EDIT - Editas Medicine Inc. (EDIT) RBC Capital Markets Global Healthcare Conference 2023 Transcript
2023-05-16 15:43:09 ET
Editas Medicine, Inc. (EDIT)
RBC Capital Markets Global Healthcare Conference 2023
May 16, 2023 10:30 AM ET
Company Participants
Gilmore O'Neill – Chief Executive Officer
Baisong Mei – Senior Vice President and Chief Medical Officer
Conference Call Participants
Luca Issi – RBC Capital Markets
Presentation
Luca Issi
All right, great, thanks. Hello, everybody. Luca Issi, Senior Biotech Analyst here at RBC Capital Markets and today is our great privilege to have Editas with us for a fireside chat. Representing the company we have Gilmore O'Neill, Chief Executive Officer; and Baisong Mei. Gilmore and Baisong, thanks so much for joining us. How are you doing today?
Gilmore O'Neill
Great. Lovely to be here. Thank you.
Luca Issi
Fantastic. So we have a long list of questions. But maybe Gilmore we would love to start with you with a bigger picture question. I think you joined the organization as a CEO about a year ago reflecting on this past year. What has been the biggest positive surprise since you joined Editas? What do you think could have gone better? And maybe most importantly what's next here for Editas?
Gilmore O'Neill
Yes. Thanks very much Luca. So it has been actually a privilege to be here now for the last 11 months or so, we're coming up on the year and it's been a very exciting and interesting year. One thing I do like to try to avoid is surprises. I think it is in the nature of the business that we should avoid surprises at all costs. Obviously, biology can always throw you a curve ball, but otherwise you should really manage risk and look out far to avoid surprises. I will say, however, on the very positive side, I've been very pleased with the data that we have seen from 301. We presented our data in December, and then just last week the abstracts for EHA presentation came out.
And you would have seen that we have – we really continue to validate what we saw in December. We have a competitive product with robust expression of fetal hemoglobin. And indeed now in two patients, we have again confirmation of a key point of differentiation where we have seen rapid normalization of the total hemoglobin, not just fetal hemoglobin, total hemoglobin for the first two patients dosed. And we're obviously very excited to present even more data at EHA. The other really wonderful thing has been how the leadership at Editas and the people at Editas have actually embraced the refocusing and pivoting of our strategy where we basically doubled down on three key pillars, which was advancing 301 with significant redeployment of capital to our CMC capacity as well as clinical execution.
And indeed that positive response reflects very objectively in a doubling of the enrollment just over the last three months since we rolled out that strategy that doubling of our enrollment and enrollment in need of 19 patients in the RUBY Study. I think you asked me what we could have done better. I would say the one thing that I feel that we could have done better is I wish that I had recruited Baisong on the first day I arrived there. He has along with many other people in the organization, but he has been really a significant driver in the execution of 301. And frankly, in reading out data that enable us to make some critical decisions in actually developing, refining and rolling out our strategy and then what lies ahead in the year.
Well, I talked about our strategy. We basically rolled that out with three pillars focusing on 301, doubling down on in vivo discovery and not actually developing or discovering, I should say, additional standalone cell-based therapies. A reorganization in the second pillar of our research to strengthen it into a technology group focused on targeted delivery and growing our tools for editing as well as then a targeted – therapeutics development where we actually use those technologies as we look into in vivo. We've actually talked about looking at in vivo hematopoietic stem cell editing, but actually we're also looking beyond that. And then a third pillar, which was around changing our business development posture to really looking to bring in those additional capabilities and technologies that would enable us to deliver that strategy.
And then in this year, what's in the future are to continue to drive towards having dosed or completing dosing of 20 patients in the RUBY study by the end of the year. As I said, we've actually enrolled 19 patients, so we're feeling very good about the – our delivering on that objective. We're obviously dosing thalassemia patients in EDITHAL and then we're driving towards some key catalysts with our data readout in June, and then at the end of the year the June readout from RUBY sickle cell at the end of the year for RUBY and EDITHAL. So we've done a lot. We've a lot more to do, but it's actually really wonderful to actually see that Editas has now moved its technology into the clinic. We are executing on that. We are driving through our transformation from a platform or technology platform company into a therapeutics company. And really what's one of the most thrilling things is to know that we've already had an enormous impact on patients' lives with the patients we've dosed, who've engrafted and who are doing so well.
Luca Issi
Great, great, great. Super helpful and well done on what could have gone better. Maybe if I may on maybe – based on for sickle cell disease. Could you just – maybe you guys already touched upon it, and maybe recap on the highlight of that dataset maybe how you're thinking about differentiations versus CRISPR and Bluebird. And maybe if I may, on safety, we've seen a few cases of AML and MDS for the Blue bio dataset, and there was, I think, one case of a patient that required phlebotomy in the ICER report for CRISPR. Is this just driven by the combination of busulfan and hyperplastic bone marrow, meaning everyone in the space is going to see that safety issues because everyone is using busulfan and these patients have hyperplastic bone marrow, or are you confident that those AEs are actually driven by lenti or BCL11A or some other factors in the molecular biology, and so you will be able to actually spare some of the toxicity we're seeing from others?
Baisong Mei
Yes, I think, your question probably two parts, one about the data, the other one about safety perspective. From the data perspective, at – next month we're going to release four patients data and with one patient have 10 months follow up, and the other patient has six months follow up. And then of course, we actually have enrolled in 19 patients already and on the track we dosed 20 patients this year and those 19 patients at different stage of the clinical trial, some I would say already manufactured ready to be dosed at just schedule time and other patient in the process of pheresis. And of course, we're continuing to enroll patients on that too. So that's why we are very pleased to see the progress of the trial. And so we – next month we'll have EHA presentation, oral presentation. We also have a webinar – a company sponsored webinar, and to allow us to have a more conversation with friends like you guys here and get more details.
From safety perspective, we are very pleased with that safety profile we have so far and we have all the patients dosed and have no SAEs that – or AEs related to the treatment. And in terms of specific events, and you're talking about the Bluebird and we have using different technology, they use lentivirals and we use the gene editing, which CRISPR and Cas12a. And then regarding the ICER report on the Vertex and CRISPR, we do not know much detail of that, and the sponsor did not release any information on that. So we do not know the specifics about the [indiscernible]. And from our end, and we do not expect that from our mechanism of action. And so, we are looking forward to seeing more clinical data from our end.
Gilmore O'Neill
Just one thing I just wanted to close out on the differentiation is that I know I touched on it earlier was that with the abstract publication last week, we've actually seen that our first two patients actually corrected their anemia very early on after their transplant. Why does this matter? Well, sickle cell disease in – certainly when I was in medical school, I was taught it was sickle cell anemia. And the reason I emphasize that is that there are kind of – there's a trifecta of pathobiologies going on in sickle cell disease. The first is sickling, obviously, which causes vascular occlusive events, which manifest as pain, but can actually manifest as significant infarcts to end organs like the brain, for example. Anemia is another and anemia can be very troubling. Anemia is required – actually in many meta-analyses both across anemia in general and in sickle cell thalassemia specifically.
The degree of anemia is actually associated with specific risks of end organ damage. And indeed we use transfusions, or rather when I say we, the field, the medical field and the treating physicians use transfusions to try and actually manage patients. So correcting anemia is an important piece. And then obviously hemolysis is the third element, which creates oxidative damage both for the lining of the blood vessels as well as shortening the lives of the red cells. So the important point I'm making is from a differentiation point of view is that seeing that robust signal in our first two patients really drives us to believing that this differentiation is real. And very importantly, it is consistent with the non-clinical data that we have seen and generated and presented in the past and actually suggesting that a hemoglobin B12 promoter targeting strategy is a superior approach from the point of view of improving red cell output and red cell survival. And again, it validates the non-clinical data. And that data also validated the original biologic hypothesis of our discovery scientists when they decided to use a targeting strategy for HBG1, HBG2 rather than a BCL11A.
Luca Issi
Sure, sure. Super helpful. And since you mentioned editing the promoter is – my understanding is that Novartis had at least conceptually a similar approach to your approach. I think we've seen limited data there. Maybe we've seen some preclinical data. However, we know that they have discontinued that program. Can you just talk about some of the differences between their approach and your approach that gives you confidence that they have discontinued, but you will not?
Gilmore O'Neill
Yes.
Luca Issi
Any thought there?
Baisong Mei
Yes. So we are using different region of the promoter of HBG1, HBG2 and we are targeting the region [indiscernible] mutation that's being seen in most of the hereditary persistence fetal hemoglobin patients and Vertex – well, Novartis also released their editing region, which is different from ours. So we are completely different. And that that difference of the fetal hemoglobin expression level is not a surprise to us. In fact, actually, we, of course not before me, our scientist five years ago, actually more than five years ago did all the scanning of the larger region of the promoter region. And this – the region that reported by Novartis is actually the region where our scientists already scan through. We passed that region, we through the region we're choosing now, and that's actually demonstrated that our region, indeed, clinically is also beneficial.
Gilmore O'Neill
In indeed, when we looked at our fetal hemoglobin expression, our hemoglobin expression, it really is quite different and very superior to what they had published in their abstract and presented at ASH. So I think that sort of difference or the validation of our choice is clear in the actual clinical outcomes. And so, we feel very good about our construct and, as I say, are driving to continue its clinical development because we believe that this is a highly competitive and differentiator product.
Luca Issi
Yes, super helpful. You mentioned a few times, obviously data upcoming at EHA. Can you just frame expectations for that dataset? How many patients are going to show us? What parameters should we be focused on? I think obviously hemoglobin you mentioned a few times, and obviously VOC are going to be key elements. But are we going to see additional biomarker like editing efficiency in peripheral bloods or bone marrow? I think you are doing biopsy for bone marrow. How should you think about bilirubin or LDH, like any other biomarker we should be focused on there?
Baisong Mei
Yes, we will show some editing efficiency from the drug product perspective, a clinical blood perspective, but our data is a little bit early to show all these editing bone marrow, but we will show that editing data in the future on that too. So in a general data scope perspective, we have four patient data with hematological data as well as VOE and safety and engraftment. And we are very pleased with the consistency of the both neutrophil and platelet engraftment for all the patients we observed and as well – as the favorable safety profile.
Gilmore O'Neill
And just to sort of close that out, with hematologic parameters, fetal hemoglobin percentages, some of the cellular parameters with the distribution of fetal hemoglobin. And obviously the total hemoglobin will be presented.
Luca Issi
Yes. Super helpful. How should think about regulatory, you have mentioned 20 patients by the end of the year. What would it take to make RUBY a registrational trial here? If I recall it correctly, CRISPR actually filed on 31 patients with a total of one year follow up. Are those like the numbers that we should have in the back of our mind? How should we think about that part?
Gilmore O'Neill
Yes, no, I'm glad you asked that question, Luca. I'm going to start and then hand it over to Baisong. One of the things that Baisong and I have the advantage in bringing to Editas is an experience in between the two of us bringing 10 different compounds to approval and launch. And so with that experience we believe that one can actually countenance a quite aggressive approach to bringing forward important medicines for very serious diseases.
I say that against the background of experience against a background of an evolving CBER. But obviously all of that is contingent on agreement with the FDA. But certainly when we think about numbers, the duration of follow up and also the use of hematologic parameters in addition to VOEs, we can actually see a path that we want to discuss with the agency, but Baisong, you might want to?
Baisong Mei
Certainly. I think we feel the rare disease space has been a lot of things in common in terms of regulatory strategy perspective. And from our own perspective, of course, we consider RUBY study as registrational trial pending all the further alignment with the regulatory agency. And for the RUBY study, we have alignment on the potency trial – potency assay with the FDA and to be able to use that data to support registration. And it's probably noticed in clinicaltrial.gov, we actually change our primary endpoint as a resolution of VOE, which is consistent with the other BLA filing. And we also think that biomarker could be very important in a sickle cell space, for example, that GBT has been used in the total grouping increase of one gram as the primary endpoint for approval.
And for fetal hemoglobin has been well demonstrated naturally by the increase of fetal hemoglobin in the HPFH patient with a sickle cell can have no sickle cell symptom. Then of course, this recent filing can also further demonstrate the biomarker in this space. And if you look into the evolution of the agency also there, FDA especially is very science driven agency and very recent examples last Friday, Sarepta has a AdCom, has a favorable outcome from that that is really bad based on very innovative biomarker to be able to support that accelerator approval, of course, final approval still pending for FDA, but the outcome from the AdCom is very encouraging.
Luca Issi
Sure. That's actually helpful. I get the differentiations, again, you're editing the promoter 12A, different editor versus some of your competitors and all that. However, when I think about the efficacy bar that your competitors are setting in terms of like reduction of VOC, that's pretty high bar, obviously so what are some of the other end points that you're thinking about it that can prove a clinical differentiation, not a differentiation term of molecular biology, but actually clinical differentiation? Is there anything that you're thinking about, like exercise capacity or, silent stroke or how you think about that part?
Gilmore O'Neill
Yes, so like many rare disease, when it's a devastated rare disease with very little choices of treatment, you start with severe patients, you start with endpoint such as VOE. But my expectation also in this field for sickle cell of disease, that we will see that many therapy be able to control VOE. Certainly we are very confident with our model to be able to control VOE, but we are looking much more beyond VOE in terms of clinical outcomes in differentiation perspective, right.
We're looking essentially street buckets, right. When is – hematological parameters are the values on that for patients, but the second one will be important to see the endpoint damage. And because the – total hemoglobin level, the anemia can really damage and the organ system. So that's something we are looking into that. We are looking from CNS to liver, to pulmonary and the kidney in there too.
The last category is also very, very important is actually patient reported outcome. So when we are talking about what is the significance of correcting anemia, for example, their life will be different. They probably can go upstairs very easily without a short of breath. They probably can go to Cradle in the mountains than without short of breath. So that's kind of the direction we're looking to the quality of life. Just give them the examples. We're looking for multiple different angle to demonstrate clinical outcome.
Luca Issi
Got it.
Gilmore O'Neill
So I think you touched on, important points where we look at, and by the way, end organ damage is the thing we're talking about. So, silent stroke is when we're looking at, you can actually renal health by measuring urine parameters and obviously looking at various cardiopulmonary intricacies as well as exercise tolerance. So I think those are all things that we are actually considering as we look beyond to actually generate additional supportive data for clinical differentiation. But I think the key thing is that I think we're pointing out that when it comes to actually the translatability of fetal hemoglobin and very importantly, hemoglobin two, long-term health outcomes, these are very robust. And actually what I would say is well validated if not qualified biomarkers for predicting clinical benefit.
And indeed, we have many decades of meta-analysis, analysis that actually correlate levels or degrees of anemia with end organ damage and health outcomes.
Luca Issi
Got it, got it. Super helpful. The holy grail, I think of sickle cell disease in the broader space is obviously moving on from busulfan and having better pre-conditioning that can drive better compliance and hopefully capture a larger patient population. What's the latest on that front, and if I can what's the latest on the CD117? Again, we've seen Magenta and Jasper, maybe not showing the data we're hoping for. Walk us, what's your thinking in term of preconditioning –novel preconditioning?
Gilmore O'Neill
Sure. So I'll start with – we actually have included that as part of our strategy. We're sort of in early days, as I would say in our discovery around that, a large part of that is actually scanning the scientific and frankly the clinical landscape. While Magenta was a very unfortunate and obviously very sad for the patient and frankly indeed patients, because I think they certainly had a very interesting and potentially still viable path forward. But unfortunately events and the clinical tragedy really created issues. Jasper is advancing it’s program. And so actually we are still very interested by the CD117, what I would say is that with Jasper advanced, it actually does create an opportunity that impacts the entire field. Actually where a product comes to market for use in one type of transplant, it can actually be generalized in its use across that.
And what does that mean? That essentially means that the eligibility or the eligible patient population in the context of sickle cell disease or thalassemia, actually enlarges. I think another thing that's important is that a second part of our strategy is actually to look at in vivo editing of hematopoietic stem cells. Why do we choose that approach? Well, we feel that if you look at the three things or three problems you have to solve, we have the enzyme, we have AsCas12a, which is actually doing a great job efficiently editing with high fidelity in humans.
From a target point of view, we have the HBG1 and 2 promoter target, again, well validated already in humans exciting data that remains – that leaves the third problem to solve, not a trivial problem by any means, but the actual targeting of hematopoietic stem cells, that's one of the reasons we actually have talked openly about it. And so that scenario, which is in our discovery, why do I raise this in context of your question? To actually even further increase eligibility is go for in vivo. Because you actually take away not just conditioning as a challenge, but you take away the burden of cell collection, et cetera, and you superbly reduce the burden on patients, and frankly, the burden on the healthcare system, both in this country and in rich, well-developed countries as well as other countries with less well-financed healthcare systems.
So all-in-all that this is I think we have two approaches, and I do want to say one other thing about sickle cell disease. We're just talking about sickle cell, but even thalassemia is relevant. These are really serious diseases. I know people sort of say, well, the severe patients, but when you actually look at the disease in the context of the absence of management, if you look in a world like Sub-Saharan Africa, 80% of children born with sickle cell do not see their fifth birthday, that would argue that when we talk about severity of the disease, it's not really restricted to VOCs. That's what we're using right now for our clinical trials. For obvious reasons, it's a new technology. We're characterizing safety.
And so as we characterize that benefit risk, I think we have to look at the real issue of how serious this disease is, even with supportive care in advanced healthcare systems like here in the United States, where even then survival is constrained and the quality of life and the functionality of patients is massively constrained.
Luca Issi
Super, super helpful. I know I'm running out of time, but maybe last one if I may. What's the latest thinking on IP? Obviously, there is an ongoing legal debate going on and I think the final ruling from the Federal circuits should come somewhat in the foreseeable future, assuming that the final ruling goes your way. What's the strategy there? Could you potentially block Vertex and CRISPR from launching their product?
Gilmore O'Neill
Well, I think there are a couple of points we should make. First of all we are actually very confident that we will prevail in this interference. Why? Because this is an interference that has been ongoing, it's already been through PTAB twice and the court of appeal Federal Circuit wants and each patient broad, and therefore we have exclusive licensees of that Cas9 or those patents for Cas9, the licensees to us actually have prevailed. And so we are confident that we've prevailed, notwithstanding that I think it's important to say that there is other IP that we have in, which we have licensed from Broad, Harvard and MIT that actually is not subject interference and therefore already is in place and we believe covers many Cas9 human therapeutics in development.
And for that reason that we are very happy to actually grant licenses to this and would look forward to doing that because we think it's important to obviously enable the delivery of the power of CRISPR Therapeutics and specifically in this case Cas9 therapeutics to patients. But actually it's also important that we – with our investment in developing – licensing, developing enabling that IP have that value recognized for us. And obviously we would always want to grant licenses, but actually also we protected the IP.
Luca Issi
Got it. Super helpful, I have another 30 questions, but no time, so I appreciate the time. Thank you for joining us here at RBC and we'll talk soon. Thank you.
Gilmore O'Neill
Thank you, Luca.
Baisong Mei
Thank you.
Question-and-Answer Session
Q -
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Editas Medicine, Inc. (EDIT) RBC Capital Markets Global Healthcare Conference 2023 Transcript