal is a competitive potential medicine with a differentiated profile characterized by correction of anemia at a normal physiologic ranges of hemoglobin. 2nd, we strengthened our in vivo discovery capabilities and organization and hired a new Chief Scientific Linda Berkeley, who brings 3 decades of experience in successfully inventing, developing and moving new human medicines forward. And third, we increased our business development activities and monetized our IP, leveraging our robust IP portfolio. A critical example was our granting Vertex a non exclusive license for our Cas9 IP in a focused way to enable the XSL launch. Finally, we strengthened our senior leadership team with people who have a proven track record in bringing new medicines through development to approval and commercialization.

Speaker 2

So how we executed against these strategies and these objectives? Well, let's start with GrannyCell. 1st, on enrollment, we have now enrolled 40 sickle cell and 9 beta thalassemia patients in our RWBY and Edithal studies respectively, and enrollment continues at a good pace. 2nd, on dosing, we have dosed 18 RWBY patients and 7 Edithal patients and we have multiple patients scheduled for dosing in the coming months. Patient screening and demand in both studies continue to remain robust.

Speaker 2

3rd, on clinical data, We remain on track to present a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024 with a further update by year end 2024. On the regulatory front, we have engaged with the FDA regarding the RUBI sickle cell trial. The FDA agrees that Rubie is a single Phase 1, 2, 3 study and has aligned with us on the study design. Our discussions with the FDA will continue as Rubi and Edithal progress and will be enhanced by our RMAT designation for severe sickle cell disease. Beisson will share further details regarding the development of Remicel in his remarks as well as recap the RWBY and EDITHAL takeaways and clinical data that we provided in December and share more information on the adolescent cohort.

Speaker 2

Now let's turn to in vivo and our pipeline development, where we strengthened our in vivo discovery capabilities in 2023 and began lead discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues. As we announced earlier this year, we aim to establish in vivo preclinical proof of concept for an undisclosed indication this year. Linda and her team are leveraging key capabilities that we have in house and she look forward to sharing more at a future date. Regarding our hemoglobinopathy focus, after a thorough evaluation of the development landscape, we have decided not to pursue interim development of a milder conditioning regime. We believe standalone milder conditioning regimens will be widely available once FDA approved and therefore we have determined that research, clinical development and regulatory investment in hemoglobinopathies can be better deployed for our continued development of in vivo HSC methods.

Speaker 2

Turning to business development. In the Q4, we announced a license agreement with Vertex Pharmaceuticals. Editas provided Vertex a nonexclusive license for Editas Medicine's Cas9 gene editing technology for ex vivo gene editing medicines targeting the BCL11A gene in the field of sickle cell disease and beta thalassemia, including Vertex's cash JV. And the upfront and contingent payments pursuant to this agreement extended our cash runway into 2026. This and other agreements, the strength of our patents and the number of companies developing CRISPRCas9 medicine reaffirm our confidence that our IP portfolio of foundational U.

Speaker 2

S. And international patents covering Cas9 use in human medicine are a source of meaningful value. So what are our objectives for 2024? For Running Cell, we will provide a clinical update from the RWBY trial for severe sickle cell disease and the Edithal trial for transfusion dependent beta thalassemia in mid-twenty 24 and by year end 2024. We will complete adult cohort enrollment and initiate the adolescent cohort in Rubi, which we've already initiated and continue enrollment in APL.

Speaker 2

For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication. And for BD, we will leverage our robust IP portfolio and business development to drive value and complement core g netting technology capabilities. We are energized by our progress and execution in 2023. 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. Now, I will turn the call over to Baisang, our

Speaker 3

Chief Medical Officer. Thank you, Gilmore. Good morning, everyone. Let's talk about Renesel, which is under clinical development for severe sickle cell disease and transfusion dependent beta thalassemia. As of today, in the RUBY trial for sickle cell disease, we have enrolled 40 patients and dosed 18 patients.

Speaker 3

We have multiple patients scheduled for dosing in the coming months. We're also pleased to announce that we have initiated adolescent cohort in the Rubine study, which is one of our 2024 objectives. The interest and demand are high and adolescent patients have already started screening. In the EDIFL trial for transfusion dependent beta thalassemia, to date we have enrolled 9 patients and dosed 7 patients. As I shared earlier, I continue to visit our RUBI and Edicel clinical trial sites and continuously speak with the investigators.

Speaker 3

I appreciate the enthusiasm and support from the investigators and study sites. I'm pleased with the momentum of Renacell in patient recruitment, apheresis, editing and dosing in both studies. I'm excited to hear from the investigators that patients dosed with Renacell have already seen positive changes in their lives. As Gilmore mentioned, we have aligned with the FDA that RUBY clinical trial is now considered a Phase onetwo-three trial for BLA finding. We have also aligned with the FDA on the study design and endpoints and the FDA has agreed to our activation of adolescent cohort.

Speaker 3

We look forward to future discussion with FDA and continued collaboration. Turning to clinical data. In December 2023, we shared safety and efficacy data from 17 patients, 11 ruby patients, 6 Eddycel patients. Once again, the data confirmed observation from our prior clinical readouts, including Renicel driving early robust correction of anemia to a normal physiological range of total hemoglobin in sickle cell patients. Renicel drove robust and sustained increase in fetal hemoglobin in excess of 40%.

Speaker 3

All Rubi sickle cell patients have remained free of vessel occlusive events following the renal cell treatment. Ranacell treated sickle cell and beta cell simulation have shown successful improvement have stopped red blood cell transfusion. And the safety profile of stem cell observed to date is consistent with bussulfide and barbell active conditioning and autologous single track stem cell transplant. In addition, the trajectory of the correction of anemia and expression of fetal hemoglobin is consistent across renal cell treated sickle cell disease patient and beta thalassemia patient at the same follow-up time course. This data reinforce our belief that we have a competitive product and the product potentially differentiated from other treatments with rapid correction of anemia.

Speaker 3

Thanks to the deliberate choice that our discovery group has made early in the program. As we have previously stated, the choice of CRISPR enzyme and the targeted to edit for increased hemoglobin expression matters. Renacell uses our proprietary ASCAP12A enzyme to edit HBV-two twelve promoter. ASCAP12A increases efficiency of editing and significantly reduce off target editing when compared to other CRISPR nucleus including Cas9. Editing HBG-twelve promoter in human CD34 partial cells resulted in greater red blood cell production, normal proliferative capacity and improved red blood cell health when compared to editing of BCL11A.

Speaker 3

We look for differentiation in 3 categories of outcome in clinical trials, hematological parameter and organ function and patient reported outcome or quality of life. Based on the clinical data thus far, we believe that sustained normal level of total miglobin could be a potential point of differentiation for RENACEL. 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 and organ damage. We look forward to sharing additional updates, including RUBY and Edicel clinical trial data with more patients and longer follow-up period in midyear and additional data by year end. Now, I'll turn the call over to Eric, our Chief Financial Officer.

Speaker 3

Thank you, Baisong, and good morning, everyone. I'm happy to

Speaker 4

be speaking with you and I'd like to refer you to our press release issued earlier today for a summary of financial results for the Q4 and full year 2023, and I'll take this opportunity to briefly review a few items for the Q4. Our cash, cash equivalents and marketable securities as of December 31 were $427,000,000 compared to $446,000,000 as of September 30, 2023. We expect our existing cash, cash equivalents and marketable securities, together with the near term annual license fees and contingent upfront payment payable under our license agreement with Vertex to fund our operating expenses and capital expenditures into 2026. Revenue for the Q4 of 2023 was $60,000,000 which primarily relates to revenue recognized under our license agreement with Vertex, which as Gilmore referenced earlier on this call, we announced in December of 2023. R and D expenses this quarter increased by $18,000,000 to $70,000,000 from the Q4 of 2022.

Speaker 4

The increase reflects additional sublicense expenses offset

Speaker 3

by the decrease in

Speaker 4

R and D spend resulting from our reprioritization and targeted focus on our Rynocell program. G and A expenses for the Q4 of 2023 were $14,000,000 which decreased from $18,000,000 for the Q4 of 2022. The decrease in expense is primarily attributable to reduced patent and legal costs. Overall, Editas remains in a strong financial position bolstered by our sharpened discovery focus, June capital raise and our recent out licensing deals. Our cash runway into 2026 provides ample resources to support our continued progress in the Rubi and Editau clinical trials at Renecel, continued commercial manufacturing preparation and the advancement of our discovery and research efforts.

Speaker 4

With that, I'll hand the call back to Gilmore. Thank you, Eric.

Speaker 2

We are very proud of our progress in 2023 and look forward to accelerating the momentum into 2024 as we continue to evolve from a driving stage technology platform company into a commercial stage gene editing company. We look forward to continuing our transformation and sharing our progress with you. As a reminder, our 2024 strategic objectives include for ReniCell, we will provide a clinical update from the ReniCell RWBY trial for severe sickle cell disease and the Epicel trial for transfusion dependent beta thalassemia in mid-twenty 24 year end 2024. We will complete adult cohort enrollment and we already initiated the adolescent cohort in Ruby and will continue enrollment in edithop. For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication.

Speaker 2

And for PD, we will leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities. 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. Thanks very much for your interest in Editas and we're happy to answer questions. Thank you.

Operator

At this time, we will be conducting a question and answer session. Our first question comes from Joon Lee with Truist Securities. Please proceed with your question.

Speaker 5

Hi, good morning and congrats on that quarter. I'm sorry for my voice. My question is that could you please elaborate on the hemolysis markers that you're tracking and tell us how they will relate to patient reported outcomes such as quality of life? Thank you.

Speaker 2

Thanks very much, June. I hope that your voice gets better. I'm going to pass that question over to Baesung.

Speaker 3

Yes. Thanks for the question, Jun. So for the hemolysis marker, we look into multiple markers for indicating for hemolysis, including reticulocytes, LDH, bilirubin among others. And for the patient report outcome, we use several instrument to measure that clinical outcome and quality of life. And that related to like the general, PRO instrument as well as sickle cell specific instrument.

Speaker 5

Thank you.

Operator

Our next question comes from Samantha Simankov, Citi. Please proceed with your question.

Speaker 6

Hi, good morning. Thanks very much for taking the question. Can you share just any additional insights into your FDA conversation as you aligned on the RUBY trial, specifically in terms of the number of patients you'll need and the amount of follow-up you'll need to file a potential BLA?

Speaker 2

I'm going to have Baisong address that question.

Speaker 3

Thank you for the question. So we aligned with the FDA about the Ruby trial to be a Phase 1, 2, 3 trials to support BLA, including endpoint, sample size and study design. And we are still in we are continuing to have engagement with the FDA about the FDA with FDA about the DOA data package and the follow-up and so we'll have further discussion with the FDA.

Speaker 7

Got it. Thank you.

Operator

Our next question comes from Brian Chiang with JPMorgan. Please proceed with your

Speaker 8

Hey guys, thanks for taking our questions this morning. Can you just kind of give us a sense of what does a Phase 1, 2, 3 designation for Ruby really mean from a timeline perspective? And on the potential differentiation, I think based on you about investigators' feedback so far. I'm curious if you can also talk about just feedback that you have been hearing from investigators. Are they seeing any potential differentiation this early on?

Speaker 8

Thank you.

Speaker 2

Thanks very much, Brian. So I think there were 3 parts to your question. What is the Phase 1, 2, 3 and its impact on sort of the VLA path? What was the investigator feedback on differentiation and were they seeing signs or what were the things that they might be seeing in patients at this point. What I'll do is just address the first part and then ask Baisong to follow-up on the other 2.

Speaker 2

So with regard to Phase 1, 2, 3, I think the key point here is that it is a single. We've agreed that there's a single Phase 1, 2, 3 study. We have important agreement on what the outcomes are and the size of the study. What that basically means is that we remain on track and are even more confident about being on track to a BLA. I think it's worth calling out that the VERTEX study was also the study that was used for their BLA application was designated a Phase 1, 2, 3 before or prior to that BLA.

Speaker 2

So I hope that actually helps from the point of view of our path to BLA. And I think just mentioning Vertex, which is worth calling out that we sort of have a benchmark based on the BLA filing from last year with regard to the size of the filing that was originally used for that approval.

Speaker 3

Thanks. So Brian, for the differentiation and investigator feedback wise, so we actually have quite a bit engagement with the investigator and from their own observation of their patients as well as to see the data, they're very pleased to see the correction of anemia. And the hematologist that very much appreciate that the level of program globin be able to correct the media and they see their patient is less fatigue and they have more energy and they just they are directed for observation. And then also they told us that total hemoglobin level as published also impacted the end organ function. So those are the direction that we're also looking for.

Speaker 2

And one other thing I'd just like to quote just with regard to the Phase 1, 2, 3. I think the important thing is that the RUBI study has been as we've agreed with the FDA converted from a Phase I to a Phase I, II, III, which allows because it's a single study, a seamless transition to that study support

Speaker 3

BLA. I hope that's helpful. Yes. Just add on Gilmore's point, what Gilmore means is also to say we'd be able to use all the patient data from the study to support the BLA.

Speaker 8

Great. Thanks guys.

Operator

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

Speaker 9

Hey, good morning. Thanks for taking the question. Now that there's a gene editing treatment approved in sickle cell, What are your latest thoughts on how Renucel would fit in the space? And what have you learned from the early launch by the competitor?

Speaker 2

Thanks very much, Greg. I'm going to ask Karen to address that question.

Speaker 6

Yes. Greg, thanks for your question. What we've been hearing from the various stakeholders in this space is a lot of interest and some really good initial momentum. I think we're also hearing that across all of the groups, so your stakeholders, your patients' families, your centers, which are transplant, maybe gene therapy centers, your qualified centers and as well as your payers. There's just a lot of work that needs to happen, and I think you all are picking up on that.

Speaker 6

But it's starting and it's happening. So I think it's the balance of saying there is tremendous interest even from the government in the CMMI pilot that CMS has kicked off. So the way we see it as, it is very encouraging. It's going to take time and we really believe that the fast follower of Renacell is going to be timed very well, gives us time to be able to continue to collect data that is meaningful, differentiated to understand where centers may be struggling, where else we can optimize our vein to vein process to deliver a product that's differentiated not just in efficacy and safety perhaps, but also in our operational aspects. So we see the market developing in a very robust way.

Speaker 6

We just think it's going to take a little bit of time. So we're very pleased with initial interest, certainly the ongoing interest in our clinical studies, and look forward to talking more with you about it.

Speaker 2

Great. That's helpful. Thanks so much.

Operator

Our next question comes from Mani Farajara with Leerink. Please proceed with your question.

Speaker 5

Great. Thanks for taking

Speaker 2

the question. You talked a

Speaker 5

little bit about improvements in vein to vein time as an incremental source of differentiation independent of clinical data. Can you walk through how you guys think of the timing on which we might see that show up in terms of CapEx investments, in terms of clinical trial execution, etcetera, like where we're going to start seeing data points to de risk that part of your advantage in the eyes of investors?

Speaker 3

Yes. Thanks for the question. This is Baisong. Thank you, Randy. We are in the clinical trial stage, right?

Speaker 3

We're already trying to optimize all the process from band to band as you mentioned in there too. So we amend our protocol and work with our expert in 3 seats for example and to help the sites on the in the 3 sites cycle and help the site to prepare the patients and provide support. So that's kind of the experience we gather now will help for our future commercial launch. I'll pass that to Karen on that.

Speaker 6

Yes. And just to add, as we continue to be very engaged in our clinical sites and expanding our outreach to other centers, we have the opportunity to really understand how the process is working, how we make the introduction of a product like RENACEL as seamless as possible, do the advanced work, fit into their existing processes. But we're always looking at opportunities across just again the efficiency, the timing, and we'll certainly be able to talk more as we get closer.

Speaker 2

Great. That's helpful.

Operator

Our next question comes from Terence Flynn with Morgan Stanley. Please proceed with your question.

Speaker 10

Great. Thank you, team. This is Max Skoron for Terence Flynn. Can you provide an update on the CRISPRCas9 appeal case and whether you expect an oral argument in the first half of twenty twenty four? Thank you.

Speaker 2

Thanks very much, Max. We have the Court of Appeals Federal Circuit has yet to schedule that oral hearing. It should be sometime this year. And once we have that scheduling, we can update you on that.

Speaker 10

Great. Thank you.

Operator

Our next question comes from Gena Wang with Barclays. Please proceed with your question.

Speaker 7

Thank you for taking my questions. So, if I heard it correctly, Gilmore, you mentioned that the FDA and Bison, I think that both of you maybe mentioned single study, if they agree on the single study, also number of a patient. I'm not sure if they agree on the duration of the study for Ruby trial. So wondering if we think about the CRISPR trial, Vertex trial, it's about 45 to 50 patients. Is that aligned with that numbers?

Speaker 7

And what is the duration that FDA require? And related questions, how many active sites you have now? And what is your goal of total sites for the pivotal study?

Speaker 2

Thanks very much, Gina, for your question. Before I point of view of the study design, I think first of all, the benchmark that was set by the BLA with Vertex's approval by the FDA for Exacel. It's actually very good benchmarking against which we're operating. And that has certainly informed our discussions with the FDA. We were actually very pleased with the discussion with the FDA and we believe that it actually really puts us on a track that lines up with the benchmark.

Speaker 2

And as a result, when we actually talk about having enrolled our 40 patients, how we've initiated the adolescent enrollment and so on, we believe we're actually on a very good track for BLA. With regard to the number of active sites, I'd actually want to clarify something. We're not talking about a separate study. Essentially, the RUBY study, which is ongoing with its sites activated, is the Phase 1, 2, 3 study that will be used for BLA and that is the agreement that we have with the agency.

Speaker 7

Okay. Sorry, the reason I'm asking more thinking about in the future commercial

Speaker 2

Yes. I understand that and appreciate that clarification. And certainly, we agree with that principle. I can think, Karen, if you want to add.

Speaker 6

No, no, no. I mean, I know we've already we had already expanded the number of sites previously to get to a number that would support the full study, right, Baisong? And so that was a very thoughtful approach to ensure that we had a good strong number of sites with geographic coverage.

Speaker 3

Yes. Maybe I can add on, Bongi. We already shared we have activated over 20 sites. And so we are with that over 20 sites, we already enrolled 40 patients. And we already those sites for adolescent cohort that you have seen overlap between the adult and adolescent from the same study size and we also are activating a few more size that specifically for pediatric patients.

Speaker 7

Thank you very much.

Operator

Our next question comes from Degen with Stifel. Please proceed with your question.

Speaker 10

Good morning, guys. Thanks for taking our questions. I apologize, it's actually a 2 part question. But just to clarify on the retinuecell progress in RUBY, if I heard you correct 18 dosed, I thought the prior conversation was 20 dosed by January. So can you talk about sort of the dropouts there?

Speaker 10

What was the reason behind that? And then another clarification on the FDA side. When you talk about differentiation, have you guys actually engaged them on the angle you're taking on the differentiation, whether total hemoglobin or end organ function? How are they perceiving that in terms of the conversation? Thanks so much.

Speaker 2

Thanks very much, Jaigar. First of all, I think we're actually very happy with where we are with our dosing, 18 patients dosed. And that really has us on track with that dosing pace to get us on track for a presentation of substantial data set in the middle of the year and actually with regard to our driving towards BLA. We have not had dropouts. So I just want to be sure that there's no confusion about that.

Speaker 2

And I think the final thing is that based on myself with our clinical development experience and particularly when you're dealing with complex therapeutics like that, you're going to get some waves, ups and downs and waves of not just enrollment, but dosing, particularly around scheduling, around holiday periods, etcetera. So as Baesong also said, we have many more patients scheduled for dosing in the coming months. And as I say, remain on track for a substantive data set in the middle of the year. With regard to differentiation and our conversations with the FDA, we have actually highlighted our potential differentiation, the mechanistic differences behind that, etcetera. But I think it's too soon to comment on where the FDA and where our discussions with the FDA are on that.

Speaker 2

Great. Thank you very much.

Operator

Our next question is from Debjit Chattopadhyay with Guggenheim. Please proceed with your question.

Speaker 11

Good morning. This is Ry Forsyth from Debjit's team. Did the alignment with the FDA include any feedback on off target editing profiling akin to sort of the Adacom's criticism around KAS JV's characterization, for the breadth of genetic What characteristics of this program are you most excited about the market size, the opportunity for 1st in class, the specific editing chemistry, etcetera?

Speaker 2

Thanks very much, Debjit. So, let me actually pass the first question to Baesung.

Speaker 3

Yes. When we have continuous engagement with FDA. So we are looking the engagement is scientific driven, is to understand the size of our molecule, the data we have and then how the patient was managed and we have a whole range of engagement with FDA from preclinical CMC to clinical. So because as Gilmore mentioned, we have our met with designation and we have a lot of leverage and a lot of opportunity to actually engage with FDA. So we are very happy with the collaborative nature of the FDA engagement.

Speaker 2

And I can just add to that is that as we said before, when we actually watched the AdCom discussion, we were very gratified by what we heard and saw, because our confidence both in the comprehensive nature of our off target editing oversight package was actually very robust relative to the discussion of the AdCom. And frankly, our off target editing data package is actually very good and not surprisingly because we are using our own engineered AS Cas12a enzyme, which is a high fidelity as well as high efficiency enzyme. And it's worth saying that in our hands and in the hands of others, off target editing is not detectable across a genome wide screen as opposed to Cas9. So we feel very good about that. And then with regard to the in vivo characteristics, I think I just want to say, as I said before that, the key things or factors that we are focusing on is to select a set of targets that are high conviction based on their potential for critical differentiation from the current standard of care.

Speaker 2

And it actually does include a number of variables, include the probability of technical success as well as regulatory success

Speaker 3

and commercial success.

Speaker 11

Thanks for the rundown.

Speaker 3

Thank you.

Operator

Our next question comes from Phil Nadeau with TD Cowen. Please proceed with your question.

Speaker 12

Good morning. Thanks for taking our question. Our question is on manufacturing. Can you remind us where you are in the scale of process, the commercial manufacturing scale of process? And in your discussions with the FDA, have you agreed upon a CMC package?

Speaker 12

And in particular, is there a requirement for patients in ruby to be dosed with the commercial material? Thanks.

Speaker 2

Thanks very much for your question. From a CMC point of view, we actually are in a very good place. We have, as you know, had discussions with the FDA and are actually progressing very well along that line. We actually are, as you know, we have are building our commercial capacity. And obviously, that capacity will be ready for the demand that would exist at the time of our launch and is ready for supporting demand beyond that launch.

Speaker 2

And then with regard to the processes, I'd say we're making excellent progress there in support of our BLA so that we would be BLA ready and inspection ready at that time.

Speaker 3

Thank you.

Operator

Our next question comes from Jay Olson with Oppenheimer and Co. Please proceed with your question.

Speaker 5

Hey, congrats on all the progress and thank you for providing this update. Our question is about your in vivo program. Can you talk about how and when you're planning to share preclinical proof of concept? And since it seems like there's 2 undisclosed targets in your corporate deck, are you planning to share preclinical proof of concept for both programs? And also any thoughts you could share on your choice for editing tool and delivery tool?

Speaker 5

Thank you.

Speaker 2

Thanks very much. So from the in vivo pipeline point of view, with regard to the how and the when, we're excited to be on track towards POC this year for a in vivo preclinical POC. And we're going to be able to share more and look forward to sharing more later in the year about the forum and the timing, whether it be a scientific forum or other forum in which we would share the data. And we haven't made a determination yet about that. And as I say, our focus is on driving towards a POC for in vivo this year.

Speaker 2

Oh, sorry, with regards to the editing tools, well, we have I think to be very clear that we are focusing on our ASC Cas12a editor, and we are really focused on that for a number of reasons. First, it's our proprietary enzyme that we have selected going forward because of its high fidelity and high efficiency, because of the benefits of it using a smaller guide and the advantages for quality, etcetera, in the manufacturing. And then finally, because we have human proof of concept, we have very exciting robust editing data in human cells from ASK12A, from our reticel program. All of those are the reasons why we're favoring and using that editing tool. And then with regards to delivery, we are using a non viral focusing on non viral delivery and nanoparticles specifically.

Speaker 5

Super helpful. Thank you so much.

Speaker 2

Thank you.

Operator

Our next question comes from Yan Zhu with Wells Fargo. Please proceed with your question.

Speaker 11

Great. Thanks for taking our questions. We're just wondering about the midyear readout from the RUBY trial. I think you have 18 patients dosed to date. Are you going to report data on these 18 patients plus any additional patient dosed with a certain amount of follow-up at the time of readout?

Speaker 11

And also seems like this is a much bigger number compared with the last readout. So I was just wondering your confidence level of continuing to show the total hemoglobin

Speaker 2

Thank you, Anand. Before passing to based on some of the details, I agree with you. Yes, this is a much bigger number of patients that we have dosed. And our confidence, as we've said, has increased with the accumulation of data that are continue and repeatedly show that not only are we achieving robust fetal hemoglobin expression in excess of 40%, which is well above the 30% threshold that natural history would tell us is relevant. But we actually also see that consistent correction of anemia to a normal physiological range in all men and all women treated and followed past 4 months to date.

Speaker 2

And yes, we're excited about the midyear disclosure. But with that, I'm going to pass it to Baisong to give you a little more detail.

Speaker 3

Yes. Thanks, Yim. I mean, your understanding is absolutely correct. We already dosed 18 patients and we'll continue to dose patients in the coming months. So the data set will be 18 patients and plus more that we're going to be dosing before the middle year.

Speaker 3

And as you can see, we yes, as you can see, we published data in ASH and some patients already over a year, then this patient will have continued to monitor for those patients longer follow-up period. And then we have 18 dose now. And by the middle of the year and this will have this patient, this 18 patient will have 3 or 5 months more data by the time we release that. That's why we describe as really very meaningful substantive data we will be able to share in the middle of the year as exactly you mentioned. This data set is pretty strong.

Speaker 2

Yes. And we actually I think, Baisong, I think you said it, but is it worth reemphasizing, we're talking about ranges of follow ups from an efficacy point of view between 3 and 18 plus months. So when you actually got the total cohort of patients now, we are now really building not just a data set that is robust in number, but actually at robust in follow-up period time, which obviously relevant not just to our hematological and efficacy outcomes, but actually also increasing our confidence in durability.

Speaker 11

Great. Thanks. Looking forward to that.

Operator

Our next question comes from Luca C with RBC Capital. Please proceed with your question.

Speaker 13

Great. Thanks so much for taking my question. Congrats on all the progress. Maybe based on any update on the grade 2 polycythemia case that was potentially related to retinacel? I remember the poster at ASH actually noted the causality of the AEs was being investigated pending additional lab tests.

Speaker 13

So just wondering if you have any update on that one. And then maybe just quickly, any update on partnering sickle cell disease ex U. S? Thanks so much.

Speaker 2

So, Beisson will take that first question. And with regard to partnering, I will just say that we are keen that a partner with a global footprint could help us with a global and thalassemia programs here in North America. And as I say, partnering will be something that we will look to in the future as upside. With regard to the erythrocytosis, Basal?

Speaker 3

Yes. Thanks. That specific patient will have a transient elevation of protein globin as we reported in ASH. At the time of ASH reporting, it's already been normal for more than 6 months. And that continued the patient hematological care made including total hemoglobin continues to stay normal.

Speaker 3

And then the investigator has a further investigation of the patient data and we view that too and the investigator consider this event is not related to the sickle the renal cell treatment.

Speaker 13

Got it. Thanks so much.

Operator

Our next question comes from Steve Seedhouse with Raymond James. Please proceed with your question.

Speaker 2

Hi, good morning. This is Timur Ivankov on for Steve Seedhouse. So we just had a clarification question on your PRO tools in Ruby. To what extent are you going to be using the same tools that Vertex and CRISPR used before, like EQVAS, FACG and BMT? And to what extent do you think of including new tools on the issue being you're not going to be able to do a clean cross trial comparison potentially here?

Speaker 2

Thank you.

Speaker 3

Yes. Thank you for the question. As I mentioned, commented earlier, we use tool from 2 end, when is it more general, the quality of life tool as well as the sickle cell specific. And as you mentioned, the specific of the tool we're using, we have a domain for check the evaluate the fatigue of the patient, which is important to complain from a sickle cell patient, just give you example wise. And you are very much that's exactly the direction we were thinking, trying to see, okay, what are the specific instruments be able to detect that major complaint from the sickle cell patients such as fatigue, such as pain, a number of other things?

Speaker 2

Yes. So we are actually using a number of instruments. Some were used by Vertex and we have additional instruments in our PRO armamentarium and they are actually being collected in the RUBY Phase 1, 2, 3 trial as we speak.

Operator

Our next question comes from Jack Allen with Baird. Please proceed with your question. Great.

Speaker 14

Thanks so much for taking the question and congratulations on the progress.

Speaker 13

I wanted to touch a

Speaker 14

little bit on the patient experience with Vermicel. Have you provided any disclosures around the number of apheresis cycles that are required to receive Vermicel? And I was wondering if the higher editing efficiency of cast salve allows for shorter amount of apheresis cycles? And then on the back end after treatment, what are you seeing as it relates to time to neutrophil engraftment? And then how do you think that compares to some of the competing products in the space?

Speaker 14

Thanks so much.

Speaker 2

Thanks very much, Jack. I'm actually going to ask Baisong to talk about the clinical experience with Pheresis and other elements of the patient experience and obviously touch on neutrophil engraftment with which we have been very pleased to date.

Speaker 3

Thank you, Jack. We for patient experience, I mean, firstly, it's definitely a very important part of that. As I mentioned earlier, since I joined, I worked with the team and experts. We manage the protocol and trying to optimize the free speech process. So now we are very happy with the number of cycles that patients have been gone through and we can see that's already improvement from what we had before.

Speaker 3

In terms of the engraftment, as we disclosed that in ASH, we have all the patients have been randomized under within 30 days. So we're very happy about that. And we continue to see the similar data we follow through the follow-up studies.

Speaker 2

Great. Thanks so much for the color. Thank you very much.

Operator

We have reached the end of our question and answer session. This concludes today's conference. Thank you for your participation. You may disconnect your lines at this time.

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Key Takeaways

  • The company’s three‐pillar strategy—advancing Renicel toward BLA and commercialization, building an in vivo editing pipeline, and monetizing its IP—saw strong execution in 2023 with clinical acceleration, key hires, and a major Cas9 license to Vertex.
  • In the RWBY (sickle cell) trial, Editas has enrolled 40 patients and dosed 18, while in the EDITHAL (beta thalassemia) trial it has enrolled 9 and dosed 7, with interim data showing rapid hemoglobin correction, >40% fetal hemoglobin, zero vaso‐occlusive events, and transfusion independence.
  • The FDA agreed that RUBY will serve as a seamless Phase 1/2/3 pivotal study supporting a BLA, aligning on design, endpoints and the recently initiated adolescent cohort, and granting RMAT designation for severe sickle cell disease.
  • As of December 31 2023, Editas held $427 million in cash, equivalents and marketable securities, recognized $60 million in Q4 revenue from the Vertex deal, and expects its balance sheet plus contingent payments to fund operations into 2026.
  • For 2024, Editas aims to deliver mid‐year and year‐end Renicel clinical updates, complete adult and adolescent cohorts, establish in vivo preclinical proof of concept for an undisclosed indication, and drive further business development leveraging its IP portfolio.
AI Generated. May Contain Errors.
Earnings Conference Call
Editas Medicine Q4 2023
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