Editas Medicine Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
November 3, 2023

There are 18 speakers on the call.

Operator

Good morning, and welcome to Editas Medicine's Third Quarter Conference Call. All participants are now in 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 Christy Barnett, Corporate Communications and Investor Relations at Editas Medicine.

Speaker 1

Thank you, Rob. Good morning, everyone, and welcome to our Q3 2023 conference call. Earlier this morning, we issued a press providing our financial results and recent corporate updates. A replay of today's call will be available in the Investors section of our website After our prepared remarks, we will open the call for Q and 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.

Speaker 1

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 ks, which is on file with the SEC as updated by our subsequent filings. In addition, any forward looking statements represent our views Only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, Now, I will turn the call over to our CEO, Gilmore O'Neill.

Speaker 2

Thanks, Christie, and good morning, everyone. Thank you for joining us today on Editas Medicine's 3rd Quarter Earnings Call. I am joined today by 4 other members of the Editas executive team, Baisong Mai, our Chief Medical Officer Eric Lucera, our Chief Financial Officer Linda Berkley, our Chief Scientific Officer and Karen Deardorff, our new Chief Commercial and Strategy Officer. We are pleased with Editas' momentum and progress in the Q3 and I look forward to sharing these details. Before that however, Let's take a quick step back to provide perspective.

Speaker 2

Editas' goal is to deliver life changing medicines to patients with previously untreatable For undertreated diseases. I joined Editas in June 2022 to help realize this goal, Tasked with guiding the company's evolution from a platform development company to a commercial therapeutics company. As many of you know, in January of this year, we shared Editas' vision and strategy to position Editas as a leader In programmable gene editing. As a reminder, 3 pillars underpin our strategy. 1st, to accelerate the clinical development of EDIT-three zero one, Our autologous ex vivo gene edited medicine for severe sickle cell disease and transfusion dependent beta thalassemia and drive it towards approval and launch.

Speaker 2

2nd, to sharpen our discovery focus to in vivo editing therapies and third, Expand our business development activities to partner complementary technological capabilities that can advance our in vivo pipeline development In addition to out licensing our robust IP and know how to maximize the use of CRISPR based medicines. At the start of 2023, we outlined the following 2023 objectives. For EDIT-three zero one, To provide a clinical update from the EDIT-three zero one RUBI trial for severe sickle cell disease or SCD by the end of 2023. To provide a clinical data update for MEDDOT301 EDITHOUT trial for transfusion dependent basal thalassemia or TDT by the end of 2023 And we have dosed 20 total patients in the RUBI trial by the end of 2023. For in vivo medicine development, Hire a new Chief Scientific Officer with specific expertise aligned to our vision and to advance the discovery of in vivo editing of hematopoietic stem cells or HSCs and other tissues and for business development to leverage our robust IP portfolio and business development capabilities These objectives in the Q3.

Speaker 2

Let's start with EDIT-three zero one. First, on clinical data, we will present a Company sponsored webinar in tandem with a poster presentation at ASH both on December 11, that is next month. We plan to share clinical data from 11 sickle cell patients in the RUBY trial and 6 beta thalassemia patients in the Edithal trial. Baisong will share more details about our presentation later on the call. 2nd, on enrollment.

Speaker 2

We have enrolled 27 sickle cell And 8 beta thalassemia patients into our RUBY and Edithal studies respectively and screening continues at a good pace. 3rd, on dosing, We now expect to dose the 20th patient in the RUBY trial in the January 2024 timeframe due to individual patient schedules. And finally, for 2024 data disclosures, we remain 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. Baisong will share further details regarding our December data readout And clinical progress of EDIT-three zero one is remarks. On the regulatory front, we are also pleased At just 2 weeks ago, the FDA recently granted us a regenerative medicine advanced therapy or RMAT designation to EDIT-three zero one for the treatment of SPEAR sickle cell disease.

Speaker 2

Advantages of the RMAT designation include all the benefits of the fast track and breakthrough therapy designation programs, including but not limited to Intensive FDA guidance on efficient and expedited drug development, possible rolling review and priority review of the BLA. With respect to commercial plans, as we previously shared, we made another important hire as we continue to gain momentum in pursuing a leadership position In hematopoietic stem cell medicines for hemoglobinopathies, in late September, we announced that Karen Deardorff, a highly experienced and successful therapeutics commercial leader Has joined Editas as our new Chief Commercial and Strategy Officer. Karen has a proven ability to translate early discovery and clinical assets into robust business strategies With disciplined portfolio prioritization and value creation. Additionally, she has led multiple successful U. S.

Speaker 2

And global product launches. Karen's expertise and track record make her the ideal leader to help Editas reach this goal for patients. To further enable commercialization, As previously shared in July, we will increase our clean room capacity when we move our CMC team into the new Asia Devon's facility in early With this increased capacity, we ensure our ability to scale EDIT-three zero one manufacturing, Both for clinical supply for our RWBY and EDITHAL trials as well as to prepare us for commercial readiness. In a step forward for the gene editing industry and Patients alike, we were delighted to see the recent XSL AdCom. The very focused review by FDA and the AdCom confirmed our confidence In the robust nature of our own off target assessment, the patient testimonials in addition were incredibly moving and powerful And demonstrate the significant need for new and transformative medicines for the treatment of sickle cell disease.

Speaker 2

Turning now to in vivo and our pipeline development. As stated earlier this year, our drug discovery group began lead discovery work On in vivo therapeutic targets in hematopoietic stem cells and other tissues. And in July, we hired Linda Berkley as our Chief Scientific Officer to spearhead these efforts. Linda looks forward to sharing more at the appropriate time. As a reminder, under our new target selection criteria, We will select therapeutic targets that will allow our genome editing approach to differentiate maximally from the current standard of care for serious diseases.

Speaker 2

The target selection criteria will work to identify targets that maximize the probability of technical, regulatory and commercial success. Now let's turn to business development. In August, we shared that we entered into an agreement with Vor Bio Providing a nonexclusive license for ex vivo Cas9 gene edited HSC therapies for the treatment and or prevention of hematological malignancies. Under this agreement, Editas received an upfront payment and will be eligible for future development, regulatory and commercial milestone payments As well as royalties on medicines utilizing the related intellectual property. Turning to our intellectual property position.

Speaker 2

As a reminder, Editas holds a large portfolio of foundational U. S. And international patents and is the exclusive licensee of Harvard University And the Broad Institute's Cas9 patent estates covering Cas9 use in developing human medicines. Only a small fraction of these patents are to the ongoing U. S.

Speaker 2

PTO interference proceedings. As the exclusive licensee, we are uniquely positioned to issue exclusive and nonexclusive sublicenses For Cas9 to any company seeking to use these enzymes to make human medicines, including in vivo and ex vivo uses. Our recently announced licensing deal with Vor Bio further bolsters our confidence that our IT portfolio provides meaningful value now and in the future. To conclude my remarks, we are energized by the promising efficacy and safety data we shared in June, to patients with sickle cell disease and beta thalassemia in the long term, specifically driving early and robust correction of anemia And sustained increases in fetal hemoglobin. With our sharpened 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 diseases.

Speaker 2

I will now turn the call over to Baisong, our Chief Medical Officer.

Speaker 3

Thank you, Gilmore. Good morning, everyone. Let's start with EDIT-three zero one in development of severe sickle cell TLDs and transfusion dependent beta thalassemia. As Guillermo mentioned in his remarks, we continue to enroll and dose patients in the RUBY trial for severe sickle cell disease and in the EDITOR trial for transfusion dependent beta thalassemia. As of today, in the RUBI trial, we have enrolled 27 patients And the 20 patients in the UBI trial is expected to be dosed in the January 2024 timeframe.

Speaker 3

In the Editale trial for transfusion dependent beta thiastimida, to date we have enrolled 8 patients. As I shared earlier this year, I have been visiting and Continue to visit our Ruby and Edisale clinical trial sites, continuously speaking with our investigators and I appreciate the enthusiasm and the support From the investigators and study sites, I'm pleased with the momentum of 8,301 in patient recruitment, apheresis, editing and dosing in both studies. I'm excited to hear from the investigators that patients dosed with ED-three zero one have already seen positive changes in their lives. As we have previously shared, we will engage with FDA in the second half of the year. On a related note, We found the recent exacel Eddycomb in cycle and it reaffirmed the power and potential of this gene editing technology.

Speaker 3

As a physician, I'm excited for patients living with serious diseases that gene editing has the potential to transform the treatment of the diseases And ultimately, patient lives. As a drug developer, I'm eager to see the first medicine approved And swiftly followed by more medicine from other companies including Editas. More importantly, I'm expected to announce that we will share Ruvi and EdiCell clinical data in a poster presentation at ASH As well as in the company sponsored webinar, both on Monday, December 11. So what we will show? The ruby data set will include clinical data from 11 patients.

Speaker 3

We will present efficacy data including total hemoglobin, fetal hemoglobin and vessel occlusive events or BOEs and safety data including neutrophil and platelet engraftment. The follow-up period of these 11 patients includes 2 patients with at least 12 months follow-up and an additional 4 patients with at least a 5 months follow-up. The other patients will have a 1 to 4 month follow-up period. The EdiSale data set We will present efficacy data including total hemoglobin and fetal hemoglobin And the safety data including neutrophil and platelet engraftment. The follow-up period after EDIT-three zero one treatment Includes at least 5 months data from the first two patients treated.

Speaker 3

The other patients will have 1 to 4 months follow-up period. As a reminder, this past June, we shared promising Rubi clinical data in oral presentation at the European Hematology Association Congress or EHA. Followed by our company sponsored webinar, we also presented positive initial data from the first patient treated in the EDITOR trial. The Rubi dataset covers safety and efficacy data from the first four patients, including 10 months data from the first patient treated and 6 months data From the second patient treated, including total hemoglobin and fetal hemoglobin, demonstrating AD301 drives Early robust correction of anemia to a normal physiological range of total hemoglobin in as early as 4 months after EDIT-three zero one treatment. EDIT-three zero one drives robust sustained increase in pre-thomeoglobin in excess of 40%.

Speaker 3

All 4 dosed to Rubi sickle cell patients remained free of vessel occlusive events since 831 treatment. Additionally, all dosed participants, including all Ruby patients and 1 EdiCel patient, showed successful engraftment within 1 month of dosing and have stopped the red blood cell transfusion. EDIT-three zero one was well tolerated by patients and the safety profile of EDIT-three zero one Was consistent with the myeloid to use soft and conditioning and autologous human proraxam cell transplant. And the trajectory of correction of anemia and expression of fetal globin was consistent across EDI-three zero one treated sickle cell patient and place the estimated patient at the same follow-up time points. We continue to believe that 8,301 can Potentially provide robust clinical benefit to patients with severe sickle cell disease and the transfusion dependent beta thalassemia, Potentially provide clinical differentiation in the long term.

Speaker 3

We look forward to our presentation of additional clinical data and a longer follow-up in December. As we have previously stated, the choice of CRISPR enzyme and the target to EDIT to switch on fetal hemoglobin expression matters. EDIT-three zero one use our proprietary ACE-two twelve enzyme to edit HB-two twelve promoter. ACECaslupta, increases the efficiency of editing and significantly reduce off target editing when compared to other CRISPR enzyme including Cas9. Editing HBG1 promoter editing HBG1two promoter in human CD34 particle cells Resulting greater red blood cell production and normal proliferative capacity and improved red blood cell health We look at the differentiation in 3 categories of endpoints in clinical trials: Hematological parameters and organ function and the patient reported outcome or quality of life.

Speaker 3

Based on the clinical data so far, we believe that sustained normal level of hemoglobin could be a potential point of differentiation for NKTR-three zero one. As a reminder, a sustained normal total hemoglobin level is an important clinical outcome for patients As the correction of anemia can significantly improve quality of life and ameliorate the end organ damage. We look forward to sharing additional data including Rubi and Edithair clinical data next month. Now I will turn the call over to Eric,

Speaker 4

Thank you, Beisson, and good morning, everyone. I'm happy to be speaking with you today and with 1 quarter under my belt at Editas, I'm even more impressed by the quality of our science, our leadership in the gene editing field, the strong intellectual property portfolio Our highly differentiated work from other players in the field. I was excited to join this summer and I continue to be impressed with what I see. With that, I'd like to refer you to our press release issued earlier today for a summary of our financial results for the Q3 2023. I'll take this opportunity to briefly review a few items.

Speaker 4

Our cash, cash equivalents and marketable securities As of September 30 were $446,000,000 compared to $480,000,000 at June 30, 2023. We expect our existing cash, cash equivalents and marketable equity securities to fund our operating expenses and capital expenditures into the Q3 of 2025. Revenue for the Q3 of 2023 was $5,300,000 which primarily relates to the upfront payment under the nonexclusive Cas9 license to Vor Bio in August 2023. R and D expenses this quarter were $41,000,000 essentially flat from the Q3 of 2022, which reflects various offsetting expenses, Including decreases in R and D spend related to our reprioritization and targeted focus on our EDIT-three zero one program, Offset by increased spending and pre commercialization efforts including medical affairs and patient advocacy, G and A expenses for the Q3 of 2023 were $15,000,000 which decreased from $16,000,000 for the Q3 of 2022. The decrease in expense is primarily attributable to decreased headcount expenses, including stock compensation and reduced legal costs.

Speaker 4

Overall, Editas remains in strong financial position bolstered by our sharpened discovery focus, June capital raise, Recent out licensing deal. Our cash run rate into the Q3 of 2025 provides ample resources support our continued progress in the RWBY and EDIT-three zero one, continue commercial manufacturing preparation and advance our discovery and research efforts. As I've shared before, I'm a former buy side investor and I know the value of buy side and sell side knowledge. I look forward to hearing from our shareholders as we work to advance our gene editing medicine. We value your feedback.

Speaker 4

And with that, I'll hand the call back to Gilmart.

Speaker 2

Thank you, Eric. As we continue our momentum And the execution of our goals remains an exciting year for Editas. We look forward to continuing our transformation and sharing our progress with you. 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, Investment Community, thanks very much for your interest in Editas and we're happy to answer questions. Thank you.

Operator

Thank you. We'll now be conducting a question and answer session. Our first question comes from the line of Brian Chiang with JPMorgan. Please proceed with your question.

Speaker 5

Are you doing a whole genomic sequencing and any other insights that you see are potentially through to your path to approval? Thank you.

Speaker 2

Brian, thanks very much. I'm afraid it was incredibly difficult to hear you with the background noise. And I know you're suffering from some Connection problems there. I think I heard you talk about off targeting. So I'm assuming you're referring to this week's test prompt.

Speaker 2

Yes. And so let me just go with that and then we can follow-up if it's incorrect. But I think you're fair to the outcome. I have to say is that the AdCom represents an incredibly and drove a great excitement for this week. It was a great day for sickle cell warriors, where patients now can think about not battling a disease, but actually living a life.

Speaker 2

It was a significant milestone for CRISPR genome editing as that AdCom represents or almost a penultimate step Towards approval for the 1st CRISPR based medicine. What struck us in the very focused discussion of the AdCom Was the positive tone, but actually also as we listened to the commentary, it really Substantially strengthened our confidence in the very robust data package that we've generated about off target ethics. I hope I've answered your question because with off targetetics what I heard, I think the only other thing I want to emphasize of course is that we have chosen to advance Our proprietary owned AF Cas12a enzyme, which indeed has higher fidelity and a significant reduction in off target edits when compared to At Cas9.

Speaker 6

Thanks, Gilmore. I guess my I don't know if you can hear me better now.

Speaker 2

Yes, that's better. I wonder

Speaker 6

if I could question. Okay, okay. Yes, so I'm just wondering if there were a lot of focus specifically on off target effects. So I'm just wondering if There is any work that you're doing now that is different than the gene editors, players that are in the market There are different to make sure that the regulators will be happy with the way that you're monitoring these off target effects. Thank you so much.

Speaker 2

Yes. Thanks, Brian. I mean, without going into details, I don't think it's appropriate this time to go into details, we are doing more That was discussed at the AdCom. And that's where our confidence about the robustness of our data package comes from. I hope that was the question.

Speaker 6

Yes, that was very helpful. Thanks, Gilmore.

Speaker 2

Thanks very much, Brian. It sounds like you're on a plane, so have a good trip. Okay.

Speaker 1

Yes. Just to follow-up on the last question Gilmore, and you sort of touched on this, the difference between CAS12a and CAS9. Can you just talk a little bit more in detail about what you're seeing as the different off target risk and how you'd be able to show that to regulators when you get to that step?

Speaker 2

Indeed happy to. Let me just preface again with the sort of high level that in published data, We have and others have shown a substantial reduction in off target editing when comparing AS Cas12a Versus the Cas9 enzyme. With regard to the data package that we have generated and continue to generate off target, It is substantial. I'm not sure that we are in place to share more details.

Speaker 3

I don't know, Linda, if you have anything to add.

Speaker 7

Yes. I would just add this is Linda Berkley, CFO. Yes, I would just Add and echo what Gilmore just said that we're using multiple orthogonal methods, Additional method as compared additional methods as compared to what we heard at the AdCom. And so we're very confident in our package as we proceed in our path to the BLA. And, yes, we in our preclinical data, we are not seeing more target editing in our preclinical experiments.

Speaker 7

So, We're very confident in our package going forward.

Speaker 8

Great. Thank you for taking the question.

Operator

The next question is from the line of Joon Lee with Truist Securities. Please proceed with your questions.

Speaker 6

Hey, thanks for the update and for taking our questions. Based on all that's been presented during the adcom, where do you see room for clinical differentiation? And is that

Speaker 5

Thank you.

Speaker 3

So I think the key thing

Speaker 2

is that we are very excited already by the clinical data that we have presented and what we see as a competitive fast follower With potential for differentiation and what we've seen to date was a consistent highest level of correction of anemia to the normal physiological Which is by design in our choosing of ASCAS12A to edit a gamma globin promoter. I'm going to ask Baisong just to tell you a little more about what we can about what we're going to share at ASH on December 11.

Speaker 3

Yes. Thanks, Gilmore. Thanks for the question, Jun. So as I mentioned that in the ASH Presentation will have data from 11 Ruby patients and 6 Adel patients and we will have a longer follow-up period with 2 patients in the movie trial with at least 12 months and then we have additional data from 5 months for the movie trial. I'll go back to your question also on these and AdCom in there.

Speaker 3

And we are very actually Pleased to see, as Gilmore mentioned, the very successful outcome and reaffirm, I believe, in technology and also The MOA of using phenylglobin as a target to treat sickle disease and beta thalassemia. And we for differentiation, we are confident that we are fast follower, we have differentiated molecule And we are very pleased to see that we presented data that we'll be able to correct the anemia. And in our case, the normal total hemoglobin for female was 12 to 16 gram per deciliter And for male, it's 13.8 to 18 gram per deciliter and we're pleased to see our patients going to the normal range and we're pleased to share more data during the ASH and web no presentation data next

Speaker 2

month. Yes. I think the only other thing is it's we do note that we've had very successful engraftment timelines. It's too early to say more than that in the space. And I think we're also very happy with where our hemolytic markers are.

Speaker 2

Excellent. Thank you so much. Thanks. Thank you very much.

Operator

Our next question is from the line of Greg Harrison with Bank of America, please proceed with your questions. Hey, good morning. Thanks for taking the question. Just thinking, when should we expect an update on the in vivo editing efforts? And How do you think the commercial opportunity is there relative to ex vivo in sickle cell?

Operator

And then what other indications or tissues do you

Speaker 2

Thanks very much, Greg. With regard to future updates, This is a company who philosophically wants to make promises and make discussions that we believe that we can absolutely deliver on. We have been doing work over the last year. Linda has already been here about 3 months, and we want to ensure that she has the time To again engaging with our medical and commercial team now led by our new Chief Commercial and Strategic Officer, the ability to make sure that we choose And progress against high conviction targets based on our selection criteria. With regard to your second question,

Speaker 4

let's just remind you again.

Speaker 2

Target Tissues. Target Tissues, yes, forgive me. So we have actually advanced work. In fact, Linda, I might ask you to talk about Target Tissues.

Speaker 7

Yes. Thank you. Yes, thank you for the question. So of course, we're very excited to develop an in vivo HSC program based on the success of the our targeting approach for sickle cell disease and PDT and so moving The targeting of the HBG-twelve locus to an in vivo approach. And so we're very well positioned for that, considering The emerging success that we're seeing in the clinic that Beisong has described, and so we're working very hard to Come up with the delivery strategy for in vivo HSC and we're doing that both internally and through potential And so that's a very I'm very excited about that avenue.

Speaker 7

And then in terms of other tissues of interest, We'll be talking about those in the future. We are interested in the liver, but I'll be talking about other tissues as In the future. Thank you.

Speaker 2

Thanks very much, Linda. And then with regard to the third part of your question, you asked about the commercial opportunity for in vivo. Essentially, what you can actually see is a strategy that we're driving, which progressively expands the number of patients And the fraction or portion of the patient population that can actually use the tissue or use these treatments. Allogeneic Open the door to therapeutics, but the substantial issue there was finding matched donors, where about only about onetenth Our patients can find a matched donor by going to autologous ex vivo, we've increased that tenfold. By going to in vivo And thus eliminating the risks and burdens of conditioning, We can actually further expand the patient population and address the unmet need that extends into patients who by not described Severe, it's worth remembering that the median survival for this disease in a developed healthcare system like that of the United States is about 45 50 as again was impressed upon us at the AdCom by those incredibly moving testimonies from patients and their parents and family members.

Speaker 2

And indeed in economies with no health care system, it's an 80% mortality about 5 years of age. So there is a substantial unmet need and in vivo We'll massively increase the commercial, the eligible patient population.

Operator

Great. That's helpful. Thanks again and looking forward to the update. Our next question is from the line of Gena Wang with Barclays. Please proceed with your question.

Speaker 8

Hi, questions. I think a lot of questions ask about The differentiating profile for your the EDI-one hundred and one. So maybe I wanted to Ask, in a way, actually, it was surprising we saw VOE events happen so early during Eksocell, Adacom. Wondering what is your thoughts there? And then for your efficacy clinical profile, what kind of See factors you can pay attention to in order to monitor these events and try to develop differentiated profile

Speaker 2

Thank you very much, Gena. So I just want to recapitulate your questions, be sure I get it all, you want to talk about the differentiation of our EDIT-three zero one product for As we're focusing on severe sickle cell disease, you were interested in or surprised to see VOEs Reported in some patients post treatment at the AdCom. And I think, Riese and also understanding what are the elements that we're monitoring for differentiation in our efficacy profile. What I will start and then pass I can start and then I'll have Baisong comment on The differentiation of our efficacy profile. With regard to the BOEs, I think understanding a full explanation will be hard for us at this point.

Speaker 2

There were many elements of the data that were not presented, which is not surprising in a very truncated presentation. But obviously, looking at the correlation of fetal hemoglobin expression, the other factors that can drive VOEs, etcetera, is something that we obviously look forward to get with more data being able to understand. I think what does stand and remains true is that the upregulation of fetal hemoglobin Actually has a substantive impact on controlling VOEs. Now as we look to differentiation for EDIT-three 301, we're looking beyond not just the control of the OEs, but actually correcting other elements of the disease. And with that and with a particular focus on the correction of anemia to normal physiologic range and its impact, I'll ask Baisang to talk more about that.

Speaker 3

Yes. Thanks, Gilmore. Yes, Gina, yes, absolutely. We are still very confident that we believe that Eddy's run is a differentiated molecule. Given that what we've seen so far, we have to see that we can actually correct it Correction of the limbic to physiological range of total hemoglobin.

Speaker 3

And with that, we look into that Not only hematological parameter, but in organ function and as well as patient reported outcome. So we continue to believe that direction Well, allow us to demonstrate differentiation.

Speaker 2

One key thing I think is worth highlighting when you talk about patient reported outcomes Is that fatigue is a significant complaint. In fact, again, we heard it as the patient testimonials, lack of energy, fatigue, not just The hospitalizations and pain, but fatigue and loss of energy. And so those are important elements or specific sub domains of the Patient 4 outcomes that we're paying attention to.

Operator

Our next question comes from the line of Jack Allen with Baird. Please proceed with your question.

Speaker 9

Great. Thanks so much for taking my question and congratulations to the team on the progress made throughout the quarter. I wanted to ask a little bit about the RMAT discussions. To what degree was the differentiation on total hemoglobin discussed in the RMAT? And then I believe during the prepared remarks you mentioned a more substantial data set In mid-twenty 24, during the RMAT discussions, did you have any conversations around what could be viewed as a pivotal data set here and I'd love to hear any thoughts, if so?

Speaker 2

Thanks very much, Jack, for your question. I think the first thing is, it's premature to go into the details of discussions about the FDA. However, I am glad that you highlighted RMAT because indeed the FDA does and did review clinical data Including hematologic parameters, which as you quite correctly pointed out include the correction of anemia. And as we said, we also included the non clinical package to demonstrate how that happened by design. I think the other point about the RMAT obviously as we said in the prepared remarks is that it essentially Increases our confidence in the timeliness review through the various mechanisms that are available to us both with high frequency engagement with the agency going forward As well as the possibility of our priority review and rolling submission.

Speaker 2

You asked about the substantive data set. And I think what I would say is that if you look to Exacel as a benchmark, We've actually seen that the original Exacel BLA accepted by the FDA included an efficacy data set of 20 patients with 16 month An additional efficacy data set of 10 patients was added to that during the review period. Well, that actually tells us when you look at our being on track to dose our 20th patient by January in the January 24 timeframe And the continuing robust enrollment that we're seeing in our Ruby study, it really validates our line of sight to Creating or generating and present being able to present in the middle of 2024 a substantive data set with robust follow-up Around a period that shows the correction of anemia and fetal hemoglobin expression and validates line of sight to a BLA into 2025.

Speaker 9

Great. Thanks so much for that color.

Operator

Thank you. Our next question is from the line of Dae Gon with Stifel. Please proceed with your questions.

Speaker 10

Hey, good morning guys. Thanks for taking the questions. Maybe I'll Briefly go back to the off target editing and then a BD one for Karen. On the off target editing, I guess, Gilmore, you talked a lot about the differentiation of ASCAS 12A versus the CAC9 being used. Just Curious, does that in your view think you need a little bit more characterization work on the molecular side given that Cas9 is being a little bit more prevalent we use on the CRISPR Cas based medicine field.

Speaker 10

And maybe as an offshoot of that, I think there were also around how Exacel ran all these analyses in a more theoretical manner, but didn't really test the treated patients' blood samples pre and post. So you confirm if you guys are doing the pre and post testing of the blood samples to see if off target editing is actually happening or not? And then question for Karen. To an earlier question about BDN expansion opportunity, you talked about the in vivo HSD delivery, but I don't know

Speaker 6

if that was intentional or not, but

Speaker 10

I didn't hear you talk about non genotoxic conditioning. So I don't know if you can comment on a little bit more on that. Do you see that as Part of your armamentarium going forward, perhaps your Magenta experience can speak to that. Thanks so much.

Speaker 2

So thanks very much, Jaigong. With regard to the AS Cas12 versus Cas9, I think the first takeaway is that we have Published. We have published data from ourselves and other labs showing that there is A differentiated significant reduction of targets with ASCAS12a. Secondly, we have a variable we don't actually believe That the prevalence of Cas9 would change the requirements for off target data package generation. 3rd, Our data package that we've generated to date is very robust.

Speaker 2

And as Linda said, we're using multiple orthogonal both in silico And in vitro evaluations, also including by the way our non clinical talks In vivo, but evaluations that go beyond what we saw presented and discussed at the AdCom. So again, all of that adds to our confidence. And then finally, we are actually testing the drug product. So that's kind of the old target. If I could then turn to your question around non or Non genotoxic conditioning.

Speaker 2

This is an area that remains of interest to us. We have done internal work. We're also monitoring the external landscape. One of the things one of the additional benefits of having Karen join us is that she knows, as you quite correctly pointed out, that space very well. So Karen, I don't want to add further commentary.

Speaker 1

Yes. Thank you. Thanks for the question. And just want to comment how excited I am to be here with the Editas team to help move these therapies forward. You bring up a really important point, something that's important to all of us and will absolutely be part of the evolution Of this market space and treatment modality, I think the benefit today is that the risk benefit for severe sickle cell And TBT does remain very strong with the current offering, but we take it very seriously and we're doing a lot Important work to try to make sure we are part of moving forward, to evolve this to be overall better treatment.

Speaker 2

Excellent. Thanks so much.

Speaker 11

Sorry, Linda, in addition to the call.

Speaker 7

I just wanted to add to what Gilmore had said, like to affirm that we do test, We have tested drug product lots from a larger number of sickle cell disease patients To confirm the and have not detected off target editing in that larger number of sickle cell disease patients with samples.

Speaker 11

Thanks guys. Thank you, David.

Operator

Our next question is from the line of Phil Nadeau with C. D. Cowen.

Speaker 12

Good morning. Congrats on progress and thanks for taking our questions. 2 from us. First, In terms of continued recruitment in the clinical trials, do you assume any change in the rate that you'll be able to recruit patients Following what seems likely to be the approvals of the first two genomic medicines for sickle cell disease, by the end of the year? That's the first question.

Speaker 12

And then 2nd, a follow-up on differentiation. How long a follow-up do you think you'll need to determine whether fatigue or the hemoglobin levels are truly differentiated. Is that something that you'll know kind of relatively quickly? Or will that take Months, if not years of follow-up to Determine. Thanks.

Speaker 2

Thanks very much, Phil. With regard to recruitment, no, we do not expect Any change? We believe that our enrollment will continue to grow robust. I'll pass That's a Bae Song, who can tell you about his personal experience and conversations with sites and investigators.

Speaker 3

Thanks, Phil, for your question. Really, I've been continuously visiting study sites. I see really a very strong momentum and feedback about it. And we actually have many patients on our list for this trial. So we actually do not see the impact, but we continue to see the positive momentum.

Speaker 3

And not only now, but I will see it for next year and we will continue to see the momentum on that.

Speaker 2

And indeed, the investigators said that notwithstanding This is still an area that they are particularly interested in with regard to our therapy and the trials. You asked the question about differentiation And with regard to the time to actually see differences in total hemoglobin and then what some of the more downstream Clinical impacts would be around fatigue or other outcomes and I'm going to ask Baisong to talk about that.

Speaker 3

Yes, yes. Yes. So this is actually a very important question. We are looking into that is, as I mentioned, we're looking to our 3 categories of Clinical endpoints for the differentiation. Certainly that for hematological parameter, you will be taking shorter time to see.

Speaker 3

And for the patient reported outcome, for example, you specifically mentioned the fatigue. Usually based on my experience in other studies that when you kind of see this patient reported outcome, Usually it takes 6 months then for the CBDC you see something that usually takes 6 to 1 year you will see some kind of improvement, but you monitor longer you will see a much more Impact fall compared to the baseline. So we are very optimistic and confident that we will be both be able to see something in that direction for patient reported outcome on that. And the other category I mentioned is also for the end organ damage and we actually look into the cardiac, pulmonary, liver and CNS and as well as the kidney, so we'll also see that looking forward to see the improvement. These areas are relatively new, But there are publications for allogeneic bone marrow transplant for sickle cell patient, for example, in the brain Blood vessel or blood the vascular system in brain and also the in cardiac system, So there are some reports relatively limited, see that allogeneic transplant for CCCL patients could potentially actually improve the organ The improved organ function.

Speaker 3

So we're looking forward to that direction. Yes.

Speaker 2

Phil, one of the things I would say is That, you know, Beisong and I have been around the block long enough as drug developers, to know that, you know, when you are start applying New outcomes, measures in clinical trials using potent new medicines that have sort of have an unprecedented potency in disease, Your ability to absolutely firmly predict the absolute time point, the number of patients, etcetera needed to actually demonstrate that benefit Can vary and require additional work. So while we are very enthusiastic about the work that we're doing here, We also are pragmatic and experienced enough to know that, we will see hematologic parameters Quickly, we may see end organ functional physiologic parameters in a slightly longer term. And then with regard to other outcomes, Some of that will be, as I say, we're optimistic, but we have to just temper that with the realism that it may take somewhat longer.

Speaker 12

That's very helpful. Thanks again and congratulations on the progress.

Speaker 2

Thanks very much.

Operator

The next question is from the line of Yanan Xu with Wells Fargo. Please proceed with your questions.

Speaker 5

Hi, thanks for taking my questions. So I was wondering, a focus at the AdCom was the adequacy of the number of patient samples Tested for off target and whether that's enough to characterize the risk in Certain patients with genetic variance, I think I was wondering in your off target Analysis work, are you targeting again single digit sample numbers or Are you targeting a number significantly higher than that? The next question is about Percent fetal hemoglobin as a differentiator. I think you talked a lot about total hemoglobin. But I was wondering, based on your on the data you have reported so far and also in abstract At ASH, seems like you had 3 patients of your first four patients Who had greater than 50% fetal hemoglobin.

Speaker 5

I was wondering about your confidence of that being replicated in additional patients and also That being a differentiator. And lastly, I was wondering about your thoughts on whether there is A correlation between total hemoglobin and hemolytic markers and whether you can comment on your thoughts there, I. E. Higher maybe at a patient level, whether a higher total hemoglobin Is correlated with better hemolytic marker observations? Thank you.

Speaker 2

Thanks very much, Yanan. So I'm going to Try and choreograph a set of answers to a complex set of questions, if you will, or a quite diverse set of questions. So With regard to

Speaker 3

the AdxSu sample, I think

Speaker 2

the first thing we should do is just remind ourselves that the discussion, the very so what I would say, the informed discussion at the AdCom Demonstrated that a robust evaluation of at risk Really shows that from an off target point of view, the risk management even with the data set presented to the AdCom was actually very good. I will say that we are using additional, anomoltoplicity or orthogonal in silico and vitro and I need some in vivo, that's no, I can't say, but in silico and in vitro assessments, which go well beyond what was shown at the AdCom In our data package, I'm not going to go into the specifics of the numbers of patients just to say it's more. And obviously, we'll share more detail about that at an appropriate time in the future. I think the other thing about the variance, again, I just want to reaffirm that I thought actually that The discussion by the geneticists at the AdCom was very illuminating. I thought Both parties, the experts on the panel as well as in the sponsor really articulated very clearly how The nature of variation, the nature of common ancestry for all humanity and how we can really manage and identify variance and the risks Associated with that, I think it was a very robust discussion.

Speaker 2

And again, it gave us great confidence in our management of risk And the data package that we're generating there. Linda, I don't know if you want to add to that.

Speaker 7

No, I think that was a very good summary. I think that there was yes, I think that was a very good summary. Gilmore, I'm not going to add.

Speaker 2

Thanks very much, Linda. With regard to the percentage of fecal hemoglobin as a differentiator, obviously, we're excited about the data we show. It's early days yet. And what is clear from the experience described for People who have coincident inheritance of hereditary persistence of fetal hemoglobin with sickle cell disease or indeed thalassemia Is that the higher the level of fetal hemoglobin or percentage or fraction of fetal hemoglobin, The greater the benefit certainly for sickle cell disease. I'd say it's early days for us.

Speaker 2

But based on what you want to add to that? Yes. Yes. I'll come back to the 3rd question.

Speaker 3

Yes. Thank you, Inan, for this question. As Kim mentioned, we are very pleased to see the total the pivotal data as you refer to actually see patients over 50%. And this is we are excited on that. It's also because this is a rational design approach for ED-three zero one.

Speaker 3

We compared that this approach After targeting the HBG12 promoter, with HBG12 promoter versus BCL11A, we found that we have better Philsen globin expression. But we are in

Speaker 2

the early stage.

Speaker 3

We actually want to see more data to this end And we're looking forward to see more that ourselves on that.

Speaker 2

Thanks very much, Baisong. I think your final question was around the While hemolytic hemolysis is a critical part of sickle cell disease, The key driver we believe for driving total hemoglobin by design is enhanced erythroid production. Maison, I don't know if you want to add anything.

Speaker 3

Yes, that's exactly right, Guillermo. That's what we're going to say. I think what I want to mention that We are very positive about our hematologic marker data on that. And then the So the total hemoglobin level is related to 2 aspects of that. 1 is hemolysis, only the every 3 process.

Speaker 3

So we I think in our design, we designed to have this molecule have high fetal hemoglobin expression and also With the targeting of the HBG-one hundred and twenty two promoter, we have better atherosclerosis and better red blood cell production. So we are looking forward to see more data on that, but we are very pleased with our hemolytic biomarkers.

Speaker 5

Great. Thanks for the color.

Operator

Thanks. Thank you. Our next question is from the line of Eric Schmidt with Cantor Fitzgerald.

Speaker 2

The overall level of interest in potential platform type collaborations. Thanks. Thanks very much, Eric. With regard to the total hemoglobin, we believe that correcting That's what we've seen. Hemoglobin Physiology range is of substantial benefit.

Speaker 2

I think it's we haven't we're not going to it's hard to speculate about a level that is Too high. Indeed, there has been an experience in general with polycythemia In sort of a broader patient population with some conflicting data about the risks of SAME. As I say, we feel very confident about the data we're getting in regard to our total hemoglobin and the way that we are correcting it to normal physiological ranges. I think you asked a question about some recent gene no editing deals just this week That are announced. What I would say is that what is striking about it is, it is great to see pharma, I say big pharma now in a period where we've seen some dearth of deals leaning in And increasing their excitement around the genome editing space.

Speaker 2

In other words, what I would say is this has been a very good week For CRISPR genome editing space with both that sort of critical near to final step towards approval for a first CRISPR based therapy And to see now pharma actually looking essentially to the lens of substantial derisking of their view of the value of genome editing As they look to grow their portfolios. I don't know, Dave.

Speaker 1

Yes. Thanks, Eric. It's Karen. What I would add is, I think Editas is so well positioned right now having refocused the portfolio. We are in a great place to be able to move our own programs forward And are very excited by the continued interest, and it opens the door for partnering should that be the right path for us.

Speaker 5

Thank you.

Operator

Our next question comes from the line of Steve Seedhouse with Raymond James. Please proceed with your questions.

Speaker 13

Good morning. Thank you. Two quick ones. First, are lymphocyte and neutrophil counts at baseline and post transplant something That you are going to share in either the poster or the associated presentation at ASH. And then separately, is it your intent at Editas to commercialize EDIT-three

Speaker 2

Thanks very much for that question. With regard to neutrophil engraftment data, That is something that we actually did present at our EHA and it would comprise Could be summarized in our presentations at the end of the year because it's actually a measure of engraftment is part of the safety Monitoring that we do in our studies. And then with regard to your second question, which was around Commercializing 301 on our own. Well, we actually look to commercializing 301. We're actually building towards that, because we believe that's important.

Speaker 2

We have indicated previously that we're interested in an ex U. S. Partner With a large footprint, obviously the details of any such partnership and how that might expand would really depend very much in those negotiations that we would share upon any kind of agreement, but only then.

Speaker 13

Gilmore, just to clarify, I was asking about lymphocytic and neutrophil counts Like longitude only post transplant just because in the exo cell data they don't recover to baseline. So I'm just curious if That's something you plan to share and it would be interesting to know whether it's different or the same given the different genomic target and different editor?

Speaker 2

So well, we have not seen we've been actually very happy with our accounts. We're actually very happy with our accounts to date. But we can follow-up on that.

Speaker 9

Thank you.

Operator

Our next question is from the line of Luca Eze with RBC. Please proceed with your question.

Speaker 11

Great. Thanks so much for taking my question. Two quick ones here. Maybe based on, it sounds like you're obviously on track to those 20 By January 2024, are you enrolling any adolescents? Just trying to understand if there is a scenario Where your initial label will just include adults versus some of your peers, you'd also get a broad label that also includes adolescent.

Speaker 11

So again, any color there, much appreciated. Maybe second one, quick one for Linda here. I think during the AdCom earlier this week, one of the potential suggestions to further characterize off Target editing risk goes to actually do whole genome sequencing in 20 patients before and after Genetic manipulation, so I just wonder if that's something that you're contemplating to do? Thanks so much.

Speaker 3

Thank you for your question. I'll take your first question and then I'll pass that. I think we have a plan To dosing adolescent patients and also for the general clinical programs, we are intended to go to all patients of all ages. So that's kind of what because this disease is essentially starting with the genetic disease start from very young age. So we intend to actually Be able to have this molecule be a benefit patient from all ages.

Speaker 3

So that's kind of our intention. I mean, all those things, of course, The label you mentioned will have further discussion and alignment with FDA.

Speaker 7

Yes. Thank you for your question. Yes, that was a very interesting conversation at the AdCom. One of our orthogonal methods and this also came up at the AdCom was the method of using a biochemical Method applied to Mika DNA and this is a method, one of the methods that we use, Which is unbiased method, in which the naked DNA is taken from And you subjected to cutting with your RMP and then you do whole genome sequencing basically to look And so this is called diagenome. And so this is one of our methods that we use and look at With our drug product before putting that drug product into patients.

Speaker 7

So I think this is one of the robust criteria that we one of the robust methods that we use in our approach. So I think that's basically one of the reasons that we are confident in our approach to in addition to the other methods We use in Silico and GuideSeq that were described. I guess that's basically what I'm Prepared to share at this moment, but there are many other aspects to our approach that will also make us very confident About our approach to the off target editing package that we're preparing.

Speaker 11

Got it. Thanks so much.

Operator

Our next question is from the line of Jay Olson with Oppenheimer. Please proceed with your question.

Speaker 14

Hey, congrats on the progress and thank you for taking the question. Maybe just another question on read across from the So Adcom, since there was some discussion about long term monitoring and surveillance of these patients, can you just Share your thoughts and plans to follow EDIT-three zero one patients long term in a post approval setting? Thank you.

Speaker 3

Yes. Thanks for the question, Jay. So we certainly will have a long term follow-up for patients and So that study is designed to actually form a patient up to 15 years for anybody who actually dosed with EDIT-three zero one and that's also consistent with the regulatory requirements. So that's absolutely our plan.

Speaker 14

Great. Thank you.

Operator

Next question is from the line of Lisa Bacow with Evercore ISI. Please proceed with your question.

Speaker 15

Hi, this is Jingming on for Lisa. Thanks for taking And congrats on the progress. So we have three questions. First, we know that CVC has filed an appeal to the Court of Appeals. When do we expect to hear the decision for that?

Speaker 15

And then second, as I know you mentioned that more Data set for sickle cell is coming in the middle of 2024. I'm just wondering when should we expect more substantial data set for the TDP patients? And then the third is, you mentioned that in the second half, you plan to engage with the FDA to seek alignment on regulatory path for 301. We are wondering, will you inform The Street on the results of the discussion? And if so, what's the timing for that?

Speaker 15

Thank you.

Speaker 4

Hi, this is Eric. Just with respect to any courses in front of court cases in front of the CVC or anything like that, well, don't really want to comment on those until the final decision is actually rendered. So we'll just be anxiously awaiting for all of that just like you.

Speaker 3

Yes. So this is based on for your second question about the middle of next year for the program. And as a two part of that, one is as we just shared that we will have 20 patients dosed by January timeframe next year, By middle of next year, we will have substantial follow-up for the 20 patients and we also have continued dosing patients over the course. So we'll have a lot of data the middle of next year for sickle cell disease. Yes.

Speaker 3

Regarding the We'll

Speaker 15

have that for the beta thalassemia patients.

Speaker 3

Yes, absolutely. Absolutely. Yes. So because I thought your question probably covered both, but I just make sure that we cover on that. And we actually have very strong momentum for AdiCell study also and that we just shared that we actually already have 8 patients enrolled And we continue to enroll and dosing patients.

Speaker 3

And but we have not shared what is the goal for next year, how many patients additional patients were dosed yet. We will share that in appropriate time. And your third part of your question is about FDA engagement and outcome. And so we are we're well engaged with FDA and we continue to have engagement with FDA. As we just mentioned that we actually have this RMAT Designation allow us a lot more frequent interaction with the agency, including senior management over there over the agency.

Speaker 3

But we have not I have a timeline to share the outcome yet. We'll share that in corporate time.

Speaker 15

Got it. Thank you.

Operator

Our next question is from the line of Mani Forhar with Leerink. Please proceed with your question.

Speaker 16

Hi, good morning. This is Lillian Songo on line for Manny. Thank you for taking our question. I just wanted to ask if you could potentially give us An update on the progress of the manufacturing scaling for 301, both for clinical development and for potential commercialization. And then on the other side, second question, in terms of the package for BLA, so with the I think you had mentioned potential package readiness by 2025.

Speaker 16

By then, we might have post marketing data from Potentially 2, gene therapy program. I was wondering if you and how you would see that, impacting potential pivotal design?

Speaker 2

Thank you.

Speaker 4

Hi. This is Eric. I'll take the first question with respect to the manufacturing scaling and timing. As a reminder, we're very confident in what we're doing and making the investments in manufacturing for the commercial launch. We haven't specifically commented on the scale or timing, but just reiterate our confidence in everything we're doing on a manufacturing standpoint.

Speaker 3

Yes. So, yes, this is based on for your second part of your question. As we share that we will have 20 patient dose by January time from next year By the middle of next middle of 2025, then we will have substantial debt of high digits probably equivalent To the AXA BLF filing, which is accepted by FDA, which have like 20 patients in the efficacy data cohort. So they subsequently added additional 10 patients in their addendum with the 4 months additional 4 months data afterwards. So we expect that we will be able to file the FDA equivalent package to we will have equivalent data package by the middle of next year.

Speaker 3

But what exactly the FDA data package when it's aligned with FDA. So that we are that will have The agreement with that, yes, on that too. And you mentioned about post marketing or the commercialization of these 2 molecules. And as I shared earlier that We do not see that recruitment momentum perspective and you mentioned about data package and we're actually very excited by the Outcome discussion, we feel that these outcomes have further validation of CRISPR technology, For the validation of the fetal hemoglobin as a mechanism of action to treat sickle cell and beta thalassemia, we actually see all those work have a positive impact of EDIT-three zero one.

Operator

Thank you. Our final question comes from the line of Terence Flynn with Morgan Stanley. Please proceed with your question.

Speaker 17

Great. Thank you for taking our question. This is Max Skor on for Terence Flynn. So looking to the future a bit, can you expand on your approach Target selection, how we should think about your pipeline evolving going forward? Also,

Speaker 9

as

Speaker 17

you think about tissue Specific delivery for your future in vivo programs, how are you thinking about the advantages and disadvantages to investing in AAV and or LNP? Thank you.

Speaker 7

Yes. Hi. Thank you very much for your question. So as far as target selection, Our approach is really to apply criteria so that we are well differentiated from standard of care. It's Very important that we're delivering medicines that are meeting needs that the patients have that are not Already met by existing therapeutics.

Speaker 7

And so we are going to look for targets in which we have high conviction Chin as well as targets that have high probability for technical as well as clinical and commercial success. And so I'm Very excited to have Karen having joined, so that I can partner with her as well as Beisong in triangulating this To very much select our targets, I think we're really well positioned now to be selecting these. We're as I said Before, I think we're very excited about the in vivo sickle cell disease, TD2 target, Because we already have emerging data supporting that target and getting to your question about delivery, Our strategy, which Gilmore described in January, is non viral delivery. And so we are Prioritizing LNP delivery amongst the non viral deliveries and working internally as well as through external partners To derive a approach for in vivo HSC targeting for our HBG-twelve promoter With an LNP strategy. As far as other targeting tissues, of course, LMTs are validated for delivery to deliver.

Speaker 7

So We're interested in that and I think we're well positioned there as well with our technology and especially with the recent deal that we saw Announced and just showing the interest, continuing interest in pharma in this space. And but we're also interested in other tissues. And so there are many targets out there amenable to Edesys Technology and we're excited To move forward and we'll certainly be sharing information with you as we as it emerges in the future

Operator

Thank you, everyone. This will conclude today's conference. You may disconnect your lines at this time.

Speaker 2

We thank you for your participation.

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Earnings Conference Call
Editas Medicine Q3 2023
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