Q3 2023 Editas Medicine Inc Earnings Call

Yeah.

Good morning, and welcome to edit test medicines 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 Kristy Barnett corporate communications and Investor Relations at <unk> Medicine.

Thank you Rob good morning, everyone and welcome to our third quarter 2023 conference call.

Earlier. This morning, we issued a press release, providing our financial results and recent corporate updates.

Replay of today's call will be available in the investors section of our website in approximately two hours after its completion.

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

As a reminder, various remarks that we make during this call about the company's future expectations plans.

And prospects.

Institute forward looking statements for the purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC as updated by our subsequent filings in addition.

Any forward looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date.

Except as required by law, we specifically disclaim any obligation to update or revise any forward looking statements, even if our views change.

Now I will turn the call over to our CEO Gilmore O'neill. Thanks.

Thanks, Christine and good morning, everyone.

Thank you for joining us today on our head to test medicines third quarter earnings call I.

Im joined today by four other members of the edits has executive team based on my our Chief Medical Officer, Eric <unk>, Our Chief Financial Officer, Linda Berkeley, Our Chief Scientific officer, and parent Deardorff, our new chief commercial and strategy officer.

We are pleased with Eddie passes momentum and progress in the third quarter and I look forward to sharing these details before that however, let's take a quick step back to provide perspective.

It is fastest goal is to deliver life changing medicines to patients with previously untreatable or <unk>.

<unk> diseases.

Joined Eddie's has in June 2022 to help realize this goal tasked with guiding the company evolution from platform development company to a commercial therapeutics company.

As many of you know in January of this year, we shared at it has the vision and strategy to position that he passed as a leader in programmable gene editing as a reminder, three pillars underpin our strategy first to accelerate the clinical development of edit 301, our autologous ex vivo gene edited.

Medicine for severe sickle cell disease, and transfusion dependent beta thalassemia and drive it towards approval and launch.

Seconds to sharpen our discovery focused 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 or some robust IP and knowhow.

To maximize the use of CRISPR based medicines.

At the start of 2023, we outlined the following 2023 objectives.

For edit 301.

To provide a clinical update from the edit 301, Ruby trial for severe sickle cell disease or <unk> by the end of 2023.

To provide a clinical data update from edit 301 trial for transfusion dependent beta thalassemia for TVT by the end of 2023 and two have dosed 20 total patients in the rupee trial by the end of 2023.

For in vivo medicine development to hire a new chief scientific officer with specific expertise aligns to our vision and to advance the discovery of in vivo editing of hematopoietic stem cells or HFC and other tissues.

And for business developers to leverage our robust IP portfolio and business development capabilities to drive value and to complement our core gene editing technology capabilities.

So how we executed against the strategy and these objectives in the third quarter less.

Let's start with edit 301.

First on clinical data, we will present, a company sponsored webinar in tandem with a poster presentation at ash. Both on December 11th that is next month.

We plan to share clinical data from 11, sickle cell patients and the Ruby trial and six beta thalassemia patients in the edits all trials.

Based on with share more details about our presentation later on the call.

Second on enrollment, we have enrolled 27th sickle cell and eight beta thalassemia patients into a Ruby and Eddie found studies, respectively and screening continues at a good pace third on dosing, we now expect to dose the 20th patient and there will be tried in the January 2024 time frame due to.

Patient schedules.

And finally for 2020 for data disclosures, we remain on track to present, a substantial clinical data set of sickle cell patients with considerable clinical follow up in the Ruby study in the middle of 2024.

Based on will share further details regarding our December data Readouts and clinical progress of edit 301 in his remarks.

On the regulatory front. We're also pleased that just two weeks ago. The FDA recently granted us a regenerative medicine advanced therapy or <unk> designation to edit 301 for the treatment of severe sickle cell disease.

The advantages of the Army designation include all the benefits of the fast track and breakthrough therapy designation programs, including but not limited to intensive FTA guidance on efficient and expedited drug development possible Rolling review and priority review of the BLA.

With respect to commercial plans as we've previously shared we made another important higher as we continued to gain momentum in pursuing a leadership position in hematopoietic stem cell medicines for hemoglobin office in late September we announced the current deardorff, a highly experienced and successful therapeutics commercial leader has joined Eddie's has cause our.

New chief commercial and strategy officer.

Parent has a proven ability to translate as early discovery and clinical assets into robust business strategies with disciplined portfolio prioritization and value creation. Additionally, she has led multiple successful U S and global product launches has expertise and track record make her the ideal leader Alcibiades has reached this gold 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 age or Devin facility. In early 2024 with this increased capacity, we ensure our ability to scale edit 301 manufacturing.

For clinical supply for our Ruby in any field 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 extra sell AD com, but very focused review by FDA and the AD comm confirmed our confidence in the robust nature of our own off target assessments.

Patient testimonials. In addition, we're incredibly moving and powerful and demonstrate the significant need for new and transformative medicines for the treatment of sickle cell disease.

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 targeting hematopoietic stem cells and other tissues and in July we hired Linda Berkeley, 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.

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 four bio providing a nonexclusive license for ex vivo past nine gene edited HSC therapy for the treatment and prevention of Hematological malignancies.

Under this agreement and it has 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 as a reminder, Eddie task holds a large portfolio our foundational U S and international patents and he is the exclusive licensee of Harvard University and the broad Institute past nine patented states covering past nine used in developing human medicines.

Only a small fraction of these patents are involved in the ongoing U S PTO interference proceedings at.

Is the exclusive licensee we are uniquely positioned to issue exclusive and nonexclusive sub licenses for cast nine 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 four bio further bolsters, our confidence that our IC 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 they couldn't do that edit 301, maybe a clinically differentiated onetime durable medicines that can provide life changing clinical benefits to patients with sickle cell disease and beta thalassemia in the long term specifically drive.

<unk> early and robust correction of anemia.

And sustained increases in fetal hemoglobin.

With our sharper strategic focus are world class scientists and employees at our keen drive and execution, we continue to build momentum to progress our strategy to deliver differentiated editing medicines to patients with serious genetic diseases I will now turn the call over to based on our Chief Medical Officer.

Thank you Guillermo.

Good morning, everyone.

Let's start with edit 301 in development for severe sickle cell disease, and transfusion dependent beta thalassemia.

As Guillermo mentioned in his remarks, we continue to enroll those patients in the Ruby trial for severe FICO LTV and in the NFL trial blood transfusion dependent beta thalassemia.

As of today, and the Ruby trial, where we enrolled 27 patients in the Twenty's patients in the trial expected to be dosed in January 2024 time frame.

In the D C O trials like transfusion dependent beta thalassemia to data, we haven't enrolled eight patients.

As I shared earlier this year.

Visiting and continue to visit our Ruby and how do you sell clinical trial sites.

The newest fleet speaking with our investigators and I appreciated the easy Adam and the support from the investigators and study sites.

I'm pleased with the momentum of Eddie for you one in patient recruitment a free seat editing and dosing in both studies.

I'm excited to hear from the investigators the patients dosed with Eddie for you one have already seen positive changes in their lives.

As we have previously shared we were engaged with the FDA in the second half of the year.

On a related note we found in the recent extra sale outcome insightful and it is we affirmed the power and potential of these gene editing technology.

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 Adidas.

More importantly, I'm ecstatic and alongside that we will share Ruby and Eddie cell clinical data in a poster presentation at ash as well as even a company sponsored a weapon that both on Monday December 11th.

So what we will show.

There will be that a fair way, including clinical data from 11 patients.

We will present efficacy data, including total hemoglobin fetal hemoglobin and nobody saw cookie banks, all B O S.

And a safety data, including mutual feel and tabulating government there.

The follow up period of these 11 patients, including two patients with at least 12 months follow up and an addition of four patients with at least five months follow up.

The other patients that we have.

Our one to four months follow up period.

The only thing I'll get it that way through the clinical data from six patients.

We will present efficacy data, including total hemoglobin and the fetal hemoglobin and a 50 data, including mutual feel and Pep looking back on it.

The follow up period after Eddie Sweden when treatment includes at least five months data from the first two patients treated.

The other patients that have one two for my follow up period.

As a reminder, this past June we shared promising movie clinical data in an oral presentation at the European Hematology Association Congress or E.

Followed by our company sponsored weapon. We also presented positive initial data from the first patient treated in the trial.

There will be datasets cover safety and efficacy data from the first four patients, including 10 months that up on the first patient treated and six months data from the second patient treated.

Including total hemoglobin and feed them.

Demonstrating Eddy Street widen drives early robust correction of anemia to a normal physiological range of total hemoglobin and as early as four months after asking three in one treatment.

And if we weren't drives robust a sustained increase in feet on the globin in excess of 40%.

All forward those two movie sickle cell patients remained free of vessel completed banks since 83, one treatment.

Additionally, all dose dependent children equally all will be patients and one <unk> patient showed a successful grafman within one month of dosing and has stopped the red blood cell transfusions.

Hey, just real one was well tolerated by patients and the safety profile.

One was consistent with the microchip was talking conditioning and autologous stem cell transplant.

And the trajectory of correction of anemia, and especially with freedom Globin was consistent across Eddy Street. One for you just stick with your patient and basically assume a patient at the same time points.

We continue to believe that editorial one can potentially provide robust clinical benefit to patients with severe sickle cell disease and transfusion dependent beta thalassemia.

Potentially provide clinical differentiation in the long term.

We look forward to our presentation of additional clinical data and a longer fall off in December.

As we have previously stated the choice of CRISPR enzymes, and the target to edit to Souchong fetal hemoglobin expression matters.

And it's weird one use our proprietary ace got 12 or eight enzyme to edit H beat you want to promote it.

<unk> 12, a increases the efficiency of editing and significantly reduce off target editing when compared to other CRISPR enzymes equaling has not.

Editing H B G. One promoter H H H.

<unk> you want to promote it in human CD 34 possible sales readout in greater redbox out production and the normal proliferate to capacity and improve red blood cell count when compared to anything or PTO 11 eight.

We look at the differentiation New street categories of endpoints in clinical trials.

It's a logical parameters and organ function and patient reported outcome of quality of life.

Based on the clinical data so far we believe that sustained normal level hemoglobin could it be a potential point of differentiation for edit 301.

As a reminder.

Stand normal total hemoglobin level is an important clinical outcome for patients.

Is the correction of anemia can significantly improve quality of life and ameliorate the end organ damage.

We look forward to sharing additional data, including whoopie and edit their clinical data next month.

Now I will turn the call over to Eric Our Chief Financial Officer. Thank you Beth and good morning, everyone I'm happy to be speaking with you today and with one quarter under my belt at edit tests I'm, even more impressed by the quality of our science our leadership in the gene editing field, the strong intellectual property portfolio and our highly differentiated.

She didn't 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 third quarter 2023, and I'll take this opportunity to briefly review a few items, our cash cash equivalents and marketable securities as of September 30th were $446 million.

Third to $480 million at June 30th 2023.

We expect our existing cash cash equivalents and marketable equity securities to fund, our operating expenses and capital expenditures into the third quarter of 2025.

Revenue for the third quarter of 2023 was $5 3 million.

Which primarily relates to the upfront payment under the nonexclusive cats nine license to for Bayou and August 2023.

R&D expenses this quarter were $41 million essentially flat from the third quarter of 2022, which reflects various offsetting expenses, including decreases in R&D spend related to our re prioritization and targeted focus on our edit 301 program offset by increased spending in pre commercialization.

Asian efforts, including medical affairs and patient advocacy.

G&A expenses for the third quarter of 2023 or $15 million, which decreased from $16 million for the third quarter of 2020 two.

The decrease in expense is primarily attributable to decreased head count expenses, including stock compensation and reduced legal costs.

Overall edits house remains in strong financial position bolstered by our sharpen discovery focus June capital raise recent out licensing deal.

Our cash run rate into the third quarter of 2025 provides ample resources to support our continued progress and the Ruby and edits all trials of edit 301 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.

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

Thank you Eric.

As we continue our momentum and the execution of our goals. It remains an exciting year for any test 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.

Givers investigators employees Congress corporate partners and you the investment community.

Thanks very much for your interest in edits has and we're happy to answer questions. Thank you.

Thank you will now be conducting a question and answer session.

If you'd like to ask a question at this time. Please press star one on your telephone keypad and a confirmation tone will indicate your line is in the question queue.

You May press star two if you'd like to move your question from the queue.

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 questions. Thank you.

Our first question comes from the line of Brian Cheng with J P. Morgan. Please proceed with your question.

Yes.

Good morning, guys.

Good afternoon, and thanks for taking my questions.

Okay.

So far this year.

On our part.

I can take it.

Can you give us a lot of that.

So you have to always here.

I apologize if anything and any other insights that moved who has the time for me to see them.

Okay.

Yeah, 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 or targeting so I'm, assuming you're referring to is the first tranche.

Yeah. So let me just go with that and then we can so if if if it's incorrect, but you know I think you were first the outcome and I have to say is that the AD com represents an incredibly and drove great excitement for this week and it was a great day for sickle cell warriors.

Are you you know where patients now can think about it not battling a disease, but actually living a life. It was a significant milestone.

For CRISPR genome editing as that AD com represents almost a penultimate step towards approval for the Chris first CRISPR based medicine, what struck us in the very focused discussion off the outcome was the positive tone, but actually also as we listen to the commentary.

Is really substantially strengthened our confidence can be very robust data package that we've generated about off target editing I hope I've answered your question because with all target Alex 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 a S Castro the enzyme, which indeed has higher fidelity at a sustained significant reduction in off target edits when compared to our cast night.

Thanks, Joe Moore M. I guess my I don't know if you can hear me better now Oh, yes, that's better.

Oh, okay. Okay. Yeah. So I'm just wondering if you thought that there were a lot of focus specifically on off target effect. So I'm just wondering if there's any work that you are enjoying now there is their friend.

That's an editor or players that are in the in the market alright their friends from extra that the wako later I spoke to you.

We'll be happy with the way that you know I bought it trying to ease off target effects and thank you so much.

Yeah, Yeah, Thanks, Brian I mean without going into details I don't think it is an appropriate time to go into the details. We are doing a more then was discussed at the AD com and and that's where our confidence about the robustness of our data and data package comes from.

I hope I.

I hope that was the question.

Yeah that was very helpful. Thanks type tomorrow.

Thanks, very much Brian.

It sounds like you're on the same so have a good trip.

Okay.

Our next question comes from the line of Samantha several count with Citi. Please proceed with your question.

Hi, Good morning. Thank you for taking my question just a follow up on the last question.

Just wanted to touch on that.

And the difference between small banks right.

Talk a little bit more R&D talent.

Are you seeing.

Right.

Just to show that.

Our regulators.

I am indeed happy to let me just preface again with a sort of a high level that in in published data.

We have and others have shown a substantial reduction in off target editing when comparing a S. Castro today versus the cast night enzyme.

With regard to the data package that we have generated on contingent generally of targets. It is substantial I'm not sure that we are in a place to share more details I don't know Linda if you have anything to add yeah. I would just add this is Linda Berkeley's CFO.

Yeah, I would just add and echo what Gilmore I'm, just said that we're using multiple orthogonal methods.

Additional method as compared to traditional methods as compared to what we heard at the AD com and and so we're very confident in our package as we proceed in our in our and our path to the BLA and yeah, we in our preclinical.

Data, we're not seem off target editing in our preclinical experiments. So I'm, we're very confident in our package going for it.

Great. Thank you for taking the question.

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

Hey, yeah. Thanks for the update that it's like taking our questions.

Based on all of that has been presented during the AD Comm, where do you see room for clinical differentiation and is that something that we can expect to see at ash. Specifically can you comment on your plate letting graph meant a particular site count and markers of hemolysis. Thank you.

So I think the key thing is that we are very excited it already.

Data that we have presented and what we see as a competitive fast follower with a potential for differentiation.

And what we've seen to date was a consistent you know the highest level of correction of anemia. It's the normal physiological range, which is by design and are choosing us <unk> 12, eight two edits and Campbell gluten promoter I'm Gonna ask based songs just to tell you a little more about what we can about what we're going to share at all.

On December 11th.

Thanks, Guillermo Thanks for question drew.

So I I.

As I mentioned that in the ash presentation, well have data from 11, Ruby patients and six <unk> patients and we will have a longer follow up here. It a week to a patient in the movie trial with at least 12 months and then we have additional data from five months I thought it would be trial.

And go back to your question also on the on these and.

And at a come in there and we are very actually pleased to see as Guillermo mentioned to be the base, except for AD com and reaffirmed my belief that technology and also the M O a L b using a feed them clothing as a target it to try to stick with it even better than it.

EMEA and we what differentiation. We all we are confident that we are a fast follower differentiation molecule and we are very pleased to see that we presented data that we'd be able to correct the anemia and in our case the normal total hemoglobin.

Female was 12 to 16 Gram per deciliter and four male is 13 eight to 18 grams per deciliter, and we're pleased to see our patients going into the normal range and we will share more data during the ash and weapon representation data next month I think.

The only other thing is that it's it's you know we do know that we've had very successful in Grasberg timelines are 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.

Excellent. Thank you so much.

Thank you very much.

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 one should we expect an update on the in vivo editing efforts and.

How do you think the commercial opportunity is there a relative to ex vivo in sickle cell and then what other indications are tissues. Do you think are attractive candidates for your in vivo technologies.

And thanks, very much Greg with regard to our future updates.

This is a company who philosophically wants to make promises and make discussions that we are I believe that we can absolutely deliver on we have been doing work over the last year. Linda has already been here about three months and we want to make sure that she has her time at <unk>, two again engaging with our medical and commercial.

The team now led by our new Chief commercial strategic Officer, David is to make sure that we choose and progress against high.

High conviction targets based on our selection criteria.

With regard to your second question.

That's just remind me again.

Okay targets.

Target tissues, Yes, forgive me. So we have actually you know advanced for FX, Linda I might ask you talked about a target tissues. Yeah. Thank you yeah. Thank you for the question. So of course, we're very excited to teach to develop an in vivo HSC program based on the success of the AR our targeting approach.

For sickle cell disease, and T D T and so moving the the targeting of the HPE when she locates too in the in vivo approach and so we're very well positioned for that considering the emerging success that we're seeing in the clinic that based on his described and so we're working very hard to.

To come up with the delivery strategy for in vivo HSC and what do you mean that both internally and through potential external partners and so that's a very I'm very excited about that that Avenue and then in terms of other tissues of interest will be talking about those in the future. We are interested in it.

On liver fat.

I'll be talking about other tissues as well in the future. Thank you very much Linda and then with regard to the third part of your question you asked about the commercial opportunity for in vivo essentially once you can actually see is a strategy that we're driving which progressively expands the number of patients and I and the traction our proportion of the <unk>.

<unk> population that can actually use the tissue or use these treatments allogeneic opened the door to therapeutics, but the substantial issue. There was finding matched donors whereabouts only a about 110th Ah patients can find a matched donor or by going to autologous ex vivo we've increased our.

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 buy not described to severe it's worth remembering that the media.

And survival for this disease in the developed healthcare system, that's out of the United States is about 45 to 50 as again was impressed upon us at the AD com bite that was incredibly moving testimonies from patients and their parents and family members and indeed in economies with no health care system.

It's in Asia percent more tonnage about five years of age. So there is a substantial unmet need and in vivo will massively increase the commercial the eligible patient population.

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 questions.

My question is I think a lots of questions asked about.

Differentiating profile for you all.

Hum.

Yeah.

So maybe I wanted to ask.

Ask you now in a way actually the surprising we saw V O U S and happened so early.

Elite access that will add to come I'm wondering what is your thoughts there and then for York efficacy clinical profile, what kind of C.

The factors you can't pay attention to.

In order to monitor events and to try to develop differentiated profile.

XL.

Thank you very much genius. It doesn't go to just recapitulate. Your question to be sure I get them. All you know you want to talk about the differentiation of our edit 301.

For as we're focusing on severe sickle cell disease, you were interested in or a.

Surprised to see the Oes reported in some take patients post treatment at the AD Com I think recent also understanding what are the elements that we're monitoring for for differentiation in our efficacy profile.

Well I will start and then pass I can start and then I'll have based on comment on the differentiation of our efficacy profile.

With regard to the Oes I think you know understanding a full explanation would be hard for us at this point there were many elements of the data that you know we're not present, so it's not surprising in a very truncation presentation, but obviously looking at the correlation of a fetal hemoglobin expression. The other factors that could drive that.

Cetera is something that we have a support ticket 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.

Now as we look to differentiation for edit 301, we're looking beyond not just the control of the Oes, but actually correcting other elements of the disease and with fashion with a particular focus on the correction of anemia to normal physiologic range on its impact and that's based on to talk more about that.

Thanks Guillermo.

Absolutely. We are we are still very confident in that that we believe that it is a differentiated molecule.

Given that what we see so far we have to see that we can actually correct. It have correction you up with anemia to fit your logical range of total hemoglobin and with that we're looking to that not only hematological pyramid.

Organ function and ER as well as a patient reported outcome. So we continue to be that direction will allow us to demonstrate differentiation.

One key thing I think it's worth highlighting we talk about patient reported outcomes is.

Is that fatigue is a a significant complaint in fact again be harnessed the patient testimonials lack of energy fatigue, not just the hospitalizations and pain, but fatigue and lots of energy and so these are important elements of our specific sub domains of the Ah patient outcomes that were.

We're paying attention to.

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

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 our map discussions taught degree with a differentiation on whole total hemoglobin discussing the arm at and then I believe during the prepared remarks, you mentioned a more substantial dataset expected in mid 'twenty four.

During the RMS discussions did you have any conversations around what can be used to pivotal data set here and would love to hear any thoughts if so.

Thanks, very much Jack for you. Your question you know I think the first thing is it's premature to go into the details of discussions about the F. D. A however, I do I am glad that you highlighted are mass because indeed, the FDA does Ah and did review clinical data, including a hematologic parameters.

Which as you quite correctly pointed out if you include the correction of anemia and as we said. It also included the non clinical package to demonstrate how that happened by design I think the other point about the arm out obviously as we said in the prepared remarks is that each essentially.

Increases our confidence in the timeless reviewed 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 a priority review and rolling submission.

You asked about the substantive datasets and I think well.

What I would say is that if you look to exercise as a benchmark.

We've actually seen a that's the original exercise BLA accepted by the FDA included in efficacy dataset of 20 patients with 16 months follow up.

In addition, the ethics today's 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 of two into January 'twenty, four time frame and the continuing robust enrollment that we're seeing in our Ruby study it really validates our line of sight to.

To creating or generating and present to be able to present in the middle of 'twenty 'twenty four a substantive datasets are with.

Robust follow up around the period that shows the correction of anemia, and fetal hemoglobin expression and validates line of sight to a delay into 2025.

Great. Thanks, so much my color.

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

Hey, good morning, guys. Thanks for taking the question maybe I'll briefly go back to the off target editing and then M. D. D. One for Karen on the off target editing, our I guess, our Gilmore you talked a lot about the differentiation of the AST has 12 eight versus the cash can be used I'm just curious does that in your.

Your views, thank you need a little bit more characterization work on the molecular side, given that cash guidance being a little bit more popular we used on the Christopher class based medicine field and maybe as a as an offshoot of that I think there were also discussions around how extra cell ran all of these analyses and a more theoretical matter.

But it doesn't really pass the treated patients blood samples pre and post. So can you confirm if you guys are doing the pre and post testing of the blood samples to see if the off target editing is actually happening why not and then question for Karen.

On an earlier question about E D. An expansion opportunity you talked about the in vivo HSC delivery, but I don't know if that was intentional or not but I didn't hear you talk about non genotoxic conditioning.

So I don't know if I, if you can comment on a little bit more on that do you see that as part of your armamentarium going forward, perhaps from a gentex James can speak to that thanks, so much.

So thanks, very much Dae gon ha with regard to the a S. Castaways referenced cast nine I think the first takeaway is that we have a published we have published a data from ourselves and other labs showing that there is a a differentiation.

Significant reduction in off targets with ask has thrown a secondly, we have a very well, but we don't actually believe that the president of the past nine would change their requirements for off target data package generation third our data package that we've generated to date is very robust and as as is.

Linda said, we're using multiple worth talking about both instead of coal and in our in vitro.

Evaluations are also including by the way our non clinical tox in vivo, but at evaluations that go beyond what we saw are presented and discussed at the AD com and so again all of that adds to our confidence and then finally, we are actually testing the drug.

Alex.

So that's kind of the old targets, if I could then turn.

To your question around a non or non genotoxic conditioning and this is an area that remains of interest to us and 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're quite correct.

He pointed out that stays very well so Karen it goes without further commentary yeah. Thank you. Thanks for the question and just want to comment how excited I am to be here with you in the past team to help move these therapies forward and you bring up a really important point something that's important to all of us and we will absolutely be part of the evolution of this market.

<unk> and treatment modality.

I think the benefit today is that the risk benefit for severe sickle cell and T. D. T does remain very strong with the current offering but we take it very seriously and we're doing a lot of important work to try to make sure. We are part of moving forward and we found this to be a overall better treatment.

Excellent. Thanks, so much.

Linda just to add to what Mohit said like waiting to affirm that we do test we have tested trunk pratique lots from a larger number of sickle cell disease patients to see confirmed E and have not detected I'm off target editing and that larger number.

Of sickle cell disease patients.

Yes.

Thanks, guys.

Our next question is from the line of Phil Nadeau with TD Cowen. Please proceed with your questions.

Good morning, Congrats on progress and thanks for taking our questions.

Two from US first in terms of.

Our continued recruitment in the clinical trials do you assume any change in the rates that you'll be able to recruit patients. Following what seems likely to be the approvals are the first to genomic medicines for sickle cell disease and by the end of the year.

The first question and then second 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 are truly differentiated is that something that you'll know.

Kind of really relatively quickly or will that take.

Months, if not years of follow up to determine thanks.

Thanks, very much Phil with regard to recruitment no. We do not expect any change and we believe that our or are we relevant with continued robust I'll pass that to Bay song, who can tell you about his personal experience and conversations with sites and investigators. Thanks, Yeah. Thanks, Phil for Ya.

Question.

Really that I have been you know continues to visiting in study size I see really a very strong momentum and feedback about it and we actually have a many patients on our list fortify. These trials. So we actually do not see the impact that we continue to see the pockets of a manager and are not only now but it was good for next.

At year end, we will we will continue to see the momentum on that.

And indeed, the investigators said that you know notwithstanding approvals. This is still an area that they were particularly 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 but some of the more downstream.

Dream, a cynical impacts would be around fatigue, or other outcomes and I'm going to ask they song to talk about that yeah. Yeah.

Yeah. So this is actually a very important question. We are looking into that is we as I mentioned, we're looking to have three categories of clinical end points to probably a differentiation.

So it's in a bad for Hematological pyramid, or you will be taking a short of time to see enforced for.

For the the Ah patient reported outcome, but you talk about your specific imation, the petite and usually based on my experience in the other studies that when you just kind of pinpoint where you kind of see this ah patient recorded outcome, usually takes six months for the CBD do you see something that usually takes six to one year you will see some kind of improve.

But if you want a longer you will see a much more impactful compared to the baseline. So we are very optimistic and confident that we will be both be able to see something in that direction and poor patient reported outcome on that and then in the other category. I mentioned is also for the end organ damage and we actually look into the IV cardiac Pamela.

Every liver and CNS and as well as the kidney. So we'll also see that I'm looking.

Looking forward to see the improvement these areas quite a relatively new but they are publications for allogeneic bone marrow transplant for sickle cell patients for example in the brand.

A lot of basketball.

The vascular system in brand and also the in cardiac system. So there are some reports relatively limited C that allogeneic transplant for sickle cell patients could potentially actually to improve the August improve organ function. So we're looking forward to that direction, Yeah and you know.

One of the things I would say is that you know based on and I have been around the block long enough as drug developers to know that you know when you are starting applying a new outcomes measures into two trials using potent new medicines that have sort of have an unprecedented potency and disease you your vision absolutely firm.

He predict the absolute time point, the number of patients et cetera needed to actually demonstrate that benefits can be 10, very and require additional work. So you know why we are very enthusiastic about the work that we're doing here. We also are pragmatic and experienced enough.

So know that we would see hematologic parameters quickly we may see and Oregon are functional physiologic parameters are in slightly longer term and then with regards to other outcomes. Some of that will be as I say, we are optimistic, but we have to just temper that with the realism that it may take so much longer.

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

Thanks very much.

Our next question is from the line of Sue with Wells Fargo. Please proceed with your questions.

Hi, Thanks for taking my questions.

So I was wondering a focus at the AD com 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 who you are where are your off target analysis work.

Are you targeting again single digit central numbers or.

Are you targeting a number significantly higher than that.

Our next question is about.

Percent fetal hemoglobin.

As a differentiator I think he talked a lot about total hemoglobin Oh, but I was wondering you know based on your on the data you have reported so far and also in the abstract are at.

At Ash.

It seems like you.

You had three patients I feel first for patient.

Who had a greater than 50% 60% 50%.

If he does seem a little but I was wondering about your confidence.

But that being replicated in additional patients came off without being a differentiator.

And lastly, I was wondering about I guess thoughts on whether there is a correlation between total hemoglobin and hemolytic markers and whether you can call me at home.

Yeah I E.

Higher maybe at a patient level.

There are higher total hemoglobin.

It's correlated.

Better hemolytic marker population. Thank you.

Thanks, very much you're not so I'm going to try and cardio graph are a set of answers to a complex set of questions. If you will or quite diverse set of questions. So.

With regard to the attics do something but I think the first thing we should do is just remind ourselves that the discussions are very so what I would say the informed discussion at the AD com AR demonstrations that you you know a a robust evaluation of risk are really shows that from an off target point of view the risk management.

Even with the data set presented the AD com was actually very good.

I will say that we are using additional animals with Christy orthogonal in silicone and vitro and indeed, some illegal that's something that until let's say, but instead of go and in vitro assessments, which go well beyond what was shown at the AD com and our data package not going to go into the specifics of the numbers.

Patients just to say, it's more and obviously are you would you share more detail about that are in in the 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 the discussion by the geneticists asked the outcome was very illuminating.

I thought both parties.

Experts on the panel as well as in.

In the sponsor you know really articulated very clearly how the nature of variation a the nature of common ancestry for all humanity and how we can really manage and identified variants and the risks associated with that I think it was a very robust discussion and again it gave us great confidence in our management.

Of at risk and the data package that we're generating there.

Linda I don't know if he wants to add to that no I think that was a very good summary, I think that there was yeah I think that was a very good summer and come on.

Thanks, very much lit up with regards to the percentage of fetal hemoglobin as a differentiator you know obviously, we're excited by the data we show. It's early days, yet and you know what is clear from the experienced described for our people who are have coincident in Harrison.

As of hereditary persistence of fetal hemoglobin with sickle cell disease, or indeed, a female.

Is that.

The higher the level of fetal hemoglobin, a percentage a fraction fees hemoglobin, the greater the certainty for sickle cell disease.

I'd say, it's early days for us Hum, but based on your own with you on after that yeah, yeah yeah.

Yes, yeah. Thank you. Thank you for this question Oh excuse me mentioned, we're very pleased to see the total of the pit of incoming data as you referred to actually see patients over 50% and this is we're excited that it's also because this is a rational design approach for edit 301, we compared that this approach.

Targeting the speed you went to promoter Ah at UPC went to promoter was it 11, a we found that we have a better fetal hemoglobin expression, but we are in the early stage. We are we actually want to see more data to see these and and we're looking forward to see more of that I'll say up on that.

Thanks, very much based on I think your final question was around the correlation between total hemoglobin hemolytic markers I I think that that is a interesting question beforehand as a base on that just remind one thanks.

While hemolytic anemia hemolysis is a critical part of our sickle cell disease. The key driver will be as we leave for driving total hemoglobin by design is enhanced erythroid production.

Besides as you want to add.

That's exactly right Gamble, that's why we're going to say I think what I want to mention that you know we are very positive about our multi market data on that.

Then the.

So the total hemoglobin level is related to aspect of that one is hemolysis, but wanted to get through everything.

Okay process. So I think in our design, we designed to have these molecules have hired people good people, who make a living expression and it also we've been targeting the HBC won two promoter we have better extra proceeds embedded rent blackout protection production. So we're looking forward to see more data on that but we are there.

We are pleased with our symbolic.

Similarly biomarkers.

Great. Thanks for the color.

Thank you.

Our next question is from the line of Eric Schmidt with Cantor Fitzgerald. Please proceed with your question.

Oh good morning, Thanks for taking my questions and congrats on the progress.

Maybe the first the H B S production levels were obviously quite impressive is there a total hemoglobin above which you start to grow concerned in sickle cell disease with patients of too much hemoglobin, so what that might be.

And then maybe a follow up for Karen we saw a couple of large pharma or gene editing deals. This week, perhaps you could comment on the overall level of interest in a potential platform type collaborations. Thanks.

Thanks, very much Eric.

With regard to the total hemoglobin.

We believe that correcting and that's what we've seen hemoglobin physiologic range is of a substantial benefit.

I think it's we haven't we're not going to it's hard to speculate about a level that is too high Ah indeed.

There has been an experience in general with polycythemia in sort of a broader patient population with some conflicting data about the risks are saying what does it say, we feel very confident about the data we're getting with regard to our total hemoglobin.

And the way that we are correcting to normal physiological range.

I think you asked a question about some recent.

Jean <unk> Neault Edison deals.

This week that are announced you know what I would say.

Is that what is striking about it is it is great to see you know pharma big pharma now in a in a in a period, where we've seen some sort of a dearth of deals leaning in and increasing their excitement around the genome editing.

Phase I in other words, what I would say is this has been a very good week for CRISPR genome editing space with both that's for critical near to final step towards approval for our first CRISPR based therapy and to see now pharma actually looking especially through the lens of substantial de risking of their view of the value.

Genome editing as they look to grow their portfolios I don't know Dave.

Yeah. Thanks, Eric It's Karen what I would add is I think at its heart 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.

Okay.

Thank you.

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

Good morning. Thank you two quick ones first our lymphocyte of neutrophil counts at baseline and post transplant something that you are going to share in either the poster of the associated presentation at ash.

And then separately is it your intent that attached to commercialize edit 301 on your own. Thanks.

Thanks, very much for that question.

With regard to huge food and grasp and data that is something that we actually did present at ehealth and it would comprise oh it could be summarized in our presentations at the end of the year because it's actually you know a measure of Ah Congrats on his part of the safety.

Monitoring that we do in our studies and then with regards to your second question, which was around.

Commercializing three to one on our own well, we actually looked at commercializing 301 are actually building towards that because that we believe that's important we have indicated previously that were introduced in an ex U S partner with a large footprint obviously the details.

Any such partnership and how that might expand I would really depend very much on those negotiations are something that we would share upon any kind of agreement, but only van.

Get more just to clarify I was asking about lymphocyte of neutrophil counts like longitudinally post transplant, just because and access all data they don't recover to baseline. So I'm just curious if that's something you planned share and there'd.

It would be interesting to know whether it's different or the same given the different genomic target in different editor.

Well, we have not seen we've been actually very happy with our accounts, we actually very happy with our accounts to date, but.

But what I can follow up on that.

Thank you.

Our next question is from the line of Luke I E C. With RBC. Please proceed with your question.

Oh, great. Thanks, so much for taking my question I have two quick one here maybe based on it sounds like you're obviously on track to dose 20 patients by January 2024 are you enrolling any other lesson just trying to understand if there is a scenario where your initial label will just include adults versus some of your peers, who also.

Broadened label that also includes other lesson so kind of any color there much appreciated and then the second one quick quick one for Linda here I think you're in the AD com earlier this week.

Suggestions to further characterize off target editing rascals to actually do whole genome sequencing and 20 patients before and after the genetic manipulation. So I just wonder if that's something that you're contemplating today. Thanks, so much.

Yeah. Thank you for your question I take your first question then I'll pass that on.

I think we are we are we have a plan to to dosing adolescent patient and also for the general clinical program were intended to go to all the patients of all ages. So that's kind of what because this disease is essentially you know starting with connected television side from very young age. So we.

And change you actually be able to have these picking these marty can be a bit patient benefit a patient from all ages. 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.

Oh, yeah. Thank you for your question, Yeah that was very interesting a.

Conversation that the outcome you know one of our one of our orthogonal methods and this also came up at the AD Com was.

The method of using a biochemical nephew.

Net said apply to me and DNA and we this is a massive one of the methods that we use which is and.

I'm biased your message.

In which the naked DNA is taken for themselves and subjected to cutting with your R&D and then you do a whole genome sequencing basically to look for off target editing and so this is COVID-19 of them.

And so this is one of our methods that we use and look at with our drug product before before.

Before putting that dry powder each patient. So so I think this is one of the robust criteria that we wanted to robust methods that we use in our in our approach them. So I think that's basically one of the reasons that we are confident in our approach to.

In addition to the other methods that we use in silicone and guide sheath that were described I guess, that's basically what I'm Oh.

Prepared to share at this moment, but there are many other aspects to our approach that we're also making us very confident about our approach to the off target editing them a path.

Package that we're preparing.

Got it thanks, so much.

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

Oh, Hey, congrats on the progress and thank you for taking the question maybe just another question on read across from the extra sell AD com. Since there was some discussion about long term monitoring and surveillance and these patients can you just share your thoughts and plans to follow edit 301 patients long term and post approval.

Thank you.

Yeah, Yeah. Thanks for the question Jay.

We certainly will have a long term fallout for patients and so that study is designed to actually pull that patient up to 15 years for anybody who actually dosed with edit 301, and that's also consistent with our regulatory requirements. So that's absolutely our plan.

Great. Thank you.

Yeah.

The next question is from the line of least tobacco with Evercore ISI. Please proceed with your questions.

Hi, This is Jamie on for Lisa Thanks for taking our questions and congrats on the progress. So we have a few questions first we know that C. D. C has filed an appeal to the court of Appeals one do we expect to see that that assertion for that and then second as I know you mentioned that.

Well I substantial data that first cycle. So I was kind of in the middle of 'twenty 'twenty four.

Just wondering when shall we expect more substantial data that's what it should be to the patients and then the third as you mentioned that.

Second half we plan to engage with the FDA to seek alignment a regulatory pathway for you all one we owe on Langwell you inform the street on the results of that discussion and if so what's the timing for that thank you.

Yes.

Hi, This is Eric just with respect to any.

Courses in front of a court cases in front of the CVC or anything like that well, we don't really want to comment on those until the final decision is actually rendered said well, we'll just be anxiously awaiting for all of that just like you.

Yeah. So at least based on Paul for your second question about the mid of next year for the for the program.

And as you know two part of that one is as we just shared that we will have a 20 patient dose by a January timeframe next year, then bid up by Middle of next year, we will have a substantial fall out for the 20 patient and we'll also have continued dosing patients over the course, so we'll have a lot of data over the middle of next year for sickle cell disease.

Yeah regarding.

For the beta thalassemia, yeah, yeah, absolutely absolutely.

Yeah, Yeah, sorry, because I saw the part your question probably cover both but I'd just make sure that we cover on that and the the way we actually have very strong momentum for editorial study also is that we just we just see how do we actually already have.

Eight patients enrolled and we continue enrolling and dosing patients and but we have not sure. What is the goal for next year, how many patients every single patient with dose yet we'll share that at an appropriate time.

And your third part of your question is about you know FDA engagement and outcome and so we are we are we will engage with FDA and we continue to have engagement with FDA as soon as we just mentioned that we actually have these amit designation allow us a lot more frequent interaction with the agency and including senior management.

Agent over there over the over the agency, but we have not too sure how the timeline to share the outcome, yet we'll share that at an appropriate time.

Got it thank you.

Our next question is from the line of money for her with Leerink. Please proceed with your question.

Hi, Good morning. This is Lillian Suncal online for money and thank you for taking my question I just wanted to ask if you could potentially give us an update on the progress of the manufacturing scaling our fourth via one both for clinical development and for potential commercialization and then on the other side a second question.

In terms of the package for BLA. So when's the timing I think you had mentioned potential package right readiness by 2025 by then we might have.

Post marketing data from <unk>.

Potentially to a gene therapy program I was wondering if you and how you would see that impacting potential pivotal design.

Yeah.

Oh, Hi, this is Eric I'll take the first question with respect to the manufacturing scaling and timing you know 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.

Yeah.

Yeah. So for your second part of your question and as we shared that we will have 20 patient dose by January timeframe of next year and debated by middle of next.

<unk> been up next but made up 2025, and then we will have no substantial debt package, it's probably equivalent to the ER to the access to a F. P. O F bonding, which is accepted by <unk> by FDA, which have like 20 patients in the efficacy data cohort.

So they they subsequently added additional came patient in the addendum with a four months additional four months data. Afterwards, so we expect that we will be able to file the FDA equivalent package to two we have equivalent data package by mid of next year, but what exactly the theater at the idea of exactly what you're always out of pocket.

When you combine that with FDA, so that we are well.

Woke up the agreement with FDA on that too and you mentioned about post marketing or the commercialization of these two molecule and as I shared earlier that we do not see that improve recruitment and momentum perspective, and you mention about that a package and we actually very excited about the outcome.

<unk> discussion and we feel that.

These <unk> have a further validation of Christopher technology further validation of the.

Fetal hemoglobin.

At the mechanism of action to treat a secrecy around better vis EMEA. So we actually see all of those will have a positive impact of Eddie for awhile.

Thank you.

Final question comes from the line of Terence Flynn with Morgan Stanley. Please proceed with your question.

Great. Thank you for taking our question. This is Mac score on for Terence Flynn, So I'm looking to the future a bit can you expand on your approach to target selection. How you. How we should think about your pipeline evolving going forward also as you think about tissue specific delivery for your future in vivo programs. How are you thinking about the advantages and <unk>.

This advantages to investing in AAV and or LNG. Thank you.

Yeah, Hi, Thank you very much for your question, so as far as a 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.

<unk> that are meeting them.

He needs that the patients have that are not already met by existing therapeutics and so we're going to look for targets in which we have high conviction as well is targeting a high possibility for a technical as well as clinical and commercial success and so on.

Very excited here at <unk>.

Karen having joined just so that I can partner with her as well as based on and Triangulating. This to a very much a select our targets I think we're really well positioned now to deselecting knees, where as I said before I think we're we're very excited about.

The our in vivo sickle cell disease T can target them, because we already have has emerging data supporting that target and getting to your question about delivery where.

Our strategy, which gomorrah described in January is non viral delivery and so we are.

Prioritizing LNP delivery amongst the non viral deliveries and I'm working internally as well as through external partners to.

Drive a approach for in vivo HSC targeting them for our H B team wanted to promote or isn't LNP strategy as far as other other targets in tissue and supports <unk> validated for delivery to deliver somewhere where I'm 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 I'm just showing the interest continuing interest environment in this space and but we're also interested in other tissues and so there are many targets out there are minimal to NSS technology and where it is.

Cited to can move forward and we'll certainly be sharing information with you as as we as it emerges in the future.

Perfect. Thank you.

Thank you.

Thank you everyone. This will conclude today's conference you may disconnect. Your lines at this time and we thank you for your participation.