Q3 2024 Beam Therapeutics Inc Earnings & ASH Abstracts Call
Thank you operator, good morning, everyone and welcome to <unk> Conference call to review third quarter 'twenty 'twenty for a business update including abstracts accepted for presentation at the American Society of Hematology annual meeting you can access slides for today's call by going to the investors section of our website.
<unk> Dot com with me on the call today with prepared remarks are John Evans, our Chief Executive Officer.
Doctor just Sunday, he knows chairman President and Dr. Amy Finance, our Chief Medical Officer before we get started I would like to remind everyone that some of the statements. We make on this call will include forward looking statements for purposes of the Safe Harbor provision under the private Securities Litigation Reform Act of 1995 actual events or results.
And different materially from those expressed or implied by any forward looking statement as a result of various risks uncertainties and other factors, including those set forth in the risk factors section of our most recent annual report on Form 10-K as updated by our quarterly reports on Form 10-Q, and any other filings that we may make.
The SEC. 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.
Speaker Change: Except as required by law, specifically disclaim any obligation to update or revise any forward looking statements. Even if our views change with that I will turn the call over to John.
John: Thanks, Colin good morning, everyone and thank you for joining us for this exciting moment for beam for our employees and for the patients we aim to serve.
John Evans: And beam our vision is to provide lifelong cures for patients suffering from serious diseases.
<unk> has never felt more tangible than it does today as we report the first clinical data from our portfolio of a one time treatment.
John Evans: At the beginning of beam, we saw an opportunity to advance the gene editing field.
Christopher Nucleases are able to precisely target a location in the DNA, but they lack the ability to precisely edit genes.
John Evans: With our innovative next generation technology called base editing, we can now make more precise single base changes in specific locations and jeans, resulting in predictable all cells without needing to damage or make double stranded breaks in the DNA.
The central hypothesis behind beam is that this breakthrough could provide a superior way to modify genes you could open up entirely new applications in gene editing for a wide range of severe diseases.
John Evans: Given the incredible breadth of potential applications for being Saturday. It was critical to sharpen our focus and execution on areas, where we can have the greatest impact in the near term.
John Evans: This led to our two core franchises in hematology and deliver genetic diseases.
John Evans: In both cases, we were advancing highly differentiated and potentially best in class lead programs with being 101 in sickle cell disease, and then 302 in Alpha one antitrypsin deficiency or <unk>.
John Evans: Each of which have increased probability of technical success based on strong preclinical validation as well as recent advances in the field.
John Evans: In sickle cell disease, we have a validated regulatory pathway available for being one of them, one which the beacon trial is designed to pursue.
John Evans: We also have a next generation program using our scale technology designed to expand the addressable patient population by eliminating chemotherapy or transplant.
John Evans: Beginning today and continuing to Ash, we're reporting the first clinical data from our hematology franchise.
John Evans: Initial data from our Beacon phase <unk> trial support the potential for meaningful clinical differentiation of <unk> hundred one compared to currently available treatments for sickle cell disease.
John Evans: We will also be reporting non human primate data for RC technology that validate our vision of enabling gene editing in stem cell transplant, using only antibody based conditioning avoiding human therapy altogether.
John Evans: In our liver franchise <unk> also has the potential for rapid proof of concept in the clinic and represents the first program with potential to be a one time treatment with benefit for both lung and liver manifestations of the disease.
John Evans: We expect to report the first clinical data from our ongoing phase one two trial of <unk> in patients with ACD in 2025, marking another potentially transformative event for the company our platform and for patients.
Speaker Change: I'd like to highlight several important updates from our third quarter financial results press release.
John Evans: We have exceeded enrollment expectations in the Beacon trial with 35 sickle cell patients enrolled.
John Evans: These eight patients have been treated with <unk>, one on one with the remainder going through pre transplant stages, including solid collection and drug product manufacturing.
John Evans: We are also excited to share that we have nominated development candidates for our escape technology, which Peter will detail shortly.
John Evans: For in vivo therapies. This summer we dosed the first patient with <unk> hundred two in HCV and continued to enroll and treat patients while opening new sites globally.
John Evans: As of last month, we have completed dosing in the first cohort of the study and as I noted, we expect to share initial data for multiple cohorts in 2025.
John Evans: In addition in June we received U S. IND clearance for our second in vivo program <unk> hundred one for the treatment of glycogen storage disease, <unk> or GSD <unk>.
John Evans: Since then our team has been preparing to advance <unk> 301 into the clinic with site activation underway and patient dosing is expected to commence in early 2025, and importantly, we continue to be in a strong financial position.
John Evans: Turning now to Ash, we are honored to have four abstracts accepted for presentation at the meeting in December.
John Evans: <unk> two oral presentations, one featuring initial clinical data from the Beacon trial, and one with our non human primate data for our escape technology as well as poster presentations showcasing exploratory biomarker data for being 101 and preliminary clinical data for being 201, our quad edited car T cell for T cell malignancies.
John Evans: Abstracts will be available on the ash website at nine a M eastern today.
John Evans: I'll now turn to sickle cell disease.
John Evans: At the Jpmorgan conference in January I asked the question, what if we could develop better onetime therapies for people living with sickle cell disease.
John Evans: I am pleased today to report that yes, we believe we are on the road to do just that.
John Evans: For sickle cell disease, we are pursuing a long term stage development strategy that envisions three waves of innovation to progressively reach broader subsets of patients over time.
John Evans: Our wave one approach is being 101, a genetically modified investigational cell therapy administered via hematopoietic stem cell transplantation with default and conditioning.
John Evans: We believe <unk> 101 has the potential to be a best in class option for the roughly 10% of sickle cell patients who have severe disease. Despite receiving standard of care treatments and are considered appropriate for chemotherapy based transplant.
John Evans: So the market for autologous genetic therapies in sickle cell disease is just getting started it is important to note that allogeneic transplant for patients with severe sickle cell disease are already a reality with several hundred conducted annually in the U S.
John Evans: And that number only represents those patients who could find a suitable Matt stone, which we know represents a small minority of total eligible patients.
John Evans: And finally, we know that autologous transplants are expected to have real advantages over allogeneic transplants, including a lack of graft versus host disease and no need to coordinate the procedure with Don.
John Evans: We have to take the same being one on one platform and now incorporates our escape technology to enable non genotoxic conditioning.
John Evans: If successful escape would eliminate chemotherapy, which we believe is one of the main hurdles for patients considering the transplant based therapy and that's meaningfully expand the patient population for ex vivo gene editing by three to four fold.
John Evans: A little further out as wave three where we're using our leading capabilities in lipid nanoparticles to explore the potential for in vivo base at a date for sickle cell disease, which would eliminate the need for transplantation, thus, enabling even broader patient access around the world.
John Evans: Now, let's start by reviewing the one on one.
John Evans: Sickle cell disease is a genetic disorder that affects hemoglobin, which delivers oxygen to sell throughout the body.
John Evans: People with this disease make abnormal hemoglobin molecules called hemoglobin S or HTS.
John Evans: This abnormal hbf's conform stiff polymers, which distort red blood cells into a sickle or crescent shape blocking the flow of blood and oxygen throughout the body.
John Evans: Sickle cell disease begins in early childhood and leads to anemia infections and episodes of severe pain, which can manifest as basal occlusive crises or voc's.
John Evans: Patients also experienced life threatening complications such as stroke and significant organ damage, resulting in decreased life expectancy.
John Evans: While recently approved gene therapies have been shown to significantly reduce the ocs patients are still generally left with HB asset more than 50%, suggesting there are opportunities for further improvement.
John Evans: Elevating our protective form of hemoglobin called fetal hemoglobin or hbf is a clinically validated strategy to prevent the consequences of sickle cell disease by preventing hbf's from prelim arising, thereby preventing red blood cell destruction and organ damage.
John Evans: 101 was designed to induce a more efficient editing leading to greater and more uniform induction of HVO, a deeper reduction of hbf and normalization of hemoglobin and red blood cell function.
John Evans: Welcome to 90 of outcome from genetic production look like.
John Evans: As shown on slide 13, total hemoglobin for a person with sickle cell disease has 100% hbf in circulation, which causes signaling and result in decreased red blood cell lifespan anemia pain crises and organ damage.
John Evans: The disease threshold as exemplified by people with sickle cell trait, where carriers with only one mutation and are typically asymptomatic. These people generally have about 60% normal hemoglobin and only 40% hbf.
John Evans: The recently approved gene therapies for sickle cell disease don't clearly providing significant benefits to patients do not achieve that threshold.
John Evans: The base editing, we are aiming for a deeper correction of the hemoglobin profile that is at least on par with or even better than that but typical person with sickle cell trait.
John Evans: <unk> also has the additional biochemical benefit of being anti cycling, which may provide additional protection.
John Evans: In preclinical models being 101 achieved these goals potently inducing hbf to more than 60% and proportionately, reducing sickle hbf to less than 40% without the need to make double stranded DNA breaks.
John Evans: Today, we are reporting the first data from our ongoing clinical trial of <unk> hundred one in patients with sickle cell disease that validate our preclinical findings and support our goals for this program.
Speaker Change: Let me now turn the call over to Amy to review the Beacon trial and the initial clinical data in our ash abstract.
Speaker Change: Thanks, John.
Amy: With the trial design Beacon is a single arm open label study evaluating the safety and efficacy of a single dose of <unk> in patients with sickle cell disease and severe DSD. The trial enrolling adult patients 18 to 35 years old with sickle cell disease that experience for more severe DSD.
Amy: And the two years prior to screening patients.
Amy: Patients are novel ICT incorrect Empire accurately autologous CD 34 positive.
John Evans: I extend and progenitor cells are collected by Leukapheresis genetically modified at immune based editor.
John Evans: Patients that receive myeloid by introducing a T cell therapy, followed by a single infusion is being more than one.
John Evans: Key endpoints are outlined here on slide 16.
Speaker Change: As John highlighted to date, it exceeded enrollment projections with 35 patients have been cleared screening and enrollment in the study.
Amy: The data will review today are as of the July 2024 data cut and increased six patients in the safety analysis and for patients in the efficacy analyses.
Amy: In our presentation at Ash will share additional data with more patients and longer follow up.
Speaker Change: Baseline demographics are shown in slide 17.
Speaker Change: Five of the six patients for beta as data genotype and one patient with beta as David <unk>.
John Evans: We're suffering or it is black African American, 50% were female and Egypt range from 19 to 27 years.
John Evans: 101 manufacturing process allows for efficient production with all six patients requiring just one or two cycles of mobilization to achieve a dose with a mean one five cycles.
John Evans: As a reminder, midnight in the number of cycles. The mobilization is a key goal for both patients and providers to reduce days in hospital and the overall time required to manufacture in dose.
John Evans: Safety data were captured for all six patients in one on one was considered generally well tolerated and demonstrated a safety profile consistent with violent ablative conditioning with T cell phone and autologous net Atlantic stem cell transplant.
John Evans: Rotation diabetes respiratory failure four months after they are being run in one indication, which is determined by the investigator and he likely related to some pain condition.
John Evans: He felt there is a cytotoxic drug is <unk>.
John Evans: Transplant settings is known.
John Evans: With significant side effects, including lung injury and death.
John Evans: This is a complex case and the unfortunate outcome a rare has been reported previously that same subject.
John Evans: <unk>.
John Evans: Is that would deteriorate to be unrelated to being one one by the investigator.
John Evans: Mrs with you.
John Evans: Data safety monitoring committee and the FDA.
John Evans: In our patient does.
John Evans: Great Theyre higher adverse events or serious adverse events related to <unk>.
John Evans: As shown on slide 19 tension Gratinate is for the <unk> patients with the follow up period of one month or more.
John Evans: Rapid nature non graphic was observed for outpatient atropine, whether it warrants treatment with a median of 17 days.
John Evans: <unk> <unk> 19 days.
John Evans: Platelet Iraq needs will be achieved at median of 20 days.
John Evans: The 11% to 34 days. These data are similar inflation arguably allogeneic stem cell transplantation.
John Evans: Stem cells.
John Evans: <unk> is particularly important as this is one of the key factors that determine the length of hospital stay patients after undergoing.
John Evans: Mitigating hedging as rapid as another important goal transfer therapy in sickle cell disease is not only can it result in reduced hospital days, but also to potentially decrease risk of developing opportunistic infections.
John Evans: On slide 20, we detailed total hemoglobin you can afford patients included in the efficacy analyses when patients had six.
John Evans: Two one months of outlet respectively.
John Evans: After treatment with <unk> <unk> and early in market index at H B.
John Evans: And a significant increase in total hemoglobin.
John Evans: The patients total new lending increased to a new 809, three grams per deciliter and $17 $18 two on Monday.
John Evans: Eight grams per deciliter at the last three points.
John Evans: The other systems integrations, we're undertaking.
John Evans: <unk>.
John Evans: Elevated total hemoglobin.
John Evans: Notably all four patients achieved greater than 60% Hbf emergency employment levels.
John Evans: Is this David elevations in Hawaii trade Lane.
John Evans: <unk> got to less than 40% in all four patients, which again was sustained in the last three important new.
John Evans: David Patton.
John Evans: Importantly, these data are consistent with our preclinical results.
Speaker Change: Individuals with sickle cell trait, where as John mentioned patients generally have 60% normal due above it in 40% single globally.
Speaker Change: In addition, <unk> analysis, including lactate dehydrogenase indirect believe haptics.
John Evans: We're seeing normalized or improve a one for patients.
John Evans: <unk> reported by investigators finally be whether one treatment.
John Evans: Collectively these findings represent deep correction consumer lending profile and the blood after being more than one treatment.
John Evans: In addition to our primary into critical mass that we have an additional abstract detailing exploratory biomarker assessments of red blood cells expressing <unk>.
John Evans: <unk>.
John Evans: As shown in slide 22 in the first few patients included in the analysis <unk>, 8% Red blood cells Express Hbf as early as month, one with near complete elimination of Red blood cells expressing solely Acs post treatment.
Speaker Change: Your line.
John Evans: <unk> only cells and the cells, which would be most likely stay calm and cause pain organ damage overturned.
John Evans: Biomarker data also showed that treatment with being with someone with Stewart red blood cell function across a range of parameters.
John Evans: On slide 23, we absolutely agree with significantly reduced through the first two patients treated with <unk> hundred one below the levels associated with trade.
John Evans: Great.
John Evans: <unk>.
John Evans: Other improvements in lung function included increased turns red blood cell decreased illicit and decrease red blood cell infusion all of which are associated with disease severity.
John Evans: In summary, we are encouraged by this emerging being one of our critical data, which we believe are consistent with our preclinical findings and demonstrate the potential for differentiation from other cell and gene therapy, and the algorithms and the key takeaways on slide 24.
John Evans: T cell collection, and manufacturing process, where efficient, resulting in just one to two mobilization cycles.
John Evans: 101 was generally well tolerated with a safety profile consistent with the known effects of mila related conditions and stem cell transplant.
Speaker Change: Can you just real advantage is rapid with all pieces of racking and greater than 2000, Eighteen's, both geographic trade area.
John Evans: Our collection efficiency contributed to shorter hospital stays and a faster path for <unk> for patients.
John Evans: 101, effectively induce hbf.
John Evans: They have a 60% <unk>.
John Evans: Meaningfully reduced to less than 40% consistent with the profile of individuals.
John Evans: Individuals with sickle cell trait.
John Evans: And finally, multiple biomarkers Sheldon year elimination of HTS, only counts and improved red blood cells functions <unk> taken.
John Evans: Taken together, we believe this initial data set demonstrates being where the words and symantec.
John Evans: So it can be best in class, one time treatment for people living with sickle cell disease.
John Evans: We look forward to reporting data from the more recent data through our Beacon trial in oral presentation at Ash in December which will feature additional patients and Barbara <unk>.
Speaker Change: I'll now pass the call over to PM to get into our initial data.
Speaker Change: Thank you Aaron.
Speaker Change: Returning to our overall vision for bringing new options to patients with sickle cell disease escape forms the foundation of our wave two sickle cell disease strategy, which aims to provide the same transformative efficacy potentially see wave one, but with an alternative to genotoxic conditioning during the transform questions. Please.
Speaker Change: <unk> offer significant upside, including the potential to improve patient safety and overall treatment experience and becoming compelling option not only for severe patients, but also for more moderate disease patients.
Speaker Change: As a result, we believe that such a product with expand the eligible patient population to gene editing therapies by two full points.
Speaker Change: So by conditioning so important.
Speaker Change: Condition is a critical component to the transplant.
Speaker Change: It is necessary to make space in the patient's body to receive the ex vivo edited cells.
Speaker Change: <unk> innovations Beaumont in order to be effective.
Speaker Change: The field of stem cell transplant is generally the dramatic outcomes with many dermatology patients with upwards of 22000 transplants nonrecurring in the U S.
John Evans: However, all such trend funds still rely on chemotherapy, most commonly diesel to enable the replacement of bloodstream.
John Evans: <unk> was first approved in the 950 and as Amy mentioned is associated with both acute and comment on.
John Evans: That includes infertility the potential for increased rates of malignancy anyway instances can be fatal.
John Evans: Improving upon the adoption represents the next frontier in hematology and could bring the transformative impact of transplant to many more patients with many more diseases.
John Evans: This is technology has potential to finally enable the vision on the non deal on box and conditional approach does bringing in bonds a paradigm shift in transplant medicine for the first time in nearly 70 years.
John Evans: Our escape program consists of two investigational therapies, which remains of being one of them and be one of them for as part of our development talent in the nation announced Tonight.
John Evans: And more than three is our conditioning antibody designed to bind amended chemotherapy.
John Evans: <unk> in the mountains and eliminate them.
John Evans: We've won them for in the multiplex basis, some product that includes $2 million.
John Evans: The first is the same therapeutic and F&B.
John Evans: To elevate fetal hemoglobin.
John Evans: The second is an additional edits to introduce an <unk> mutation in the extra cellular domain of CD 117.
John Evans: Expressed by inspire and present themselves, they're regulated survival proliferation and differentiation of the zones.
John Evans: The <unk> 17, 90 does not alter Sydney, 170, biology, but only disrupts the binding of being 132 receptor.
John Evans: This allows that leads itself to escape the antibody with the globe, enabling engraft and growth of edited cells and clearance of disease.
John Evans: And the data shown on the right you can see that in the presence of the mixed population of a negative energy themselves increasing levels again.
John Evans: Some populations to shift to become completely as you did.
John Evans: We are evaluating the system extensively months, but to establish proof of concept. We wanted you to conduct a comprehensive study in nonhuman primates.
John Evans: We're collaborating with multiple leading experts in the field and this initial study was conducted by Dr. John <unk>, there won't be an items a preeminent leader.
John Evans: Autologous transplant and nonhuman primate models with transplant.
John Evans: The data to be presented at.
John Evans: At Ash.
John Evans: Two key fundamental questions.
John Evans: <unk> investment of hematopoietic stem cells, we achieved without chemotherapy and <unk>.
John Evans: Then in therapeutic level of fetal hemoglobin being achieved.
John Evans: As detailed on the right side of slide 30, the monkey autologous transplant process being conducted here is comparable to an ex vivo gene editing product in humans with the caveat that by necessity various steps in the process.
John Evans: Optimize to the same degree that we have done for humans.
John Evans: We mobilize <unk> four cells from two reasons macaque monkeys, and editing them ex vivo incorporating both the hbf added embassy CD 117 Inscape added.
John Evans: The animals when conditions will give 100 <unk> hundred 17 antibody and then infused with being one of them for Andes itself program.
John Evans: Subsequently, there's animals received monthly antibody treatments after transformation to maximize the competitive advantage that you can sell.
John Evans: And confused suppression of unlimited zones.
John Evans: It would be one of <unk> was well tolerated both doses and no supportive care was necessary for the antibody can loosen unknowns.
John Evans: Importantly, they did not go through a few of the monetization.
John Evans: Is that we'd see chemotherapy condition.
John Evans: Remarkably we observed significant reduction of hbf totally fine points post transplant.
John Evans: <unk> levels rose to 61% in the periphery.
John Evans: They've weeks post transplant, among the avenues and stabilize at approximately 85% and 35 for both endpoints.
John Evans: Early adoption of Sps was also observed level surpassed 50% in both markets.
John Evans: Unprecedented results established preclinical proof of concept for condition with <unk> hundred 17, antibody and known chemo chemotherapy, leading to robust long term and.
John Evans: And high levels of Hbf expression for ex vivo editing CD 34 cells.
John Evans: Replicated in humans. These results will achieve a wave two vision of non genotoxic conditioning with gene editing.
John Evans: In hematology.
John Evans: Intriguingly the lack of modulation also suggests the possibility that the transplant of escape at <unk> four cells could eventually become an outpatient procedure further.
John Evans: The access and scalability of this products for patients.
John Evans: On the back of the strong preclinical results. We are now accelerating the development of our escaped technology towards the clinic.
John Evans: We are currently conducting additional NSP studies to explore antibody dosing regimens dose response, and communism and we don't track to initiate the phase one enabling studies by the end of the year.
John Evans: Once complete we plan to conduct a phase one healthy volunteer study of the B one of the antibody before moving into studies in both the one and three and be wonderful and sickle cell disease and beta.
John Evans: Patients.
John Evans: As we now look forward to the development of this promising technologies I want to highlight the strong synergies between one month and escape.
John Evans: With an identical Ed is an underlying base editing technology today has been 101 clinical data I'll also give its people escape and each investment and advanced remaking manufacturing clinical regulatory and commercial provisions will be 101 has direct applicability to accelerating in the future.
John Evans: The success of escape.
John Evans: The two programs that both will main symbol integrated franchise, which we believe can deliver successive improvements to patients with sickle cell disease.
Speaker Change: I'll now turn the call back over to John to level.
John Evans: Thanks Peter.
John Evans: As you can see we are very encouraged by these emerging datasets.
John Evans: First for being 101 in patients with sickle cell disease, where so far achieving a potentially differentiated clinical profile using base editing consistent with our preclinical data and comparable to sickle cell trait, while also potentially requiring fewer days in the hospital for bolt mobilization and in Grafman.
John Evans: Second with escape achieving robust preclinical proof of concept and now moving rapidly towards the clinic. We are opening up the potential for non genotoxic conditioning and transplant, which would expand the initial being 101 market to reach a broader group of patients, but the last mile ablative profile that even has the potential to become an outpatient procedure for conditioning and transplant.
John Evans: And finally these datasets support that base editing does appear to have significant advantages and predictability efficiency and lack of double strand breaks with strong translation from preclinical to clinical data minimal impact on cell viability and promising efficacy outcomes.
John Evans: Before I close I'll provide a brief review of the clinical data on deemed <unk> hundred one which will be in a poster at ash.
John Evans: Initial clinical data for <unk> hundred one which is the first quadruplex edited allogeneic car T cell therapy candidate in clinical development, establishing clinical proof of concept for a high level of multiplex based out of there.
John Evans: The safety profile of <unk> hundred one was consistent with these patients advanced underlying disease as well as with lymphoid depletion in car T therapy.
John Evans: We also observed early evidence of clinical efficacy with two or three patients treated with <unk> hundred one achieving a complete response, allowing them to pursue transplant, which is potentially curative.
John Evans: While not a priority program given our decision to focus on hematology and liver genetic diseases. We continue to seek a path forward for <unk> hundred one with a partner and look forward to supporting its future advancement as well as other potential applications of multiplex base editing and cell therapy.
John Evans: Wrapping up.
John Evans: As you've heard 2024 has been an incredibly fruitful time and beam with broad based execution and validating data across our portfolio of base editing programs.
John Evans: We have a number of meaningful catalysts on the horizon, starting with updated data at Ash in December.
John Evans: Again I'd like to thank the <unk> team for their continued hard work and dedication to our shared vision the patients and physicians, who participated in our clinical trials and to each of you for your continued support of beam.
John Evans: With that operator, please open the line for Q&A.
Speaker Change: Thank you at this time, we will conduct a question and answer session.
Speaker Change: As a reminder to ask a question you will need to press star one one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one one again.
John Evans: Participants are limited to one question only.
John Evans: Please standby, while we compile the Q&A roster.
John Evans: Our first question comes from Gena Wang with Barclays. Your line is now open.
Gena Wang: Thank you really impressive update I have asked so many questions since I can only ask one question maybe I'll ask.
Gena Wang: Less exciting question.
Gena Wang: The safety, one patient death, with just a little bit puzzling.
Gena Wang: Why after four months and that patient die and then.
John Evans: Why it could be due to the consumption. If you can give a little bit more color here. Thank you.
Speaker Change: Sure maybe I'll start and then I'll have Andy give a little color on the on the time course, and what we know about we saw fan.
Speaker Change: So thanks, Gena so yes.
John Evans: It's a very sad outcome of course, I think what it shows maybe at a high level is the very real risks of transplants and chemotherapy.
Speaker Change: Where do you think of yourself and in this case that we use the same protocol and dosing regimen.
Speaker Change: <unk> San as others do in the field, obviously informed by by World experts on our trial.
Speaker Change: That chemotherapy transplant do have significant toxicity and in rare cases can have mortality something that the field continues to optimize but it's but it's a real choice that patients have to think about.
John Evans: At the same time I like to say that I think it's also underscores the severity of severe sickle cell disease.
John Evans: We've seen sickle cell survival rates improved about 50 years on media in here in the U S. But that's medium the most severe 10% are much sicker than that.
John Evans: And so.
John Evans: Severity of the disease really is what makes that transplant potentially.
John Evans: Essentially compelling option despite the risks so so importantly.
John Evans: Amy will outline the case is consistent with our prior experience with yourself and with transplant. So we don't see any change in the risk benefit profile of <unk>.
John Evans: Our agent or of the field.
John Evans: Based on this our goal of being one of them. One is ultimately to give a better option to patients in transponders, who are seeking transplant.
John Evans: It begins with a shift from aloe to auto which is happening now.
John Evans: Of course with the data we're sharing today, we believe that being 101 as a potentially best in class profile out of the autologous therapies.
Speaker Change: So maybe with that preamble I gave me to say just a little bit about what we know about we felt that in the time course of this kind of toxicity sure.
Speaker Change: So it turns out <unk> is as John mentioned, a chemotherapeutic and cytotoxic agent and it is known to be associated with dose dependent pulmonary toxicity. So as you go up to higher doses.
Speaker Change: More toxicity and in some cases can actually be fatal in general.
Speaker Change: Milo ablative conditioning with agents, such as B cell thinking possible.
Speaker Change: That we referred to as the idiopathic pneumonia syndrome.
Speaker Change: This can occur in up to 60% of patients without autologous transplant and this idiopathic pneumonia syndrome really represents a spectrum of pulmonary diseases, including lung injury respiratory failure that tend to start around day, 20, or 30 post transplant and kind of manifest through about day 100.
Speaker Change: The rates as I mentioned are up to 6% and these can often wind up with multi kind of.
Speaker Change: Multi lever El Paso, along respiratory failure and in some cases as I mentioned before though I think that the team at the site did it extensive work up.
Speaker Change: Usually what Youll do is roll out other potential contributing causes which they did such as infection or other types of etiologies or pulmonary dysfunction, and any and the timing of this dysfunction as well as debt extensive clinical workup really point to the fact that this is consistent with what has been seen previously in <unk> cell phone.
Speaker Change: And what is the point in the label as well as the literature about stem cell transplantation.
Speaker Change: Implications with the cell phone.
Speaker Change: In other literature.
Speaker Change: Notably the patient's blood with corrected and normalizing in line with what we're seeing in other patients. So while it's an unfortunate case.
Speaker Change: It is a known complication that Milo ablative conditioning can have.
Speaker Change: Really kind of profound effects.
Speaker Change: Even though it is required for a successful transplantation and I think investigators take this into account when thinking about selecting patients who are appropriate for the risk benefit profile as well as talking with their patients. So that it's clear that the patients understand the risk benefit.
Speaker Change: And that they are signing up for somebody that they understand what they're getting into.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question comes from Jonathan Your line is now open.
Speaker Change: Great. Thanks for taking our question at the end.
Jonathan: Whereas on the data again, a very impressive hbf induction.
Jonathan: Was wondering how it would.
Speaker Change: The H higher hbf induction translate into.
Speaker Change: Additional clinical benefit compared with.
Speaker Change: Approved product and also.
Speaker Change: Other upcoming products in our pipeline.
Speaker Change: If you can shed some light because I.
Speaker Change: <unk> has been.
Speaker Change: Data has been pretty strong for the approved product so wondering.
Speaker Change: Where could we see additional clinical benefit thank you.
Speaker Change: Sure like printer to cover this one yes, hi, gentlemen, thank you very much for the question.
Speaker Change: As you can see really we do believe that these higher hemoglobin F is also associated with a comment on the decline of hemoglobin S. Two levels less than 40% 60 to 40 ratio is really the ratio that you typically see in sickle trait individuals who obviously do not have symptoms unless.
Speaker Change: And Barry.
Speaker Change: Sort of severe condition. So we do feel that that combination of $60 40 can be.
Speaker Change: Like a sickle trait and potentially even better since hemoglobin F is.
Speaker Change: And as quickly and as opposed to hemoglobin and so that should lead to a variety of deeper resolution we share some biomarker as they show that the blood as function as a normalized to the extent that we can measure it.
Speaker Change: We also show that we have almost completely eliminated cells that express hemoglobin S. On its own. These are really the the cells that potentially can cause cyclic under some severe conditions and so even though it is great to see a strong resolution of <unk> and the launch products. So far I think we have also.
Speaker Change: So potentially the opportunity to improve even upon that and so the overall combination of the parameters that we have really for the first time.
Speaker Change: Reproduce the sickle trait that others have not yet done.
Speaker Change: Great. Thanks for the color.
Speaker Change: Thank you. Our next question comes from Dae Gon Ha with Stifel. Your line is now open.
Speaker Change: Hey, good morning, guys. Thanks for taking our questions and I'll add my congrats on <unk>.
Speaker Change: Initial data as well look forward to a 302 updates next year.
Speaker Change: Circling back on the efficacy side question for either Sean or Ami patients 300 for the female patients. Just wondering if you can comment on the progress you're seeing there specifically on the fetal hemoglobin induction and when you look at both.
Speaker Change: Across the board it seems like one to two seems to be sort of a startup a plateau. If you will on the total hemoglobin.
Speaker Change: I was just wondering how we should think about sort of the longer term efficacy for these two patients and specifically on the patient foresight. Thanks very much.
Speaker Change: Yeah, Thanks, Doug so.
Speaker Change: I think it's.
Speaker Change: I think there's not much to see between the patients theres going to be some variability all of these patients have what I would consider to be a robust early induction of apps.
Speaker Change: In patients ran for its also worth noting they received their last transfusion closer to the month, one time point, which means you have more transfused bought around that has to clear before the marrow is going to turn on its endogenous production quite as strongly so that's a subtle variable I think ultimately we will just wait for longer follow up and we.
Speaker Change: Should be able to compare these datasets.
Speaker Change: Alright sounds good.
Speaker Change: Yes.
Speaker Change: Thank you. Our next question comes from Eric Joseph with Jpmorgan. Your line is now open.
Eric Joseph: Hi, good morning, Thanks for taking the questions just.
Eric Joseph: Digging into the first two patients wanting to get the total hemoglobin count.
Eric Joseph: Is fairly high.
Eric Joseph: Yes.
Eric Joseph: As much as five and six so I'm just wondering how we whether there is any concern about the.
Eric Joseph: Total hemoglobin counts being sort of where they are with initiatives to sort of normalize or come back down.
Eric Joseph: With time.
Eric Joseph: Any sort of concern I guess with long term follow up with it.
Eric Joseph: Persisting hemoglobin around that level.
Speaker Change: Yes, Thanks, Eric Amy.
Speaker Change: Two patients as you've noted have.
Speaker Change: Experienced mild elevation through hemoglobin.
Eric Joseph: And importantly, there have been no clinical signs or symptoms from those patients or medical interventions required.
Eric Joseph: These are really considered laboratory abnormalities at this point by the investigators and have not even been considered as adverse events.
Eric Joseph: <unk> Pinot alluded to recently.
Eric Joseph: With that elevated hemoglobin asks to asset ratio of 60 to 40.
Eric Joseph: We feel that these patients are no longer patients, who have sickle cell disease, but in fact with editing their blood housing functions have improved to what would be similar to that of a trade or a healthy person and those include as I already mentioned the hemoglobin F to ask ratio improvements or normalization hemolysis the decreased RBC cyclic.
Eric Joseph: RBC density in RBC adhesion and for all those reasons.
Eric Joseph: There has been really no concern by the investigators and these mild elevations seem to date and as you mentioned, we will continue to follow these.
Eric Joseph: But at this point in time this reflects really just a lab abnormality.
Eric Joseph: Yeah.
Speaker Change: Got it appreciate if you could just one quick follow up if I could on the safety front any changes too.
Eric Joseph: Either screening criteria or modifications to the conditioning regimen and as a result of the unfortunate death.
Eric Joseph: Attributed to the softening.
Speaker Change: Yeah, Great question Theres been no change to our eligibility criteria.
Eric Joseph: <unk> by the DMT and concurred with the FDA that the safety profile of the study had not changed after this event. However, we already had in place what's called therapeutic drug monitoring for B cell phone and that type of therapeutic monitoring is often done when there is a narrow therapeutic window for a drug. This is typically done by.
Eric Joseph: Various studies in gene editing as well as investigators in ESP cell phone for conditioning and just to note that the patient's T cell phone level was within the target range that we are basic.
Eric Joseph: Basically trying to obtain to try to make sure both conditioning was appropriately done but at the same time trying to guarantee safety.
Speaker Change: Okay great.
Speaker Change: Thanks for taking the questions.
Speaker Change: Thank you. Our next question comes from coastal spill Auris with BMO capital market. Your line is now open.
Speaker Change: Good morning, Thanks for taking out question.
Speaker Change: That's on the progress and the date Ikea.
Eric Joseph: One clarification and one question from US. Please I think you already kind of described that but can you clarify whether you will have observed any off target editing or bystander edited in the patients who died I know there is no clinical evidence for that but.
Eric Joseph: A question that comes up from investors and then.
Eric Joseph: The second question on commercialization of one to one and SK. How are you thinking about the sequencing of commercializing two products in potential cannibalization.
Speaker Change: 101 from S K.
Speaker Change: Great. Thank you so I'll, let <unk> answer. The first question then I'll have a second high dose does.
Speaker Change: Thanks for the question, Yes, we are.
Eric Joseph: We have not noted any off target biology of concern in any of the studies that we've done specifically, we do not do off target biology on every single drug product, but it is part of our preclinical package you do extensive I'll talk a bulge on several donuts, including the adjustment and silica are looking at.
Eric Joseph: Different genomic background, which was the context of the <unk> JV.
Eric Joseph: Advisory Board conversation that added and through none of that activity that was any off target biology of concern.
Eric Joseph: Great.
Eric Joseph: Yeah, and then on the on the market perspective, I think our plan has always been we consider this a lifecycle strategy across this franchise. So beginning with am 101, then leading to to escape now being one of three and 104.
Eric Joseph: When you're thinking about in vivo as well so we see this as a progression.
Eric Joseph: I think if escape fully achieves its profile, which would be the.
Eric Joseph: <unk> Z comparable to <unk>.
Eric Joseph: 101, or other gene therapies in the field, but without chemotherapy I would expect that to overtake and replace one on one of the market but of course, we'll have to see the profiles and considered at the time.
Eric Joseph: In terms of the market progression I think we've talked about this as well and I had it in my slides, but we continue to believe that the market for these sort of wave one therapies as we call them.
Eric Joseph: About one in 10 patients really those patients who are severe enough to consider a transplant and there. Our goal is to give transplant is a better option. It's quite clear that autologous will be preferred over allogeneic, there's already several hundred allogeneic transplants that occur.
Eric Joseph: Every year in the U S for sickle cell patients have severe disease and that's after including the fact that most of those patients who might seek a transplant can't find a match.
Eric Joseph: So so I think that implies a certain market size that we expect will be there and we believe with today's data assuming it holds up over time.
Eric Joseph: We'll show that being 101 is the best in class option for patients in this first market. Once we can bring escape forward of course that really changes the game. Because now you have of course eliminated a lot of the risks of transplant and chemotherapy.
Eric Joseph: Also expanded the addressable patient population, so that many more patients who might not have been a good fit for transplant before now can come in and Thats. Pino said, we think that leads to an addressable population that is up to four times larger so.
Eric Joseph: The final point to make in terms of the staging of the programs is the one that <unk> highlighted as well which is there.
Eric Joseph: The escape program is almost identical to being 101.
Eric Joseph: One single guide RNA to get to the C. Kit citywide 17 edit and of course, the antibody so from a regulatory preclinical package the clinical trial sites and design, a regulatory strategy and endpoints and ultimately even commercial infrastructure. All of that is shared between the two programs, which will make for a much more.
Eric Joseph: More efficient.
Eric Joseph: <unk> program and I think ultimately well accelerate what we can do with escape.
Speaker Change: Thank you very helpful.
Speaker Change: Thank you. The next question comes from Samantha Southern Cao with Citi. Your line is now open.
Speaker Change: Hi, Good morning, and thank you for taking my question, sorry, I heard of expanding on that last question on the <unk> data that you will share today they.
Speaker Change: They look pretty encouraging numbers in Rockville and.
Speaker Change: Hbf induction.
Eric Joseph: Great.
Eric Joseph: Safety advantage with avoiding chemotherapy I'm just curious on your thoughts on the potential tradeoff for a slightly less efficacious profile.
Eric Joseph: On the trade off for the better safety profile, and then Relatedly for luxury.
Eric Joseph: Anybody are there any safety concerns for targeting smaller ones have any plan that we should be aware of.
Speaker Change: Yes, maybe I'll have.
Speaker Change: <unk> answer the second question I'll, just I'll just highlight on the first question I think of course, if you have.
Speaker Change: You know.
Speaker Change: Safety advantage, but lose some efficacy then there's more of a debate to be had I think what you see from the data that Pino shared is we're achieving fairly full efficacy with escape and then we get that safety advantage. So so far that looks quite compelling obviously as I noted it will take some time to evolve the full product profile, but maybe I'll hand over to Peter to expand on that.
Speaker Change: <unk>.
Speaker Change: Okay.
Speaker Change: I'm sorry could you repeat the second question just for a moment.
Speaker Change: Yes, so Chris I was just thinking about as you move forward.
Eric Joseph: Three the phase one healthy volunteer study next year are there any safety concerns with targeting <unk> 7 billion.
Eric Joseph: We should be aware.
Eric Joseph: Ross.
Ross: Yes, Thanks Laura.
Ross: Repeating the question. The so there will be naturally several studies already conducted with antibodies against <unk> hundred 17 actually sell BEC was the latest company to reveal some of the data they're using anti CD 117 for the treatment of ultra carrier and basically what you're seeing those individuals' is that you see.
Ross: A transient mild neutropenia being the major sort of outcome that youll see and so really these antibodies do not lead to monitor ablation as you would see with chemotherapy and that's why as Don mentioned earlier. It opens the possibility theatrically that these kinds of treatment may even become in the future.
Ross: Outpatient treatment paradigm, because they obviously that do not run the risk of opportunistic infections due to neutropenia. So so we think that it really the healthy volunteer is a very expeditious and efficient way of quickly gets into a PK PD understanding of the of the antibody and then he gave.
Ross: Is there more assured essentially dosing regimen for us to go into the sickle cell and beta thalassemia patient without having to have extensive.
Eric Joseph: Treatment options.
Eric Joseph: Steve that during those those tribes.
Eric Joseph: Yes.
Eric Joseph: Okay.
Speaker Change: Thank you. Our next question comes from Sami Corwin with William Blair. Your line is now open.
Sami Corwin: Good morning, Congrats on the data and thank you for taking my question.
Sami Corwin: Peter You just mentioned this and I noticed on the slide that you plan on exploring escaped technology and data seen yet in addition to the cost obviously I guess I'm just curious what kind of prompted that expansion and then as you're thinking about the clinical trials for the escape platform.
Eric Joseph: Are you thinking about running Notionally you asked what are what those likely be conducted ex U S. Thank you.
Speaker Change: So a couple of things on there just in terms of the beta thalassemia consideration is really the fact that we think that escape essentially oldest the the risk benefit profile in particular, it reduces the risk to the point that.
Eric Joseph: Even in the beta thalassemia patients.
Eric Joseph: Transplant might be justified, particularly in the broader beta thalassemia patient, which goes beyond that the transfusion dependent anemia patients switch, which as you know is a relatively small number of patients obviously very sick, but.
Eric Joseph: We think that.
Eric Joseph: Escape opens up the opportunity to treat even beyond TVT.
Eric Joseph: And so.
Eric Joseph: That's fundamentally the main reason to consider that and then in terms of the various places where it will go to healthy volunteers, we have not yet decided exactly where.
Eric Joseph: U S or ex U S. We will.
Eric Joseph: <unk> be really efficiency and.
Eric Joseph: Rapid exploration of that phase one is really what's going to guide us in the in the choice that we make.
Speaker Change: Thank you. Our next question comes from Luca <unk> with RBC capital. Your line is now open.
Luca: Oh, great. Thanks, so much for taking my question, maybe John Big picture.
Eric Joseph: Yes.
Speaker Change: <unk> is becoming increasingly more important now, especially in the context of the kind.
Eric Joseph: And finally got the risks associated with it so fast.
Eric Joseph: The three hour escape is actually not game changing.
Eric Joseph: Committed to commercialize <unk> hundred one stone or would you be open.
Eric Joseph: 101 or license it similar to what <unk> has recently communicated any color there much Krishna thanks, so much.
Speaker Change: Yes, Thanks, Doug that's a great question.
Eric Joseph: I think as you noted we're playing the long game here in hematology and we see <unk>.
Eric Joseph: Very exciting progression of technology that takes advantage of base editing not to mention are now significant capabilities in CD 34 manufacturing.
Eric Joseph: And then the surfaces.
Eric Joseph: Blood therapies to create a lot of impact for patients over time and it is a progression that begins with one on one as a potentially best in class product for this wave one market leading to escape, which is no question incredibly exciting and would be a really revolutionary product in the conditioning field expanding us from sickle cell to also include beta thalassemia.
Eric Joseph: Et cetera, and as I have noted before I think a lot of the capabilities. We built along the way there now adding the ability to change your blood system essentially without chemotherapy could lead to a lot of other places right. So we see a lot of growth opportunity here in hematology over the long term that's why it's one of our two core pillar.
Eric Joseph: <unk>.
Eric Joseph: I think when it comes to partnering I think we've always said that we have the luxury here. If we don't have to partner for financial reasons, we would only partner strategically and so the partnership would be considered if a party could help us reach more patients more quickly.
Eric Joseph: <unk>.
Eric Joseph: And then we could do ourselves and then it would be something that we would we would consider.
Eric Joseph: To your hypothetical I think some of the elements of that pillar where to start to change. If we didn't have the escape technology for instance.
Eric Joseph: Or it Didnt work in some fundamental way I do think that would change the long term outlook and in hematology that might change the balance of our of our strategic thinking.
Eric Joseph: But in the near term I don't think it would change the value we have with with being 101 potentially.
Eric Joseph: Essentially help a lot of patients who need help so I think they ask us what basically would be the same it would be this is these are products that I think can make a big impact for patients and generate sustainable revenue and market value. If there is a party out there who can help us do any of this better.
Eric Joseph: <unk>.
Eric Joseph: Getting in the way of what we need to build.
Eric Joseph: That's a conversation that we'll entertain otherwise we're prepared and well financed to do this ourselves.
Speaker Change: Thanks, so much.
Speaker Change: Thank you. Our next question comes from Michael Yee with Jefferies. Your line is now open.
Michael Yee: Good morning.
Michael Yee: If I may since this is an earnings call as well right.
Michael Yee: Some other pipeline developments.
Michael Yee: You did announce that you had completed dosing the first cohort in a team, which I think is a big achievement.
Michael Yee: Can you just remind us.
Michael Yee: To what extent you believe that there will be material enough information to disclose at what time point given my understanding is the AAP levels should be rising pretty quickly.
Michael Yee: And certainly based on todays data I'm sure you have more confidence in the editing in.
Michael Yee: In vivo sure at what point.
Michael Yee: Would there be enough proof of concept disclosed and given you've already dosed three patients already thank you so much.
Speaker Change: Thank you Mike good.
Speaker Change: Good to hear from you so.
Speaker Change: Youre absolutely right.
Michael Yee: We have a lot going on in the portfolio. We're very excited about the progress on liver side as well as I noted in the in the <unk> results.
Michael Yee: With Alpha one obviously first co are completed and now moving forward with that dose escalation and it is true as a reminder to everybody. We were dose escalating beginning at a low dose but allowed us that is done what's expected to have biological activity. That's important ethically and then we will seek to understand the optimal biological range as we.
Michael Yee: Go so we've guided to a 2025 data released on that program I feel confident in that guidance I think when we will.
Michael Yee: Narrow that as we can obviously.
Michael Yee: What we've always said is we would look to bring our data when there is a clear profile of the drug and I think that I think clearly means at least multiple cohorts exactly.
Michael Yee: Exactly how we define that will be TBD.
Michael Yee: But we'll be watching it closely and as you know this is a program that does have the potential for early clinical proof of concept based on levels of <unk>.
Michael Yee: One normal ml, so one going up based on Z protein hopefully going down and then of course, we'll be looking at safety in a phase one study so stay tuned.
Speaker Change: But thats certainly an update that we'll be looking forward to 2035.
Speaker Change: Thanks.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Rick <unk> with Cantor Fitzgerald. Your line is now open.
Rick: Hey, good morning, Congrats on the update and thanks for taking the question I was just hoping to get a little more color on the expected pace of dosing in pekin.
Rick: There is 35 patients enrolled in the study in HAE patients dosed to date. So if we can just get a little more detail on where we are for cell collection of the 27 patients who were in test yet.
Speaker Change: Potential timeline for all of these patients to be dosed.
Speaker Change: Yes. Thanks, Thanks, Rick So so I think as we as <unk>.
Speaker Change: You rightly noted that we're quite pleased with the enrollment thats actually exceeded expectations at this point.
Speaker Change: 35 patients doubtful enrolled that does not include additional patients who are in screening and consenting. So.
Speaker Change: As a pretty robust pipeline and moving quite quickly now.
Speaker Change: Had hopes I think when we set up the clinical program that we did in and thanks, Ann and her team for driving it.
Speaker Change: <unk>.
Speaker Change: Dosing is now basically as you know it takes a long time to create the dose at this point, we have doses rolling off the the line fairly regularly so theres going to be a big uptick in doses in the near future.
Michael Yee: As that trial commences as a reminder of the overall trial, we're looking for 45 total patients.
Michael Yee: Who will be dosed here, so clearly, we're well on our way to that.
Michael Yee: Also interestingly, we've always design this trial has the potential.
Michael Yee: To be a registration trial.
Michael Yee: And our best understanding of that package based on the benchmark set by the ex Cel program was 30 patients followed for about 15 months to get their endpoint SaaS and so clearly in this 35 patients we've already got those patients moving so the clock has started at this point.
Michael Yee: As we as we execute on these doses and look to enable what could be a potential filing package for one on one.
Speaker Change: Thank you.
Speaker Change: Our next question comes from <unk> <unk> with Guggenheim. Your line is now open.
Speaker Change: Hi, everyone. This is Ryan <unk> on for Doug.
Michael Yee: What are your human translational expectations from the an HP escape data do you expect outperformance or underperformance relative to 101 and does having.
Michael Yee: 101 clinical data help bolster your confidence and escaped clinical performance.
Speaker Change: Yes, Dana yes. Thank you very much for the question.
Michael Yee: Expect frankly.
Michael Yee: Equivalent if not better performance.
Michael Yee: In humans and Thats driven by the sequence of the guide that we use.
Michael Yee: Is.
Michael Yee: And the antibody being cross-react actually between nonhuman primates and humans. So.
Michael Yee: We obviously, we are refining a little bit.
Michael Yee: The treatment paradigm of the antibody so that we can optimize it even further.
Michael Yee: I think it is nonhuman primate data gives us tremendous confidence that we can move forward to the clinical studies.
Michael Yee: <unk>.
Speaker Change: Thank you.
Speaker Change: Our final question comes from Mani for Hora with Leerink Partners. Your line is now open.
Michael Yee: Okay.
Mani: Thanks for taking the question guys a quick follow up on Mike's question on our ACD.
Michael Yee: We think about the market opportunity in this indication. This is obviously a fairly heterogeneous population how should we think about the path forward. Both in terms of enrollment and clinical data and then ultimate sort of commercial opportunity between patients with a predominantly long phenotype and those.
Michael Yee: With a liver phenotypes.
Michael Yee: How will your enrollment strategy reflects the opportunity set across both.
Speaker Change: Yes, great question Ronny, Thank you and thanks to everybody for engagement today.
Mani: So.
Speaker Change: Alpha one it is a somewhat heterogeneous population you have of course the majority of patients are primarily lung involved a minority have primary liver involvement and of course, there's a spectrum of patients who share both.
Mani: On the.
Mani: The beauty of being three or two is that it addresses both sides of that equation. So for every allele. We added we are going to start secreting normal protein.
Mani: Which should benefit the lungs, and the under armour regulation.
Mani: And we're going to decrease the production of this toxic protein that is causing so much trouble deliver so I think at the end of the day, we don't need to choose down the trial itself, where initially studying this in patients who are primarily long just to make sure. We had a clean profile. Given this is a liver delivered therapy, then we will treat patients who have much more liver involvement, but our expectation base.
Mani: Some preclinical data and our goal would be to deliver a single dose that is.
Mani: Usable across the entire population.
Michael Yee: And develop the drugs across the entire population.
Michael Yee: I think by the time, we get to that to considering market potential.
Mani: Ultimately all patients are in view here. Both currently diagnosed and then continuing to identify additional patients who have that is easy phenotype and are really severe need of new therapeutic options.
Speaker Change: Can I get a quick follow up here.
Speaker Change: Yes, it makes a lot of sense to me that the technology can address the underlying genetic.
Speaker Change: Cause of disease, and therefore address the molecular genetics that drive all of your phenotypes that makes a lot of sense to me.
Mani: Biologically and clinically.
Mani: From a regulatory perspective, the time horizon approval end points for the two phenotypes.
Mani: Necessarily aligned.
Speaker Change: So if you give us how you're thinking about how to get approved for treatment.
Mani: For liver.
Mani: Yes.
Mani: Long et cetera, what that looks like a regulatory practical perspective.
Speaker Change: Yes understood.
Speaker Change: I mean look I think our first job here is to deliver hopefully compelling phase one data set right, which shows the kind of fundamental correction of the gene in the body for the first time. So that's step one and that of course that data opens the door to the conversation with the regulators for a lot of the different options here.
Speaker Change: Youre right that formally.
Speaker Change: One endpoint may have a certain set of requirements and characteristics that may be different than a liver endpoint of course, the RNA <unk> knockdown therapies have been exploring the liver pathway, we can learn from that.
Speaker Change: And so certainly for the different types of patients. We may explore both at the same time across both of them theres the opportunity to consider the use of just the biomarkers themselves.
Speaker Change: And the protein deficiency, which defines this disease.
Speaker Change: As.
Speaker Change: As endpoints and Mark is a benefit that we would it be exploring as well and that of course would be universal across patients. So.
Speaker Change: Definitely grant your point I think it's early days, there's a lot to work through I think our first step is generate a compelling data set that will then drive the conversations with regulators investigators on how to develop the drug.
Speaker Change: Alright, thank you.
Speaker Change: This concludes the question and answer session. Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Yes.
Speaker Change: Okay.
Speaker Change: [music].