EDIT - Editas Medicine Inc. (EDIT) Cantor Global Healthcare Conference 2023 - (Transcript)
2023-09-26 16:45:02 ET
Editas Medicine, Inc. (EDIT)
Cantor Global Healthcare Conference 2023 Call
September 26, 2023, 01:35 PM ET
Company Participants
Baisong Mei - Senior Vice President and Chief Medical Officer
Erick Lucera - Executive Vice President and Chief Financial Officer
Conference Call Participants
Rick Bienkowski - Cantor Fitzgerald
Presentation
Rick Bienkowski
Good afternoon, everyone. Welcome back to the Cantor Fitzgerald Global Healthcare Conference. My name is Rick Bienkowski, a biotech analyst here on the research team. And today we're lucky enough to have two representatives from Editas here with us. We have Baisong Mei, the CMO of Editas, and also Erick Lucera, CFO. Welcome.
Baisong Mei
Thank you.
Erick Lucera
Thank you.
Rick Bienkowski
All right. Great. So I thought we could begin the talk just with a brief introduction to the company. 90 second intro for those not familiar.
Baisong Mei
Sure, yeah. So Editas is established exactly 10 years ago. So this is our 10th anniversary. And we are the first one to actually using the CRISPR enzyme gene-editing technology to develop drugs.
So that we are the pioneer in this space and we have been very strong in the science and over the years and we have been put into two molecules in clinical development and then we are actually also significantly invested in the CMC manufacture. We are the probably one of the leaders in this space to do the CMC manufacture for gene-editing by ourselves in that too.
And also, we are exclusively licensure from Harvard MIT and Broad Institute for the CRISPR-9 enzyme for gene editing and to develop the human medicines. And since January, we actually announced our strategic change to really have a focus on EDIT-301, which you'll hear more from our conversation and also focus on in vivo editing, and to develop a pipeline, and also to really leverage our IP position, and also have a BD activities, not only our license for our Cas9 enzyme, but also about the in-licensing technology that can help us to expedite the drug development.
Question-and-Answer Session
Q - Rick Bienkowski
All right. Perfect. So let's just dive right into the WEED program then EDIT-301. Over the summer, there was a recent, the most recent data update was over the summer. You released data from both the sickle cell disease program and one patient treated with beta thalassemia. So to start, could you just walk us through some of the key data there and where we are in the trial, you know, number of patients dosed and, you know, what we expect to see later on this year?
Baisong Mei
Yeah, absolutely. Yeah, so we are very excited to have that data released in June. And actually, we had our presentation at European Hematology Association at Frankfurt in June, and afterwards we have a company sponsored webinar. And the webinar, in addition to the sickle cell data, we also have one patient from [indiscernible] but it's a similar data and we're very excited to see that for those patients, we see that not only a high fetal hemoglobin expression level, but also normalized total hemoglobin correction of anemia for the two patients who have more than six months of follow up in sickle cell disease. And we are very excited even though we have relatively small data set, it is because that we're choosing a different approach to treat sickle cell and beta thalassemia disease by gene editing while targeting two different editing region. We are targeting the promoter region of the gamma-globin gene 1 and 2 and using a CRISPR enzyme called AsCas12a instead of Cas9. And the reason we choose these is because our preclinical data did a head-to-head comparison, we find out that this target region of promoter region is give us better red blood cell production and better health of red blood cells. And when we see that clinical data to see that normalization of total hemoglobin and correction of anemia, we're very excited because that's what's expected from pre-clinical data. And we feel this potential point of differentiation. And for these four patients, the sickle cell patients, we see that for the two patients we have normalized hemoglobin, for the other two patients with a shorter duration of follow-up, also follow the same trajectory of total hemoglobin expression level as well as fetal hemoglobin expression level. And we are looking forward actually to share more data in the year for those patients as well as additional patients in those things.
Rick Bienkowski
Okay. Great. I guess there is a few different directions we can go from there, but I'm glad you brought up the mechanism of gamma-globin locus. So that is one of the mechanistic points of differentiation from computing CRISPR therapies targeting gamma-globin rather than BCL11A. Maybe could you speak to how that mechanism could potentially lead to differentiation in the clinic? I understand you may be seeing differences in some of the preclinical characterization, but how could that mechanism emerge into a clinical phenotype or a potential clinical benefit down the road?
Baisong Mei
Yeah, yeah, absolutely. So when we, you know, kind of back-up a little bit of treating disease, especially rare disease, and for those who have disease, have no treatment options, we were targeting for severe symptoms. For example, in sickle cell, we're targeting the vaso-occlusive events. But that disease is not just a vaso-occlusive events for sickle cell patients. There are anemia, there's hemolysis and the patient have end organ damage. So what we're trying to see is actually if we can correct the anemia, we'll be much beneficial to the patient to correct their end organ function, their daily life and patient reported outcome on that too. So we feel that at a different level, we'd be able to demonstrate the potential for differentiation from clinical perspective, not only based on the pre-clinical data and clinical data on that. We are looking into that, you know, we feel that the normalization of total hemoglobin will help for end organ damage, will be giving patients better quality of life. For example, sickle cell patient, one of the important complaint is fatigue. And the fatigue is very directly related to the anemia. And we also, ourselves as normal hemoglobin, if we go to high attitude, we see a feel short of rest and when we go to the mountains. So that's kind of how the mild anemia that a patient will feel on that too. Then also from sickle cell, there's already a meta-analyzed study demonstrate that anemia is directly related to the end organ damage. So that's kind of the direction we're looking into that.
Rick Bienkowski
Great. So in the clinic, looking at end organ damage specifically, do you think you'd be indirectly measuring that based on anemia parameters or is there a more direct way you could specifically look at end organ damage in a clinical trial?
Baisong Mei
Yeah, it's a very good question. So we are looking into that several layer of endpoints from clinical trial perspective, right. Certainly we're looking firstly, looking to the hematological parameters and total hemoglobin level. Actually just last Friday, I was working with the KLA and Harvard Medical School and he said this is no-brainer. If you see a patient with a nine gram deciliter of hemoglobin with 16 gram of deciliter of hemoglobin. So that's kind of from that hematological parameter perspective then from end organ damage perspective for clinical trial, we actually were looking for multiple organ system, including cardio echo from pulmonary function test, liver function and also kidney functions in there too. So that we were looking into that. Then we are also looking into the patient report outcome and as I mentioned, they did also by quality of life change. So with the totality together, we'd be able to demonstrate that how these molecule may be able to actually provide a much more benefit to the patient of sickle cell patient.
Rick Bienkowski
Great. And just thinking about the logistics of including those potential secondary endpoints, looking at those parameters that may be indicative of end organ damage, would there need to be a protocol amendment to the clinical trial to start evaluating those secondary endpoints or is this something you could start doing today with your existing patients?
Baisong Mei
Yeah, our existing protocol already including a lot of things such as cardio echo, their pulmonary function and liver, and also the kidney functions. Of course, we can certainly add more in there too, but we covered most of that from end organ function perspective.
Rick Bienkowski
Great. So going back to the trial itself, I believe the most recent guidance is for dosing a total of 20 patients by the end of the year. Has there been any indication for the year-end readout? Is there a target number of patients that we're going to see or a target amount of patient follow-up there for the clinical readout that investors will see at the end of the year?
Baisong Mei
Yeah, yeah. So we are on track to dose a total of 20 sickle cell patients by the end. And the reason we proposed the 20 patients to be dosed at the beginning of this year was that we feel that given the rare disease, given the mechanism of action and the disease pathophysiology, we feel 20 patients could give us reasonable indication from efficacy and safety perspective, right. So you can see that other trials that actually have a data set about 17 patients from an efficacy set perspective on that too. We are planning to release more data at the end of the year. We have not provided guidance to say exactly how many patients will be released at the data on that too, but we can tell that we certainly will have longer follow-up period for the five patients. We release data in June then we have additional patients to dose the [indiscernible]. Then we'll be able to share the data in the year for both sickle cell and beta thalassemia patients.
Rick Bienkowski
All right. And if we could just talk about more longer-term goals of the clinical trial and the path to approval. So you know this is a competitive space. There are two, there's a gene-editing program and a gene therapy program that are ahead of you in the clinic. And if you look at those pivotal data sets they included somewhere north of 30 patients for the pivotal data set. So what I wanted to ask was do you think that you'd be able to have a potentially pivotal trial with a similar amount of patients? Do you think you'd potentially need more than that? You know just the most recent thoughts there on trial design?
Baisong Mei
Yeah, yeah. Certainly the final sample size will need to be aligned with the regulatory agency and we are on track to actually engage with the agency this year. But we understand that now for the two [BOA] (ph) under review and one of them have 35 patients for sickle cell patients. And our RUBY trial, which is for sickle cell disease is called for approximately 40 patients. So we're in a similar range. We will have to align with the agency on exactly the sample size required for the registration.
Rick Bienkowski
Got it. And are there timelines for meeting with the agency and potential disclosure of the outcome of that meeting with the agency?
Baisong Mei
So we have not provided guidance on the specific dates on that, but we are on track to engage with the regulatory agency.
Rick Bienkowski
Okay. So one other aspect of this, I want to talk about, right? Just given that the current regulatory environment we're in, where there is no potentially curative therapy for sickle cell disease approved yet, that might change this December. There might be two potentially curative treatments approved. Would the approval of competing treatments change anything about the pathway to registration for you guys? Do you anticipate it may have any impact on clinical trial design or endpoints that you need to show?
Baisong Mei
Yeah, we feel that these two [BOA] (ph) under review is good news for the patient and good news for the community. And not only I think the impact will be beyond actually sickle cell and beta thalassemia because this is going to be first CRISPR gene editing therapy to get approved. So our view is actually positive towards adding 301. We feel that the technology will be further validated by multiple different approaches and it will be good for patients and provide more patients more choices. So those are good. So we feel that in general would be positive for us. And there will be an outcome at the end of next month and we're looking forward to see that also.
Rick Bienkowski
Got it. One other aspect of scaling up to larger patient populations in clinical trials and potential commercialization, I want to talk about was the partnership with the Azzur Group. So this was just news from a few months ago. You recently expanded the collaboration there. I was just wondering if you could speak to the history of the partnership there and what exactly was covered by that expansion of the partnership.
Baisong Mei
Erick?
Erick Lucera
Yeah, thanks. So I'll handle that one. So we've been working with Azzur for quite some time in their Waltham facility for the producing the product for the clinical trial. The announcement that we made a month or so ago was for the establishment of a commercial facility in Devens, Massachusetts. So it's our people, our staff and our stuff essentially what we're renting a clean rooms.
Rick Bienkowski
Got it. So with that partnership, do you forecast that you'd be able to have enough manufacturing capacity for all clinical trials and into commercialization just based on that partnership?
Erick Lucera
Yeah, we think that will be enough. Certainly the existing capacity we have gets us through the clinical trial. And the expansion of the new clean rooms will allow us to get the launch going.
Rick Bienkowski
Okay, great. And before we move on from EDIT-301, if we could just talk about the beta thalassemia for a moment, you know, that trial is ongoing as well. Are there any updates for enrolment or the next data set we're going to see there?
Baisong Mei
Yeah, certainly. I mean the EDIT-301 trial actually moving along very well for beta thalassemia patients, and we have released data in June for one patient. At that time, only like one and a half month data, but we already see more than four grams of deciliter of fetal globin expressed in that data. And this patient data, we will have more data to release for this patient. And since then, we already have dosed multiple patients in their trial. And so we're looking forward to share more data about this trial at the end of the year. It's moving along very well. Especially given this disease is actually relatively small in the US, we have greater momentum and a lot of interest from the clinical study sites.
Rick Bienkowski
All right. Great. You know, you said in the introduction there has been a bit of a strategic shift since January where you're moving away from just ex vivo gene editing therapies and moving into in vivo. I was hoping you can talk about this a little bit more. Can you help us understand some of the decision making process behind this shift and what progress has been made since January when this was announced?
Baisong Mei
Yeah, yeah. Certainly, we feel that EDIT-301 for ex vivo gene editing is a great product, but to be able to, for the gene editing, to benefit more patients, and in vivo will be the way to go. Not only in a developed country like the US, and we are thinking about globally, that in vivo will have a lot more people. So, of course, we recently have our new CSO, and Linda Burkly joined us, and she's working with the team very diligently on the pipeline for the in vivo gene editing and we already have some internal activity going on already and before Linda joined, but Linda will bring us tremendous of expertise and with her, we don't want to say many, over 30 years of experience, multiple track going from discovery to approval will really help us to beef up our pipeline development for in vivo gene editing. So we will be looking forward to share more data, more information in the future.
Rick Bienkowski
Great. Ex vivo gene editing and in vivo gene editing, there's some overlap there obviously with the CRISPR enzymes and how you actually modify the DNA. But there are a number of challenges that in vivo gene editing has that you don't have with ex vivo delivery, for instance, is the number one problem in my mind. So thinking about the program itself, right? So there are LNPs that exist out there that are very good at targeting the liver, tissues outside the liver have been more of a challenge. So when you think about the in vivo program, do you think you will focus first on diseases that could be potentially cured by targeting the liver with gene editing LNPs or could we be seeing other tissue types targeted here?
Baisong Mei
Yeah, yeah. So certainly we are looking for multiple targeted tissues. Liver is one of them and another thing we discussed before was actually hematopoietic stem cells that we can be leveraged the EDIT-301 program already. We have a target, we have the enzyme, we know that it works. So then the left piece is delivery, right. Go back to your point about delivery, and we certainly have some internal activity on the delivery, but we also very much are looking forward to have collaboration with other parties to have on the delivery system. And over the last probably two to three years, there has been actually significant progress in the delivery system. Liver certainly is one of them. There are actually been these hematological disease being a lot of progress. Immunology disease has been a lot of progress in terms of targeting of the blood cells and there has been a lot of progress. And as well as other tissues that we've been monitoring in there too, that we're very optimistic that not just by ourselves, we actually community together that we'll have a lot of progress in the delivery system. Just a little bit back on that too, I was working a lot with the siRNA and have collaboration with Alnylam on that before. Think about like 10 years ago with the siRNA and the delivery system there was almost nothing. And now that it's booming from the siRNA delivery system. So we're expecting the similar trend for the gene editing and gene therapy system for the delivery. And there are companies actually set up specifically for delivery technology, nothing else. So we are very optimistic on that too.
Rick Bienkowski
Got it. So thinking about, I don't think there are any timelines for when we may see any data from these pre-clinical programs, but if you could maybe just elaborate or maybe some conjecture here about what we may see first. Could we potentially see announcement of targets for the in vivo program? Could we potentially see a poster with some in vivo proof of concept in animal models? Just wondering if there may be some internal timing for sharing some of this data, and what could be shared first?
Baisong Mei
Yeah, of course, certainly there's a lot of questions on that, and we understand that. We're also eager to share. So we are working very diligently and Linda's team been really working on that. And we do not have a guidance on the timeline on this sharing this information yet, but we are looking forward to share when we are on time appropriate on that. Yeah, we are diligently work on that because we feel this technology has so much potential. There are so many diseases can be tackled. In my over last 20 years, more than 20 years of a career, I work mostly on the rare disease space. We feel this is actually a good opportunity for novel technology like gene editing that rare disease space can be a place to go.
Rick Bienkowski
Got it. And as a part of the strategic shift in January, there were two halves of that. One was the in vivo pipeline, and another was the development of gentler conditioning regimens. If you could just talk about the strategy there and any progress that has been made throughout the course of the year.
Baisong Mei
Yeah, yeah, yeah, certainly. For the hemopoietic stem cell transplant and these condition, myeloblastic condition certainly is a very, very important piece that first of all you want to have to cure the cells, right, so that can have room for the transplant, but also there's a significant side effect, including fertility and other side effects, so that certainly is a focus of ours too. But if you come back a little bit on that too, and this kind of mild conditioning is not just for sickle cell disease or beta thalassemia, it's actually for all the bone marrow transplant and especially for leukemia and other things in there too. So anything in development in this space will not only benefit for sickle cell and beta thalassemia in there too. So we're watching this space very closely and we have some internal activity on that too. So we are thinking about to say, look, one is actually you could develop something specific for sickle cell and beta thalassemia or you can actually leverage that mild conditioning that can be broadly used, not only for sickle cell and beta thalassemia, but also for leukemia and other things in there too. In fact, you see, you know, several companies work in this space and FDA provide guidance. You actually work with the malignancy first before you actually work on sickle cell. So we are working in this space very closely. We understand the benefit for that, but I think that still working in this space needs to be done, so we are watching very closely.
Rick Bienkowski
Understood, and no timelines there for when we could potentially see an update for the conditioning?
Baisong Mei
At this point, we have not provided guidance on that.
Rick Bienkowski
Okay, understood. All right. One other thing I wanted to go over was the target selection for the in vivo program. So, you know, there's always a balance, right? There's these genetically validated targets that are well understood and it seems like once you have a really good genetically validated target, there are a number of companies that all go after the target at the same time and then there are different targets and maybe smaller diseases that have a little bit more biological risk to them because there aren't, there isn't the good animal models and validating data from other companies. So when you're thinking of target selection here, how does that come into play? Do you think it's important to have a really well genetically validated target? Or would you be more willing to accept some biological risk and go after a target maybe no other companies are looking at right now?
Baisong Mei
Yeah, yeah. So certainly, I think when we look into the target, I think we are focused on you want to have a competitive product, but also a differentiated product on that too. I mean, toward that end, we're looking into that direction. For this disease, we're looking to that. I mentioned a bit of rare disease could be our focus on that given that the, you know, the unmet need and benefited risk. But also, you're looking for the possibility of first class or best class in the molecule in that too. So you'd be able to differentiate and compete in that too, and provide more benefit to the patient community.
Rick Bienkowski
Got it. I understand. Early stages. So limited what you could talk about, but looking, there's about four minutes left here. I wanted to bring Erick into the conversation. So everyone's favorite question, can you tell us about the current cash balance, the runway the company has, and what are some of the potential value-driving catalysts we'll see in that time as far as the cash runway lasts.
Erick Lucera
Yeah, thanks. So we ended the second quarter with around 480 million of cash, and at the time we gave guidance into the second half of 2025 for the cash runway. So about two years from the date of the quarter. In terms of value drivers over the next couple years, obviously we're going to have clinical data at some major medical meetings that you can all guess what they'll be for this kind of technology. So we expect to continue to update the street on the progress of the 301 trial. In addition, we are looking from a business development standpoint at executing licenses for the Cas9, Cas12 portfolio that we have from the Broad. So we'll hopefully have some stuff to talk about with respect to that over the two year period. And then finally, as we mentioned with respect to in vivo technologies, we are looking for technologies for delivery to end license in addition to at some point discussing what Linda's working on from the pipeline. So lots of news flow over the next couple years.
Rick Bienkowski
Understood. I know the company has talked about the strong IP positioning a number of times on conference calls. I guess thinking about the cash runway. Are the underlying assumptions in the cash runway no potential royalties from any licensing?
Erick Lucera
Yeah, it would be upside.
Rick Bienkowski
Okay, it would be upside and extend the runway. And if you could speak to IP briefly, I know there's the ongoing patent dispute, but could you just talk about the company's IP positioning a little bit, I guess both outside of that patent dispute and both including the potential ruling there, we'll see the first half of next year.
Erick Lucera
Yeah, so obviously we have multiple sets of patent estates. One is the Broad estate and the other is the Harvard estate. So the dispute in which you're referring to is only one of those sets of patents. And as we described in the analyst meeting, there's a completely different set of patents from a different innovator that are not subject to the interference suit. So we feel that we have a strong position regardless of the outcome of the interference suit.
Rick Bienkowski
Excellent. And we have a couple minutes left. I'd like to give Baisong an opportunity to give any closing remarks you might have?
Baisong Mei
Yeah, thank you. So we are really excited to have a change since January. We have the strategy change. And given the size of the company, and we cannot actually tackle too many things. We have to focus and really to prioritize and when I was previously in the previous company which is actually a large pharma, we already talked about priority, prioritization and this size of company we actually have to prioritize. So that's kind of, we already see the benefit of that and we actually increase the investment in 301 clinical program, not only for clinical study perspective, but also from CMC perspective. As I mentioned, we actually have internal capacity to do the manufacture. We actually invest a lot in there too to be able to support that. And then we also allow us to focus on the in vivo pipeline development. So we'll be able to actually develop the capital for that too. So we essentially think like three pillars. We have a 301 program really moving along for the two disease indications. And we have our strong science and we actually have Linda join us as a new CSO to be able to drive the pipeline. And then you mentioned also we actually have a business development including IP position, including in licensing technology to be able to beef up our pipeline. So this three period together, we're very much looking forward to bright future for Editas.
Rick Bienkowski
Great. Well, I'm also looking forward to the data release at the end of the year. So, thank you so much for the time. This has been fantastic.
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Editas Medicine, Inc. (EDIT) Cantor Global Healthcare Conference 2023 - (Transcript)