Q4 2023 Editas Medicine Inc Earnings Call
Operator: Good morning, and welcome to Editas Medicine's fourth quarter and full year 2023 conference call. All participants are now in a listen-only mode.
Good morning, and welcome to edit past medicines fourth quarter and full year 2023 conference call. All participants are now in a listen only mode there'll 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.
Operator: 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 Christy Barnett, Corporate Communications and Investor Relations, at. Thank you, Maria.
Kristy Barnett: Corporate communications and Investor Relations at a tough medicine.
Kristy Barnett: Thank you Maria.
Christy Barnett: Good morning, everyone, and welcome to our fourth quarter and full year 2023 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.
Kristy Barnett: Good morning, everyone and welcome to our fourth quarter and full year 2023 conference call.
Kristy Barnett: Earlier. This morning, we issued a press release, providing our financial results and recent corporate updates.
Speaker Change: A replay of today's call will be available in the investors section of our website approximately two hours after its completion.
Christy 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 at the SEC, as updated by our publicant filing, in addition.
Speaker Change: After our prepared remarks, we will open the call for Q&A.
Speaker Change: 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 1990 thought.
Speaker Change: Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors.
Speaker Change: Creating those discussed in the risk factor section of our most recent annual report on Form 10-K, which is on file with the SEC as updated by our subsequent filings.
Speaker Change: C inhibition.
Christy Barnett: Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date, except as required by law. We specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. Now, I will turn the call over to our CEO, Gilmore O'Neill. Thanks, Christy, and good morning, everyone.
Speaker Change: Any forward looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date.
Speaker Change: As required by law, we specifically disclaim any obligation to update or revise any forward looking statements, even if our views change.
Speaker Change: Now I will turn the call over to our CEO Gilmore O'neill.
Gilmore O'neill: Thanks, Christina and good morning, everyone.
Gilmore O'neill: Thank you for joining us today on Editas' fourth quarter and full year 2023 earnings call. I am joined today by four other members of the Editas executive team. Our Chief Medical Officer, Baesong Mai, our Chief Financial Officer, Eric Lucera, our Chief Scientific Officer, Linda Barclay, and our Chief Commercial and Strategy Officer Karen Deardorff.
Gilmore O'neill: Thank you for joining us today on any asset fourth quarter and full year of 2023 earnings call.
Gilmore O'neill: I'm joined today by far are the members of the executive team.
Gilmore O'neill: Chief Medical Officer based on my our Chief Financial Officer, Eric The Sierra are signed Chief Scientific Officer, Linda Parker, and our Chief commercial and strategy Officer, Kevin Deardorff.
Gilmore O'neill: We are pleased with Editas' momentum and progress in the fourth quarter and all of 2023. In early 2023, we shared our vision and the three pillars of our strategy to position Editas as a leader in in vivo programs for gene editing at hemoglobin I. The first of these tenors, to drive Renicel, formerly known as Edit 301, toward BLA and commercialization.
Gilmore O'neill: We are pleased with Eddie passes momentum and progress in the fourth quarter and all of 2023.
Gilmore O'neill: In early 2023, we shared our vision and the three pillars of our strategy to position <unk> as a leader in in vivo programs with gene editing of hemoglobin.
Gilmore O'neill: The first of these pillars to drive rent yourself, formerly known as editorial work toward BLA and commercialization.
Gilmore O'neill: The second, to strengthen, reorganize, and focus our discovery organization to build an in vivo editing pipeline. And the third, to increase business development activities with a particular focus on monetizing our very strong IP. So how do we do that? Well, we achieved a lot. First of all,
Gilmore O'neill: Second to strengthen reorganized and focused our discovery organization should there's an in vivo editing pipeline in the third to increased business development activities with a particular focus on monetizing our very strong IP.
Speaker Change: So how did we do last year, while we achieved them up.
Speaker Change: First.
Gilmore O'neill: We accelerated the clinical development of Renicel, exceeding our enrollment goal of 20 patients and sharing clinical updates from our Ruby and Editas studies in June and December of 2023. And those accumulating data have strengthened our belief that renicel is a competitive potential medicine with a differentiated profile characterized by correction of anemia and normal physiologic ranges of hemoglobin.
Speaker Change: The acceleration of the clinical development of NFL exceeding our enrollment goal of 20 patient been sharing clinical updates from our Ruby and Eddie failed studies in June and in December of 2023.
Speaker Change: It was accumulation data has strengthened our belief that Renaissance is a competitive potential medicine with a differentiated profile characterized by correction of anemia and normal physiologic ranges of hemoglobin.
Speaker Change: Second we strengthened our in vivo discovery capabilities and organization and.
Speaker Change: Hired a new Chief Scientific officer, Linda Barclays will be three decades of experience in successfully inventing developing and moving new human medicine for it.
Gilmore O'neill: We strengthened our in vivo discovery capabilities and organization and hired a new chief scientific officer, Linda Barker, who brings three decades of experience in successfully inventing, developing, and moving new human medicine forward. And third, we increased our business development activities and monetized our IP, leveraging our robust IP portfolio. A critical example was our granting Vertex a non-exclusive license for our Cas9 IP in a focused way to enable the exercise. Finally, we strengthened our senior leadership team with people who have a proven track record in bringing new medicines through development to approval and commercialization. So how are we performing against these strategies and these objectives? Well, let's start with Ronny's talk first.
Speaker Change: Third we increased our business about your activities and monetize their IP leveraging a robust IP portfolio.
Speaker Change: Example, without granting a vertex a non exclusive license for our cost nine IP in a focused way to enable the exercise lunch.
Speaker Change: Finally, we strengthened our senior leadership team with people, who have a proven track record in bringing new medicines through development to approval and commercialization.
Speaker Change: So how we executed against these strategies and these objectives well that struck with one first.
Speaker Change: First.
On enrollment we have now enrolled 40 sickle cell nine beta thalassemia patients Ruby and NFL studies, respectively, and enrollment continues at a good pace.
Speaker Change: Second on dosing, we have dosed 18 will be patients with seven nights outpatient I mean, most of the patients scheduled for dosing in the coming months.
Speaker Change: Patient screening on demand in both studies continued to remain robust.
Speaker Change: First on clinical data, we remain on track to present extensive clinical data stash of sickle cell patients with considerable clinical follow up in the Ruby study in the middle of 2024 with a further update by year end 2024.
Speaker Change: On the regulatory front, we have engaged with the FDA regarding the Ruby sickle cell trial.
Speaker Change: F T. Eight weeks that really is a single phase 123 study has aligned with us on the study design.
Gilmore O'neill: On enrollment, we have now enrolled 40 clickle cell and nine beta thalassemia patients in our Ruby and Edith Health studies, respectively, and enrollment continues at a good pace. Second, on dosing, we have dosed 18 RUBY patients and 7 EDSAL patients, and we have multiple patients scheduled for dosing in the coming months. Patient screening and demand in both studies continue to remain robust.
Speaker Change: Our discussions with the FDA. It will continue as Ruby at Eddy power progress and will be enhanced by our math designation for severe sickle cell disease.
Speaker Change: Based on with share further details regarding the developing that Randy said in his remarks as well as recap the Ruby and any sort of takeaways that clinical data that we provided in December and share more information on the adolescent cohort.
Speaker Change: Now, let's turn to in vivo and our pipeline development, where we strengthened our illegal discovery capabilities at 2023, and she can be discovery work on in vivo therapeutic targets in hematopoietic stem cells and other tissues.
Speaker Change: We announced earlier this year, we aim to establish in vivo preclinical proof of concept for an undisclosed indication this year Linda and her team are.
Speaker Change: Leveraging key capabilities that we have in house actually look forward to sharing more at a future date.
Speaker Change: Regarding our Haemoglobinopathy focus after a thorough evaluation of the development landscape, we have decided not to pursue in terms of Elephant reminder, conditioning regime.
Gilmore O'neill: Third, on clinical data, we remain on track to present a standard clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY study in the middle of 2024, with a further update by year-end 2020. On the regulatory front, we have engaged with the FDA regarding the RUBY sickle cell trial. The FDA agrees that RUBY is a single phase 1, 2, 3 study and has aligned with us on the study.
Speaker Change: We believe Standalone module conditioning regimens would be widely available once FDA approved and therefore, we have determined that research tens of thousands of regulatory investment they seem to go up enough of these can be better deployed for our continued developing both in vivo HSC.
Speaker Change: Turning to business development in.
Speaker Change: In the fourth quarter, we announced a license agreement with vertex Pharmaceuticals edits has provided protects a nonexclusive license for EDA test medicines cats, nine gene editing technology for ex vivo gene editing medicines targeting the PC eliminate Jean.
Speaker Change: It sounds to me that they see.
Speaker Change: The interesting part, Texas country.
Speaker Change: And the Upfronts and contingent payments pursuant to disagreements extended our cash runway into 2026.
Speaker Change: This at other agreements the strength of our patents and the number of companies developing CRISPR Cas nine medicine, reaffirm our confidence that our IP portfolio, our foundational U S and international patents covering Castanon Houston Human medicine are a source of meaningful Bob.
Speaker Change: So one of our objectives for 2024.
Gilmore O'neill: Our discussions with the FDA will continue as RUBY and EDIFAL progress and will be enhanced by our R-MAP designation for severe sickle cell disease. Bethong will share further details regarding the development of Renifal in his remarks, as well as recap the Ruby and Renifal takeaways and clinical data that we provided in December and share more information on the adolescent cohort. Now, let's turn to in vivo and our pipeline development, where we strengthened our in vivo discovery capabilities in 2023 and began lead discovery work on in vivo therapeutic targets in hematopoietic stem cells and others. As we announced earlier this year, we aim to establish in vivo preclinical proofing concepts for an undisclosed indication. Linda and her team are leveraging key capabilities that we have in-house, and Regarding our hemoglobinopathy focus, after a thorough evaluation of the development landscape, we have decided not to pursue the development of a milder conditioning regime.
Speaker Change: So anyhow, we will provide a clinical update from the rupee trial for severe sickle cell disease.
Speaker Change: Pal trial for transfusion dependent beta thalassemia in mid 2024 and by year end to 27 four.
Speaker Change: We will complete the adult cohort enrollments and initiate the adolescent cohorts and Ruby, which we've already initiated and continue enrollment Tonight.
Speaker Change: For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication.
Speaker Change: For P. D. We will leverage our robust IP portfolio and business development to drive value and complement core peanuts and technology capabilities.
Speaker Change: We are energized by our progress and execution in 2023 with our sharpened.
Sharpen strategic focus are world class scientists and employees and our team's drive and execution. We continue to build momentum to progress our strategy to deliver differentiated medicines to patients with serious genetic diseases.
Speaker Change: Now I will turn Dakota to base, all our Chief Medical Officer.
Speaker Change: Thank you Kim all.
Speaker Change: Good morning, everyone.
Dakota: Let's talk about the brand itself, which is under couldn't get to all of them in more severe he calls the ltvs and transfusion dependent beta thalassemia.
Dakota: As of today and it will be trial for sickle cell disease, we havent, even more at 40 patients dosed 18 patients we have multiple locations scheduled for dosing in the coming months.
Dakota: We're also pleased to announce that we have initiated adolescent cohort in the movie study.
Dakota: We shouldn't go off our 'twenty 'twenty four jackups.
Dakota: The interest and demand a high and adolescent patients have already started screening.
Dakota: In the area of field trial for transfusion dependent anemia to data, we haven't enrolled nine patients and dosed seven patients.
Dakota: As I shared earlier I continue to visit our Ruby and how do you say all clinical trial sites and continuously speak with investigators I appreciate the enthusiasm and support from the investigators and study site.
Dakota: I'm pleased with the momentum of Venezuela in patient recruitment, a free seat editing and dosing in both states.
Gilmore O'neill: We believe stand-alone, milder conditioning regimens will be widely available once FDA-approved, and therefore, we have determined that research, clinical development, and regulatory investment, and Huma Globinopolis can be better deployed for our continued development of in vivo HSE. In the fourth quarter, we announced a license agreement with Vertex Pharmaceuticals. Editas provided Virtex with a non-exclusive license for Editas Medicine's Cas9 gene-edging technology for ex vivo gene-edging medicines targeting the BCLNA gene in the fields of sickle cell disease and beta palatemia, including Virtex, and the upfront and contingent payments pursuant to this agreement extending our cash runway into 2020. This and other agreements, the strength of our patents and the number of companies developing CRISPR-Cas9 medicine reaffirm our confidence that our IP portfolio of foundational U.S. and international patents covering Cas9 use in human medicine is a source of meaningful value. So, what are our objectives for 2024?
Dakota: I'm excited to hear from investigators that patient dose with radnet. They all have already seen part due to changes in their lives.
Dakota: As Gill mentioned, we have aligned with FDA that movie clinical trial is now complete in our phase 123 trial for BLA filing.
Dakota: We have also aligned with the FDA on the study design and endpoints.
Dakota: And the FDA has agreed to our activation of adolescent cohort.
Dakota: We look forward to your future discussion with FDA and continued calibration.
Dakota: Turning to clinical data in December 2023 we should have safety and efficacy data from 17 patients 11, Ruby patient six Eddie fabrication.
Dakota: Once again the eight.
Dakota: <unk> confirmed the observation from our apply clinical readouts.
Dakota: The benefit was driving early robustly correction of anemia to a normal people watch for a range of of total hemoglobin in sickle cell patients.
Dakota: The only thing I'll kill robust and sustained increase in feet on the globe.
Dakota: That's up 40%.
Dakota: Oh, it will be a sickle cell patient have remained free of vessel crews defense following rebalancing our treaties.
Dakota: The only thing I would treat sickle cell benefit excuse me a patient showing successful beckman have stopped to best class They are transfusion.
Dakota: And the safety profile of benefit observed to date is consistent with what you saw kind of marpol actually a condition and Hollywood excuse me crack stem cell transplant.
Gilmore O'neill: For Renningfell, we will provide a clinical update from the RUBY trial for severe sickle cell disease and the EDIFEL trial for transfusion-dependent beta thalassemia in mid-2024 and by year-end. We will complete adult cohort enrollment and initiate the adolescent cohort in RUBY, which we've already initiated, and continue enrollment in AFL. For our in vivo pipeline, we will establish in vivo pre-clinical 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. We are energized by our progress in execution in 2023. With our sharp and strategic focus, our world-class scientists and employees, and our keen drive in execution, we continue to build momentum to progress our strategy to deliver differentiated editing medicines to patients with serious genetic disease. Now, I will turn the call over to Basel, our Chief Medical Officer. Thank you, Gilmour. Good morning, everyone.
Dakota: In addition, the trajectory of the correction of anemia and expression of fetal hemoglobin is consistent across the NFL treating sickle cell disease patient and basically a female patient at the same full uptime costs.
Dakota: These data reinforce our belief that we have a competitive product and the product potentially differentiated from other treatments with a record collection with Dominion.
Dakota: Thanks to the deliberate choice that our discovery group has made early in the program.
Dakota: As we have previously stated the choice of CRISPR enzymes, and then talking to edit for increase the hemoglobin fetal hemoglobin expression matters.
Dakota: When I say our uses our proprietary <unk> kept all the enzyme to added etch beat you went to promote it.
Dakota: Hey, He's got 12, eight increases the efficiency of editing and significantly reduce off target editing when computing fabric.
Dakota: CRISPR nuclease, including test not.
I didn't mean Hps you went to promoter humanistic Heathrow default hospira sales without even greater bed class a protection normal curriculum for capacity and improved red blood cell counts will come back to I think you know P. J O. Another day.
Dakota: We look for differentiation is street categories of Polycom in clinical trials.
Dakota: Hematological, powermeter and organ function and patient reported outcome or quality of life.
Dakota: Based on the clinical data, thus far we believe that sustained normal level of totally gonna be could be a potential point of differentiation for Renaissance.
Baesong Mai: Let's talk about renicel, which is in clinical development for severe sickle cell disease and transfusion-dependent beta-plasmia. As of today, in the RUBY trial for sickle cell disease, we have enrolled 40 patients and dosed 18 patients. We have multiple patients scheduled for dosing in the coming months. We're also pleased to announce that we have initiated an adolescent cohort in the Ruby study, which is one of our 2024 objectives. The interest and demand are high, and adolescent patients have already started screening.
Dakota: As a reminder, our stand.
Dakota: Scanned normal total hemoglobin level is an important clinical outcome for patients.
Dakota: The correction of anemia can significantly improve quite of life and immediately and end organ damage.
Dakota: We look forward to sharing additional updates, including the movie and Eddie cell clinical trial data with more patients and longer follow up period midyear.
And additional data are you at.
Dakota: Now I will turn the call over to Eric our Chief Financial Officer.
Eric Thomas Schmidt: Thank you Beth and good morning, everyone I'm happy to be speaking with you and I'd like to refer you to our press release issued earlier today for a summary of financial results for the fourth quarter and full year 2023, and I'll take this opportunity to briefly review a few items for the fourth quarter.
Baesong Mai: In the EDITHEL trial for transfusion-dependent benathaleucemia, to date, we have enrolled nine patients and dosed seven patients. As I shared earlier, I continue to visit our RUBY and EDITHEL clinical trial sites and continuously speak with investigators. I appreciated the enthusiasm and support from the investigators and study sites. I'm pleased with the momentum of Renafil in patient recruitment, freezes, editing, and dosing in both studies.
Eric Thomas Schmidt: Our cash cash equivalents and marketable securities as of December 31st or $427 million compared to 446 million as of September 30th 2023.
Eric Thomas Schmidt: 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.
Eric Thomas Schmidt: Revenue for the fourth quarter of 2023 was $60 million, which primarily relates to revenue recognized under our license agreement with vertex, which as Joe referenced earlier on this call we announced in December of 2023.
Baesong Mai: I'm excited to hear from the investigators that patients, those with renal cells, have already seen positive changes in their lives. As Gilbert mentioned, we have aligned with the FDA that the Ruby-Clingor trial is now considered a Phase 1-2-3 trial for BLA5. We have also aligned with the FDA on the study design and end point, and the FDA has agreed to our activation of adolescent cohorts. We look forward to future discussions with FDA and continued collaboration. Turning to clinical data, in December 2023, we shared safety and efficacy data from 17 patients, 11 Ruby patients, and 6 Edythele patients. Once again, the data confirmed observations from our prior clinical readouts, including random cells driving early and robust correction of anemia to a normal physiological range of total hemoglobin in sickle cell patients, and Rhinoceratio a robust and sustained increase in phytoglobin in excess of 40%. All ruby sickle cell patients have remained free of vasoconstrictive bands following renal cell treatment.
Eric Thomas Schmidt: R&D expenses this quarter increased by 18 million to $70 million from the fourth quarter of 2022.
Eric Thomas Schmidt: The increase reflects additional sublicense expenses offset by the decrease in R&D spend resulting from a re prioritization and targeted focus on a rent or sell program.
Eric Thomas Schmidt: G&A expenses for the fourth quarter of 2023 were $14 million, which decreased from $18 million for the fourth quarter of 2022.
Eric Thomas Schmidt: The decrease in expense is primarily attributable to reduced patent and legal costs.
Eric Thomas Schmidt: Overall <unk> remains in a strong financial position bolstered by our sharpen. This discovery focus June capital raise in our recent out licensing deals are.
Eric Thomas Schmidt: Our cash runway into 2026 provides ample resources to support our continued progress and there will be an edit bio clinical trials that run itself.
<unk> commercial manufacturing preparation and the advancement of our discovery and research efforts with that I'll hand, the call back to Gilmer. Thank you Eric.
We are very proud of our progress in 2020 three I look forward to accelerating the momentum into 2024.
Gilmer: We continue to evolve from a crisis stage technology platform company into a commercial stage gene editing company.
Gilmer: Forward to continue our transformation and sharing our progress with you as well.
It was minor our 'twenty 'twenty four strategic objectives and food for rent itself will provide a clinical update from the rate itself will be trials for severe sickle cell disease, and the oedipal trial for transfusion dependent beta thalassemia in mid 'twenty 'twenty, four and year end 2024.
Baesong Mai: Rendezell trees, sickle cell, and beta thalassemia patients have shown successful improvement and stopped the red blood cell transfusion, and the safety profile of Renner cells observed to date is consistent with biosulfate and myoblastic conditioning and autologous hemopoietic stem cell transplant. In addition, the trajectory of the correction of anemia and expression of fetal hemoglobin is consistent across renal cell-treated sickle cell disease patients and benaziracemial patients at the same follow-up time course. These data reinforce our belief that we have a competitive product, and the product is potentially differentiated from other treatments with rapid correction of meaning. Thanks to the deliberate choice that our discovery group made early in the program. As we have previously stated, the choice of CRISPR enzyme and the target to edit for increased fetal hemoglobin expression matters. Renifail uses our proprietary ASEF-2A enzyme to edit the HB212 promoter. ASCAS-12a increases efficiency of editing and significantly reduces off-target editing when compared to other CRISPR nuclei, including Cas9, editing the HBG1-2 promoter in human 3034 positive cells without any greater red blood cell production, normal proliferative capacity, and improved red blood cell health when compared to editing of BCL11.
Gilmer: We will compete adult cohorts enrolled and we already initiated the Atlas importantly continue enrollments in early fall.
Gilmer: For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication and a P. D. We will leverage our robust IP portfolio and business development to drive value and complement core gene editing technology capabilities.
Gilmer: As always it must be said that we could not achieve our objectives without the support of our patients caregivers investigators employees corporate partners and you. Thanks very much very interesting other tests and we're happy to answer questions.
Speaker Change: Thank you.
Speaker Change: At this time, we'll 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: A confirmation tone will indicate that your line is in the question. Kim you May Press Star two if he would like to remove your question from the queue. We ask that you limit yourself to one question. So that others may have an opportunity to ask questions for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star keys, one moment, please while we poll for <unk>.
Speaker Change: <unk>.
Speaker Change: Our first question comes from Joon Lee with Truth Securities. Please proceed with your question.
Joon Lee: Hi, good morning, and congrats on that.
Joon Lee: Quarter I'm, sorry for my voice.
Joon Lee: My question is that could you. Please elaborate on that how many lives. This markers that you're tracking and tell us how they will relate to patient reported outcomes.
Joon Lee: Such as quality of life.
Speaker Change: Thank you.
Speaker Change: Thanks very much.
Speaker Change: June I hope that your voice gets better.
June: I'm going to pass that question over to base all.
Base: Yeah. Thanks for that question June so far this modest as Marc how are we looking to a multiple oh, my crystal ball or indeed any ball hemolysis.
Base: In a very close eye LDH bilirubin among others.
Base: And for the.
Speaker Change: Patient report outcome, we use several of instrument and to measure that.
Speaker Change: That clinical outcome and quality of life and that's related to like the general.
Speaker Change: Piao instrument as well as sickle cell specific eight instrument.
Baesong Mai: We look for differentiation in three categories of outcome in clinical trials, hematological parameters, end-organ function, and patient-reported outcome of quality of life. Based on the clinical data thus far, we believe that a sustained, normal level of total hemoglobin could be a potential point of differentiation for RENUS. As a reminder, a sustained, normal total hemoglobin level is an important clinical outcome for patients, and the correction of anemia can significantly improve quality of life and ameliorate end organ damage. We look forward to sharing additional updates, including RUBY and EDIFEL clinical trial data with more patients and longer follow-up periods in mid-year, and additional data by year-end. Now, I will turn the call over to Eric, our Chief Financial Officer. Thank you, Baesong. And good morning, everyone.
Speaker Change: Thank you.
Speaker Change: Yeah.
Samantha: Our next question comes from Samantha Southern Cal City. Please proceed with your question.
Samantha Southern: Hi, good morning, Thanks, very much for taking the question can.
Samantha Southern: Can you share just any additional insights onto your FDA conversation as you outlined on that really Chile, specifically in terms of the number of patients you'll need in the amount of follow up you'll need to file a potential BLA.
Speaker Change: And I'm going to Ah Ha based song address that question.
Speaker Change: Thank you for the question. So we are aligned with that.
Speaker Change: F D. A about the Ruby trial and two to be a phase two three trial to support a BLA, including endpoint sample size and study design and we are still in that we have continue to have engagement with the FDA about the that's D. It we'd have to be a box that you always get a package and.
Speaker Change: The follow up and so we all have a further discussion with FDA.
Speaker Change: Got it thank you.
Speaker Change: Our next question comes from Brian Cheng with J P. Morgan. Please proceed with your question.
Brian Cheng: Hey, guys. Thanks for taking our questions. This morning.
Eric Thomas Schmidt: I'm happy to be speaking with you, and I'd like to refer you to our press release issued earlier today for a summary of financial results for the fourth quarter and full year 2023. And I'll take this opportunity to briefly review a few items for the fourth quarter. Our cash, cash equivalents, and marketable securities as of December 31st were $427 million compared to $446 million as of September 30th, 2023.
Brian Cheng: Just kind of give us a sense of you know what what does that phase 123 destination for movie really mean from a timeline perspective and on the potential differentiation I think based on you talked about you know investigators feedback so far I'm curious if you can also talk about just a feedback that you've been hearing from investigators are they seeing any potential.
Speaker Change: And Jason can fairly on thank you.
Jason: Thanks, very much Brian So I think there were three parts to your question why does the phase 123, and its impact on sort of the DLA past what was the investigator feedback on differentiation and what are they seeing signs or butler thinks that they might be.
Eric Thomas Schmidt: 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. Revenue for the fourth quarter of 2023 was $60 million, which primarily relates to revenue recognized under our license agreement with Vertex, which, as Gilmore referenced earlier on this call, we announced in December of 2023. R&D expenses this quarter increased by $18 million to $70 million from the fourth quarter of 2022. The increase reflects additional sub-license expenses offset by a decrease in R&D spend resulting from our reprioritization and targeted focus on our Renisell program. G&A expenses for the fourth quarter of 2023 were $14 million, which decreased from $18 million for the fourth quarter of 2022.
Jason: Eating and patients at this point.
Speaker Change: What I'll do is just address the first part and then ask Bay song.
Speaker Change: Follow up on the other two.
Bay: So with regards to the phase one two and three I think the key point here is that there is a singles. We've agreed that there is a single phase 123 study.
Bay: We have important agreement on what the outcomes are.
Bay: The size of the study and what that basically means is that we remain on track and are confident even more confident about being on track at too a BLA I think it's worth calling out that the vertex Ah study was also it's a study that was used for their BLA application.
Bay: <unk> was designated as a phase 123.
Bay: Before or prior to that BLA. So I hope that actually helps from the point of view of our path to BLA and I think just mentioning vertex.
Bay: It's just worth calling out that we sort of had a benchmark based on the BLA filing from last year with regard to the size of the filing that was originally used for that approval.
Speaker Change: Okay. Thanks.
Speaker Change: So Brian on the for the differentiation of any investigator feedback wise.
Brian Cheng: So we actually have quite a bit the engagement with the investigator and form their own their own observation of their patients as we ought to see the data they're very pleased to see the collection of anemia.
Eric Thomas Schmidt: The decrease in expense is primarily attributable to reduced patent and legal costs. Overall, Editas remains in a strong financial position, bolstered by our sharpened discovery focus, June capital raise, and our recent out-licensing deals. Our cash runway into 2026 provides ample resources to support our continued progress in the Ruby and Edythal clinical trials at Renissel, continued commercial manufacturing preparation, and the advancement of our discovery and research efforts. With that, I'll hand the call back to Gilmour. Thank you, Eric. We are very proud of our progress in 2023 and look forward to accelerating the momentum into 2024, as we continue to evolve from a bright and safe technology capital company into a commercial estate, genius, and We look forward to continuing our transformation and sharing our progress with you. As a reminder, our 2024 strategic objectives include for RenyCell, we're going to provide a clinical update on the RenyCell Ruby trial for severe sickle cell disease and the EpiPile trial for transfusion-dependent beta thalassemia in mid-2024 and year-end 2024. We will complete adult cohort enrollment, and we have already initiated the adolescent cohort in Ruby, and will continue enrollment in Edifow
Brian Cheng: And as a hematologist that.
Very much I appreciate that the level of pulling them globally and be able to crack the media and the ease of application ease.
Brian Cheng: Less fatigue, and they have more energy.
And are they just that they have to rectify observation and then also they put us that told.
Brian Cheng: What I'm gonna be level and publish all excluding Pakistan and organ function. So those are the direction. There will also be looking for.
Brian Cheng: And one other thing I'd just like to quote you know just with regard to the phase 123, I think the important thing is is that the Ruby study has been as we've agreed with the FDA. It's converted from phase one to a phase 123, which allows because it's a single study.
Brian Cheng: Seamless transition to that study to support BLA.
Brian Cheng: Helpful.
And I don't care most point when we get one means it's also to say we'd be able to use all the patient data from the study to support the V O N.
Speaker Change: Okay. Thanks, guys.
Speaker Change: Our next question comes from Greg Harrison with Bank of America. Please proceed with your question.
Greg Harrison: Hey, good morning, and thanks for taking the question.
Greg Harrison: Now that there is a gene editing treatment approved and.
Greg Harrison: In sickle cell what are your latest thoughts on how rent or sell it would fit in the space and what have you learned from the early launch by the competitor.
Speaker Change: Thanks, very much Greg I'm going to ask Karen.
To address that question yeah, great. Thanks for your question.
Karen: Well, we've been hearing from the various stakeholders in this space is is a lot of interest and some really good initial momentum I think we're also hearing that across all of the great. So let's take a look here patients families. Your centers, which are transplant, maybe gene therapy centers.
Karen: I know Youre qualified centers and I talked to your parents Theres just a lot of work that needs to happen and then I think you all are picking up on that but it's starting and it's happening. So I think it's the balance in saying there is tremendous interest even from the government and the CMI pilot that CMS has kicked off so you know.
Gilmore O'neill: For our in vivo pipeline, we will establish in vivo preclinical proof of concept for an undisclosed indication, and for PD, we will leverage our robust IT portfolio and business development to drive value and complement core gene editing technology capabilities. As always, it must be said that we could not achieve our objectives without the support of our patients, caregivers, investigators, employees, corporate partners, and you. Thanks very much for your interest in Editas, and we're happy to answer any questions. At this time, we will 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 that your line is in the question queue. You may press star 2 if you would like to remove your question from the queue.
Karen: The way, we see it as it is very encouraging it's going to take time, and we really believe that the fast follower.
Karen: Renaissance is going to be timed very well it gives us time to be able to continue to collect data that is meaningful differentiated to understand where centers maybe struggling warehouse, we can optimize our vein to vein process to deliver a product that's differentiated not just in efficacy and safety, perhaps but also in our <unk>.
Karen: Operational aspects. So we see the market developing in a very robust way. We just think it's going to take a little bit of time. So we're we're very pleased with initial interest certainly the ongoing interest in our clinical studies.
Karen: And I look forward to talking much about it.
Speaker Change: Okay. That's helpful. Thanks, so much.
Our next question comes from many of Ferrara with Leerink. Please proceed with your question.
Mary Ferrara: Oh, great. Thanks for taking my question, you talked a little bit about improvements in vein to vein time as an incremental source of differentiation independent of clinical data.
Operator: We ask that you limit yourself to one question so that others may have an opportunity to ask questions. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. One moment, please, while we poll for questions. Our first question comes from June Lee with Truist Securities. Please proceed with my question. Hi, good morning, and congrats on the... My question is, could you please elaborate on the hemolysis markers that you are tracking and tell us how they will relate to patient-reported outcomes such as quality of life?
Manny Ferrara: Can you walk through how you guys think of.
Ferrara: The timing of which we might see that show up in terms of Capex investment in terms of you know clogged transfusion etcetera, like where we're going to start seeing data points you could derisk that part of your advantage in the eyes of investors.
Speaker Change: Yeah. Thanks for the question.
Speaker Change: Thank you Bonnie we are in the clean coach high stage right. We're already trying to optimize all the office from bank to bank as you mentioned and that too shall.
Speaker Change: So we are men all quota call and work with our expert and a free seats for example, and to help with the size and on the E in the AR.
Gilmore O'neill: Thank you. Thanks very much, June. I hope that your voice gets better.
Baesong Mai: I'm going to pass that question over to Basel. Yeah, thanks for the question, June. So, for the hemolysis marker, we look into multiple markers for indicating hemolysis, including reticulocyte, LDH, and bilirubin, among others.
Speaker Change: As we cycle and help us size the prepare the patients and provide support so that's kind of the experience we gather now well how far while future market, our commercial launch I'll pass that to carrying on that yeah, and just to add as we continue to be very engaged in our clinical sites and expanding.
Baesong Mai: And for the patient outcome outcome, we use several instruments to measure that clinical outcome and quality of life, and that's related to the general PIO instrument, as well as sickle cell specific instruments. Thank you. Our next question comes from Samantha Semenkow, Citi. Please proceed with your question.
Carrying: Our outreach to other centers, where have the opportunity to really understand how the process is working how do we make the introduction of a product like rent itself as seamless as possible do the advance work fit into their existing processes.
Carrying: Well, we're always looking at opportunities across just again here the efficiency the timing and we'll certainly be able to talk in more as we get closer.
Operator: Thanks very much for taking the question. Can you share just any additional insights into your FDA conversation as you aligned on the RUBY trial, specifically in terms of the number of patients you'll need and the amount of follow-up you'll need to file a potential BLA? And I'm going to have a song addressed by
Speaker Change: Great that's helpful.
Speaker Change: Our next question comes from Terence Flynn with Morgan Stanley. Please proceed with your question.
Great. Thank you team. This is Mac score on for Terence Flynn could you provide an update on the CRISPR Cas nine appeal case, and whether you expected oral argument in the first half of 2024. Thank you.
Baesong Mai: Thank you for the question. So we agreed with the FDA about the RUBY trial to be a phase 1, 2, 3 trial to support DOA, including endpoint, sample size, and study design. And we are continuing to have engagement with the FDA about the DOA data package and the follow-up, and so we will have further discussions with them.
Speaker Change: Hi, Thanks, very much Max we have the.
Speaker Change: <unk> Court of Appeals Federal circuit has yet to schedule that oral hearing.
Speaker Change: It should be sometime this year and once we have that scheduling we can update you on that.
Operator: Our next question comes from Brian Chang with JP Morgan. Please proceed with your question. Hey, guys, thanks for taking our questions this morning. Can you just kind of give us a sense of what a phase one, two, three destination for Ruby really means from a timeline perspective and as far as potential differentiation is concerned?
Speaker Change: Great. Thank you.
Speaker Change: Our next question comes from Gena Wang with Barclays. Please proceed with your question.
Gena Wang: Thank you for taking my questions. So I'm not.
Gena Wang: If I heard correctly <unk>, you mentioned that the ft, and my son, and I think that most of you maybe mentioned a single study FDA agree on a single study also number of a patient a I'm not sure if they agree on the duration of the study.
Gilmore O'neill: I think based on what you talk about, you know, investigators' feedback so far. I'm curious if you can also talk about just the feedback that you have been hearing from investigators. Are they seeing potential differentiation this early on?
Gena Wang: Overby trial. So wondering you know if we think about the CRISPR Ah trial vertex trial, it's about 45 to 50 patients exactly in.
Gena Wang: Online was that numbers and what is the duration that FDA required and a related question. How many at the sites you have now and what is your goal of total sites for the pivotal study.
Gilmore O'neill: Thank you. Thank you very much, Brian. So, I think there were three parts to your question. You know, what is phase 1, 2, 3, and its impact on sort of the DLA path?
Gilmore O'neill: What was the investigator feedback on differentiation? And were they seeing signs, or what were the things that they might be seeing in patients at this point? What I'll do is just address the first part and then ask Baesong to follow up on the other two. So with regard to Phase 1, 2, 3, I think the key point here is that it is a single study. We agreed that there was a single Phase 1, 2, 3 study. We have important agreement on what the outcomes are and the size of the study, and what that basically means is that we remain on track and are more confident about being on track to a BLA.
Speaker Change: Thanks, very much gena for your question before I.
Speaker Change: Let me just address a couple of things from point of view of the study design I think first of all.
Speaker Change: The benchmark that would satisfy the BLA, but for Texas approval by.
Speaker Change: By the FDA for extra Sal its actually a very good benchmark against which were operating.
Speaker Change: And that is certainly an informed our discussions with the FDA are we were actually very pleased with the discussion with the FDA and we believe that it's actually really puts us on a track that lines up with the benchmark.
Gilmore O'neill: I think it's worth calling out that the Vertex study was also, the study that was used for their BLA application was designated a Phase 1, 2, 3 before or prior to that BLA. So I hope that actually helps from the point of view of our path to BLA. And I think, just mentioning Vertex, it's just worth calling out that we sort of have a benchmark based on the BLA filing from last year with regard to the size of the filing that was originally used for that approval. Thanks. So, Brian, I mean, for the differentiation and the investigator feedback, so we actually have quite a bit of engagement with the investigators, and from their own observation of their patient as well as to see the data, they're very pleased to see the correction of anemia, and the hematologist that, very much appreciate that the level of total hemoglobin be able to correct the veneer, and they see their patient is less fatigued, and they have more And then they also told us that the total hemoglobin level, as published, also impacted end-organ function.
Speaker Change: And as a result, when we actually talk about having enrolled 40 patients how we finish the age of the adolescents enrollment and so on we believe we're actually in a very good track.
Speaker Change: For to BLA.
Speaker Change: With regard to the number of active sites I just want to clarify something.
Speaker Change: We're not talking about a separate study essentially the Ruby study, which is ongoing with at sites activated is b phase 123 study that would be used for BLA and that is the agreement that we have with the agency.
Speaker Change: Okay, I'm, sorry, the reason I'm asking more thinking about in the future commercial perspective.
Speaker Change: If you have already established the active sites for your clinical child, and it's very easy to transition to commercial launch chocolate proofing future.
Speaker Change: Yes, I understand that and appreciate that clarification.
Speaker Change: And certainly we agree with that principle.
Speaker Change: I can think I don't know if you want that no no no I mean, I I know we've already we had already expanded the number of sites previously to get to a number that would support the full study right PE fund and so that that was a very thoughtful approach to ensure that we had a you know.
Speaker Change: A good strong number of sites with geographic coverage, yeah, maybe I can add a bunch of you know we already shared we have active.
Baesong Mai: So those are the directions that we're also looking for. And one other thing I'd just like to quote, you know, just with regard to phase one, two, three, I think the important thing is that the Ruby study has been, we've agreed with the FDA, converted from phase one to phase one, two, three, which allows, because it's a single study, a seamless transition to that study to support BLA. I hope that it's helpful.
Speaker Change: Activated over 20 sites and so we are we've got over 20 sites already enrolling 40 patients and we already we will fight for adolescent cohort that Bob.
The overlap between adult and adolescent from the same study size and we are also activating a few more oxides that specifically for a pediatric patients.
Thank you very much.
Speaker Change: Our next question comes from Dan <unk> with Stifel. Please proceed with your question.
Dan: Good morning, guys. Thanks for taking our questions I apologize, it's actually a two part question, but just to clarify on the rent yourself progress in rupee. If I heard you correct 18, dosed I thought the prior conversation was 20 dosed by January So can you talk about sort of the drop outs. There what was the reason behind that and then another clarification.
Operator: Just to add to Gilmore's point, what Gilmore means is also that we would be able to use all the patient data from the study to support the VOA. Okay, thanks, guys. Our next question comes from Greg Harrison with Bank of America. Please proceed with your question. Hey, good morning.
Dan: Occasion on the FDA side, when you talk about differentiation have you guys actually engage them on the angle you were taking on the differentiation, whether total hemoglobin or end organ function how are they perceiving that in terms of the conversation. Thanks so much.
Karen Deardorff: Thanks for taking the question. Now that there's a gene editing treatment approved for sickle cell, what are your latest thoughts on how Renaissance would fit in the space, and what have you learned from the early launch by the company? Thanks very much, Greg. I'm going to ask Karen to address that question.
Speaker Change: Thanks, very much Aegon first of all I think we're actually very happy with where we are with our dosing 18 patients dosed.
And that really has us on track with that dosing pace to get us on track for a presentation of substantial data set and in the middle of the year and actually with regard to our driving towards a BLA at we have not we have not had to drop out. So I just wanna be sure that Theres no.
Karen Deardorff: Yeah, Greg, thanks for your question. What we've been hearing from the various stakeholders in this space is a lot of interest and some really good initial momentum. I think we're also hearing that across all of the groups, so your stakeholders, your patients' families, your centers, which are transplant, maybe gene therapy centers, your qualified centers, as well as your payers. There's just a lot of work that needs to happen, and I think you all are picking up on that.
Speaker Change: Confusion about that.
Speaker Change: And I think the final thing is that Ah you know based on that myself without clinical development experience and particularly when you're dealing with a complex therapeutics like that you're going to get some ways, you know ups and downs in waves of not just enrollment dosing, particularly around scheduling around holiday periods et cetera, So as they song.
Karen Deardorff: But it's starting, and it's happening, so I think it's the balance of saying there is tremendous interest, even from the government, in the CMMI pilot that CMS has kicked off. The way we see it is that it is very encouraging. It's going to take time, and we really believe that the fast follower of Renacel is going to be timed very well.
Speaker Change: That said we have many more.
Speaker Change: Patients scheduled for dosing in the coming months and as I say remain on track for a substantive data set in the middle of the year with regard to the differentiation and our conversations with the F D. A.
Speaker Change: We have actually highlighted a potential for differentiation the mechanistic differences behind bass et cetera, but I think it's too soon to comment on where the F D a where our discussions with the FDA around that.
Karen Deardorff: It gives us time to be able to continue to collect meaningful, differentiated data to understand where centers may be struggling, where else we can optimize our vein-to-vein process to deliver a product that's differentiated, not just in efficacy and safety, perhaps, but also in our operational aspects. So we see the market developing in a very robust way. We just think it's going to take a little bit of time.
Speaker Change: Great. Thank you very much.
Speaker Change: Yeah.
Digit Chat: Our next question is from digit chat up attached with Guggenheim. Please proceed with your question.
Digit Chat: Good morning. This is ray for Seth from Deb just team did.
Ray: Did the alignment with the FDA include any feedback on off target editing profiling akin to sort of the outcomes criticism around cash chevy's characterization for the breadth of genetic diversity.
Ray: And our second question for the yet to be disclosed program, where you're going to offer a primate proof of concept now what characteristics of this program are you. Most excited about the market size the opportunity for first in class the specific editing chemistry, etc.
Karen Deardorff: So we're very pleased with the initial interest, certainly the ongoing interest in our clinical studies, and look forward to talking more with you about it. That's helpful Thanks so much. Our next question comes from Manny Fajrara with Learinc. Please proceed with your question. Great, thanks for taking the time to answer my question. You talked a little bit about improvements in vein-to-vein time as an incremental source of differentiation and independent clinical data. Can you walk through how you guys think of...
Speaker Change: Hi, Thanks, very much Dev Jed so.
Speaker Change: Let me actually a pass the first question to.
Speaker Change: To based song.
Speaker Change: Yes.
Based Song: We have bought we have a continuous engagement with the FDA. So we are looking at the the engagement is scientifically driven just to understand the size of our molecule that we have and then.
Based Song: And how would a patient with manager and we are have a whole range of engaging with the FDA.
Operator: Timing on which we might see that show up in terms of CapEx investments, in terms of clinical prosecution, etc., like where we're going to start seeing data points that could de-risk that part of your advantage in the eyes of investors. Yeah, thanks for the question. This is based on
Based Song: <unk> preclinical or CMC preclinical so because as Gill mentioned, we havent Ahmed with explanation and we have a lot of elaboration and a lot of opportunity to actually engage with FDA. So we are very happy with the Colorado nature of the equity engagement.
Speaker Change: Can I just add to that is that we as we said before when we actually watched the AD comm discussion we were very gratified by what we heard and saw because our confidence both in the comprehensive nature of our.
Baesong Mai: Thank you. Thank you, Ronny. We are in the clinical trial stage, right? We're already trying to optimize the process from band to band, as you mentioned there too. So, we amend our protocol and work with our expert in asphyxia, for example, and to help the sites in the asphyxia cycle and help the sites to prepare the patients and provide support. So, that's kind of the experience we gain now will help our future commercial launch process to carry on. Yeah, no, and just to add, as we continue to be very engaged in our clinical sites and expanding our outreach to other centers, we'll have the opportunity to really understand how the process is working, how we make the introduction of a product like Renacelle as seamless as possible, do the advanced work, fit into their existing processes. But we're always looking at opportunities across just, again, efficiency, and timing, and we'll certainly be able to talk Great, that's very helpful.
Speaker Change: Off target editing.
Speaker Change: Oversized package was actually very robust at relative to the discussion of the AD com and frankly, our off target editing data package is actually very good and not surprisingly because we are using our own engineered S. Cast 12, a enzyme which is a high fidelity as well as high efficiency enzyme and it's worth saying that.
Speaker Change: In our hands than in the hands of others I'm off target editing is not detectable across a genome wide screen as opposed to cats nine. So we feel very good about that and then with regard to the in vivo characteristics I think I just want to say I said before that the key things.
Speaker Change: Our factors that we are focusing on is to select a set of targets.
Speaker Change: That are high conviction based on their potential for critical differentiation.
Speaker Change: From the current standard of care and it actually does include a number of variables include the probability of technical success as well as regulatory success and commercial success.
Operator: Our next question comes from Terence Flynn with Morgan Stanley. Please proceed with your question. Great, thank you, team. This is Max Skoron for Terence Flynn.
Speaker Change: So the run down.
Speaker Change: Thank you.
Speaker Change: Okay.
Speaker Change: Our next question comes from Phil Nadeau with TD Cowen. Please proceed with your question.
Gilmore O'neill: Can you provide an update on the CRISPR-Cas9 appeal case and whether you expect an oral argument in the first half of 2024? Thank you. Thanks very much, Max. The Court of Appeals, Federal Circuit has yet to schedule that oral hearing. It should be sometime this year.
Phil Nadeau: Good morning. Thanks for taking my question. My question is on manufacturing can you remind us where you are in the scale up process the commercial manufacturing scale with process.
Phil Nadeau: And in your discussions with the FDA have you agreed upon CMC package and in particular, because their requirement for patients and Ruby to be dosed with commercial material.
Speaker Change: Thanks very much for your question from a CMC point of view, we actually are in a very good place. We have as you know had discussions with the FDA and are actually progressing very well along that line. We actually are as you know we.
Operator: And once we have that schedule, we can update you on that. Great, thank you. Our next question comes from Gena Wang with Barclays. Please proceed with your question. Thank you for taking my questions.
Speaker Change: Half our building our commercial capacity and obviously that capacity will be ready for the demand.
Gilmore O'neill: If I heard it correctly, Gilmore, you mentioned that the FDA, and I think both of you maybe mentioned single study, FDA agree on the single study, also the number of patients. I'm not sure if they agree on the duration of the study for the RUBY trial. So wondering, you know, if we think about the CRISPR trial, the Vertex trial, which is about 45 to 50 patients, is that aligned with those numbers? And what is the duration that FDA requires? And related questions; how many active sites do you have now?
Speaker Change: That would exist at the time of our launch and is ready for a supporting demands beyond fast launch and then with regards to the processes that to say, we're making excellent progress there.
Speaker Change: In support of our our BLA, so that we would be BLA ready and inspection ready at that time.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Jay Olson with Oppenheimer <unk> co. Please proceed with your question.
Oh, Hey, congrats on all the progress and thank you for providing the update our question is about your in vivo program can you talk about how and when you're planning to share preclinical proof of concept and since it seems like there's two undisclosed targets in your corporate deck are you planning.
Gilmore O'neill: And what is your goal for the total number of sites for the pivotal study? Thanks very much, Gena, for your question. Before I do, let me just address a couple of things. From the point of view of study design, I think, first of all, the benchmark that was set by the BLA with Vertex's approval by the FDA for XSL is actually a very good benchmark against which we're operating, and that has certainly informed our discussions with the FDA.
Speaker Change: Sure preclinical proof of concept for.
Speaker Change: Most programs and also any thoughts you could share on your choice for editing tool and delivery tool.
Speaker Change: Thanks, very much so from the in vivo pipeline point of view with regard to the Highlander. When are you know we're excited to be on track.
Speaker Change: <unk> towards a P O C. This year for a in vivo preclinical POC <unk> and we're going to be able to share more and look forward to sharing more later in the year about the the forum and the timing whether it be a scientific form other forum in which we would share at the data and we haven't made a determination.
Gilmore O'neill: We were actually very pleased with the discussion with the FDA, and we believe that it actually really puts us on a track that lines up with the benchmark. And as a result, when we actually talk about having enrolled our 40 patients, how we've initiated the adolescent enrollment, and so on, we believe we're actually on a very good track for BLA. With regard to the number of active sites, I just want to clarify something.
Speaker Change: Yes.
Speaker Change: About that and as I say, our focus is on driving towards a POC for in vivo this year.
Speaker Change: Oh, sorry, with regards to the editing tools well, we have I think it'd be very clear that we are focusing on our <unk> cost 12, a editor.
Speaker Change: And we are really focused on math because for a number of reasons first.
Speaker Change: It's a proprietary enzyme that we have selected going forward because of its high fidelity and high efficiency because of the benefits of it using a smaller guides and the advantages for a quality et cetera in the manufacturing and then finally because.
Gilmore O'neill: We're not talking about a separate study. Essentially, the Ruby study, which is ongoing with its sites activated, is the phase 1, 2, and 3 study that will be used for BLA, and that is the agreement that we have with the agency. Okay, sorry, the reason I'm asking more thinking about the future commercial perspective; if you have already established the active sites for your clinical trial, then it's very easy to transition this to commercial once the drug is approved in the future. And certainly, we agree with that principle. I can take it, Karen, if you want to add to that.
Speaker Change: We have human proof of concept, we have very exciting robust editing data in human cells from mass Castro day from our Renaissance program. So all of those are the reasons why we're favoring and using that editing tool and then regards to delivery we are using a non viral focusing on non viral delivery and nanoparticles.
Speaker Change: Okay.
Speaker Change: Super helpful. Thank you so much.
Thank you.
Speaker Change: Our next question comes from Yun Zhong with Wells Fargo. Please proceed with your question.
Gilmore O'neill: No, no, no, I mean, I know we've already expanded the number of sites previously to get to a number that would support the full study right on, and so that was a very thoughtful approach to ensure that we had, you know, a good, strong number of sites with geographic coverage. Yeah, maybe I can add a bunch, you know, we already share, we have activated over 20 sites, and so we are, with that over 20 sites, we have already enrolled 40 patients, and we already have those sites for the adolescent cohort. You have the overlap between the adult and adolescent population from the same study size, and we are also activating a few more sites specifically for pediatric patients.
Yun Zhong: Oh, great. Thanks for taking our questions.
Yun Zhong: I I alert just wondering about the movie Air readout.
Yun Zhong: From a really trial.
Yun Zhong: I think you had 18 patient.
Yun Zhong: Ghost.
Yun Zhong: To date.
Yun Zhong: You are going to report data on.
Speaker Change: Oh, These 18 patients plus any additional patients dosed with a certain amount of follow up at the time of fleet out.
Speaker Change: And also it seems like this is a much bigger number.
Speaker Change: Compared with the last readout.
Speaker Change: So I was just wondering.
Speaker Change: Your confidence level of.
Speaker Change: Continued continuing to show the total hemoglobin normalization.
Speaker Change: Kind of a goal all of this.
Speaker Change: Media readout. Thank you.
Speaker Change: Thanks, Dan and before passing to based on some of the details you know I I agree with you. Yes. This is a much bigger number of patients that we have dosed and our confidence as we said has increased.
Speaker Change: With the accumulation of data that are continued and repeatedly show that not only are we achieving robust fetal hemoglobin expression in excess of 40%, which is well above the.
Baesong Mai: Thank you very much. Our next question comes from Degan Ha with Stiefel. Please proceed with your question. Good morning, guys.
Operator: Thanks for taking our questions. I apologize, it's actually a two-part question, but just to clarify on the Renny cell progress in Ruby, if I heard you correctly, 18-dosed; I thought the prior conversation was 20-dosed by January. So can you talk about sort of the dropouts there? What was the reason behind that?
Speaker Change: Well above the 30% thresholds that natural history would tell us is relevant.
Speaker Change: But we actually also see that consistent correction of anemia due to normal physiologic range in all men and all women are treated and followed our past four months after the date.
Gilmore O'neill: And then another clarification on the FDA side: when you talk about differentiation, have you guys actually engaged them on the angle you're taking on differentiation, whether total hemoglobin or end-organ function? How are they perceiving that in terms of the conversation? Thanks so much. Thanks very much, Dagon. First of all, I think we're actually very happy with where we are with our dosing, 18 patients dosed, and that really has us on track with that dosing pace to get us on track for a presentation of a substantial data set in the middle of the year. And actually, with regard to our driving towards BLA, we have not had any dropouts, so I just want to be sure that there's no confusion about that.
Speaker Change: And yes, we're excited about the mid year disclosure, but with that I'm going to passive debate song.
Speaker Change: Give you a little more detail yeah.
Song: Thanks, Ian I mean, your understanding is absolutely correct, we've already dosed 18 patient and well continue to do those patients in the coming months. So that data set will be 18 patients and plus mall that we're gonna be dosing before midyear and as you can see we.
Song: Yeah as you can see we.
Song: Published data in Ash and some patients already over a year. Then these patients will have continued to monitor those patients longer part of the follow up period, and then than we have 18 basin patient both now and then by the middle of the year and this will help with patient that's 18 patient warehouse three or five months more data by the time, we would be.
Song: He believes that they will and that's why we just describe it as really very meaningful substantive data we won't be to shed mid of the year as exactly you mentioned, we've got this data set is pretty strong and we actually I think based on I think you said it but it was re emphasizing we're talking about a range itself follow ups from an efficacy point of view between three and <unk>.
Gilmore O'neill: And I think the final thing is that, based on my clinical development experience and particularly when you're dealing with complex therapeutics like that, you're going to get some waves, you know, ups and downs and waves of not just enrollment but dosing, particularly around scheduling around holiday periods, et cetera. So, as Beifong also said, we have many more patients scheduled for dosing in the coming months, and as I say, we remain on track for a substantive data set in the middle of the year. With regard to differentiation and our conversations with the FDA, we have actually highlighted our potential differentiation, the mechanistic differences behind that, et cetera. But I think it's too soon to comment on where the FDA is on that and where our discussions with the FDA are on that.
Song: At 18 plus months. So when you think about the total cohort of patients now.
Song: We are now really building not just a days assessed Ah that is robust in number but actually as robust and follow up periods of time, which obviously, rather not just to our hematological and efficacy outcomes, but actually also are increasing our confidence in your ability.
Speaker Change: Great. Thanks, looking forward to that.
Speaker Change: Our next question comes from Luca <unk> with RBC capital. Please proceed with your question.
Luca: Oh, great. Thanks, so much for taking my question Congrats on all the progress maybe they song and any update on the great to Polycythemia case, there was potentially related to rent yourself I remembered a poster at ash actually noted the causality of the Aes was being investigated a pending additional lab tests. So just wondering if you have any update on that one.
Gilmore O'neill: Great. Thank you very much. Our next question is from Devjit Chattopadhyay with Guggenheim. Please proceed with your question. Morning, this is Rai Forsak from Debjit's team.
Luca: And then maybe just quickly any update on partnering sickle cell disease ex U S. Thanks, so much.
Operator: Did the alignment with the FDA include any feedback on off-target editing profiling akin to sort of the Atacoms criticism around Kastjevi's characterization of the breadth of genetic diversity? And our second question, for the yet-to-be-disclosed program where you're going to offer primate proof of concept, what characteristics of this program are you most excited about? The market size, the opportunity for first-in-class, the specific editing chemistry, etc.
Speaker Change: So based on we will take that first question and you know with regard to partnering I would just say that we are a keen that's a partner with a global footprint could help us with a global commercialization and development.
Speaker Change: We see that as an upside.
Speaker Change: But right now our you know our focus is on at driving our at sickle cell.
Speaker Change: Until the senior programs here in North America, and as I say, a partnering will be something that we would look to in the future as upside with regard to the Erythrocytosis peso, yes. Thanks.
Gilmore O'neill: Thanks very much, Debjit. So, actually, I will pass the first question to Besant. Yes, when we have, we have continuous engagement with FDA. So we are looking, the engagement, you know, is scientifically driven, to understand the science of our molecule, the data we have, and then how the patient was managed. And we have a whole range of engagement with FDA, you know, from preclinical CMC to clinical. So because, as Gilmore mentioned, we have an arm and a destination, and we have a lot of leverage and a lot of opportunity to actually engage with FDA. So we are very happy with the collaborative nature of the engagement. And can I just add to that, as we said before, when we actually watched the ADCOM discussion, we were very gratified by what we heard and saw, because our confidence in the comprehensive nature of our off-target editing Oversight Package was actually very robust relative to the discussion of the ADCOM, and frankly, our off-target editing data package is actually very good, and not surprisingly, because we So we feel very good about that.
Speaker Change: Specific patient what had a transient elevation of fetal hemoglobin that we reported at ash.
Speaker Change: If I'm a ash reporting is already be normal fall more than six months and then continued their patients.
Speaker Change: Cultural Academy, including toward homebuilding continues to stay normal and then the investigator for the investigation of the patient data and we review that too and the patients. The investigators consider these E band is not related to the cycle on the vendors you got cheated.
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Speaker Change: Got it thanks, so much.
Speaker Change: Our next question comes from Steve seat House with Raymond James. Please proceed with your question.
Speaker Change: Hi, Good morning. This is tomorrow morning come on for Steve as he calls. So if you just had a clarification question on your P. R O tools and Ruby.
Tom: To what extent are you going to be using the same tools that vertex and CRISPR use before like EQ bass fact G. M. P. M C.
Tom: And to what extent do you think of including new tools.
Tom: They should be and you're not going to be able to do a clean cross trial comparison potentially here. Thank you.
Speaker Change: Yeah. Thank you for the question as I mentioned commented earlier, we used the tool from two and when is it more general the the quantity of live twice, whereas the CCAR specific and as you mentioned the specific of the tool we are using capital meaningful checked out.
The value of that fatigue application, which is important in a complaint form a sickle cell patient just give you example, wise and you are very much of it that's exactly the direction. We were thinking trying to see okay. What are the specific instrument be able to get attached to that major complain from the sickle cell patients such as fatigue, such as Japan.
And my mom, who face yep.
Speaker Change: So we were actually using a number of instruments somewhere it used by vertex and we have additional instruments in our payroll.
Operator: And then with regard to the in vivo characteristics, I think I just want to say, as I said before, that the key things or factors that we are focusing on are to select a set of targets that are high-conviction, based on their potential for critical differentiation from the current standard of care, and it actually does include a number of variables, including the probability of technical success, as well as regulatory success, and commercial success. Thanks for the rundown. Thank you. Our next question comes from Phil Nadeau with TD Cowen.
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Speaker Change: Armamentarium and they are actually being collected in the Ruby phase 123 trial as we speak.
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Speaker Change: Our next question comes from Jack Allen with Baird. Please proceed with your question.
Jack Allen: Great. Thanks, so much for taking the question and congratulations on the progress I wanted to touch a little bit on the patient experience with fair Michelle have you provided any disclosures around the number of if recent cycles that are required to receive from Esso and the and I was wondering if the higher embedded editing efficiency of Cashcall data allows for.
Jack Allen: A shorter amount of Ah if recent cycles, none of them are back and after treatment.
Gilmore O'neill: Please proceed with your question. Good morning, thanks for taking our question. Our question's on manufacturing.
Jack Allen: What are you seeing as it relates to time to neutrophil and Grafman.
Jack Allen: And how how do you think that compares with some of the competing products in the space. Thanks, So much.
Gilmore O'neill: Can you remind us where you are in the scale of process, the commercial manufacturing scale of process? And in your discussions with the FDA, have you agreed upon a CMC package? And in particular, is there a requirement for patients in Ruby to be dosed with the commercial material?
Speaker Change: Thanks, very much Jack I'm actually going to ask at Bay song at to talk about the clinical experience with.
Bay: With for ECS and other elements of the patient experience and obviously touch on neutrophil Mcgrath with which we have been very pleased today.
Bay: Thank you Jack.
Bay: We fault patient experience I mean, firstly, it's definitely a very important part of that as I mentioned earlier since I joined I work with a team and an expert we amended the protocol and trying to optimize the receipts process. So now we are very happy we'd be the number of cycles.
Gilmore O'neill: Thanks very much for your question. From a CMC point of view, we are actually in a very good place. We have, as you know, had discussions with the FDA and are actually progressing very well along that line. We actually are, as you know, we have our building, our commercial capacity, and obviously, that capacity will be ready for the demand that would exist at the time of our launch and is ready for supporting demand beyond that launch. And then, with regard to the processes, I say we're making excellent progress there in support of our BLA so that we would be BLA ready and inspection ready at that time. Thank you. Our next question comes from Jay Olson with Oppenheimer & Co.
Bay: The patient that has been gone through and we can see that's already improvement from where we had it before.
Bay: And in terms of the the improvement as we disclosed data in an ash and we have all of the patients having bought minutes within 30 days. So we'll be happy about that and we continue to see the similar data as we follow through with their political for follow on studies.
Speaker Change: Great. Thanks, a lot for the color.
Thank you very much.
Gilmore O'neill: Please proceed with your question. Oh, hey, congrats on all the progress, and thank you for providing this update. Our question is about your In Vivo program. Can you talk about how and when you're planning to share preclinical proof of concept? And since it seems like there are two undisclosed targets in your corporate deck, are you planning to share preclinical proof of concept for both programs? And also, any thoughts you could share on your choice of editing tool and delivery tool?
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Speaker Change: We have reached the end of our question and answer session. This concludes today's conference. Thank you for your participation you may disconnect your lines at this time.
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Gilmore O'neill: Thank you. Thanks very much. So, from the in vivo pipeline point of view with regard to the how and the when, you know, we're excited to be on track towards POC this year for an in vivo preclinical POC, and we're going to be able to share more and look forward to sharing more later in the year about the forum and the timing, whether it be a scientific forum or another forum in which we would share the data. And We haven't made a determination yet about that.
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Gilmore O'neill: And as I say, our focus is on driving towards a POC for in vivo this year. Oh, sorry. With regard to the editing tools, well, we have, I think, been very clear that we are focusing on our AS-Cas12a editor, and we are really focused on that for a number of reasons. First, it's a proprietary enzyme that we have selected going forward because of its high fidelity and high efficiency, because of the benefits of it using a smaller guide and the advantages for quality, et cetera, in manufacturing, and then, finally, because we have human proof of concept.
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Gilmore O'neill: We have very exciting, robust editing data in human cells from AS-Cas12a from our Renicel program. So, all of those are the reasons why we're favoring and using that editing tool. And then, with regard to delivery, we are using a non-viral delivery system and nanoparticles. Super helpful, thank you so much.
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Operator: Thank you. Our next question comes from Yanzu with Wells Fargo. Please proceed with your question. Great. Thanks for taking our questions. We're just wondering about the midyear readout from the RUBY trial.
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Gilmore O'neill: I think you have 18 patients dosed to date. Are you going to report data on these 18 patients plus any additional patients dosed with a certain amount of follow-up at the time of readout? And also, it seems like this is a much bigger number compared with the last readout.
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Baesong Mai: So I was just wondering your confidence level of continuing to show the total hemoglobin normalization kind of goal in this midyear readout. Thank you. Thank you, and before passing to, based on some of the details, you know, I agree with you. Yes, this is a much bigger number of patients that we have dosed, and our confidence, as we've said, has increased with the accumulation of data that continue and repeatedly show that not only are we achieving robust fetal hemoglobin expression in excess of 40%, which is well above the 30% threshold, that natural history would tell us is relevant, but we actually also see that consistent correction of anemia to a normal physiologic range in all men and all women treated and followed past four months to date.
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Gilmore O'neill: And yes, we're excited about the midyear disclosure, but with that, I'm going to pass it to Basong to give you a little more detail. Yeah, thanks. I mean, your understanding is absolutely correct.
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Baesong Mai: We've already dosed 18 patients, and we'll continue to do those patients in the coming months. So the data set will be 18 patients, plus more that we're going to be dosing before the middle of the year. And as you can see,
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Gilmore O'neill: As you can see, we published the data in ASH, and some patients have already been over a year; then this patient will have continued monitoring for this patient for a longer period. And then we have 18 patients now, and by the middle of the year, these 18 patients will have 3 or 4 months more data by the time we release that. So that's why we describe it as really very meaningful, substantive data we will be able to share in the middle of the year. As you exactly mentioned, this data set is pretty strong. Yeah, and we actually, I think, Basang, I think you said it, but it's worth reemphasizing.
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Operator: We're talking about a range of follow-ups from an efficacy point of view between 3 and 18 plus months. So when you look at the total core of the patients now, we are now really building not just a data set that is robust in number but actually robust in follow-up period time, which is obviously relevant not just to our hematological and efficacy outcomes but actually increases our confidence in durability. Great. Thanks. I am looking forward to that.
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Baesong Mai: Our next question comes from Luca C. with RBC Capital. Please proceed with your question. Oh, great.
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Operator: Thanks so much for taking my question. Congratulations on all the progress. Maybe you could give an update on the grade 2 polycythemia case that was potentially related to Renicel.
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Baesong Mai: I remember the poster at ASH actually noted the causality of the AEs was being investigated, pending additional lab tests. So just wondering if you have any update on that one. And then, maybe just quickly, any update on partnering sickle cell disease, XUS. Thanks so much. So, based on that first question and, you know, with regard to partnering, I will just say that we are keen that a partner with a global footprint could help us with global commercialization and development. We see that as an upside, but right now, you know, our focus is on driving our sickle cell and thalassemia programs here in North America. And as I say, partnering will be something that we will look to in the future as an upside.
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Baesong Mai: With regard to erythrocytosis, Basav. Yeah, thanks. That specific patient had a transient elevation of total hemoglobin, as we reported in ASH. However, at the time of ASH reporting, it had already been normal for more than 6 months. And then continue The patient hematological parameters, including total hemoglobin, continue to stay normal. And then the investigator does a further investigation of the patient data, and we review that too. And the investigator considers this event not related to the venous cell treatment.
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Operator: Got it. Thanks so much. Our next question comes from Steve Seathouse with Raymond James. Please proceed with your question. Hi, good morning. This is Timur Ivanikov on behalf of Steve Seathouse. So, we just had a clarification question about your PRO tools in Ruby. To what extent are you going to be using the same tools that Vertex and CRISPR used before, like EQVAS, FACT-G, and BMT? And to what extent do you think of including new tools? And on the issue of you're not going to be able to do a clean cross-trial comparison here?
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Baesong Mai: Thank you. Yeah, thank you for the question. As I mentioned a comment earlier, we use the tool from two ends. One is more general, the quality of life tool, as well as the sickle cell specific, and as you mentioned, the specific of the tool we're using, we have a domain for, check the, evaluate the fatigue of the patient, which is important, not complain from a sickle cell patient, just give example wise, and you are very much, that's exactly the direction we were thinking, trying to see, okay, what are the specific instruments to be able to detect that major complaint from the sickle cell patient, such as fatigue, such as pain, among other things.
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Baesong Mai: So we are actually using a number of instruments. Some were used by Vertex, and we have additional instruments in our PRO. Armamentarium, and they are actually being collected in the Ruby Phase 1, 2, 3 trial. Our next question comes from Jack Allen with Baird. Please proceed with your question. Great. Thanks so much for taking the question, and congratulations on the progress. I wanted to touch a little bit on the patient experience with Remdesil. Have you provided any disclosures around the number of apheresis cycles that are required to receive Remdesil? And I was wondering if the higher editing efficiency of Cat12a allows for a shorter amount of apheresis cycles.
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Operator: And then, on the back end, after treatment, what are you seeing as it relates to time to neutrophil engraftment? And how do you think that compares to some of the competing products in the space? Thanks so much. Thanks very much, Jack. I'm actually going to ask Bae Song to talk about the clinical experience with pheresis and other elements of the patient experience, and I'll actually touch on neutrophil engraftment, with which we have been very pleased. Thank you, Jack. For patient experience, I mean, a free seat is a very important part of that.
Baesong Mai: As I mentioned earlier, since I joined, I work with a team and an expert; we amended the protocol and are trying to optimize the free sit process. So now we are very happy with the number of cycles that the patient has gone through, and we can see that it's already an improvement from what we had before. In terms of the engravement, as we disclosed in ASH, all the patients had engravements within 30 days, so we're very happy about that, and we continue to see similar data as we follow through the protocol of follow-up studies.
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Baesong Mai: Great. Thanks so much for the call. Thank you very much. We have reached the end of our question and answer session. This concludes today's conference. Thank you for your participation. You may disconnect your lines at this time.
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