Q1 2024 Editas Medicine Inc Earnings Call

Operator: Good morning, and welcome to the Editas Medicine first 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.

Good morning, and welcome to the added cost of Medicine first quarter 'twenty 'twenty four conference call.

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 Kristy Barnett corporate communications and Investor Relations that Ed you talked a medicine.

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Cristi Barnett: Thank you. Good morning, everyone, and welcome to our first 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.

Cristi Barnett: Thank you good morning, everyone and welcome to our first quarter 2024 conference call.

Cristi Barnett: 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.

Cristi Barnett: 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.

After our prepared remarks, we will open the call for Q&A.

Cristi Barnett: 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.

Cristi Barnett: 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.

Cristi Barnett: 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 ONeill.

Cristi Barnett: 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.

Cristi Barnett: Now I will turn the call over to our CEO Gilmore O'neill.

Gilmore ONeill: Thanks, Cristi, and good morning, everyone. Thank you for joining us today on Editas' first quarter 2024 earnings call. With me today are four members of the Editas executive team, our Chief Medical Officer, Baisong Mei, our Chief Scientific Officer, Linda Burkly, our Chief Financial Officer, Erick Lucera, and our Chief Commercial and Strategy Officer, Caren Deardorf. We are pleased with Editas' momentum and progress in the first quarter of 2024. Editas' goal is to deliver life-changing medicines to patients with previously untreatable or undertreated genetically determined diseases, and our vision and focus are to position Editas as a leader in in vivo programmable gene editing. Three pillars underpin our strategy.

Unknown Attendee: Thanks, Christy and good morning, everyone.

Gilmore ONeill: The first of those pillars is to drive RenyCell, an edited cell therapy for hemoglobinopathies, and formerly known as Edit 301, toward BLA and commercialization. The second is to build an in vivo editing pipeline, and the third is to increase business development activities with a particular focus on monetizing our very strong intellectual property. At the start of 2024, we announced the following 2024 objectives.

Unknown Attendee: Thank you for joining us today on the edit has its first quarter 2024 earnings call.

Unknown Attendee: With me today are four members of the executive team, our Chief Medical Officer based on my My Chief Scientific Officer, Linda Berkley, Our Chief Financial Officer, Eric <unk>, and our Chief commercial and strategy Officer Carin journals.

Unknown Attendee: We are pleased with any passenger momentum and progress in the first quarter of 2024.

Unknown Attendee: It's tough to stories to deliver life changing medicines to patients with previously untreated or under treated genetically determined diseases.

Unknown Attendee: That's our vision and focused strategy is to position a test.

Unknown Attendee: As a leader in in vivo programs with gene editing.

Unknown Attendee: Three pillars underpinning our strategy.

Unknown Attendee: The first of those pillars is to drive rent itself and edited cell therapy for hemoglobin apathy and formerly known as edit 301 towards BLA and commercialization.

Unknown Attendee: Second is to build an in vivo editing pipeline and the third is to increase business development activities with a particular focus on monetizing our very strong intellectual property.

Gilmore ONeill: For RenyCell, 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 2020. We will complete adult cohort enrollment and initiate the adolescent cohort in Ruby and continue enrollment in Editas. For our In Vivo pipeline, we will establish In Vivo preclinical proof of concept for an undisclosed indication, and for BD, we will leverage our robust IP portfolio and business development to drive value and complement core gene-editing technology capabilities. So how are we doing against this strategy and these objectives in the first quarter? Let us start with Renison.

Unknown Attendee: At the start of 2024, we announced the following 2024 objectives.

Unknown Attendee: We're ready so we will provide a clinical update from the Ruby trials with severe sickle cell disease, and the NFL trial for transfusion dependent beta thalassemia in mid 2024 and by year end 'twenty 'twenty four we.

Unknown Attendee: We will complete adult cohorts enrollment and initiate the adolescent cohorts and Ruby and continue enrolment in epic.

Unknown Attendee: For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication and for BD, we will leverage our robust IP portfolio and business about to drive value and complements core gene editing technology capabilities.

Unknown Attendee: So how we executed against the strategy and these objectives in the first quarter.

Unknown Attendee: Let us start with Renaissance.

Gilmore ONeill: First, on enrollment. We've been very pleased with the growing patient and health care provider interest in RenyCell. Indeed, we are delighted to share that we have completed enrollment in the adult cohort of the RUBY clinical trial. Additionally, we have enrolled multiple patients and have more in screening in the adolescent cohort of the RUBY study, which was launched at the beginning of this year. And we continue to enroll basal thalassemia patients in our Edithal study. Dosing continues in both the RUBY and EDITAL studies.

Unknown Attendee: First on enrollment.

Unknown Attendee: Been very pleased with the growing patient and health care provider interest in ready. So indeed, we are delighted to share that we have completion of enrollment in the adult cohort of the Ruby clinical trial. Additionally, we have enrolled multiple patients and have more in screening in the adolescent cohort of a Ruby study, which was launched at the beginning of this year.

And we continue to enroll basic palestinia patients in our edit out study.

Unknown Attendee: Dosing continues in both the Ruby NFL studies.

Gilmore ONeill: Second, on clinical data, we remain on track to present a substantive clinical data set of at least 18 sickle cell patients with 2 to 21 months of clinical follow-up in the RUBY study in the middle of 2024, and we will share a further update by year-end. We are also on track to present clinical data from the Edithal study of Renicel in transfusion-dependent beta thalassemia in the middle of 2024 and again by year end. Baisong Mei will share more Renaissance data later on in this call.

Unknown Attendee: On clinical data, we remain on track to present, a substantial clinical dataset of at least 18 sickle cell patients with tubes 21 months of clinical follow up and the Ruby study in the middle of 2024, and we will share further update by year end.

Unknown Attendee: We are also on track to present clinical data from the study already sell in transfusion dependent beta thalassemia in the middle of 2024 and again by year end.

Unknown Attendee: Based on my with share more ready says acos.

Unknown Attendee: Later on in this call.

Gilmore ONeill: On the manufacturing front, I am pleased to share that we have promoted Greg Whitehead to the role of Chief Technology and Quality Officer, leading our Technical Development, Technical Operations, and Quality Department. Greg has more than 25 years of experience in the biotech industry and extensive cell and gene therapy clinical and commercial development expertise. Now, let's turn to in vivo and our pipeline development, where we continue to strengthen our in vivo discovery capabilities and continue leading discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues.

Unknown Attendee: On the manufacturing pumps I'm pleased to share that we have promoted Greg Weiss head to the role of Chief technology, and quality officer, leading our technical development technical operations and quality departments.

Unknown Attendee: Greg has more than 25 years of experience in the biotech industry and extensive cell and gene therapy clinical and commercial development expertise.

Unknown Attendee: Now.

Unknown Attendee: Let's turn to in vivo and our pipeline development, where we continue to strengthen our in vivo discovery capabilities and continued deep discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues.

Gilmore ONeill: Importantly, we remain on track to establish in vivo preclinical proof of concept for an undisclosed indication by the end of the year. Our internal development efforts are differentiated by leveraging the Indel CRISPR technology we already use to up-regulate gamma-global expression through direct editing of the HBG1-2 promoter site in our Ex Vivo ReadyCell program. Our in vivo approach is aimed at functional upregulation of gene expression in genetically defined diseases with a preliminary focus on rare and orphan patient populations.

Unknown Attendee: Importantly, we remain on track to establish in vivo preclinical proof of concept for an undisclosed indication by the end of the year.

Unknown Attendee: Our internal development efforts are differentiated by leveraging the Intel CRISPR technology, we already used to up regulate gamma globin expression through direct editing of the H B G want to promote or size in our ex vivo red cell program.

Unknown Attendee: Our in vivo approach is aimed at functional up regulation of gene expression in genetically defined diseases with a preliminary focus on rare and orphan patient populations in the medium to long term, we intend to expand to more common genetically determined diseases Lynn.

Gilmore ONeill: In the medium to long term, we intend to expand to more common genetically determined diseases. Linda Burkly, our CSO, will share more details on our in vivo strategy and progress towards building an in vivo pipeline later in the call. Finally, what is happening in business development? In March, we signed a two-year extension to the collaboration with Bristol-Myers Squibb to research, develop, and commercialize autologous and allogeneic alpha-beta T-cell medicines for the treatment of cancer and autoimmune diseases.

Unknown Attendee: Linda Berkley, our CSO, who will share more details on our in vivo strategy and progress towards building an in vivo pipeline later on in the call.

Linda C. Burkly: Finally, what is happening in business development.

Gilmore ONeill: We also have options to extend that collaboration for an additional two years. To date, Bristol-Myers Squibb has invested in 13 different programs across 11 gene targets to date. Two programs are currently in IND and APRIC studies, and four programs are in late stage discovery and Intellectual Property. Yesterday, oral arguments were held before the U.S. Court of Appeals for the Federal Circuit regarding the Federal Circus. Regarding an appeal of the Patent, Trial, and Appeal Boards, or PTABs, previous decision favoring Broad Institute and the U.S. Patent Interference Involving Specific Patents for CRISPR-Cas9 Editing in Human Cells between the University of California, University of Siena, and Emmanuel Charpentier, or CDC, and the Broad Institute, we expect a decision on the case in the second half of 2024

Linda C. Burkly: In March we signed a two year extension to the collaboration with Bristol Myers Squibb to research develop and commercialize autologous and allogeneic Alpha Beta T cell medicines for the treatment of cancer and automotive diseases.

We also have options to extend that collaboration for an additional two years.

Linda C. Burkly: To date, Bristol Myers Squibb has opted into 13 different programs across 11 gene targets to date.

Linda C. Burkly: Two programs are currently in IND, enabling studies and four programs are in late stage discovery.

Linda C. Burkly: And the intellectual property yesterday oral arguments were held before the U S Court appeals for the federal circuit rigs.

Linda C. Burkly: Regarding an appeal of the patent trial and appeal board or P. Tabs previous decisions favoring broad Institute in the U S patent interference involving specific patents for CRISPR Cas nine editing in human cells between the University of California University of Vienna, and the man, who got a sharp on Ta or C. D C and the broke we.

Linda C. Burkly: The decision on the case in the second half 2024.

Gilmore ONeill: Eric will share more BD and IP details later in the call. We are energized by our progress in execution this quarter. With our sharpened strategic focus, our world-class scientists and employees, our keen drive in execution, and our strong balance sheet, we continue to build momentum to advance our strategy to deliver differentiated editing medicines to patients with serious chest diseases. Now, I would turn the call over to Baisong, our chief medical officer.

Linda C. Burkly: Eric will share more BD and I P. Details later on in the call.

Linda C. Burkly: We are energized by our progress and execution this quarter with our sharper strategic focus are world class scientists and employees are keen drive and execution and strong balance sheet. We continue to build momentum to progress our strategy to deliver differentiated medicines to patients with serious diseases now I would turn to.

Speaker Change: A cold over debate song, our Chief Medical Officer.

Baisong Mei: Thank you, Gilmore. Good morning, everyone.

Debate Song: Thank you Guillermo and good morning, everyone.

Baisong Mei: Let's talk about renner cells, which are under clinical development for severe sickle cell disease and transfusion-dependent beta ferrocemia. As Gilmore shared, we are pleased that we have completed enrollment in the adult cohort of the Phase 1-3 RUBY trial, and the dosing continues. In the adolescent cohort of the RUBY study, we have enrolled multiple patients and several more patients are in screening. Interest and demand are

Debate Song: Let's talk about rent, it though which.

Debate Song: On the clinical development.

Debate Song: T D.

Debate Song: And transfusion dependent beta thalassemia.

Debate Song: As Guillermo shared we are pleased that we have completed enrollment in adult cohort of the phase went to see movie trial.

Debate Song: And the dosing continues.

Debate Song: In the adolescent cohort B study, we have even more of a modern location and several more patients in screening.

Baisong Mei: I'm very pleased about how quickly we have moved on screening and enrollment of the Adolescent Corps. I'd like to thank my colleagues at Editas and our clinical trial partners for the collaboration and hard work. And more importantly, I would like to thank patients, their families, investigators, and the study side staff for their trust and support. In the EDIHEAL trial for transfusion-dependent beta-plasmia, we continue to move forward with enrollment and dosing.

Interest and demand a high.

Debate Song: I'm very pleased about how quickly we have moved in screening and enrolment opened adolescent cohort.

Debate Song: I like to thank colleagues and editors and our clinical trial partners calibration and hard work.

Debate Song: And more importantly, I would like to thank patients their families investigators and study site staff for their trust and support.

Debate Song: How do you feel trial for transfusion dependent beta thalassemia with.

Debate Song: Continuing to move forward with employment and dosing.

Baisong Mei: We look forward to sharing clinical data in the middle of this year and also at year-end. As I have shared, I visited and continue to visit our Ruby and Edytheal clinical trial sites and speak with the investigators. I appreciate the enthusiasm and support from the investigators and study staff. I'm pleased with the momentum of Renacel in patient recruitment, freezes, and dosing in both studies. I'm excited to hear from the investigators, the patients, those who are in the Renaissance have already seen positive changes in their lives.

Debate Song: We look forward to sharing the clinical data in the middle of this year and also at the year end.

Debate Song: As I have shared I visited and continue to build our movies, how do you feel at clinical trial sites and speak with the investigators.

Speaker Change: I appreciate it.

Speaker Change: Awesome and the support from the investigators and study sites.

Speaker Change: I'm pleased with the momentum about readiness that patient recruitment a free space and dosing in both studies.

Speaker Change: I'm excited to hear from the investigators the patients those two would you run a sale have already seen positive changes in their lives.

Baisong Mei: As we shared in our February early call, we aligned with the FDA that the Ruby clinical trial is now considered a phase 1, 2, 3 trial for BLA5. We also have alignment with the FDA on the study design, endpoints, and sample size.

Speaker Change: As we shared on our February earnings call, we align with the FDA that will be clinical trial is now considered a phase 123 trial for BLA filing.

Speaker Change: We also have alignment with the FDA on the study design and endpoints and sample size.

Baisong Mei: We look forward to future discussions with the FDA and continuing the collaboration. Turning to clinical data, as Gilmore mentioned, we are on track to present a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024 and a further update by year-end 2024. What did we lose, Joe?

Speaker Change: We look forward to future discussions with FDA and continue the calibration.

Speaker Change: Turning to clinical data as Guillermo mentioned, we're on track to present, a substantive clinical dataset of sickle cell patients with considerable clinical follow up and the Ruby study in the middle of 'twenty 'twenty four and for the update by year end 2024.

Speaker Change: What are we will show.

Baisong Mei: The ruby dataset will include clinical data from at least 18 sickle cell patients with a 2 to 21 month follow-up, and the editorial data set will include clinical data from seven patients with four to 12 months follow-up. We will present efficacy data, including total hemoglobin, fetal hemoglobin, and the best of occlusive events, or VOE, for sickle cell patients in the Ruby study and Red Blood Cell Transfusion or Transfusion-Dependent Bariatric Female Patients in Editas, and safety data, including mutual feel and clouded environment for both studies. And a reminder.

Speaker Change: Ruby datasets, including clinical data from at least 18 sickle cell patients with a $2 21 months of follow up.

Speaker Change: And that the editing will get us that way you can be couldnt go to add up on seven patients with four to 12 months follow up.

Speaker Change: We will present efficacy data, including total hemoglobin fetal hemoglobin and the vessel crews, who you're Bang OBO E for sickle cell patients and Ruby study.

Speaker Change: And the Red blood cell transfusion or transfusion dependent beta thalassemia patients.

Speaker Change: State and.

Speaker Change: Safety data, including mutual appeal and traveling Brafman for both studies.

Speaker Change: As a reminder.

Baisong Mei: In December 2023, we shared safety and efficacy data from 11 RUBY patients and 6 EDIFEL patients. Once again, the data confirms the observation from our prior clinical results, including Reniseo Zhou's early robust collection of anemia to a normal physiological range of total hemoglobin in sickle cell cancer, runner-up to a robust and sustained increase in fetal hemoglobin levels in excess of 40%. All Ruby sickle cell patients remain free of vessel occlusion events following Renner cell treatment.

Speaker Change: In December 2023, we shared safety and efficacy data from 11, Ruby patients and six <unk> locations.

Speaker Change: Once again the data confirm the observation from our prior clinical Readouts.

Speaker Change: Quoting rent yourself, Joe early robust the correction of anemia to a normal physiologic range of total hemoglobin in sickle cell patients.

Speaker Change: Renault sales drove robust and sustained increase in fetal hemoglobin level in excess of 40%.

Speaker Change: Oh, Ruby sickle cell patient remained free of battle cookie events following treatment.

Baisong Mei: Many cell-treated sickle cell patients and transfusion-dependent beta-carotenoid patients have shown successful engraftment and stopped red blood cell transfusion, and the safety profile of Renner cell observed today is consistent with Biosoft and Marble Active Conditioning and the Tollegre's hemopoietic stem cell transplant. This data reinforces our belief that we have a competitive product and a product potentially differentiated from other treatments with a rapid correction Thanks to the deliberate choice of our discovery group, we have made early in the program.

Speaker Change: Wednesday of treating sickle cell patients and transfusion dependent beta thalassemia patients have shown successful grafman I've stopped red blood cell transfusion.

Speaker Change: And the safety profile of <unk> to date is consistent with yourself and Michael I think conditioning and apologize came up with stem cell transplant.

Speaker Change: These data reinforce our belief that if we have a competitive product.

Speaker Change: And the product potentially differentiated from other treatments with a record of correction of anemia.

Speaker Change: The deliberate choice of our discovery group have made early in the program.

Baisong Mei: The choice of CRISPR enzyme and the target to edit for increased phytochemical re-expression matters. Renesil uses our proprietary AES-Cas12A enzyme to upregulate the HB212 promoter. Based on the clinical data thus far, we believe that sustained normal levels of total hemoglobin could be a potential point of differentiation for retinitis. Now, I turn the call over to Linda, our Chief Scientific Officer.

Speaker Change: The choice of CRISPR enzymes, and the targeted to edit for increased fetal hemoglobin expression matters.

Speaker Change: Renato uses our proprietary <unk> kept hold a enzyme.

Speaker Change: H b, two and to promote it.

Speaker Change: Based on the clinical data, thus far we believe that Dan normal level of told them to go be could it be a potential point of differentiation for renesola.

Speaker Change: Now I'll turn the call over to Linda <unk>, our Chief Scientific Officer.

Linda C. Burkly: Thanks, Baisong. And good morning, everyone.

Linda C. Burkly: Thanks, Tom and good morning, everyone.

Linda C. Burkly: I'm happy to be talking to you. This morning to hear more details about our in vivo strategy and our progress towards building an in vivo pipeline.

Linda C. Burkly: I'm happy to be talking to you this morning to share more details about our in vivo strategy and our progress towards building an in vivo pipeline. I would like to take a moment to remind you why we believe in vivo medicines will be a disruptive, transformative development in medical history, with the potential to address genetically determined diseases with durable and curative outcomes for patients. First, Indivo Medicines may reduce the administration burden of delivering editing medicines to patients in need, which will provide for broader access to patients all around the world. Second, off-the-shelf administration may allow for scalable manufacturing and lower costs to produce.

I would like to take a moment to remind you why do you believe in vivo medicines will be a disruptive transformative development in medical history with the potential to address genetically determined diseases terrible inherited outcomes for patients.

Linda C. Burkly: First in vivo medicine may reduce the administration burden of delivering editing medicines to patients in need which will provide a broader access to patients all around the world.

Linda C. Burkly: Second off the shelf administration may allow for scalable manufacturing and lower cost supergene.

Linda C. Burkly: Based on these two principles, we believe that in vivo gene editing will provide accessible cures for genetic diseases and therefore may be the most disruptive development in medical history. So how will Editas position itself? There are many monogenic diseases that can potentially be cured with a gene editing approach. We have said that we will, at first, target the development of treatments that are clearly differentiated from the current standard of care and that will leverage the aspects of CRISPR editing that give it a unique advantage over other therapeutic modalities.

Linda C. Burkly: Based on these two principles, we believe that in vivo gene editing will provide excess books yours or genetic diseases, and therefore, maybe the most disruptive development and medical history.

Linda C. Burkly: So how will edit task position itself.

Linda C. Burkly: There are many monogenic diseases that can potentially be charged with a gene editing approach. We have said that we really.

Linda C. Burkly: Target the development of treatments that are clearly differentiated from current standard of care.

Linda C. Burkly: And that will leverage the aspects of CRISPR editing.

Linda C. Burkly: A unique advantage over other therapeutic modalities.

Linda C. Burkly: Our internal development efforts are differentiated by leveraging the INDEL CRISPR technology we use to upregulate gamma globin expression through direct editing of the HBG1-2 promoter site in our ex vivo renaissance program. Our in vivo approach is aimed at functional upregulation of gene expression in genetic diseases in rare and orphaned patient populations, from which we intend to expand to more common diseases.

Linda C. Burkly: Our internal development efforts are differentiated by leveraging in Dell CRISPR technology weekends to up regulate gamma Paul Wogan expression through direct editing of the H B G. One to promote our site and our X gene loved My Nacelle program.

Linda C. Burkly: Our in vivo approach, saying that functional upregulation of gene expression and genetic diseases, and rare and orphan patient populations from which we intend to expand to more common diseases.

Linda C. Burkly: I'm also pleased to share several progress updates as we advance our in vivo capabilities towards our long-term vision of being a leader in in vivo programmable gene editing. First and most importantly, as Gilmore mentioned, we remain on track to establish in vivo preclinical proof of concept for an undisclosed indication by the end of the year. Editas is well positioned with established capabilities in the four main components of in vivo gene editing medicine.

Linda C. Burkly: I'm also pleased to share several progress updates as we advance our in vivo capabilities towards our long term vision of being a leader in vivo program well gene editing.

Linda C. Burkly: First and most importantly, it's Gilmore mentioned, we remain on track to establish in vivo preclinical proof of concept for an undisclosed indication by the end of the year.

Linda C. Burkly: <unk> is well positioned with established capabilities and the four main components of in vivo gene editing medicine.

Linda C. Burkly: Guide RNA 2. Editing Enzyme 3. Messenger RNA 4.

Linda C. Burkly: One died on me two editing enzyme.

Linda C. Burkly: Free messenger RNA and for delivery technology, and we are currently evaluating lipid nanoparticles or delivery of gene editing cargo into multiple tissue types with multiple companies. Additionally.

Linda C. Burkly: Delivery Technology We are currently evaluating lipid nanoparticles for delivery of gene-editing cargo into multiple tissue types with multiple companies. Additionally, we're evaluating next generation delivery technology. Second, our in vivo capabilities with the potential to be used in developing transformative in vivo gene editing medicines are demonstrated by the preclinical data we are presenting at the American Society of Gene and Cell Therapy, or ASGCT, annual meeting in three presentations taking place on Thursday and Friday of this week.

Linda C. Burkly: Additionally, we're evaluating next generation delivery technology.

Linda C. Burkly: Second our in vivo capabilities with the potential to be used in developing transformative in vivo gene editing medicines are demonstrated by the preclinical data we are presenting at the American society of gene and cell therapy or <unk>.

Linda C. Burkly: All meeting in three presentations, taking place on Thursday, and Friday This week.

Linda C. Burkly: On Friday, in an oral presentation, we will share in vivo preclinical data from mouse studies using lipid nanoparticle mediated delivery of an optimized guide RNA and engineered AS Cas128 messenger RNA. In poster presentations on Thursday and Friday, we will share preclinical data demonstrating AF-Cas12a guide RNA modifications that enable high-potency gene editing in multiple cell types, including in the liver, and improve gene editing outcomes in vivo, enabling the development of in vivo gene editing medicine, and research on identifying potent large serine recombinases, LSRs, as a foundation to develop novel in vivo gene editing technologies for whole gene knocks.

Linda C. Burkly: On Friday, and an oral presentation, we will share in vivo preclinical data from the mouse studies using lipid nanoparticle media nasal delivery of an optimized five on me and engineered a M Castle Messenger RNA.

Linda C. Burkly: And poster presentations on Thursday, and Friday, we will share preclinical data demonstrating <unk> castrol. They guide RNA modifications that enable high potency gene editing in multiple cell types, including in the liver.

Linda C. Burkly: And improve gene editing outcomes in vivo, enabling the development of in vivo gene editing medicines.

Linda C. Burkly: And research on identifying potent largest hearing recombination L. S ours as a foundation to develop novel in vivo gene editing technologies for whole gene market expanding potential in vivo gene editing targets for develop medicine.

Linda C. Burkly: Expanding Potential in Vivo Gene Editing Targets for Developing Medicine Third, Editas' CRISPR-based in vivo gene editing capability has been clinically validated. Notably, in 2020, Editas was the first company ever to treat a human with an in vivo delivered CRISPR-based gene editing medicine, EDIT101. In fact, earlier this week, the New England Journal of Medicine published a manuscript entitled Gene Editing for CEP290-Associated Retinal Degeneration, detailing our former lead development candidate, EDIT101, for the treatment of Leber's congenital amaurosis type 10, or LCA10.

Linda C. Burkly: Third at a task CRISPR based in vivo gene editing capabilities has been clinically validated notably in 2020 and it also is the first company ever to treat in human with an in vivo delivered CRISPR based gene editing medicine edit one of them one in.

Linda C. Burkly: In fact earlier this week in New England Journal of Medicine, published a manuscript entitled Gene editing perception 90 associated retinal degeneration detailing our formerly development candidate edit 101 for the treatment of Leber congenital amaurosis type 10, our LCA 10.

Linda C. Burkly: Editas established clear in vivo human proof of concept in 2022, and we are pleased that the results from this groundbreaking clinical trial were published by the New England Journal of Medicine. These progress updates demonstrate Editas' execution on our In Vivo strategy and our proven In Vivo gene editing capabilities. And I look forward to sharing more details about our In Vivo development strategy and our progress towards building an In Vivo pipeline later this year. Now, I will turn the call over to Eric, our Chief Financial Officer.

Linda C. Burkly: And is this established clear in vivo human proof of concept in 2022, and we are pleased that the results from this groundbreaking clinical trial were published by the New England Journal of Medicine.

Linda C. Burkly: These projects updates demonstrate execution on our in vivo strategy and our proven in vivo gene editing capabilities and I look forward to sharing more details about our in vivo to mountain strategy and our progress towards building an in vivo pipeline later this year.

Linda C. Burkly: Now I will turn the call over to Erik <unk>, our Chief Financial Officer.

Erick J. Lucera: Thank you, Linda. And good morning, everyone.

Erik: Thank you Linda and good morning, everyone I'm happy to be speaking to you and I'm excited to provide updates on our business development achievements intellectual property and financial results for the first quarter of 2024.

Erick J. Lucera: I'm happy to be speaking to you, and I'm excited to provide updates on our business development achievements, Intellectual Property, and Financial Results for the first quarter of 2024. First, in regard to business development, as Gilmore mentioned, in March, we announced a two-year extension to the collaboration with Bristol-Myers Squibb to research, develop, and commercialize autologous and allogeneic alpha-beta T-cell medicine for the treatment of cancer and autoimmune diseases. We also have options to extend the collaboration for an additional two years. To date, Bristol-Myers Squibb has opted in to 13 different programs across 11 gene targets. Two programs are currently in IMD-enabling, and four programs are in late stage discovery.

Erik: First in regard to business development as Gil mentioned in March we announced a two year extension to the collaboration with Bristol Myers Squibb to research develop and commercialize autologous and allogeneic Alpha Beta T cell medicines for the treatment of cancer and autoimmune diseases.

Erik: We also have options to extend the collaboration for an additional two years.

Erik: To date, Bristol Myers Squibb has opted into 13 different programs across 11 gene targets to date.

Erik: Programs are currently in IND, enabling studies and four programs are in late stage discovery.

Erick J. Lucera: As a reminder, for each new experimental medicine that Bristol-Myers Squibb develops and commercializes using opted-into genome editing tools, Bristol-Myers Squibb will pay Editas Medicine potential future milestone payments. Additionally, following the approval of any products resulting from the collaboration, Editas Medicine is also eligible to receive tiered royalties on net sales. We are pleased that our Bristol-Myers collaboration has proved to be a productive partnership, and we are committed to future collaborations and partnerships that will allow for the continued access to and advancement of gene editing.

Erik: As a reminder, for each new experimental medicine at Bristol Myers Squibb develops and commercialize using opted into genome editing tools.

Erik: Bristol Myers Squibb will pay at a tough medicine potential future milestone payments.

Erik: Following the approval of any products, resulting from the collaboration and his house Medicine is also eligible to receive tiered royalties on net sales.

Erik: We're pleased that our Bristol Myers collaboration has proved to be a productive partnership and we are committed to future collaborations and partnerships that will allow for the continued access and advancement of gene editing.

Erick J. Lucera: And in IP, as Gilmore mentioned yesterday, oral arguments were held before the U.S. Court of Appeals for the Federal Circuit regarding the CBC's appeal of the PTAB's decision involving patents for CRISPR-Cas9 editing in human cells. As you know, the Broad Institute has previously prevailed three times against the CBC, twice with the PTAB, and once at the Federal Circuit. The Federal Circuit's review will determine whether the PTAB correctly applied the law. It is important to remember that the court will not hear new evidence.

Erik: And in IP and scale more mentioned yesterday, the oral arguments were held before the U S Court of appeals for the Federal circuit regarding the Cvc's appeal of the PTA B's decision involving patents for Christopher cast nine editing in human cells.

Erik: As you know the broad Institute has previously for failed three times against the CVC twice with the PCA B and once at the Federal Circuit.

Erik: The federal Circuit's review will determine whether the P. T a b correctly applied the law.

Erik: It is important to remember the court will not hear a new evidence.

Erick J. Lucera: An appellate court decision in the Broad's favor would reaffirm Editas' position as the exclusive licensor of the patents covering Cas9 used in human medicines in the U.S. It's also important to remember that only a small fraction of the IP we licensed from the Broad is involved in the ongoing USPTO interference proceedings. We expect a decision on the case in the second half of 2020, and we remain confident that the Broad will win once again.

Erik: An appellate court decision and abroad shaper with reaffirmed <unk> position as the exclusive licensor of the patents covering cast nine used in human medicines in the US Is also important to remember that only a small fraction of the IP. We licensed from the broad are involved in the ongoing U S PTO interference.

Erik: <unk>.

Erik: We expect a decision on the case in the second half of 2024.

Erik: We remain confident that the Bravo once again prevail.

Erick J. Lucera: Our IP portfolio of foundational U.S. and international patents covering Cas9 and Cas12 use in human medicines is a source of meaningful value, as we believe that globally there are more than 100 Cas9, Cas12a programs in development worldwide, with the majority of the programs being developed by 10 countries. We believe these potential fields represent a potential material source of non-dilutive capital. As evidenced by our deal in the fourth quarter of 2023 that extended our cash runway by two quarters. We look forward to future discussions.

Erik: Our IP portfolio, a foundational U S and international patents covering cast nine and cast well Houston human medicines are a source of meaningful value as we believe that globally. There are more than 100 cast nine Castro of day programs in development.

Erik: Worldwide with the majority of the programs being developed by 10 companies.

Erik: We believe these potential deals represent a potential material source of non dilutive capital as evidenced by our deal in the fourth quarter of 2023 and extended our cash runway by two quarters, we look forward to future discussions.

Erick J. Lucera: And now I'd like to refer you to our press release issued earlier today for a summary of our financial results for the first quarter of 2024. I'll take this opportunity to briefly review a few items for our Cash, Cast Equivalents, and Marketable Securities as of March 31, $377 million compared to $427 million as of December 31, 2021. We expect our existing cash, cash equivalents, and marketable securities, together with the near-term annual license fees and contingent upfront payment, payable under our license agreement with Vertex, to fund our operating expenses and capital expenditures into 2026.

Erik: And now I'd like to refer you to our press release issued earlier today for a summary of our financial results for the first quarter of 2024.

Erik: This opportunity to briefly review a few items for the quarter our.

Erik: Our cash cash equivalents and marketable securities as of March 31, three.

Erik: $377 million compared to $427 million as of December 31, 2023.

Erik: We expect our existing cash.

Erik: Cash equivalents and marketable securities together with the near term annual license fees and contingent upfront payment payable under our license agreement with vertex to fund our operating expenses and capital expenditures into 2026.

Erick J. Lucera: Revenue for the first quarter of 2024 was $1.1 million compared to $9.9 million for the same period in 2023. The decrease relates to the January 2023 one-time sale of the company's wholly owned oncology assets and related licenses. R&D expenses this quarter increased by $11 million to $49 million. In the first quarter of 2020,

Erik: Revenue for the first quarter of 2024 was $1 1 million compared to $9 9 million for the same period in 2023.

Erik: The decrease relates to the January 2023, one time sale of the company's wholly owned oncology assets and related licenses.

R&D expenses this quarter increased by $11 million to $49 million.

Erik: First quarter of 2023.

Erick J. Lucera: This increase relates to additional clinical and manufacturing costs that support the continued progression of the company's renaissance. The increase is also attributable to one-time payments related to sub-license and license obligations. Editas will continue to incur these types of payments as we and our collaboration partners advance certain licensed programs in gene editing. DNA expenses for the first quarter of 2024 were $19 million, which decreased from $23 million in the first quarter.

Erik: This increase relates to additional clinical and manufacturing costs that support the continued progression of the Companys Red cell program.

Erik: The increase is also attributable to onetime payments related to sublicense and license obligations.

Erik: And cost will continue to incur these types of payments as we and our collaboration partners advance certain license programs in the gene editing space.

Erik: G&A expenses for the first quarter of 'twenty, 'twenty $419 million, which decreased from $23 million in the first quarter of 'twenty three.

Erick J. Lucera: The decrease in expense is primarily attributable to one-time professional service expenses related to the 2023 strategic initiatives and business development activities, as well as reduced legal and patent expenses. With our BD and IP activities and a cash runway into 2026, Editas remains in a strong financial position. We have ample resources to continue the advancement of our Renaissance program, support the progression of our in vivo capabilities to develop our pipeline, and leverage our strong IP position for additional business development and licensing opportunities. With that, I will hand the call back to Gilmore.

Erik: The decrease in expense is primarily attributable to one time professional service expenses.

Erik: Related to the 2023 strategic initiatives and business development activities as well as reduced legal and patent costs.

Erik: With our BD and I see activity in a cash runway into 2026 and <unk> remains in a strong financial position we.

Erik: We have ample resources to continue the advancement of our Renaissance program support the progression of our in vivo capabilities to develop our pipeline and leverage our strong IP position for additional business development and licensing opportunities.

Erik: With that I'll hand, the call back to Joe Moore.

Gilmore ONeill: Thank you, Erick. We are proud of our progress in the first quarter of 2024, and we look forward to continuing to accelerate the momentum in 2024 as we continue to evolve from a development-stage technology platform company into a commercial-stage gene editing company. We look forward to continuing our transformation and sharing our progress with you. As a reminder of our 2024 strategic objectives, for Renicel, we will provide a clinical update from the Renicel Ruby Trial for Severe Sickle Cell Disease and the Edital Trial for Transfusion-Dependent Beta Thalassemia in mid-2024 and year-end 2024. We have now completed the adult cohort enrollment and have started enrolling patients in the adolescent cohort in RUBY. We will also continue enrollment in EDIFAL and dosing in both trials.

Joe Moore: Thank you Eric.

Joe Moore: We're proud of our progress in the first quarter 'twenty 'twenty four I, we look forward to continue to accelerate the momentum in 'twenty 'twenty four as we continue to evolve from a development stage technology platform company into a commercial stage gene editing company, we look forward to continuing our transformation and sharing our progress with you.

Joe Moore: As a reminder of our 2024 strategic objectives already so we will provide a clinical update from the registrar Ruby trials for severe sickle cell disease and the editorial trials for transfusion dependent beta thalassemia in mid 2024 and year end 2024.

Joe Moore: We have now completed the adult cohort enrollment and have started enrolling patients in the adolescent caution Ruby. We will also continue enrollment in NFL and dosing in both trials for.

Gilmore ONeill: For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication. And for BD, we will leverage our robust IP portfolio and business development capabilities to drive value and complement core gene editing technology capabilities. As we shared today, we are making significant progress on all three pillars of our strategy this quarter, including Renaissance, In Vivo, and Business Development, including intellectual property. We enter 2024 with great momentum, and I am proud of the Editas team's significant progress toward becoming a commercial stage company and on developing clinically differentiated transformational medicines for people living with serious, previously untreatable diseases. As always, we could not achieve our objectives without the support of our patients, caregivers, investigators, employees, corporate partners, and you. Thanks very much for your interest in Editas, and we're happy to answer questions. Thank you.

Joe Moore: For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication and for BD, we will leverage our robust IP portfolio and business development capabilities to drive value and complement core gene editing technology capabilities.

Joe Moore: As we share today, we are making significant progress on all three pillars of our strategy this quarter, including red cell in vivo and business development, including intellectual property we.

Joe Moore: We entered 2024 with great momentum and I am proud of the EDA testing significant progress towards becoming a commercial stage company and on developing clinically differentiated transformational medicines for people living with serious previously untreatable diseases.

Joe Moore: As always we could not achieve our objectives without support of our patients caregivers investigators employees corporate Parkers and U.

Speaker Change: Thanks, very much for your interest at a test and we're happy to answer questions. Thank you.

Operator: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the list. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the start key. Please limit your questions to one. One moment, please, while we poll for questions. Our first question comes from Samantha Semenkow from Citi. Please proceed.

Speaker Change: Thank you we will now be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad.

Speaker Change: Information tone will indicate your line is in the question queue.

Speaker Change: You May press Star two if you would like to remove your question from the queue.

Speaker Change: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Please limit your questions to one question.

Speaker Change: One moment, please while we poll for questions.

Unknown Executive: Thanks very much, Samantha. I'm going to ask Linda to address us. Thank you, Sam. Thank you for the question.

Speaker Change: Our first question comes from Samantha Seminole from Citi. Please proceed.

Samantha Seminole: Hi, good morning, and thanks very much for taking my question.

Samantha Seminole: Wondering about our in vivo pipeline and the proof of concept that you're expecting by end of this year and.

Samantha Seminole: What would be the bar for success that Youre looking for in this paradigm. Thank you.

Speaker Change: Thanks very much.

Speaker Change: I'm going to ask Linda to address them.

Linda C. Burkly: Thank you, Sam. Thank you for the question. We are looking for proof of concept for high efficiency delivery and editing for our target of interest in vivo in this preclinical POC that will give us confidence in our ability to target the target of interest. We are going to be sharing more information on this at a future date.

Linda C. Burkly: Sam. Thank you for the question we are looking for a proof of concept for high efficiency delivery and editing for our target of interest in vivo in this preclinical POC that will give us confidence in our ability to target.

Speaker Change: The target of interest are we.

Linda C. Burkly: We are going to be sharing more information on this set of future date. Thank you for the question.

Operator: Our next question comes from Joon Lee from Truist Securities. Please proceed.

Linda C. Burkly: Our next question comes from Joon Lee from <unk> Securities. Please proceed.

Joon So Lee: Hey, congrats on the progress and thanks for taking our question. An interesting update on your disclosure is the plan to identify large serine recombinases, which implies sort of a newer approach to many of your that many of the peers are also developing, you know, some call it gene writing, and some call it pasting. Does the size of the recombinase-mediated insertion allow for, you know, inserting a coding sequence for dystrophin, for example? And are you able to comment on whether DMD is out of the question regarding your in vivo aspirations? Thank you.

Joon So Lee: Hey, guys congrats on the progress and thanks for taking my question.

Joon So Lee: Interesting update on your disclosure is the plan to identify large ceiling combinations, which implies sort of a newer approach to many of you that many of the peers are also developing some college team, adding some college tasting.

Joon So Lee: The size of recombination mediated insertion allow for.

Joon So Lee: Inserting a coding sequence for dystrophin for example, and are you able to comment on whether <unk> is out of the question regarding Europe and Diebold aspiration. Thank you.

Unknown Executive: Thanks very much, June. I'm going to have Linda. Yes, thank you.

Speaker Change: Thanks, very much June I'm going to have Linda I'll take that.

Linda C. Burkly: Yes, thank you for commenting. We're excited about the LSR technology that we're disclosing here. We are identifying many different novel LSRs. We're not disclosing at the moment the size of the integrations that can be accommodated by these large serum recombinases, but we have quite a few novel LSRs that we've identified, and we're further characterizing them. Thank you for the question. Our next question comes from Mary Kate Davis from Bank of America.

Linda C. Burkly: Yes. Thank you for commenting we're excited about the L. S. R technology that we're disclosing.

Linda C. Burkly: Disclosing here, we are identifying many different novel L. S source, we're not disclosing at the moment the size of the.

Linda C. Burkly: Integrations that can be accommodated by these large jeremy combinations, but we have quite a few novel L. S. Ours that we've identified and we're further characterizing them. Thank you for the question.

Operator: Our next question comes from Mary Kate Davis from Bank of America. Please proceed.

Speaker Change: Our next question comes from Mary Kay Davies from Bank of America. Please proceed.

Speaker Change: Good morning, Thanks for taking my question I'm looking at the Winnie Tso program here. How are you guys looking at the mid year any sort of uptake compared to the year end update here as follow up time progresses, what should we look for from treated patients in terms of safety and efficacy moving forward. Thank you.

Unknown Executive: Thanks Mary-Kate, Baisong is going to take it. Yeah, thanks, Mary.

Speaker Change: So thanks, Mary Kate based song is going to take that one yeah. Thanks Mary.

Baisong Mei: Yeah, thanks, Mary. So in this midyear release, we expect to have at least 18 patient data for the RUBY study, and within the 18 patients, four of them will have 12 or longer 12 to 21 months of exposure, and the seven will have five months to 12 months exposure, and another seven with two to five months exposure. With that, we feel this data is very meaningful to see the direction not only of the increase in total hemoglobin normalization of total hemoglobin and increase in fetal hemoglobin but also the durability of the study and the impact on efficacy, for example, the fear of big vessel occlusion events.

Mary Kate Davis: In the midyear release, we expected to have at least 18 patient data for Ruby study and we didn't the 18 patients and for all of them will have 12 all.

Mary Kate Davis: Long ago, 12 to 21 months of exposure and the seven warehouse five months to 12 months exposure and none of those seven with two to five months of exposure with that we are we feel at least that is very meaningful to see the direction not only the increase of two of them are going to be normalization of tourism in Colombia.

Mary Kate Davis: The increase of feed them globally, but also the durability of this study and the impact from an efficacy perspective like for example of a free of vessels can see events.

Baisong Mei: For the edit cell study, we will have patients from at least seven of those patients with four to 12 months of exposure, which also will be very meaningful. That is compared to the December release. We have 11 Ruby patients and six edit cell patients. So that's substantial. More data will help us to understand the program much better. Thank you.

Mary Kate Davis: For the <unk> study, we will have patients.

Mary Kate Davis: At least the seven those patients.

Mary Kate Davis: Four to 12 months of exposure, which altria wherever you bet meaningful that is compared to the December release, we have 11, Ruby patients and six adding tail patient. So that's substantial more data that will help us to understand that much better. Thank you.

Mary Kate Davis: Yeah.

Mary Kate Davis: Okay.

Operator: Our next question comes from Jack Allen from Baird. Please proceed.

Mary Kate Davis: Our next question comes from Jack Allen from Baird. Please proceed.

Jack Kilgannon Allen: Congratulations to the team on the progress, and thanks for taking the questions. I'm going to stick with the RenySell program. I was hoping you could provide some color on dosing in the pivotal cohort. I know you've commented on the adult cohort being fully enrolled, but have all of those patients received therapy? And any other comments you can provide as it relates to the size of the cohort that you've agreed to with regulators would be very helpful. Thanks so much.

Jack Kilgannon Allen: Alright, congratulations to the team on the progress and thanks for taking the question.

Jack Kilgannon Allen: Im going to stick with the <unk> program I was hoping you could provide some color on.

Jack Kilgannon Allen: Dosing of the pivotal cohort I know you've commented on the adult cohort being fully enrolled but have all of those patients receive therapy and any other comments you can provide as it relates to the size of the cohort that you've agreed to with regulators would be very helpful. Thanks. So much.

Gilmore ONeill: Thanks very much, Jack. I'll answer the first part and then pass it to Baisong to talk about, you know, maybe give it a little more color on regulatory interactions. We have obviously completed the adult enrollment, which we're actually very excited about, not least because that is in the context of two approved therapies. It really is a very concrete reflection of the enthusiasm that Baisong has found and described, indeed, increasing enthusiasm about our program during his visits to sites and conversations with investigators, healthcare providers, and indeed with patient advocacy groups.

Speaker Change: Thanks, very much Jack I'll answer the first first and then pass it to based on feedback you know maybe give us some more color too.

Speaker Change: Two regulatory interactions.

Speaker Change: We have.

Speaker Change: Obviously completions, the adult enrollment, which we're actually very excited about.

Speaker Change: Not least because that is in the context of two approved therapies. So it really is a very concrete reflection of the enthusiasm.

Speaker Change: They song has found and describes indeed, increasing.

Speaker Change: <unk> about our program with his visits to sites on conversations with.

Speaker Change: Investigators.

Speaker Change: Health care providers, and indeed with a.

Speaker Change: Patient advocacy groups.

Gilmore ONeill: We have scheduled many of those patients already for dosing and will give you further updates on the progress of dosing at a later date. And with regard to the regulatory color, I think, Baisong, you might want to maybe just share this. Yes, for regulatory reasons, as we shared that we

Speaker Change: We have scheduled.

Speaker Change: Many of those patients already for dosing and we'll give you further updates on the progress of dosing.

Speaker Change: Later date.

Speaker Change: With regard to the regulatory color I think based on what you might want to maybe just share some more yes for regulatory as we shared that we have alignment with the FDA that there will be study is a phase two three study for POF body and we also have alignment on the sample size duration.

Baisong Mei: Yes, for regulatory purposes, as we shared, we have alignment with FDA that the Ruby study is a Phase 1, 2, 3 study for ELA filing. And we also have alignment on the sample size, duration, and study design of that. So we continue to have a collaboration with FDA on further discussions about this program.

Speaker Change: And study design of that so we continue to have a coloration with FDA on the further discussion about this program.

Speaker Change: Okay.

Speaker Change: Great. Thank you.

Operator: Our next question comes from Gina Wang from Barclays. Please proceed.

Speaker Change: Our next question comes from Gena Wang from Barclays. Please proceed.

Gina Wang: for in vivo indications such as glaucoma? And second, I know you mentioned this a little bit, but when we look at the current approved genomic therapy for sickle cell, we still have a 10% patient relapse with VOV events. What do you think are the key factors that we should look into for potential differential durability with hopefully a 100% control rate?

Huidong Wang: Thank you.

Huidong Wang: If I may a very quick two questions first shall we read in Chile S. TCT presentation for in vivo indications such as the glaucoma.

Huidong Wang: And second I know you mentioned also a little bit, but when we look at the current opinions of genomic therapy for sickle cell, we still have a 10% patient relapsed with V. O E events. What do you think is the key factors that we should look into for the potentially differentiated durability with hopefully 100% control.

Huidong Wang: Me.

Gilmore ONeill: Thanks very much, Gina. I'm going to ask Linda to handle the first part of your question about the ASGCT, and then Baisong can talk about durability and what we're seeing. Yeah, thank you very much, Gina.

Speaker Change: Thanks, very much gena I'm going to ask Linda to handle the first part of your question around.

Linda C. Burkly: Around the as GCT and then based on kind of talk about durability, what we're seeing today.

Linda C. Burkly: Yeah, thank you very much, Dina. Primary open angle glaucoma is obviously an area of very high unmet need, and while we conducted those studies because of that, we are not currently pursuing that indication, but we were able through those studies to really demonstrate extensive pre-clinical POC and showcase our in vivo capabilities with respect to three components. Our ability to deliver lipid nanoparticles in vivo with our gene editing cargo, our proven capability of our proprietary enzyme, AS-Cas12a, to edit in vivo, and our guide modifications to enhance gene editing potency. So these capabilities really position us well for delivering in vivo gene editing medicines, and we're really pleased with the ASCT disclosures. Thank you.

Linda C. Burkly: Yeah. Thank you very much Deane our primary open angle glaucoma is obviously an area of very high unmet need and while we conducted those studies because of that we are not currently pursuing that indication, but we were able through those studies to really demonstrate impressive preclinical POC.

Linda C. Burkly: And showcase our in vivo capabilities with respect to three components are our ability to deliver lipid nanoparticles in vivo with our teen editing cargo are proving capability of our proprietary enzyme and ask has told me to edit in vivo and our guide modifications to it.

Deane: Enhancing gene editing potency. So these capabilities really position us well for delivering in vivo gene editing medicines, and we're really pleased with the ASC CPE disclosures. Thank you.

Baisong Mei: Yeah, I can now take up the question about the VOE relapse for sickle cell patients. But first, I want to congratulate the entire field for the effort to treat sickle cell disease, including the recent approval of tumology. And so I think what we see is that with the continued effort of all of us, we will continue to improve and transform treatment for sickle cell disease patients.

Deane: Yeah.

Deane: Pick up on the question about the Bowie relaxed for sickle cell patients and at first I would like to say I want to congratulate the entire field of effort of treating sickle cell disease, including the recent approval of the two molecule.

Deane: And so I think what we see is that we continue the effort of all of US we will continue to improve and transform the treatment for sickle cell disease patient.

Baisong Mei: Within Renacel, and we are still continuing to collect the clinical data, as I mentioned, we expect that this is not only a competitive but differentiated molecule, and with the normalization of the total hemoglobin correction of anemia. So we're looking forward to seeing our own data on the VOE. As we have reported so far, we have seen all those patients, those with Renacel, are free of VOE events.

Deane: <unk> ran a sale and we are still continued to collect the clinical data as I mentioned that we expect that this is a different not only competitive but differentiated molecule.

Deane: The normalization of the total hemoglobin correction of anemia. So we're looking forward to see our own data on the V. O E. As we reported so far we have seen all of those patient dosing with rent a sale is free of Oh, Yeah, you bet.

Speaker Change: Thank you.

Operator: Our next question comes from:

Operator: Our next question comes from Mani Foroohar from Lerink Partners. Please proceed.

Manny O'hara: Our next question comes from Manny for O'hara from Leerink Partners. Please proceed.

Manny O'hara: Hi, Good morning. This is C J on our money.

C J: For taking my question.

C J: Ours is following the agreement with vertex last can you just how are you thinking about future IP monetization opportunities.

Mani Foroohar: Thanks very much. I'm going to ask Erick to address the mic. Yeah, thanks for the question. Obviously, as we said in the

Speaker Change: Thanks very much.

C J: I'm going to ask Eric to address that question.

Erick J. Lucera: Yeah, thanks for the question. Obviously, as we said in the transcript, we view the future potential royalty monetization and licensing activities as an integral and very important source of non-dilutive capital. As you know, these are foundational IP patents which are applied to just about everybody's projects in Cas9 and Cas12. And we expect to have conversations with those folks as soon as we can. Thank you. The next question comes from Brian Cheng from J.P. Morgan. Please proceed.

Eric: Yes. Thanks for the question, obviously as we said in the transcript we view the future potential.

Eric: Royalty monetization and licensing activities as an integral and very important source of non dilutive capital.

Eric: As you know these are foundational IP patents, which are applied to just about everybody's projects and cash noncash 12.

Eric: We expect to have conversations with those folks.

Eric: As soon as we can.

Eric: Okay.

Speaker Change: Thank you.

Speaker Change: Our next question comes from Brian Cheng from J P. Morgan. Please proceed.

Speaker Change: Okay.

Brian Cheng: Hey, guys. Thanks for taking our question this morning could.

Brian Cheng: Can you just remind us what's your latest thinking around the timing of holding discussion with regulators on sickle cell.

Brian Cheng: And you know just given the data that you're going to percents mid year.

Brian Cheng: Any updates and color on the timing of holding a productive conversation with regulators will keep appreciate it. Thank you.

Brian Cheng: Thanks very much, Brian. I'm going to ask Baisong to talk about that sort of, I think your two questions really, which are about what the data is in the middle of the year and how they integrate with our discussions with regulators. Yes. So Brian, as I mentioned, we

Speaker Change: Thanks, very much Brian I'm going to ask based songs to talk about that sort of.

Brian Cheng: Thank you two questions really which is about well if the data are in the middle of the year and how they integrate with our discussions with regulators.

Baisong Mei: Yes, Brian, as I mentioned, we are very pleased with the data we're going to release in the middle of the year, which is substantive and also gives us good direction as to how much we will get and to have, for example, a data set to have an equivalent to the CASTGB BLA filing, for example. So that's kind of one part of that.

Brian Cheng: Yes, so Brian we as I mentioned that we are very pleased with the data we released in middle of the year, and which is substantive and also give us good direction, how much work, we will get to.

Speaker Change: To have for example, a dataset to have equivalent to the cast GB a BLA filing for example, right. So that's kind of one part of that we're very happy to see the amount of data and the.

Baisong Mei: We're very happy to see the amount of data and the patient outcomes from this. And then the other thing is regulatory engagement. As I mentioned, we already have a line from this phase three study to support the BLA, and then we have continued engagement with the FDA. We have not disclosed all the details of the interaction yet. But as a reminder, we have the AMET designation, which allows us to have frequent interaction with the agency but also with a high level of interaction with the agency. And this, of course, will give us an opportunity for potential priority review and ruling submission. So we're very excited about the direction. We continue to have engagement and collaboration with FDA.

Speaker Change: The patient outcome from the data and then the other thing is about the regulatory engagement as I mentioned, we already have a line of this phase III study to support the P. O a and we have then we have a continued engagement with it we'd be we'd be with FDA, we have not disclosed all the details of the.

Speaker Change: Yeah, but as a reminder, we have a matter of fact, we've nation and which allow us to have frequent interaction with agency, but also with the high level of interaction with the agency and this of course.

Speaker Change: Give us opportunity people potential priority review and a rolling submission. So we're very excited with the direction will continue to have engagement and collaboration with FDA.

Speaker Change: Alright, thank you.

Operator: Our next question comes from Erick Schmidt from Cantor Fitzgerald. Please proceed.

Speaker Change: Our next question comes from Eric Schmidt from cancer with Cantor Fitzgerald. Please proceed.

Eric Thomas Schmidt: Thanks for the question and congratulations on the progress. Are you able to give the approximate number of patients who are enrolled in the RUBY trial with sickle cell disease? And then it sounds like you've been able to make pretty good progress in enrollment in that study, despite the availability of commercial cell therapies. I was just wondering, at centers that have both experimental and commercial cell therapy available, maybe Baisong could talk a little bit about what's driving the decision to use the Editas product over others. Thanks.

Eric Thomas Schmidt: Thanks for the question and congrats on the progress.

Eric Thomas Schmidt: Are you able to give the approximate number of patients who are enrolled in the Ruby Ah trial with sickle cell disease and then.

Eric Thomas Schmidt: It sounds like you've been able to make pretty good progress in enrollment in that study. Despite the availability of commercial cell therapies. I was just wondering it at centers that have both experimental and commercial cell therapy available maybe based on could talk a little bit about what's driving the decision to use the other tests.

Eric Thomas Schmidt: Product over others. Thanks.

Gilmore ONeill: Thanks very much, Erick. Baisong will kind of update you on where our clinicaltrials.gov site sets as a target for the cohort in our trial, and then obviously build on his perceptions of why we're doing so well with enrollment, even in the context of commercial therapies being available. Yeah, thanks, Eric. We are very pleased.

Speaker Change: Thanks, very much Eric and based on what kind of update you on where Tenneco tried Scott trials Dot Gov set as a target for the cohort in our trial and then obviously build on his perceptions of why we're doing so well with enrollment even in the context of <unk>.

Speaker Change: Commercial therapies being available yeah.

Baisong Mei: Thanks, Eric. We are very pleased with the momentum of the enrollment in both the adult cohort and the adolescent cohort. And for the adult cohort, we shared that in February we enrolled 40 patients; now we have enrolled slightly more than 40 patients, and therefore we have closed the adult cohort enrollment. And for the adolescent cohort, we started like at the beginning of this year; we already enrolled multiple patients and have multiple patient experiences.

Speaker Change: Thanks, Eric.

Speaker Change: Very pleased with the momentum bother enrollment in both of the adult cohort and the adolescent cohort and for the adult cohort do we.

Speaker Change: He shared that in February we dose we enrolled 40 patients now we're you know slightly more than 40 patients and therefore, we closely.

Speaker Change: The adult cohort your employment.

Speaker Change: And for adolescent cohort, we started like beginning of this year, we already enrolled multiple patients and have multiple patient screenings were very pleased with that.

Baisong Mei: We're very pleased with that. Then, as I mentioned, I'm on the road all the time to visit our investigators and the study sites, and they really feel that One is actually their belief in the RNA cell based on the MOA, based on the data we have continued to share on that. I also give credit to the entire field in working on that with the two gene therapy approved for sickle cell.

Speaker Change: As I mentioned I'm on the road all the time and to visit our investigators and the study size and then they really feel of that.

Speaker Change: <unk>.

Speaker Change: When he is actually they are believe the Reno sale based on the MAA based on the data. We have continued to Sherri on that I'll also give credit to the entire feud been working on that with a to a gene therapy approved for sickle cell is also to increase the interest in the direction of the.

Baisong Mei: It's also increased the interest in the direction of gene therapy for sickle cell disease. So that's how we see, you know, over the last year or so, we see really great momentum for RNA cell enrollment, especially after we release our data. Our next question comes from Jay Olson from Oppenheimer & Company. Please proceed.

Speaker Change: So if you for sickle cell disease. So that's how we see you know over the last year or so we see really great momentum that for redness. They all are women, especially after we released our data.

Speaker Change: Our next question comes from Jay Olson from Oppenheimer and company. Please proceed.

Jay Olson: Oh, Hey, congrats on all the progress and thank you for taking the question.

Jay Olson: Can you talk about the timing of her collaboration extension with pistol was there some new data that that triggered the new collaboration and is there any color on what new data personal me have seen and then.

Jay Olson: Separately can you talk about any work that you've done on developing a milder conditioning agent. Thank you.

Gilmore ONeill: Well, what I want to do is ask Erick to address the question about the BMS. What I do want to say, I can address the conditioning, which is that just at our last earnings call, we talked that we were going to continue monitoring the space. We have significant contacts in the academic and non-academic worlds around the field, but we have actually really deployed our efforts and our resources internally to focus on our in vivo pipeline, including developing hematopoietic stem cells.

Speaker Change: Well, what I'm going to do is ask Eric to address the question about the BMS, what I do want to say I can address the conditioning, which is that just at our last earnings.

Speaker Change: Earnings we talked that.

Speaker Change: We are going.

Speaker Change: <unk> going to continue monitoring this space, we have a few different context to the academic and non academic world is around the field.

Speaker Change: But we have actually really deployed our efforts and our resources internally.

Eric Thomas Schmidt: Focusing on our in vivo pipeline, including developing a hematopoietic stem cells. The rationale for that being that we see that where a minor conditioning therapy is actually approved it would be used universally adopted universally in transplant centers across multiple indications.

Gilmore ONeill: The rationale for that being that where a minor conditioning therapy is actually approved, it would be used universally and adopted universally in transplant centers across multiple indications, including stem cell transplantation and hemoglobinopathies. And with that, I'm just going to pass to Erick just to talk about the BMS. Yeah, thanks for the question.

Eric Thomas Schmidt: <unk>.

Eric Thomas Schmidt: Cell transplantation with Haemoglobinopathy.

Speaker Change: And with that.

Speaker Change: I'm just going to pass to Eric just to talk about the BMS deal.

Erick J. Lucera: Yeah, thanks for the question. With respect to the timing of the renegotiation or the extension, obviously, we put out a press release in the very recent past, a week or two ago, something like that. And that would give you an update on the timing. I'd say with respect to the data, Bristol Myers, as you know, recently completed a portfolio review, and we're pleased to see that all of the projects that we're working on are continuing to move forward.

Eric: Yeah. Thanks for the question with respect to the timing of the renegotiation or the extension obviously, we put out a press release in the very recent past a week or two ago something like that.

Eric Thomas Schmidt: It would give you an update on the timing I would say with respect to the data.

Erick J. Lucera: Bristol Myers.

Eric Thomas Schmidt: <unk> recently completed a portfolio review and we were pleased to see that all of the projects that we're working on them are continuing to move forward I think if we.

Erick J. Lucera: I think if we left discussion of specific programs to them to talk about anything that they're seeing in those programs, I would highlight the fact that at their most recent R&D day last September, which I think was the first one they'd done in several years, they did mention six products on their pipeline chart that were using our technology. So I would refer you to their R&D disclosures from that meeting to get an update on the work that they're doing with us.

Erick J. Lucera: We would leave discussion of specific programs to them to talk about anything that they're seeing in those programs I would highlight the fact that at their most recent R&D day last September which I think was the first one they've done in several years. They did mentioned six products on their pipeline chart, which we're using our technology. So I would refer you to there.

Eric Thomas Schmidt: R&D disclosures from that meeting to get an update on the work that they're doing with us, but we are very excited about working with them. This has been a partnership that has survived several mergers and.

Erick J. Lucera: We are very excited about working with them. This has been a partnership that has survived several mergers and several portfolio reviews, and we're very excited about what we're seeing. Our next question comes from Phil Nadeau from TD Cowen. Please proceed.

Philip M. Nadeau: Several portfolio reviews, so well.

Philip M. Nadeau: So we're very excited about what we're saying.

Philip M. Nadeau: Thank you.

Erick J. Lucera: Our next question comes from Phil Nadeau from TD Cowen. Please proceed.

Erick J. Lucera: Hi, This is Alex on for Phil. Thanks for taking my question. So given the association between total hemoglobin hemoglobin levels and end organ function do you plan to utilize any quantitative endpoints.

Philip M. Nadeau: Basically assessing and organ function and the Ruby trial and if so what.

Philip M. Nadeau: What might those look like and when could we maybe expect initial data. Thanks.

Philip M. Nadeau: Thanks very much, Alex. I'm going to ask Baisong to address... Yeah, thanks, Alex.

Philip M. Nadeau: Thanks, very much Alex.

Philip M. Nadeau: I'm going to ask based on to address that question, yes. Thanks, Alex.

Baisong Mei: Yeah, thanks, Alex. We certainly have measurements for end organ function. We look into several major organ systems to monitor function improvement. For example, we monitor liver function, not only with these different lab values, we look into pulmonary function to check the respiratory system, and we also have cardio-echo and other measures to measure the cardiovascular system, and that too. So we are looking forward to seeing more data on that to give us more understanding of how end organ function may behave after treatment.

Baisong Mei: We certainly have a measurement for the end organ function.

Baisong Mei: We look into that.

Baisong Mei: Several major organ system to monitor the function improvement for example, we monitor the liver function not only when we with visa.

Baisong Mei: Different to allow values, we're looking to pulmonary function to check to check the the risk rating system and we also have a cardio alcohol and other measures you're talking to measure their cardiovascular system on that too. So we are looking forward to see more data.

Baisong Mei: On that and give us more understanding and organ function.

Baisong Mei: Function may be may behave after the treatment. Just a reminder, that we also of course looking to that not only sickle cell, but also other area. In these in terms of the anemia, how would that impact the function and how that correction of anemia may be able to <unk>.

Baisong Mei: Just a reminder that we also, of course, look into not only sickle cell but also other areas in terms of anemia, how that impacts function, and how that correction of anemia may be able to improve that function after treatment. And in sickle cell specifically, over the last couple of years, you have already seen more publications about end organ function given after the allogenic transplant for treating sickle cell patients. We are very excited about that.

Baisong Mei: Prove that a function after the after treatment and sequence there specifically over the last couple of years, you already see more complications above and organ function given after the allogeneic transplant to treat sickle cell patients. We are very excited on that.

Baisong Mei: But just to be very honest to ourselves, right, this field is still fairly new, and we see some really good publications and direction in this, and we're looking forward to our own study as well as the literature on this.

Baisong Mei: But just to be honest to ourself right. These fiori is still fairly new and do we see some really good publication and direction in this and we're looking forward to our own study as well as the literature on this field.

Speaker Change: Great. Thank you.

Operator: Our next question comes from Yanan Zhu from Wells Fargo. Please proceed.

Speaker Change: Our next question comes from Matt Yanan, Zhu from Wells Fargo. Please proceed.

Yanan Zhu: Thanks for taking our questions. So first, on the differentiation of total hemoglobin normalization, I was wondering whether you've had feedback from sickle cell treaters on that differentiation and whether there's any hesitancy or pushback that perhaps the current level of hemoglobin achieved by the marketed product is sufficient. You know, how much of that kind of thinking is out there? And on the in vivo side, I was wondering whether you are focused on first-in-class targets or perhaps not first-in-class targets but hoping to have a differentiation in specificity and transaction efficiency, etc.

Yanan Zhu: Okay. Thank for taking our questions. So first on.

Yanan Zhu: The differentiation of total hemoglobin normalization.

Yanan Zhu: Wondering have you had feedback from.

Yanan Zhu: Sickle cell treaters.

Yanan Zhu: On that differentiation and weather.

Yanan Zhu: Any hesitancy.

Yanan Zhu: Hesitancy or pushback that perhaps the current.

Yanan Zhu: Neville hemoglobin achieved by the marketed product is sufficient.

Yanan Zhu: You know what.

Yanan Zhu: How much of that kind of.

Yanan Zhu: Thinking it is out there and on the in vivo side. I was wondering are you focused on first in class targets or perhaps.

Yanan Zhu: Not the first in class targets, but hoping to have a differentiation on specificity and transfection efficiency et cetera. Thanks.

Gilmore ONeill: Thanks very much, Yanan. So I'm going to ask Baisong to talk about the differentiation of total hemoglobin, and then I'll ask Linda just to talk about our approach to first-in-class or clear differentiation and where we would see that with our approach to functional upregulation.

Speaker Change: Okay. Thanks, very much so I'm going to ask based song to talk about the differentiation of total hemoglobin and then I'll ask Linda just to talk about our approach to first in class or clear differentiation and for that we would see that with our approach to functional up regulation.

Baisong Mei: Thanks, Thanks, Alan I mean, certainly we talk about the investigators as well as the <unk> and sickle cell treaters.

Gilmore ONeill: Our differentiation and how we may be able to see and what is the position of this molecule and when we're talking to are loosely hematologists in sickle cell treaters, they see our data and when when the Hematologist mentioned that it has no brand names, it's better if you have a 16 gram.

Baisong Mei: That's a liter versus 10 gram per deciliter of total hemoglobin.

Gilmore ONeill: And.

Baisong Mei: And then they also, I mentioned the enthusiasm of our study, and there are quite a few knowledgeable hematologists. They see the difference among several molecules and when investigators said that they were waiting for our trial and did not participate in other trials. So those are anecdotal examples of that. As I mentioned earlier, we certainly want to look forward to seeing the clinical data.

Gilmore ONeill: And then they also I mentioned that the enthusiasm.

Baisong Mei: Our study and they are probably a few knowledgeable hematologists they see the difference among several molecules and when your investigators said that he was waiting for our trial and did not participate either so those are the anecdotal examples on that as I mentioned earlier, we were supposed to be one of the book.

Baisong Mei: What would you see the clinical data.

Linda C. Burkly: It's also worth highlighting, of course, that the FDA has recognized that a one gram per deciliter difference is important. Talking about that, this is also, when we communicate with FDA, this is also a point we have been discussing with FDA. So thanks very much, Baisong, Linda, just regarding in vivo and where our focus is. Yes, in vivo; our in vivo approach is aimed at functional upregulation of gene expression in genetically determined diseases.

Baisong Mei: It's also worth highlighting of course that the FDA has recognized that a one gram per deciliter difference.

Linda C. Burkly: Is meaningful or started.

Linda C. Burkly: Likely to predict a clinically meaningful benefit in that they use that threshold to be of any senator approvals to authorized in the past talking about that at least is also when we communicated with F. D. A this is also appointed we have been in discussion with FDA to.

Speaker Change: So thanks very much episodic Linda.

Linda C. Burkly: Already in vivo and where our focus is yes in vivo or in vivo approaches aimed at functional up regulation of gene expression genetically determined diseases and this strategy positions us very well to be differentiated from others in terms of our targets and our target editing strategies and what.

Linda C. Burkly: And this strategy positions us very well to be differentiated from others in terms of our targets and our target editing strategies. And what this means is that we can go after targets that others can't go after. And so from an indications perspective, we can go after indications that perhaps others can't go after, and so we could have a first in class strategy. Also, within a given indication, we could devise a targeting strategy that would be best in class, if you will. So we can have first in class strategies as well as best in class opportunities. I hope that answers your question.

Linda C. Burkly: This means is that we can go after targets that others can't go after and so from an indication perspective, we can go after indications that perhaps others can't go after and so we could have our first in class strategy also within a given indication we could devise a targeting strat.

Speaker Change: G that would be a best.

Linda C. Burkly: Best in class. If you will so we can have first in class strategies as well as best in class opportunities.

Linda C. Burkly: I hope that answers your question.

Unknown Attendee: Yes, thank you, very helpful. Thanks for all the answers.

Speaker Change: Yes. Thank you very helpful. Thanks for all the answers.

Operator: Our next question comes from Luca Issi from RBC Capital. Please proceed.

Unknown Attendee: Our next question comes from Luca <unk> from RBC capital. Please proceed.

Luca Issi: Well, great. Thanks so much for taking my question and congrats on all the progress. Maybe just a quick one on Renicelle and the filing strategy. What's the vision here for the BLA? Are you planning to file adults and adolescents concurrently or sequentially?

Luca Issi: Oh, great. Thanks, so much for taking my question.

Luca Issi: And on the progress or maybe just a quick one on rainy shall into filing strategy. What's the vision here for the BLA are you planning to file adults and adolescence concurrently or sequentially any color there much appreciate it and then maybe quickly on the middle East can you just talk about the opportunity for CECO.

Gilmore ONeill: Any caller there? Much appreciated. And then maybe quickly on the Middle East, can you just talk about the opportunity for sickle cell disease in the Middle East? Virtex seems really, really excited about that market. So wondering what your strategy there is to potentially tap that market? Are you still focused on the partnership? Can you potentially access that via distributor? Again, any thoughts there, much appreciated. Thanks so much.

Gilmore ONeill: <unk> disease in the Middle East vertex seems really really excited about that market. So wondering what's your strategy there to potentially tap that market are you still focus on partnership could you potentially access that via a distributor again any thoughts there much appreciate it. Thanks so much.

Baisong Mei: I'll ask Baisong to talk about our regulatory strategy as far as we have shared it, and then Caren can talk about just how we're looking at and thinking about the Middle East, and frankly, in the context of the rest of the world.

Speaker Change: Thanks, very much Luca so and that's based on just to talk about our regulatory strategy as far as we have shared and then Karen can talk about just how we're looking at when thinking about the middle East and frankly in the context of the rest of world.

Baisong Mei: Yeah, yeah, thanks, Luca. We are very pleased with the interaction with the agency and continued interaction with the agency about Renacel and for the Ruby study as a phase 3 study to support the BLA and all aspects of the phase 3 study; we have alignment on that. And we have continued conversation with FDA on this route. We have not shared the specifics about the date of the BLA or the indication for the adult alone or adolescent, but as we shared, we are very pleased with the enrollment for both the adult cohort as well as the adolescent cohort. So that gives us a great position for this model. Good

Baisong Mei: Yes, yes, thanks Luca.

Baisong Mei: We are very pleased with the interaction with agency and continued interaction with the agency about the advent of cell and therefore, there would be study is a phase III study to support the BLA and all the all the front of the phase III study, we have alignment on that and we have continued to a conversation with FDA on.

Baisong Mei: This route we have not shared the specifics about the date of the P O E or the indication of a doubt.

Baisong Mei: Oh at the lesson, but as we shared we are very pleased with the enrollment for both at the old cohort as well as adolescent cohort so that give us in a great.

Baisong Mei: Great position for this molecule.

Caren Deardorf: Great, Luca, thanks for the question about the Middle East and certainly just the populations outside the United States. And there's absolutely a number of geographies where there is a significant population of sickle cell patients and really high unmet need for beta thalassemia as well.

Baisong Mei: Great Luca Thanks for the question about Middle East and certainly just the populations outside the United States and there is absolutely a number of geographies, where there is a significant population of sickle cell patients in really high unmet need a beta thalassemia as well.

Caren Deardorf: What I'd say is our continued drive to execute in the U.S. and to move Renaissance forward with differentiation just continues to support the opportunity for us to partner at the appropriate time. And that's certainly something that we've said we are open to, and we'll certainly provide more color in the future as appropriate. Thanks so much. Our next question comes from Steve Seedhouse from Rainbow.

Caren Deardorf: I'd say is our continued drive to execute in the U S into new friend itself forward with differentiation just continues to support the opportunity for us to partner at the appropriate time, and that's certainly something that we've said, we Eric and we are open to us and we'll certainly provide more color and if he tries to.

Caren Deardorf: Yet.

Steven James Seedhouse: Thanks, so much.

Caren Deardorf: Yeah.

Operator: Our next question comes from Steve Seedhouse from Raymond James. Please proceed.

Steven James Seedhouse: Our next question comes from Steve seat House from Raymond James. Please proceed.

Operator: Alright. Thank you. This is Nick on for Steve, We actually had a longer term question.

Operator: To what extent can you leverage the infrastructure that for Texas already building out for <unk>, given you and we will well edit 301 be able to plug into the existing authorized treatment centers once launched.

Steven James Seedhouse: Thanks very much, Nick. I'm going to ask Caren to address that. Yeah, thank you, Nick, for the question.

Steven James Seedhouse: Thanks very much.

Steven James Seedhouse: Thanks, very much Nick I'm going to ask Karen to address that yeah. Thanks. Thank you Nick for the question first we can say I would say that I'm really pleased to see some of the initial progress for the other therapies and being able to get patients started and we always anticipated that it would be a good thing many centers starting to.

Caren Deardorf: Yeah, thank you, Nick, for the question. You know, first, we'd say I'm really pleased to see some of the initial progress for the other therapies and being able to get patients started. We always anticipated that it would be a dipping, many centers starting to dip their toes as they build the infrastructure and gain confidence. But this is a field that will benefit from the increase in education with patients, which Baesong mentioned also helps with our enrollment and just building the infrastructure. But we are engaged on the KOL, patient advocacy, as well as on the payer front to ensure that we're prepared. So, thanks for the question.

Caren Deardorf: Dip their toe on as they build the infrastructure and they gain the confidence so to answer your question absolutely. We've always said that in this kind of market and the complexity of the ex vivo being a fast follower is absolutely an advantage. We we also on our own have a really strong base of over.

Caren Deardorf: 20 clinical sites in the Alaska, very strong enrollment and relationships that we're leveraging those relationships in the guidance there, giving us will be really pivotal for us as well.

Caren Deardorf: But this is a field that will benefit from the increase in education with patients, which based on mentioned also helps with our enrollment.

Caren Deardorf: And just building infrastructure, but we are engaged on the kols the patient advocacy as well as on the payer front to ensure that we're prepared so thanks for the question.

Speaker Change: Thank you.

Operator: Our next question comes from Jack Allen from Baird. Please proceed.

Caren Deardorf: Our next question comes from Jack Allen from Baird. Please proceed.

Jack Kilgannon Allen: Great, thanks so much for taking the quick follow-up here. I just wanted to touch on Renacel one more time and ask when we might hear a little bit more about the differentiation as it relates to the treatment process, have you provided any color on the number of apheresis cycles and how the editing efficiency of the Cas12a enzyme may allow you to be more efficient in manufacturing the process?

Jack Kilgannon Allen: Great. Thanks, so much for taking a quick follow up here I just wanted to flesh out a Renaissance one more time and ask when we might hear a little bit more about the differentiation as it relates to the treatment process have you provided any color on the number if reset cycles in our editing efficiency of the Casco Bay and I may allow you to be more efficient.

Jack Kilgannon Allen: Manufacturing the process.

Gilmore ONeill: Thanks very much, Jack. So I'm going to ask Baisong. Yeah, thank you.

Speaker Change: Thanks, very much Jack so I'm going to ask based songs.

Baisong Mei: Yeah, thank you. We have not shared specifics about the number of cycles on the freezes. What I mentioned before was, since I joined, we actually work together with our internal as well as an external freezes expert to improve the freezes cycle, and also provide assistance to study size for the freezes cycle, which is significant because it's a reduced patient burden. It's a smooth manufacturing process.

Gilmore ONeill: Yeah.

Baisong Mei: Thank you all we are we have not share specifics about the number of cycling the freezers when I mention before ways.

Baisong Mei: Since I joined and we actually work together with our internal as well as a free six extra external apheresis expert who actually have a protocol amendment to two two.

Baisong Mei: Improve that <unk> cycle and also provide assistance at this study size too for the free sheet cycle, which is significant because it reduce the patient burden is a smooth manufacturing process. We're very pleased to see the progress in that front.

Baisong Mei: We're very pleased to see the progress in that front, and just to add on that, we are hoping this clinical experience will be very helpful for our commercial end-do. Our next question comes from Mani Foroohar from Learink Partners.

Speaker Change: And just to add on that we are hoping this clinical experience will be very much how far off are commercial and Dubai.

Baisong Mei: Yeah.

Operator: Our next question comes from Mani Foroohar from V-Wink Partners.

Mani Foroohar: Our next question comes from Manny for O'hara from Leerink Partners. Please proceed.

Mani Foroohar: Hi, Thank you for a 10 year final question kind of similar to the last question you previously talked about optimizing the vein to vein process.

Mani Foroohar: Would you be able to walk us through how when cell could provide advantages from.

Mani Foroohar: Either both operational and logistic perspective, thank you.

Mani Foroohar: So, Baisong, I'm going to ask Baisong to address that. Yeah, yeah, happy to.

Mani Foroohar: So based on that I'm going to ask I'll ask based on to address that yeah, yeah habits habit to we all over these process really working together.

Baisong Mei: We are, throughout this process, really working together with the study sites to optimize this process, and that's coming from multiple factors. One of the factors just mentioned is viral freezes. The other factor is logistics, and we provide support for that. The third factor is actually patient condition. As we know, we are treating this severe sickle cell disease. And before the random cell treatment, they can have multiple BOEs per year, and that also can impact ventilator time. Manny, this is Karen. I would just add that again, in the

Karen: Two we the study sites to optimize these process and that coming from multiple factories all over the factors just mentioned, it's about a free says the other factor in there.

Karen: The logistics and we provide support on that the Suezmax is actually patient condition. As we we we know that we are treating severe sickle cell disease and before that ran into a treatment that can have multiple boe per year and that's also impacted the vendor bad time.

Caren Deardorf: Mani, this is Caren. I would just add that, again, in the SAS follower position, one of the things that it gives us the opportunity to do is to really understand, as the first two therapies are commercialized, what's working, what's not working, what they need to see differently, and really make sure that Editas sets itself up as the partner of choice. And so we're working very hard on that, and we'll certainly talk about that at a later time.

Baisong Mei: Manny This is Karen I would just add that again in the fast follower position one of the things that it gives us the opportunity to do is to really understand as the first two therapies are commercialized what's working what's.

Caren Deardorf: What's not working what they need to see differently and really making sure that at the top sets ourselves up as the partner of choice and so we're working very hard on that and we'll certainly talk about that at a later time.

Speaker Change: Great. Thanks, so much with any of your questions.

Caren Deardorf: Yeah.

Operator: Ladies and gentlemen, this concludes today's call. Thank you once again for your participation. You may now disconnect.

Speaker Change: Ladies and gentlemen, this concludes today's call. Thank you once again for your participation you may now disconnect.

Operator: Yeah.

Operator: Yeah.

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Operator: Okay.

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Operator: Sure.

Operator: Okay.

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