Hello everyone, and welcome to Oppenheimer's 34th Annual Healthcare Conference. I'm Jay Olson, one of the biotech analysts at Oppenheimer, and I want to thank you for joining us. It's my pleasure to welcome Editas to our conference, and it's an honor to introduce Dr. Baisong Mei, Senior Vice President and Chief Medical Officer. If you have any questions during the discussion, please feel free to submit them using the Q&A function. With that, we'll get started. Thank you so much for joining us, Baisong.
Thank you. Thank you for the opportunity, Jay.
Our pleasure. So maybe just to get started, congrats on all the progress you've made in the past year. Can you just give us a brief summary of Editas for those who may not be familiar with your story, and also if you could highlight some of the recent updates, that would be great.
Thank you. Happy to, Jay. Editas is a clinical stage company, and we specialize in CRISPR-mediated gene editing. We are a pioneer in the gene editing space, and we just celebrated our 10th anniversary last year. We have a strong scientific foundation in gene editing space. Since our CEO, Gilmore O'Neill, joined about 18 months ago, Editas is going through a transformation from a technology platform company to become a commercial therapeutic company. So that's our goal. And what we have done is to really change our strategy to focus on three pillars. One is on the reni-cel, which is a clinical stage program for indication of sickle cell disease and beta thalassemia. And we'll talk a little bit more afterwards about that. And the second pillar is actually our in Vivo pipeline.v
So for the future pipeline, we have a focus on i n vivo gene editing instead of ex vivo gene editing. The third pillar is about the business development. We are the exclusive licensure for Cas9 CRISPR enzyme. We also have our strong foundation of many other IPs. We also think about that for business development, it's not just we are licensing our IP, but also we are interested in technology from others to be able to enrich our pipeline. So those are the three pillars of our focus since the beginning of last year we shared. For reni-cel, our goal is really driving this molecule to file for BLA and commercialization. For in vivo, we're going to expand our pipeline to other disease areas, different disease areas, and using editing technology.
As you're aware that we had a new CSO last year, Linda Burkly, who is driving our new pipeline on that too. From BD end, we recently had a deal with Vertex to have a non-exclusive licensure for Cas9 enzyme for their molecule of treating sickle cell disease and beta thalassemia, CASGEVY. We feel that this BD activity is important for us because it provides non-dilutive capital for us, and this allows us to extend the cash runway till 2026. We'll continue to do that in this direction. Just briefly, in 2024, we're going to continue to drive reni-cel clinical program. We will have a huge emphasis on our in vivo pipeline. We will have pre-clinical proof of concept by the end of this year.
And then for BD side, we will have both for the outlicensing to have our CRISPR enzyme IP as well as licensing and technology to enrich our pipeline. So that's kind of generally what we're thinking about 2024.
Great. That's a perfect setup. Thank you for that broad overview. We'll get into each of those three pillars in more detail, maybe starting off with reni-cel for sickle cell and thalassemia. You had the RUBY trial update not too long ago. It's definitely a key catalyst for investors. We're all watching it very closely. Can you just remind us about the data that you shared at ASH last year?
Happy to. Yeah. So we are very pleased with the momentum for both the RUBY trial for sickle cell disease and EdiTHAL trial for transfusion-dependent beta thalassemia. At the ASH in December last year, we presented a data set of 17 patients for safety and efficacy, including 11 sickle cell patients and six beta thalassemia patients. That is representing 12 additional patients since we actually shared the data in June 2023. So we're very pleased with the momentum. From the data perspective, the reni-cel demonstrated the drive can drive early and robust correction of anemia to normal physiological range of total hemoglobin. And from fetal hemoglobin perspective, reni-cel drives substantial increase of fetal hemoglobin in excess of 40%. And in all the RUBY study, sickle cell patients are free of vaso-occlusive events. And for the EdiTHAL patients, they stop red blood cell transfusion.
Then from a safety perspective, all the patients dosed have successful neutrophil and platelet engraftment. The safety profile is consistent with the busulfan myeloablative conditioning and an autologous hematopoietic stem cell transplant. Additionally, when we see all the patients with a different follow-up time period. But the trajectory of total hemoglobin expression level and the fetal globin expression level in both sickle cell patients and thalassemia patients are in the same trajectory at similar time points. So this gives us more confidence that we have not only a competitive product, but a potentially differentiated product with the normalization of total hemoglobin. I mean, just a couple of things to add on that from a differentiation perspective. We have a different approach of treating the sickle cell disease and beta thalassemia with this gene editing approach, right? We use a different enzyme.
We're using AsCas12a, Cas12a instead of Cas9 for gene editing, which gives us more specificity and high editing efficiency. We're targeting the promoter region of the gamma-globin gene and to be able to have high fetal globin expression and also normal red blood cell health and also the red blood cell production. That's kind of consistent with our clinical observation, and we see the good fetal globin expression as well as correction of anemia.
Excellent. That's super helpful. Thank you for those details from your ASH update. Just focusing on the patients in the RUBY study who had total hemoglobin levels in the normal range, can you just talk about how that translates into clinical benefits and what should we expect to see in that clinical data?
Yes. So for sickle cell patients, it's actually called sickle cell anemia before, right? So the major manifestation is actually hemolytic anemia. And when patients have anemia, then of course they cannot have this physical activity and/or have a low quality of life and organ function and organ damage. So what we see is we'd be able to correct the anemia and not only increase the fetal hemoglobin to prevent the sickling, but also correct the anemia and bring the hematological range of total hemoglobin. We will impact not only the hematological parameter-wise, but also we'll improve the end-organ function and improve patient quality of life. So from a clinical trial perspective, we are monitoring for three categories of endpoints. One is hematological parameter and for total hemoglobin hemolysis markers.
We also monitor for end-organ function, for example, pulmonary function, cardiovascular function, liver and kidney functions, and the central nervous system. Those are the parameters we monitor during the clinical trials. Another very important thing we monitor is actually patient-reported outcome and quality of life. For example, fatigue is a major complaint for sickle cell patients. When you correct the anemia, it is likely that fatigue will be really corrected. Those are just examples of the quality of life change that we're expecting because of correction of anemia.
Great. Thank you for that. Any guidance for investors on when they should expect to see, for example, improvements in end organ function clinical data?
Yeah. Yeah. We are actually in the new territory, right? Because sickle cell has no meaningful treatment before. And now we'd be able to correct the anemia, correct the sickling. And we're trying to see how those would directly impact end organ function and quality of life. There's very little literature being studied in this space. But we do see some publication from an allogeneic transplant perspective. And from the limited data we have seen that after allogeneic transplant for sickle cell patients, they do see cardiovascular function improved. They do see central nervous system function and, for example, blood flow in the central nervous system in the brain actually changing there too. So we are looking into that space. We actually do not have good information to say how long it will take. But we do see that sign of that improvement there too.
But for hematological parameter, we expect to see sooner. For the quality of life, we would expect to see like 6-12 months, we'll see some improvement. So that's kind of the direction we're expecting, and we have to see how the data tells us.
Okay. That's helpful. Good to know. And I'm glad you mentioned hemolysis. I think that was in the ASH poster that you mentioned. You saw markers of improvement in hemolysis. Do you think that's an important part of reni-cel's differentiation?
We're certainly pleased to see the improvement for all key hemolysis biomarkers, for example, LDH, reticulocytes, and bilirubin in there. And it is very possible this hemolysis biomarker could be a potential important parameter for differentiation. We're collecting more data on that. I think that, you know, from if you correct the sickling, you will reduce the hemolysis. But for improvement or normalization of total hemoglobin, that could be contributed by at least two factors. One is reduced hemolysis. One is healthy erythrocytosis, which means actually red blood cell, healthy red blood cell production. So those are the two factors contributing to the total hemoglobin expression. But we're just very pleased to see the hemolysis biomarker improvement in all aspects.
Okay. Great. Thank you. That's good to know. Can you just talk about why did we see differences between total hemoglobin levels for sickle cell versus thalassemia patients?
Yeah. So maybe I'll step back a little bit to kind of describe a little bit about the difference between sickle cell disease and beta thalassemia. In both diseases, the pathology is actually the beta globin. In sickle cell cases, they do express beta globin, but the globin is mutated, therefore causes sickling. But in beta thalassemia, their problem is actually reduced or very minimal expression of beta globin. So that's kind of two different pathologies. So in the sickle cell case, we express fetal hemoglobin and then allow dilution of the sickle globin. Therefore, prevent the sickling. And in the beta thalassemia case, they do not or do not have enough beta globin. And we use that fetal hemoglobin expression to substitute the missing fetal globin. So the pathology is slightly different.
Therefore, especially initially, you'll see slightly lower total hemoglobin level for beta thalassemia patients because they do not have endogenous beta globin. They're purely dependent on the fetal globin expression. In our case, we see very high levels of fetal globin, fetal hemoglobin in beta thalassemia patients. The fetal hemoglobin level exceeds 9 grams per deciliter. So they're totally coming from the impact of the editing, right, mostly. That 9 grams per deciliter is considered a threshold to prevent or to be transfusion dependent. So that's kind of how the therapeutic goal for beta thalassemia patients.
Okay.
Hope that helps.
Thank you. Yeah, that's super helpful. Thank you for that. And then I guess following the FDA approval of CASGEVY, how are you seeing the interest level from investigators and patients to participate in and enroll in the RUBY study? And then were there any particular read-across or takeaways from the FDA AdCom and the approved label for CASGEVY?
Thanks for the question. We are very pleased with the approval of CASGEVY. That is very good for the patients and is very good for the field. One is from CRISPR editing itself is large because it's the first molecule being approved using CRISPR editing technology, which is only like 11 years after the first publication of this technology. It's incredible how this methodology becomes an approved drug. And then, of course, further demonstrate that fetal hemoglobin increase can really treat the disease. So that's really this will be great. And we continue to see strong momentum for our enrollment for the RUBY trial. And so we do not see any negative impact, if anything, probably positive to see, okay, this is a technology that can work well. So we're very pleased to see that. And in terms of regulatory perspective-wise, we also see very positive impact.
We actually monitor closely on the AdCom discussion. You can see that FDA and the panel of experts, how do they view the safety of the CRISPR editing in general and CRISPR editing for Sickle cell disease? That's very, very positive. From an approval perspective, we can say that, you know, FDA spent a lot of energy in this disease area. They know much more. They have a lot of engagement with the manufacturers, including ourselves. We see a very positive way to say now the agency knows this very well and also have very collaborative interaction with the manufacturing sponsors, including ourselves.
Okay. Great. And then I guess following the recent news that CMS is going to negotiate on behalf of Medicaid with sickle cell disease therapeutics manufacturers based on patient outcome measures. What's your takeaway from that announcement? And given the different pricing between CASGEVY and Lyfgenia, even though it's early, are there any initial thoughts on pricing of reni-cel?
We are very pleased to see that CMMI actually has this access model for cell and gene therapy and also choosing sickle cell as their first program. So this is significant for us, right? So this is significant in a way to say, you know, CMS as well as the entire community in the healthcare system increasingly appreciate the benefit and value of cell gene therapy. And that can change a patient's life and they have health economic value of that. And also choosing sickle cell as the first program is further indication of our medical needs for this patient population. So we're very pleased to see this the way. And towards your question about pricing, you know, I'm not going to be able to comment on other people's pricing and it's too early to comment on our own pricing strategy.
But I think generally, we feel a very positive way to say, okay, this is a new era to do cell gene therapy. Admittedly, the initial cost is high. And how we together, not only just the parents and community and then also, you know, together, how do we address this healthcare system to be able to work together to find a model? Now, CMS is leading the way to say, look, we see the value. We want to find a way to help out the patients and be able to drive the economics and help the patient's life. So we see this very positively. We're going to be very actively engaged and monitor this process.
Okay. Great. Definitely appreciate your perspective there. And then just from a timing perspective, just to set investor expectations, can you please remind us when should we expect to see the next clinical update on reni-cel? And I know you've commented on this before, but could you please remind us the expected timeline for a BLA filing and how will your regulatory submission look in terms of the data package? We're assuming the second half of 2025 for a BLA submission. Would you think that might be accurate?
Yeah. I think you have two positive questions. One is related data. The other one is data package for BLA. I can start the second part question first about BLA. We want to be very careful to say exactly what the BLA data package is going to be because we have to get alignment with the regulatory agency. What we can say is that we will have two data releases this year. Middle of this year and end of this year, we have two data releases. In the middle of this year, we're going to have large data cohort, substantial data with three to five months follow-up period, and which will further confirm the safety and efficacy data from what we have shared before. And we'll have a further data release end of this year for both RUBY and EdiTHAL trials.
We continue to dose, you know, patients, and we expect to dose a large number of patients this year. Then by the time of next year, we have a good follow-up period for those patients in 2025. So that's kind of our view on that and the specific data package that we will have to get alignment with the FDA on those specifics. So we are very optimistic about our data collection, about the enrollment, and the data being available for next year.
Okay. Great. Super. Thank you for providing that timeline. That's extremely helpful. Maybe just to focus on manufacturing for a second. Can you just talk about you had your expanded collaboration with Azzur? Can you just describe the manufacturing preparedness and the importance of that for the launch?
Yes. We have expanded the collaboration with Azzur about reni-cel manufacturing. Right now, we already have this existing collaboration with them to support our clinical trials. And we expanded that collaboration with expanded manufacturing capacity with two things in mind, right? One is for BLA filing. One is for commercialization. And this expanded collaboration will allow us to support not only BLA, but commercialization. What I want to note is that this model of collaboration is not a conventional CDMO. It's actually we use their facility from Azzur, but supply with our manufacturing staff members and to be able to manufacture in their facility. And this way, we do not have a so-called technical transfer process because it's our staff, our process, our equipment go to their facility. And also, we allow us to wisely invest using our capital.
So, we do not have to have a capital investment for a manufacturing facility, given the size of the company and our strategy focus. We feel this is ideal for our size, the size of our company and strategy focus we have, so it allows us to actually in early stage to get our BLA ready to be able to get a commercial manufacturing ready with this model.
Okay. Great. And are there any lessons or takeaways you'll be watching for from the CASGEVY launch or Lyfgenia launch in terms of reducing manufacturing time or reducing number of collections?
Certainly, we are monitoring the launch from other molecules. So I think from that launch will be several elements. Manufacturing certainly is one, but also that, you know, how to reach out to patients, how to work with treatment center physicians, how to work with payers. You asked a question about CMS, which is an important piece of that too. From a manufacturing perspective, we are, you know, taking measures to understand how the way we can do to, you know, shorten the manufacturing timeline. Especially when we do the manufacture, the majority of the time spent is actually for QC release. For those assays to see after manufacture, what's the quality of the molecule? We do, you know, extensive testing to see the quality of the manufacture. So there are opportunities to shorten this timeline, for example, to find the logistics in between on that.
We're working on that perspective.
Okay. Great. Thank you. This has been a really fantastic deep dive on the first pillar. As you described, it would be great to talk briefly a little bit about the second and third pillars, starting with the second pillar. Can you just give us a short overview of your plans for in vivo gene editing? And it seems like you have a couple of undisclosed targets. Anything that you could share with us on potential indications that Editas is working on for in vivo?
I will, you know, let our CSO, Linda Burkly, to share more in the future, but I just high-level-wise, right? So our strategy to feel that in vivo editing is important is in a way that they can address many different diseases and can also be more accessible to patients because it's easier for patients to access on that too. And then we are looking into the new target of disease indications to see that one is a deficit in disease. And two is that we can be able to differentiate from standard care, not only standard care now, standard care when the time we actually launch our drug, right? But when we look into that is we say we want to see what is the technical, clinical, regulatory success, but also what is the commercial success of that molecule. So that is very important there too.
We are working into several different diseases working on that. We'll share more in the future. Including, of course, delivery technology and tissues, we are looking into in that aspect too. Linda will share more in the future at the appropriate time.
Okay. Great. Thank you. We'll look forward to that. And then with regards to the third pillar of business development, congrats on the recent non-exclusive licensing agreement that you signed with Vertex for Cas9. Should we expect something similar to that with other gene editors using your technology?
We are very pleased to have this deal with the Vertex and allow this CRISPR technology to have more patients. And we'll continue to do that. And just in general, a different partnership, a different, you know, stage of the company, we may have a different model partnership on that too. But we're looking forward to have more collaboration with different companies, for example, whether, you know, for the mature and large company like Vertex, we'll have this model. For other early-stage companies, we may have a different model in terms of collaboration-wise. And we see quite a bit of interest in this space. And we're looking forward to the collaboration with the partnership to bring the CRISPR technology in to help patients. And we expect more activity this year.
Okay. Great. Thank you. We'll look forward to that. Then just one last question from the audience regarding your third pillar. Are there any particular technologies that you're interested in licensing?
We are in licensing our technology. Mostly is actually in rich our pipeline, right? For example, delivering technology, among other things, could be our interest. We have not shared a lot of specifics-wise, but our goal is to say we will not be able to do everything ourselves. We are here and open for business for the partnership on the CRISPR enzyme, but we're also open for business to actually collaboration with others. When they have advanced technology and other things can be used in rich our pipeline, we're very much willing to have that collaboration.
Excellent. Well, thank you so much, Baisong. This brings us to the end of our time. It's been great catching up with you. Really appreciate your bringing us up to speed on all the impressive progress you're making at Editas. So thank you for joining us and sharing your time, and thanks to our audience.