Editas Medicine , Inc. (NASDAQ: NASDAQ:EDIT) provided an update on its progress and financial position during its second-quarter 2024 earnings call. CEO Gilmore O'Neill highlighted the company's three-pillar strategy and the ongoing clinical trials for their gene therapy products.
Despite a negative decision by U.S. Health and Human Services regarding fertility preservation coverage, the company remains optimistic about its future prospects and the potential to reverse this decision. Editas reported a strong cash position and anticipated that their current funds, along with incoming payments from partnerships, will support operations until 2026.
Key Takeaways
- Editas Medicine is advancing a gene therapy for hemoglobinopathies and developing an in-vivo editing pipeline.
- Positive clinical data from the RUBY and EdiTHAL trials support the belief that their gene therapy could be best-in-class.
- The company is working to establish in-vivo preclinical proof-of-concept for an undisclosed indication by the end of 2024.
- Editas has a strong cash position of $318 million, expected to fund operations through 2026.
- The company expressed disappointment with the HHS decision on fertility preservation coverage but anticipates reversal and minimal market impact.
- Editas is open to partnerships outside the U.S. to improve access to their therapies.
Company Outlook
- Expectations to support operations until 2026 with current funds and partnership payments.
- The company is optimistic about its gene therapy product, reni-cel, and its clinical and manufacturing progress.
- Editas plans to target orphan indications initially for their in-vivo development program.
Bearish Highlights
- A negative decision by the U.S. Health and Human Services on fertility preservation coverage for gene therapy patients.
- No specific timeline provided for the Biologics License Application (BLA) for the adolescent reni-cel cohort.
Bullish Highlights
- Ongoing enrollment and dosing in clinical trials showing positive results.
- The company's fast follower timing is seen as an advantage for optimizing the reni-cel launch plan.
- Confidence in their manufacturing data and progress of multiple datasets.
Misses
- Lack of guidance on the BLA filing timeline for reni-cel.
Q&A Highlights
- Editas is evaluating lipid nanoparticles for gene editing delivery into multiple tissue types.
- The company is discussing multiple datasets with the FDA required for a BLA.
- Openness to intellectual property licensing opportunities and partnerships with other companies.
- The in-vivo approach for functional upregulation allows targeting of indications not accessible with knockdown strategies.
- The company is confident in the biological and clinical profile of their reni-cel asset.
In conclusion, Editas Medicine remains focused on advancing its gene therapy programs and overcoming regulatory hurdles. The company's financial stability and strategic partnerships position it to continue its development efforts and potentially expand access to its therapies globally.
InvestingPro Insights
In the context of Editas Medicine's recent earnings call, a look at the company's financial health and market performance can provide a more nuanced understanding of its current position. According to InvestingPro data, Editas Medicine has a market capitalization of $339.64 million, reflecting the market's valuation of the company. The data also indicates a negative P/E ratio of -1.99, suggesting that the company is not currently profitable, which aligns with the InvestingPro Tip that analysts do not anticipate the company will be profitable this year.
The company's gross profit margin is reported to be a significant negative at -171.78%, reinforcing the InvestingPro Tip that Editas suffers from weak gross profit margins. Additionally, the stock price has experienced a considerable decline, trading near its 52-week low, which is reflective of the InvestingPro Tip that the stock has taken a big hit over the last week.
Despite these challenges, Editas holds more cash than debt on its balance sheet, which supports the company's statement about its strong cash position and ability to fund operations until 2026. This is a critical factor for investors considering the company's long-term viability and potential for future growth.
For readers interested in a deeper analysis, there are additional InvestingPro Tips available on the InvestingPro platform that can provide further insights into Editas Medicine's financial metrics and market performance.
Full transcript - Editas Medicine (EDIT) Q2 2024:
Operator: Good morning and welcome to the Editas Medicine’s Second Quarter 2024 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 Cristi Barnett, Corporate Communications and Investor Relations at Editas Medicine.
Cristi Barnett: Thank you, Britney. Good morning, everyone and welcome to our second quarter 2024 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 two hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company’s future expectations, plans and prospects constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements, as a result of various important factors, including those discussed in the Risk Factors section of our most recent Annual Report on Form 10-K, which is on file with the SEC, as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. Now, I will turn the call over to our CEO, Gilmore O’Neill.
Gilmore O’Neill: Thanks, Cristi and good morning everyone. Thank you for joining us today on Editas’ second quarter 2024 earnings call. With me today are four members of the Editas executive team, our Chief Medical Officer, Baisong Mei; our Chief Financial Officer, Erick Lucera; our Chief Scientific Officer, Linda Burkly; and our Chief Commercial and Strategy Officer, Caren Deardorf. Because it is summertime, we are going to keep today’s prepared remarks brief and leave more time to take your questions. Let me start by saying that we are pleased with Editas’ momentum and progress in the second quarter of 2024 as we pursue Editas’ goal to deliver life-changing medicines to patients with untreatable or undertreated genetic diseases and to position Editas as a leader in in-vivo programmable gene editing. Three pillars underpin our strategy. The first of those pillars is to drive reni-cel, a gene edited cell therapy for hemoglobinopathies, formerly known as EDIT-301 toward BLA and commercialization. Second, to build a differentiated in-vivo editing pipeline and the third, to increase business development activities with a particular focus on monetizing our very strong IP. At the start of 2024, we announced the following 2024 objective. For reni-cel, we will provide a clinical update from the RUBY trial for severe sickle cell disease and the EdiTHAL trial for transfusion dependent beta thalassemia in mid-2024 and by year-end 2024. We would complete adult cohort enrollment and initiate the adolescent cohort in RUBY and continue enrollment in EdiTHAL. For our in-vivo pipeline, we would establish in-vivo preclinical proof-of-concept for an undisclosed indication. And for BD, we would leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities. How have we executed against this strategy and these objectives in the second quarter? Let’s start with reni-cel. First, we shared RUBY and EdiTHAL clinical data in June at EHA 2024, the European Hematology Association’s Annual Congress. The RUBY dataset included 18 sickle cell patients with 2.4 to 22.8 months of follow-up and the EdiTHAL dataset included clinical data from seven beta thalassemia patients with 4.1 to 12.8 months of follow-up. These data from the RUBY trial support our continued belief that reni-cel will be a best-in-class product for sickle cell disease. So why do we think this? All patients treated in the RUBY trial are free from vaso occlusive events post reni-cel infusion. All patients have robust correction of anemia with a mean total hemoglobin level within the normal range for both genders at greater than 14 grams per deciliter. And all patients have high fetal hemoglobin with levels well above 40% from six-months onwards. We also demonstrate fast engraftment with low variability with a mean neutrophil engraftment of 23-days, which may translate to shortened hospital stays for patients. For cell collection, we have a mean of two apheresis cycles with a range of one to four per patient. Finally, in addition to the clinical data shared at EHA on the manufacturing front for reni-cel, we have a robust manufacturing process with a low failure rate that continues to improve with experience. This low rate of manufacturing failure can decrease patient burden and reduce overall costs, as we avoid cell recollection and redundant cost of goods sold or COGS. And we are on-track to share additional clinical data for both the RUBY and EdiTHAL trials by the end of this year, 2024. Second, RUBY enrollment and dosing continues to be strong. Indeed, we have now completed enrollment of the adolescent cohort. As a reminder, we completed the adult cohort enrollment in the first quarter of this year. We are manufacturing drug product and scheduling adolescent and adult dosing concurrently. We also continue to progress EdiTHAL and are pleased to announce completion of the adult cohort enrollment and continue to dose patients. Finally, based on our continued and collaborative conversations with the FDA, we still expect our future BLA package to be similar in number of patients and duration of follow-up to what we have seen in the gene editing medicine field. Before I turn to vivo, I would also like to state that we are very focused on the best use of capital as we develop reni-cel and map to the future. As part of that focus, we frequently evaluate opportunities, including the potential for partnering reni-cel to most efficiently drive reni-cel towards commercialization and ultimately deliver it to patients in need. Now let’s turn to our in-vivo pipeline, where we continue to strengthen our in-vivo discovery capabilities and drive lead discovery work on in-vivo therapeutic targets in hematopoietic stem cells and other tissues. Importantly, we remain on-track to establish in-vivo pre-clinical proof-of-concept for an undisclosed indication by the end of the year. We want to take a moment; rather I want to take a moment to reiterate our in-vivo strategy to develop a pipeline of gene editing medicines for patients with serious genetic disease. As a reminder, our internal development efforts are differentiated from established modalities and we are not pursuing the same gene editing approach as others. First, our strategy is to use our indel technology for functional upregulation of gene expression to address loss of function or deleterious mutations. Let me be clear, our strategy is not the knockdown strategy that others in gene editing are pursuing. And it is worth highlighting that, we have already demonstrated that, our indel technology can drive functional gene upregulation, thus creating differentiated experimental medicines as in our ex-vivo development of reni-cel. With reni-cel, we leverage our indel CRISPR technology to upregulate the expression of the gamma globin gene, a functional homologue of the beta globin gene, through direct editing of the HBG12 promoter site. We are now applying the same approach to in-vivo therapeutics by using our indel technology to functionally up regulate the wild type allele or functional homolog of target disease genes as we build our differentiated pipeline. Why does the difference between our functional upregulation strategy and the knockdown strategy used by other companies matter? Because with our in-vivo strategy, we are not competing with existing modalities or technologies in development that are based on knockdown strategies. Second, our indication selection strategy targets rare and orphan diseases that we believe will allow us to be the first or best-in-class for a given indication. We expect to move into diseases with larger patient populations in the future. Our lead discovery work is in in-vivo therapeutic targets in hematopoietic stem cells and other tissues. Third, EdiTHAL is well positioned to achieve success with our in-vivo strategy and pipeline with our established capabilities in the four main components of in-vivo gene editing medicines: one, our guide RNA modifications that enable high potency gene editing in multiple cell types, including in the liver and improve gene editing outcomes in-vivo. Two, a superior editing enzyme in ASCAS12a. Three, our messenger RNA. And four, delivery technology where we are currently evaluating lipid nanoparticles for delivery of gene editing cargo into multiple tissue types with multiple companies, as well as evaluating additional next generation delivery technology. I look forward to sharing more details about our in-vivo pipeline later this year and our in-vivo proof-of-concept. Finally, I would like to refer you to our press release issued earlier today for a summary of our financial results for the second quarter 2024. I will take this opportunity to briefly review a few items for the quarter. Our cash, cash equivalents and marketable securities as of June 30th were $318 million, compared to $377 million as of March 31, 2024. As you will note, our burn rate was slightly higher this quarter than the past. This higher rate is due to increased external research and development expenses, primarily related to clinical and manufacturing costs related to the accelerated progression of our reni-cel program. We expect our existing cash, cash equivalents and marketable securities together with the near-term annual license fees and the contingent upfront payment under our license agreement Vertex (NASDAQ:VRTX) to fund our operating expenses and capital expenditures into 2026. Before we turn to Q&A, 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. We are energized by and proud of our progress and execution this quarter. With our sharpened strategic focus, our world-class scientists and employees, our keen drive in execution and strong balance sheet, we continue progress our strategy to deliver differentiated editing medicines to patients with serious genetic diseases and evolve from a development stage technology platform company into a commercial stage gene editing company. Thank you very much for your interest in Editas. We are happy to answer questions now. Thank you.
Operator: [Operator Instructions] And we will take our first question from Jack Allen with Baird. Your line is open.
Jack Allen: Great. Thank you so much for taking my questions and congratulations on all the progress you made throughout the quarter. I apologize for any background noise here. I’m traveling today. I wanted to ask about the pre-clinical proof-of-concept from the in-vivo program that is expected later this year. I was hoping you could just elaborate a little bit more, as it relates to what kind of data you look to put out, will it be in a large animal model or a small animal model and how should we think about the types of experience you are looking to do to indicate the off target editing profile for this program?
Gilmore O’Neill: So, Jack, I think you broke up near the end, but let me just restate the question the way I heard it. And then hopefully, if you need to correct us, let us know. So essentially, you just want to have an understanding of the data that we will have for our in-vivo POC, the size or the species that we will use in-vivo. And I think you want to talk about - I think I might have heard you talk about indications. I’m not sure. So I’m going to ask Linda maybe to address your question.
Linda Burkly: Yes. Thank you, Jack. You did break up a little bit. So thanks Gilmore for elaborating there. So, yes, we are on-track to establish pre-clinical POC in-vivo for this undisclosed indication by end of year. We have not yet disclosed the CGs in which we are working, but our evaluation process is going to entail, evaluating the biodistribution to the site of interest, the efficiency of editing, the level of target modulation measured, for example, by biomarker readout and, of course, the tolerability. We will be sharing more information, the forum and the timing for announcement of that data at a future time.
Jack Allen: Great, thank you so much for taking the question.
Operator: Thank you. We will take our next question from Samantha Semenkow with Citi. Your line is open.
Samantha Semenkow: Hi, great. Good morning and thanks for taking the question. Just building on the prior question. You are using an LMP in your strategy and not in viral. Do you expect to have an LMP targeted for the tissue of interest for the proof-of-concept readout indication optimize this year or, would you need to further optimize after the proof of concept is in hand? Thank you.
Gilmore O’Neill: Sam, thank you very much for your question. I will have Linda take that.
Linda Burkly: Yes. Thank you, Sam. Thank you for the question. We are evaluating, LMPs with different partners because we are interested in targeting different tissue cell types for different disease areas of interest. We haven’t yet disclosed which, tissues we are doing the non clinical POC targeting in, and we will be sharing that information at a future time when we disclose the data. So in terms of the targeting, aspects that you referred to, we will share that information in the future.
Operator: Thank you. Our next question is from Eric Schmidt with Cantor Fitzgerald. Your line is open.
Eric Schmidt: Great. Love the summertime strategy, very efficient. Maybe it will continue into the fall and winter. We will see. In terms of my questions, first, with the adolescent reni-cel cohort now completed in terms of enrollment, can you start to estimate your timeline to a BLA?
Gilmore O’Neill: Thank you, Eric. I’m going to have Baisong take that question for you.
Baisong Mei: Thank you for the question, Eric. We have announced that in June, we have dosed more than 20 patients and we are continuing to dosing patients. So that is moving along very well. And then, we continue to consider the CATXV approval as our benchmark. So that in terms of sample size, in terms of efficacy sample size as well as observational duration of 15 to 18-months and the total sample size initial submission was 20 patients and with additional 10 patients doing the review. So this is kind of the scoop of that. And we have not shared the specifics of the time line, because we have to get a final alignment with the FDA, but we are very optimistic that, we are collecting the data from - we are dosing closing to the BLA data package we are looking for.
Eric Schmidt: Okay. Thank you. Very helpful. And, maybe Baisong or Gilmore, can you talk about what we hope to learn at the late 2024 update on the program? But as Gilmore mentioned, at this point, we know a fair bit about reni-cel’s.
Gilmore O’Neill: Baisong?
Baisong Mei: Thanks, Eric. We expect to have data from longer duration of follow-up for those patients we present at EHA, which means, we are going to have more than 10 patients at one year exposure and additional patients have a different exposure. And then we also at EHA, we present data for 18 patients. We have seen dosing multiple more patients, so we are going to have more patient data also. With that, we were very excited for the data end of the year because we are going to have longer duration and we are going to have a data package similar to the - So, we are looking forward to sharing data with you all.
Operator: Thank you. We will take our next question from Terence Flynn with Morgan Stanley (NYSE:MS). Your line is open.
Terence Flynn: Good morning. This is Mia on for Terrence. Thanks for taking our question. So recognizing it is still early in the launches of Kaskavi and Liginia, but are there any learnings thus far that you hope to utilize for a future runny cell launch? Thanks.
Gilmore O’Neill: Thanks very much, Mia. Indeed, let me pass it over to Caren Deardorf, our Chief Commercial and Strategy Officer.
Caren Deardorf: Great. Thanks, Nia, for the question. First, we really want to say that we are encouraged by the Vertex update of the 20 patients in cell collection, which is a nice bump up from the five in Q1, and we really see that as an acceleration that we have anticipated, because we understand that there are multiple steps in the process to get a patient dosed. And we anticipate that they probably have a number of additional patients in earlier enrollment phase before cell collection, including getting payer reimbursement. We anticipate to significantly more uptake over the coming quarters as we look at both companies. We know from our own enrollment and the excitement in our trial that, there is a lot of patient and physician interest, and so that will continue as there is more exposure to our three therapies. In the U.S., we also know that payers are doing case by case approvals with few rejections. We know that, patients are able to get access and that policies will be in place over time. As a reminder, we really believe that our fast follower timing is an advantage, which gets to your question about the learnings. And that really allows us to be able to optimize our own launch plan. And another key component is that we understand the time it takes for centers to get up to speed, preparers to put policies in place. All of that, we anticipate, will come together around the time that the reni-cel might launch. We are already seeing a decrease in the amount of time for onboarding between [Bluebird] and Vertex and anticipate that, that onboarding cycle, from our own conversations and research will be significantly shorter at the time of our launch. We are really encouraged and we know, how much it takes behind the scenes, and we are just really glad to see patients moving closer to dosing. Thank you for the question.
Operator: Great. Thank you. We will take our next question from Gena Wang with Barclays (LON:BARC). Your line is open.
Gena Wang: Thank you. I will ask two questions. First one is what is the average process time from patient enrollment to dose any differences between adults and adolescent patients? And the second question regarding your indel technology, you say you would do up regulating. Just wanted to make sure that was the knocking down the repressor so that the target gene will be upregulated.
Gilmore O’Neill: Thank you very much, Gina. What I’m going to do is have Baisong address your question about the process time or the vein-to-vein time or enrollment to infusion time for adolescents versus adults. And then I will pass over to Linda, and I will restate your question just so we all remember. Baisong?
Baisong Mei: Yes. Thank you, Gina, for your question. From the enrollment to dosing, it varies quite significantly among patients, and some are going to be very short, like three or four months and other can be 10 months or even longer, because some patients have BOE in the middle and doing the process before dosing of reni-cel. Between adult and adolescent, and we see now is that we have very robust enrollment and that screening process was going faster than we had for adult and the apheresis process also going very smoothly. And that is probably also related to that the adolescent patients in a better health condition compared to older adult patients.
Baisong Mei: Thanks very much, Beisong. And then, Gina, you asked a question just to clarify how we are using the indel tech to functioning or regulate gene particularly the interdiction of the regulator?
Linda Burkly: Yes. Thank you, Jamie, for the question. So our functional regulation strategy is not is different. It is not a knockdown strategy. As per your question, we would not be knocking down the repressor. If we use the reni-cel example as a paradigm. In that case, we are creating an indel to disrupt the binding site for the repressor. And that way, we are upregulating gamma globin expression. Using that as an example, we could do a similar type of thing for another target of interest. There are other ways that one can create indels to upregulate gene expression. This is the approach that we are taking that is differentiated from a knockdown approach.
Operator: Thank you. We will take our next question from Mary Kate Davis with Bank of America (NYSE:BAC). Your line is open.
Mary Kate Davis: Good morning. Thank you so much for taking my question. I guess looking at your portfolio, how are you looking at the IP licensing opportunities in the future? Thank you.
Gilmore O’Neill: Thanks very much, Kete. I’m going to ask our CFO, Erick Lucera to address that.
Erick Lucera: Yes. Thanks for the question. We believe we have a very strong foundational position with respect to the IP license that we have from Harvard, MIT and the Broad. We are very open to having conversations with a range of companies, in terms of getting a structure in place that is sort of bespoke and works for both us and them. We believe, there is a high double-digits number of programs out in development and a good number of those about half are with eight to 10 different companies. We look forward to having conversations with folks. And as you can see, we have had some pretty good success in the last few years, as evidenced by some of the licenses that we have already put in place. So very excited to have that as a potential source of non dilutive capital for our company.
Operator: Thank you. We will take our next question from Brian Cheng with JPMorgan (NYSE:JPM). Your line is open.
Brian Cheng: Thank you for taking my questions this morning and happy summer. It sounds like you may have had additional discussion of the agency this past quarter. I’m just curious other than the clinical data, what other additional items have you discussed? And just based on Casgevy package at the time of the BLA, I would assume that you can potentially file sometime next year. So outside of the clinical package that we are waiting for mature data, what other additional data or gating factor do you need to line up between now and then? In other words, any color on your readiness towards a filing? Thanks.
Gilmore O’Neill: Thanks very much, Brian. I think there is sort of a complex question, in that you are asking about the multiple datasets that are required to actually go filing. First of all, let me be very clear that, we have not actually shared an estimate or given guidance to when we would file the BLA. I think that is very important just to state. The second is that, we are very happy from the clinical data point of view and the generation, how we are actually progressing towards really meeting or matching up with the benchmark set by the Casgevy approval with, of course, the additional data that we are generating from a differentiation point of view. The additional datasets obviously include the preclinical, and we know that a key focus of the agency, when you consider AdCom was looking at off target editing. We actually were very, how should I say, gratified by the AdCom last December to see that the data set that we have already generated is a very robust and probably exceeds, what was discussed at that AdCom. We feel very good about that. We are actually also very pleased with the progress of our manufacturing data. And as I said in my earlier prepared remarks, our ongoing discussions with the FDA really gives a lot of confidence about the progress of multiple data sets beyond, just the clinical to bring us towards BLA.
Brian Cheng: Okay. And maybe just one more follow-up on the in-vivo side, is that going to be first-in-class or best-in-class approach? Just curious how do you think about balancing the risk and reward for your next assets? Thank you.
Gilmore O’Neill: Thank you very much, Brian. I’m going to have Linda address that.
Linda Burkly: Yes. Thanks, Brian, for the approach, the question. I think the differentiated approach is, for going after functional upregulation is really important. I think from an indication standpoint, because of the fact that, we can go after targets that others may not be able to go after using a knockdown strategy, and that is established modalities or other technologies and development, can’t go after that target, that really gives us the ability to be first-in-class. We can also envision editing strategies that would yield a better outcome than other approaches that are going after that particular indication, giving us best-in-class. So we can either have first-in-class or best-in-class opportunities here.
Operator: Thank you. We will take our next question from Joon Lee with Truett Securities. Your line is open.
Unidentified Analyst: Hi, good morning. This is [Mehdi] (Ph) Tau on for Joon. Congrats on the progress and thanks for taking our question. So maybe a two part question. Could you please provide any additional color on your in-vivo editing approach as you previously talked about LSRs and they usually require a landing site insertion first. Any color there would be appreciated. And then, to follow on Gina’s question, how many disease you see being amenable to indel mediated functional of regulation? Thank you.
Gilmore O’Neill: Thank maybe for your questions. Let me start. I will have Linda address both questions and I will restate the second question. Obviously, your first question was, as we talk about our indel functional upregulation, how is that distinguished from the use of LSRs? Linda?
Linda Burkly: Yes. Thank you for the question. Yes, the LSR technology that we disclosed at ASGCT, we are very excited about that. That is a technology that may enable us in the future to have large gene insertions. And so, this would be gene replacement approach. This is something that we are working towards. What we are doing in the shorter term now is functional upregulation of gene expression, and this is increasing the expression of a gene in order to compensate for a loss of function or deleterious mutation in a patient with a serious genetic disease. If that answers your first question, I think then you asked a question about how many diseases are amenable to indel. And there are many - obviously, there are many, genetic diseases caused by loss of function or deleterious mutations. There are many ways in which they are regulated by various regulatory elements. And so, there should be many, many opportunities here for functional upregulation of those targets.
Gilmore O’Neill: If I may add. Thank you very much, Linda. I think one of the key things is that, as we know from the human genome, only a small quantity of the genome actually encodes proteins. There is a large amount, the vast majority of the genome actually is non-coding and much of that comprises regulatory elements that actually control the expression of genes. And as Linda very eloquently put it, this is what we are actually trying to target. And just to absolutely clear, we are talking about indel using our CRISPR technology in general and very specifically in the very near-term, leveraging our ASCAS12a, which as we highlight is we believe one of the key differentiated tools in our toolbox, as we believe it is a superior editing CRISPR enzyme because of its high efficacy and its high fidelity.
Operator: Thank you. We will take our next question from Dae Gon Ha with Stifel. Your line is open.
Dae Gon Ha: Good morning guys. Thanks for taking our questions and congrats on the progress as well. Maybe first question for Linda. Going back to the in-vivo, recognizing you are going to be disclosing, so I don’t want to probe too much, but at least help us appreciate it a little bit more. Are you guys kind of driven by the limitations of LNP mediated delivery in terms of what cell types and what organ types you can go into or, is this more dependent on how big of a size market you have potential of first indication as well as the potential subsequent indications that can come after this first one? And then second question, maybe high level Gilmore or Beisong, year-end we are also expecting BEAM’s first data set coming out of BEAM-101. You talk about retinacel being best in class. So I was just wondering what kind of data set would keep you more confident about that notion going into that ASH presentation. Thanks so much.
Gilmore O’Neill: Thanks very much, Dae Gon. So Linda?
Linda Burkly: Thank you, Dae Gon. To your first question, yes, in terms of the LNP, the delivery obviously is critical for getting POC. We have shared our interest in targeting hematopoietic stem cells, and this is obviously to translate the remarkable success we are having with our reni-cel asset. We are obviously trying to target hematopoietic stem cells in-vivo. We have also though we haven’t disclosed all of the disease areas that we are interested in. And other than HSCs, we have mentioned that, we are interested in targeting the liver. And so there are validated LNPs for targeting liver. So there is a pragmatic approach here based on delivery.
Gilmore O’Neill: If I may add, Linda. Thank you. It is not just the delivery tool that we are leading with an LNP that actually determines how we select our targets. Obviously, delivery is an important element. Obviously, amenability to function up regulation is important. We are actually also selecting diseases, based on their clinical translatability, in that we want to be ensure that we can actually get obvious clinical signals in our human proof-of-concept. And obviously then, we also further filter that by ensuring that we are truly differentiated to ensure or maximize probability, not just a technical, clinical, regulatory, but actually also commercial success. And then, with regard to your second question, what do we expect to see from the BEAM data set? Frankly, obviously, we are looking forward to seeing it. It is always good to see continued pursuit of therapeutics within a clinical space for which there is an enormous, enormous unmet need in the context of sickle cell disease and transfusion dependent thalassemia. It is very hard, I can’t speculate on what BEAM would show. I look forward to hearing it, and we all look forward to hearing it. But I will tell you that, we are very happy with the differentiated profile that we are developing for a reni-cel. It is important to point out that we are very happy with the biological profile, the hematological profile, the clinical profile, all of which are very strong. And in addition, as we have alluded to, our confidence in the evolution in the current state of and the continued evolution of our manufacturing from the success rates is very gratifying. Overall, we actually feel very good. Of course, it is important also to remember, as I said earlier that, an additional piece of the data includes our non-clinical, including our off target editing, which is very robust. As I said, in the package we have generated. And of course, some of that robustness stems from us using ASCAS12a as opposed to Cas9 with its differentiated high efficacy, high fidelity characteristics.
Operator: Thank you. We will take our next question from Luca Issi with RBC Capital. Your line is open.
Luca Issi: Great. Thanks so much for taking my question and congrats on the progress. I have two quick ones. Maybe on sickle cell disease, we have seen the U.S. Health and Human Service, issuing a negative opinion here, on covering fertility preservation for, federal insured, patients who received gene therapy for sickle cell disease. Just wondering what is your take on that. And then maybe second, Gilmore, bigger picture, you seem very excited about the in-vivo upregulation strategy here. Is there a version of the world where you just partner reni-cel both U.S. and ex-U.S. instead of building a commercial infrastructure and just focused on your in-vivo strategy? Any thoughts there much appreciated. Thanks so much.
Gilmore O’Neill: Thanks very much, Luca. I’m going to pass your first question to Karen around the HHS decision.
Caren Deardorf: Luca, thank you for calling that out. Look, we are deeply disappointed by this decision, and we joined the voices of Vertex, Bluebird, really the whole field in this decision, which seems very out-of-touch with the severity of sickle cell and the unmet need. It just continues to drive discrepancy between patients’ ability to access therapies and have companies cover the fertility preservation, as you know, and Medicaid patients. So we are very disheartened. We also know that, there are a lot of voices who are within Congress and within the industry and other organizations, including the patient advocacy groups, who have a very strong voice. And our hope is that, all of us together will be able to really raise this issue and have it reversed in the coming time. We believe that, things will sort themselves out. We are disappointed for the patients who are seeking treatment today. Our belief in our own timing as fast follower is a lot of these unfortunate decisions will be figured out at the time that we are ready to come to market. But thank you for calling it out. It is really an out of touch decision, and we will hope for the best and do our part.
Gilmore O’Neill: Thanks very much, Caren. And then, Luca, to your second question around I think it sort of stems from our prepared remarks, why we are extraordinarily excited by our reni-cel are in-vivo progress. We are also very conscious of how we deploy our capital. And I’m going to ask Eric to address that.
Erick Lucera: Yes. Luca, just following up. As we have said for many years, our intention was to look for partners outside of the U.S. And I can tell you as someone who invested in biotech for 15-years and doing business development and CFO for about 15-years. You never know where those discussions may go. But, what we can assure you is that, we are going to do the right thing in terms of what is in the best interest for getting our products to as many patients as possible and driving shareholder returns to the best level possible.
Operator: We will take our next question from Phil Nadeau with TD Cowen. Your line is open.
Phil Nadeau: Good morning. Thanks for taking our questions. Two from us. 1st on reni-cel and the prospects for clinical differentiation, we are curious what your most recent thoughts are on the time to see that clinical differentiation on things like end organ damage. Is it possible that we could start to see strong signals of that in the ASH presentation? And then second on the in-vivo development program, Gilmore, I think you said the initial indication will be orphaned and then there’ll be larger indications perhaps later. Can you give us some sense of what size patient population you think is necessary for a good return on an investment? What is too small, kind of what is the sweet spot for an orphan population? Thanks.
Gilmore O’Neill: Thanks very much, Phil. I will have, Baisong talk about the differentiation and how we see that evolving. And then, I will take your question on, how we think about the size of the population?
Baisong Mei: Yes. Thanks for the question. And as we stated before, in clinical trial, we are looking three categories of evidence about differentiation and including oncological parameters and organ function and the patient reported outcome. And then, in terms of timing of those endpoints and when we see the change, and so for the end organ function, you specifically mentioned that it is relatively new field, and but fortunately, we already see more publications in the allogeneic transplant for treating sickle cell disease. They have presented encouraging data that after allogeneic transplant, you can see the end organ function improvement, including cardiovascular, central nervous system and so on and so forth. In our clinical trial, we monitor multiple organ and end organ functions, including pulmonary, cardiovascular, liver, renal and that. And so, based on the publication, some are reporting that at the one year, you see some improvement already, so we are very encouraged by that. But other parameters, for example, the hematological parameter will give us more opportunity to directly measure that change, for example, we are talking about the correction in Bolivia. And then the third category is patient reported outcome, and we are also very encouraged by the reports and being published in this field that we will be able to see the quality of life change after the treatment. So we are looking forward to see the more data and we are very excited to see that. The data from all our patients are very consistent. Now we reported 18 patient data. We see the same direction and the same trajectory in terms of the patient data wise. We are very pleased. We are looking forward to share more data at the end of the year.
Gilmore O’Neill: Thanks very much, Baisong. And then Phil, with regard to your next your second question, which is around where do we think that a population size for an orphan indication where we are sort of focusing our initial foray in in-vivo lines up for optimal ROI. A couple of things. First of all, the reason that we are actually focusing on rare orphan, the main reason obviously is that, as we bring a new technology to patients, we want to actually maximize the probability of technical and regulatory success. While we, at the field and agencies characterize and learn the long term risk benefit associated with this technology. More importantly than when I turn or not more importantly, but then I turn to market size. The market size we talk about is really based on patients, the patient numbers with indication versus the price. And obviously, price will be determined by a number of factors, including the amount saved by what we are talking about are potentially or largely curative therapies with high potency. I mean, this is what we want. One of the things we are really excited about our technology is, we are talking about using this technology not just because it is new and cool, but because it has the potential to deliver high potency, large effect sizes in patients. And so when you actually consider those elements, our current estimates that a range of about $400 million to $500 million is about the market size that would be meaningful and enable us drive growth, and as we grow and evolve into treating larger populations, as we build that safety characterization in a number of smaller orphan-sized populations.
Operator: Thank you. We will take our next question from Jay Olson with Oppenheimer. Your line is open.
Unidentified Analyst: This is [Shay] (Ph) on the line for Jay. Thanks for taking the question. Just maybe on reni-cel. By the time you filed a BLA, I’m just curious, do you think the follow-up in the adolescent cohort is long enough so the label may cover both adult and adolescent patients? Thank you.
Gilmore O’Neill: Thanks very much, Shay. I just I want to just recap state your question because it was a little muffled on the line. I think you were asking was, will the adolescent cohort be followed for long enough to be part of the label and inclusion.
Unidentified Analyst: Yes, that is correct.
Gilmore O’Neill: Baisong?
Baisong Mei: Thanks. We are very pleased with the progress of adolescent cohort and we started enrollment of this year and we already completed enrollment in the next month. So, very pleased with that. We certainly wanted to seek for broader indication of all age cohorts, and we already have alignment with FDA about the clinical trial for all the age cohorts. So that is why we are very much looking forward to that.
Operator: Thank you. We will take our next question from Yanan Zhu with Wells Fargo (NYSE:WFC) Securities. Your line is open.
Yanan Zhu: Great. Thanks for taking our questions. For the in-vivo program, are you trying to up regulate the gene - the disease causing gene itself? Or, are you trying to up regulate a different gene to compensate for the loss of the disease causing gene? In other words, are we talking about haploinsufficiency type of indication, or are we talking about recessive gene defect here? Secondarily, I wanted to ask about any updated timing for the CAFC patent dispute process? Thank you.
Gilmore O’Neill: Thanks very much, Yanan. So with the first question, I’m going to start by saying that you have actually described - you have actually nailed both elements of the operating strategy, but I will let Linda just expand on that. And then I will restate the second question and we will address that.
Gilmore O’Neill: Yes. Thanks very much for your question. So the two scenarios that you described like both are possible approaches. One can imagine, in loss of function, homozygous recessive state, upregulating a pathway gene that can compensate for the loss of the mutated gene. That is the case with the reni-cel example, where beta globin in PDT is - there is no expression of beta globin or in sickle cell disease, it is a deleterious mutation, and so it is not functioning properly and we up regulate gamma globin to compensate in both of those cases. One can also imagine a scenario of haploinsufficiency, where you have, one allele has a mutation, pathogenic mutation, but there is a wild type allele that can be upregulated to compensate for the loss of function of the mutated allele. So either scenario is a potential target for us.
Gilmore O’Neill: Thank you very much, Linda. And I think, Yanan, you asked a second question about update on the CAFC timings. Obviously, the oral presentations occurred in the last quarter in May, and we anticipate decision probably before the end of the year. May I just wonder if I could translate haploinsufficiency into lay terms, for those who might not have done molecular biology or genetics. By haploinsufficiency, everyone carries two copies, most copies, two copies of a gene. And in the context of haploinsufficiency, one gene is not functioning, which results in the total dose of protein that is available to the person resulting in disease, so called insufficiency or haploinsufficiency. And the strategy that Linda is describing that we are pursuing to manage that, is that you drive up expression of the normal copy to actually approach or get to the same dose of overall protein that would be required for normal health. Hope that was helpful.
Operator: Thank you. We will take our next question from Steve Seedhouse with Raymond James. Your line is open.
Unidentified Analyst: Hi, good morning and thank for the question. This is [Nick] (Ph) on for Steve. Had a quick follow-up to Luca’s first question, actually. Are you able to speak to the importance in demand for fertility support in your own clinical trials experience for LCD? Also curious of your thoughts on the potential market impact if you are not able to provide the support once approved. Thank you.
Gilmore O’Neill: So I’m going to split that question into two parts. I’m going to ask Baisong to talk about our experience in our clinical trial, and then, I will have Caren to talk about the impact and very importantly, how we anticipate mitigating or ensuring that impact is not going to be there.
Baisong Mei: Yes. Thank you for the question, Nick. In clinical trial setting, we do provide fertility support, which is critical for patients, especially in this patient population, that, it is important for them to have that support to be able to go through the chemotherapy and conditioning process. I want to let Caren to emphasize the importance of that in the commercial setting.
Caren Deardorf: Yes. Thanks for the question. So we do see this as a very important component of support to patients in the context of the gene editing transplant. In terms of impact on the market, what I will say is that, for the Medicaid population within the CMMI model that, we have all discussed and we hope and anticipate will get started sometime in 2025. There actually is a carve out there, so that, within the model, which we don’t know how many states will be included, but that does cover Medicaid patients and the fertility preservation is able to be included in that. And then in the commercial setting, it is fine. So the decision that HHS or the IG made does not affect commercial and also again CMMI, which we are encouraged and very hopeful that, that will move quickly. And I am hopeful that there will be enough pressure and enough parties that will move to eventually change this. So by the time we are launching, I can’t promise, but I don’t anticipate it will be a huge market impact. And even in the coming years, I think that there are, other opportunities for patients to be able to receive the gene editing therapies and the fertility preservation.
Gilmore O’Neill: Caren, it might be worth just pausing for a second and just take people through the acronyms and the sort of the structure of the CMS. It is just what the CMMI is
Caren Deardorf: Sorry. So MS has a section, it is the CMMI model, which is created to be able to explore and launch pilot programs to patient into different areas of need. There are numbers that have been done in oncology over the last years. And they created a specific cell and gene therapy program, of which the sickle cell disease area was highlighted and the program was initiated earlier this year or kicked off, and it is voluntary for both manufacturers and for states. So TBD on exactly who is involved in it, but the opportunity is there with a lot of funding for federal CMS through the CMMI model to be able to negotiate with manufacturers on behalf of a lot of. So it takes out some of that work in that variability. Again it is a promising program that needs to be moved forward quickly. But within it, there was a waiver on the anti kickback statute around providing the fertility preservation. So hopefully, that gives a little bit better context.
Operator: Thank you. We will take our next question from Liisa Bayko with Evercore ISI. Your line is now open.
Unidentified Analyst: Hi. This is [Edwilling] (Ph) on for Lisa. Thanks for taking our questions. There is a large number of patients in the Middle East. And can you please comment on how you plan to target this region? Do you plan to execute global launch yourself or will you need a partner concerning the conflict for these? Thank you.
Gilmore O’Neill: Thanks very much, Edwilling. I’m going to have Caren address that question.
Caren Deardorf: Yes. Great. Thank you. And we agree in the Middle East and there are other geographies where there is a significant unmet need. As we have said and as was stated earlier, we continue to consider partnering for anything outside of the United States and any way that we can improve and accelerate access of therapies like reni-cel to patients in need. So we continue to maintain that strategy, and we will update that as appropriate.
Gilmore O’Neill: Thank you very much, Karen.
Operator: Thank you. Ladies and gentlemen, this concludes today’s call. Thank you once again for your participation. You may now disconnect.
This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.