Q3 2022 Editas Medicine Inc Earnings Call
Good morning, and welcome to Edison Medicines third quarter of 2022 conference call. All participants are now in a listen only mode there'll be a question and answer session. At the end of this call. Please be advised that this call is being recorded at the company's request I would now like to turn the call over to Ron.
Customer relations.
Please go ahead Sir.
Thank you Maria good morning, everyone and welcome to our third quarter 2022 conference call earlier. This morning, we issued a press release, providing our financial results and recent corporate updates a replay of today's call will be available on the investors section of our website approximately two hours. After its completion after our prepared remarks, we will open up.
The call for Q&A as a reminder, various remarks that we make during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the safe Harbor provision under the private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by these four.
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, very much Ron and good morning, everyone I'm joined today by several members of the <unk> executive team, including based on my our Chief Medical Officer, Mark Sherman, Our Chief Scientific Officer, and Michelle Robertson, Our Chief Financial Officer, I am pleased with the progress. Our team has made this quarter. We have continued to build on our company's foundational technology.
As we transform from a platform company into a clinical stage therapeutics company and focus on execution.
We continue to evaluate ways to leverage our gene editing expertise for developing new therapeutics and we will provide an update on this evaluation in the coming months.
Operationally with our focus on clinical advancement execution is a top priority going forward with that I would like to provide some recent highlights on our clinical pipeline programs.
And just 301 for sickle cell disease, and transfusion dependent beta thalassemia.
301 utilizes a unique mechanism of action that edits the promoter of the gamma globin gene to disrupt binding of the Bcl eliminates the pressure. This is designed to provide high and durable levels of fetal hemoglobin in patients with severe sickle cell disease, and TVT, thereby resulting in reduced.
Red blood cell signaling in sickle cell suffers and reduction in anemia in <unk> patients.
I would also note that our edit 301 program uses our proprietary <unk> past 12, they engineered nuclease, which our preclinical data suggests resulting in higher fidelity at higher efficiency editing that cast night.
As a reminder, the initial patient dosing with edit 301 represents the first time that an autologous ex vivo drug product was Edison using our <unk> Castro they engineered nucleus.
In the Ruby phase one two trial evaluating edit 301.
<unk> disease, we have dose the second patient and remain on track to release initial data from the Ruby trial by year end.
These data will include efficacy data from the first page of sickle cell disease patients as well as safety data for the first two treated patients.
In the edit out phase one two study for transfusion dependent beta thalassemia, we have completed a for reese's and CD 34 positive cell editing of the first patient and are currently scheduling dosing.
Let us now turn to edit 101 for LCA 10, which is a devastating inherited retinal dystrophy caused by autosomal recessive CEB to 19 mutations that cause early severe visual impairment or blindness.
And talk about phase one two brand study.
The <unk> study is designed to achieve several objectives.
To determine the safety of delivering edit 101 to retinal photo receptors to identify a sub population of LCA 10 patients characterized by based on molecular clinical or physiological parameters, who are most likely to benefit from therapy and to identify a dose that optimizes the benefit risk balance of edit 101 and to identify the uptick.
And points to consider for a registration study.
An update on the <unk> trial will be provided this month through a press release and company sponsored webinar.
That readout will include safety on all dose adult and pediatric patients and efficacy on the adults mid and high dose cohorts.
Data from our one year natural history study of 26, LCA 10 patients with mutations in the 7% to 90 gene will be used to contextualize that brings data.
In order to move forward to registration study, we would need to see a meaningful treatment benefit for a commercially viable patient segments.
<unk> will provide further details in his remarks.
Beyond the brands trial on the safety side. The edit 101 program lays the foundation for subsequent potential drug development programs that utilize our AAV based in vivo platform in inherited retinal diseases.
As far we have been able to demonstrate safety and tolerability from EDA, one one reinforcing the use of AAV delivered CRISPR based retinal therapeutics.
Mark will provide an update on our preclinical pipeline as well as a summary of data recently presented at scientific meetings.
Let me now turn to our IP portfolio, which includes patents exclusively licensed from the broad Institute at Harvard University that cover test nine for Houston Human Therapeutics in the U S.
With our exclusive license the granting of a sublicense on either an exclusive or non exclusive basis is at our discretion.
As you know earlier this year the broad Institute prevail for the third time twice of the Peach happened once it federal circuit against parties collected known as CVC.
As anticipated the CVC appeal at the most recent <unk> decision and the Federal Circuit will review the ruling determined quite this low was properly applied the court will not hear new evidence and we expect the court will deliver its decision in mid to late 2023.
We remain confident that the broad will once again prevail.
An appellate court decision and the broad Sabre would reaffirm Eddie test is positioned as the exclusive license or of the cast iron therapeutic patterns in the U S.
All companies that are developing a product utilizing <unk> nine and that plan to commercialize that product in the U S will need a license from <unk>.
It is important in addition to remember two things about edit 301 on the IP front first it uses our proprietary <unk> past 12 <unk>.
<unk>, which is not the subject of any IP disputes and therefore edit 301 will not need to cast nine license for commercialization.
We believe that our strong IP position relates to cast nine human therapeutics in the U S has the potential to be a significant value driver for our company with numerous competitor products in development using cast night, including several in late stage clinical development, we look forward to providing additional updates.
I will now turn the call over to based on our Chief Medical Officer to review the details of our clinical programs.
Thank you Guillermo.
Let's start with edit 301.
Gilmore noted, we recently dosed, our second CCAR COPD patients in the phase <unk> study.
Beyond the first two patients dosed with <unk> hundred one we also have completed our freezes and successfully edited.
34 Pence party with sales from several additional patients.
Ruby studies independent data monitoring committee or DMC is expected to review the available data this month.
Once the committee has been dosed before the dosing protocol. We can then move to parallel patient dosing.
We're taking multiple measures to accelerate patient recruitment, including expansion of our trial sites.
We will be able to including efficacy data from all treated patients in the Ruby trial in future registration package.
So what to expect from the Ruby data released by end of this year.
We plan to provide an update on safety and Tolerability from both dose patient.
Neutrophil and platelet.
<unk> and data from both patients.
And key hematological per meters from one dose patients that will include total hemoglobin.
Fetal hemoglobin as well as sale counts every suicides with measurable fetal hemoglobin.
Yes.
Taking a step back and it's real one is targeting the gamma globin promoter.
Mimicking the nature mechanism of heritage <unk> persistence of fetal hemoglobin.
H P F H.
In sickle cell patients with HP FH.
When fetal hemoglobin level is 30% of patients usually have no vessel occlusive complications or end organ damage is there.
Therefore at the threshold, we're aiming to achieve fetal hemoglobin level at least 30% at four to five months after dosing.
If we can achieve these objectives and this would meaningfully increase our confidence in <unk> hundred one being a differentiated and competitive product.
By using our engineered a CAD 12, eight with a high editing efficiency and specificity.
Targeting the promoter of Gamma globin gene one and two we expect to deliver robust fetal hemoglobin expression.
A press the Bessel Crusade crisis, and provided long term clinical benefit to boost leaving with sickle cell disease.
Moving to our development efforts in transfusion dependent benefit asemia.
In our phase one two and if they are trial of edit 301.
The study is designed to assess the safety tolerability and preliminary preliminary efficacy of edit 301.
The first patient in the study has been enrolled.
And competing a free space.
We have completed editing of the CD 34 positive sales to be infused back into the patient.
And the west scheduling the dosing date for these patients.
Do we should over to edit 101.
For AFC at 10.
The previous studies <unk> seen recently met.
Part of it and normally planned meetings.
Im pleased that <unk> has maintained a satisfactory safety profile.
Following its review of the available clinical data the <unk> recommended to continue the premium steady and has endorsed continued enrolment in all cohorts.
As Guillermo mentioned we.
On track.
An update on available clinical Readouts from ingredients study this month.
The update will include available safety data on 12, it out and to pediatric patients.
And efficacy data outpatient.
Efficacy update what including one year of data from a mid dose cohort and six months data from me about high dose cohort.
The <unk> study has a monopole efficacy related endpoints.
We'll.
Its to identify optimal outcome measures, while demonstrating clinical meaningfulness in LCA 10 patients.
Suffer from significant and disabling.
Totally offset visual impairment.
These endpoints measure.
Psychophysical outcomes that including full field sensitivity functional outcome, including visual navigation costs.
Visual function outcome, including best corrected visual acuity or <unk>.
And the measures of visual quality of life that including National Eye Institute.
<unk> 25 instruments.
I'm happy with the progress that we're making in improving the execution of our clinical program and want to thank our patients investigators and staff members at the study sites for their contribution and support in helping US advance these new therapeutics.
With that I will.
I'll now turn the call over to our Chief Scientific officer, and Mark to discuss our preclinical programs.
Thank you <unk>.
I would like to start with edit 103 for rhodopsin autosomal dominant retinitis pigmentosa.
103 uses two <unk> associated virus vectors to knockout the mutant rhodopsin and correct the toxic gain of function, while simultaneously, replacing that aberrant gene with a functional one.
This approach can potentially address more than 150 gene mutations that cause Roe AARP.
The program employs a different mechanistic approach of edit 101, and we have previously reported highly promising preclinical data.
Last month during an oral presentation at the European Society of gene and cell therapy annual meeting, we highlighted data demonstrating nearly 100% productive editing in nonhuman primates and the generation of over 30% functional rhodopsin gene replacement, which proved to be therapeutically effective in that <unk> study.
We expect to initiate IND, enabling studies next year following completion of the AAV vector analytical testing.
Moving now to our ex vivo cell therapy programs.
202, Ips derived NK cell program for solid tumors is advancing towards IND, enabling studies.
This program offers several important key advantages over many existing NK cell approaches.
In preclinical models, we have shown that edit 202 has potent antitumor activity and substantially increased persistence.
We utilize a fee to sell free system for NK cell production, thereby mitigating potential risks of introducing exogenous cellular material.
Through the development process, we are able to select a fully characterize clone, helping us avoid potential abnormalities and differentiating the Ips CS into NK cells.
And finally, the program neutralizes out proprietary exiting platform such as our engineered <unk> nuclease and sleep, knocking technology, which we believe provide superior editing capabilities and engineered NK cells.
Last month at <unk>, we presented new preclinical data further supporting the continued development of added 202.
The data showed that using sleek to Nokia and membrane bound IL 15.
Favorable <unk> 16, the edit 202 sales had prolonged cytokines independent persistence in vitro as.
As well as up regulated and continuous expression of <unk> 16, after tumors that exposure.
Thereby enabling the attitudes sales to significantly enhance serial killing of scope III tumor cells.
In the scope three intravenous solid tumor model when combined with an antibody <unk> hundred two sales resulted in a significant reduction in tumor burden and increased overall survival demonstrating.
Demonstrating a 100% survival rate after 100 days compared to zero percent using just the antibody.
As we continue development divided to two we believe our approach has the potential to create an allogeneic off the shelf NK cell therapy medicine with enhanced activity against solid tumors with.
We plan on presenting additional preclinical data at the society for immunotherapy of cancer annual meeting next week I'll now hand, the call to our Chief Financial Officer, Michelle to review our financial results.
You Mark and good morning, everyone I'd like to refer you to our press release issued earlier today for a summary of our financial results for the third quarter of 2020.
I'll take this opportunity to briefly review a few items.
Our cash cash equivalents in marketable securities at September 30 were $479 million compared to $528 million in the prior quarter.
We continue to be disciplined with our expense management and our cash runway extends into 2024.
For the third quarter, we recorded minimal revenue from an out license agreement during the same period last year, we reported $6 2 million in revenue when BMS opted into an additional program under our collaboration.
<unk> expenses of approximately $16 million were flat compared to the third quarter of 2021 R&D expenses for the third quarter were $41 million compared with $29 million for the third quarter last year. This.
This increase was driven by our investment in manufacturing and CMC capabilities to support the ongoing progress of our clinical trials.
We're all aircraft remains in strong financial position as we advance our programs with that I will hand, the call back to Kevin Maher. Thank.
Thank you very much Michelle.
I am pleased with any type of execution over the past quarter, we continued to leverage our best in class technology operational and manufacturing capabilities and our transition into a therapeutics company on the cutting edge of innovation.
This transition is underpinned by further enhancement to our gene editing platform active business development efforts in advancing discussions related to our foundational IP.
We are focused on our goal of building a robust pipeline of assets that maximize the probability of technical and regulatory and commercial success.
We look forward to providing clinical updates for edit 101, and edit 301 programs in the coming weeks and in addition, we plan to share more information about our strategic plans in the coming months.
We are happy to answer any questions.
Thank you we will now be conducting a question and answer session. If you'd like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue. You May Press Star two if you would like to remove 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.
Our first question is from Gena Wang with Barclays. Please proceed with your question.
Thank you for taking my questions I have two questions regarding the 301 and one one data update later this year.
Just wondering for <unk> one.
What would be you mentioned that 30% fetal globin should be sufficient.
To show clinical benefit, but given the competitive.
Clinical profile, we've seen so far would that be sufficient to be competitive what would be your goal regarding the fetal globin level and then for the added one one.
What is considered clinical meaningful and you will collect several different data points could you give us a sense like what kind of magnitude.
Improvement in terms of in luck Marvin CVA visual navigation that would be considered clinically meaningful.
Thank you very much Gina go more here with regards to the 301, you actually have correctly stated what we would see as a.
A minimal threshold to determine that we have a competitive product.
We believe that we have a potentially differentiated product based on some of the critical differences in our approach in the use of our <unk> cost 12, a enzyme as well as our targets.
To ultimately result in a robust.
<unk>.
Expression of fetal hemoglobin with a durable effect.
And we actually in the future would hope and plan to see that differentiation to clear itself.
We move forward. Nevertheless, we believe that the project will be competitive.
As is because the space there is space for actually a number of.
Therapeutic.
Profiles and approaches and that's actually stems around our belief amongst other things that over the next few years.
This space will evolve slowly we are confident basket vast majority of the present population will remain untreated at the time of our launch.
That will be a result of results or arise from the what we would anticipate some slower uptake owing to a number of factors around potential hesitancy.
But very importantly around the evolution of the payer landscape.
With regard to the 101.
We have done a lot of work to determine what is clinically meaningful and we will actually be sharing more details around that as we contextualize. The data based on our natural history study I think it's important to know that we have done a lot of work on this around ensuring that we have reliable parameter.
Orders for determining real change.
And also it is important to remember that because we are dealing with a.
And Harris disease with early onset of severe visual loss.
The determination of clinical meaningfulness will be related to and driven by our desire to see improved functional outcomes for patients that would actually change that have been achieved.
To BMO.
The mobile.
To participate in society.
Thank you.
Our next question is from Greg Harrison with Bank of America. Please proceed with your question.
And thanks for taking the question.
What is your level of confidence in the potential of the edit 101 program.
Are you viewing it more as a commercial opportunity in itself or maybe as a proof of concept where you could apply the <unk>.
Technology to other indications and maybe you could just elaborate on the earlier comments around the future of the program.
Absolutely.
So I think that the edit 101 program really has.
Two purposes.
It was designed first of all too.
Develop our experience with applying our technology in humans.
Youre actually correct in that statement.
I think the second one as I've highlighted in my opening remarks.
Or that is brilliant study is designed amongst other things to determine.
<unk> sub population or segment of patient population are most likely to respond with a clinical meaningful response.
To the treatment and obviously.
One of the things that will be necessary is it that patient segments or segments.
<unk> be a commercially viable patient population.
Got it that's helpful. Thanks for taking my question.
Thanks.
Our next caller is from <unk>.
Chart in Julian Lipsitz. Please. Please proceed with your call.
Hi, this is <unk>.
Thanks for taking the questions.
I'm wondering if you remain on track.
Michael.
FTE in alignment.
Okay.
At year end bump up.
Check.
Okay.
Thank you Judah I'm afraid the sound was very poor.
Could you re could you restate. Your question I think I know, what you said, but I do want to be sure I answered the question.
Yeah.
Is that better.
Price doesn't answer the question right now the big Echo Yeah.
Yeah. So the question was whether you're on track to submit.
The data package to the FDA.
To gain alignment on how to use it.
I'll start with refining.
And one.
Okay.
Yeah.
Yes.
Okay.
Yes.
So julien sounds very poor, but what I'm actually going to take I think the question Youre asking is are we on track to submitted clinical data package to the FDA to discussing a broad.
What a regulatory study would look like for <unk> is that correct right yeah yeah.
Yes so.
Well as I say this month, we will actually be sharing data from our 101 study.
And.
Amongst other things we will be sharing.
Data rather the objective is obviously to determine is there a population or subpopulation that could actually move forward are the outcomes that we can use in a registration trial should we determined that we should go forward based on the size of that sub population and the.
Clinical meaningfulness of the outcomes with regard to our interactions with the FDA that will be.
That would require obviously a.
<unk> decision and very importantly.
We would only be able to finalize the trial design and negotiation with the FDA should we go forward.
Got it thank you.
Our next question is from Joon Lee with Trust Securities. Please proceed with your question.
Hey, thanks for taking our questions.
One O three what's the rate limiting step for IMD and when can we expect that in the clinic.
And why are you using cash for that versus cash 12, which you'd think it sounds like you're very excited about and youre climbing, 100% editing transduce area, but what is that constitutes area how does it.
Late to doble, 11th retinal space. Thank you.
Thanks, Darren this is mark so we are using <unk> nine in this particular.
Product because this fits conveniently in a single AAV and as you know this is a dual AAV approach, where we are knocking down the mutant <unk> seen with the <unk> nuclease, and then replacing it with a coated and optimized.
Rhodopsin.
In terms of the data.
We admit in a nonhuman primate study, we typically administered 100 Microliter lab.
So the 30%.
Elevation is the average change.
In expression within that Latin region, So we take tissue punches from the.
Transduce areas as Amtrust used area and make that calculation.
Regarding the IND, enabling studies as we mentioned in the script when you move from a research setting into a GOP toxicology study setting, there's more rigor and detail around the analytical testing and requirements and this is taking.
Little longer than we had initially anticipated and thats.
Basically the explanation for pushing at the start R&D, enabling studies stopped and typically we don't give specific timelines our R&D submission until we.
Completed that work.
Our next question is from Matthew Harrison with Morgan Stanley . Please proceed with your question.
Hi, Thanks for taking our questions. This is what John Lifeful Matthew.
We have two questions. One is for the Ruby trial. So do you think the data could be directly comparable to other Christopher.
S C D trials or do you think there are some differences in patients or other things, we should be taking into account the sorry.
It started up whereas just following off your comments so in terms of potential FDA package submission shall we expect any update in the upcoming clinical trial update.
In terms of adding and point to include four registration or trial or what specific patient and segmentation to enrich and potential registrational trial.
Thank you very much.
So with regard to the Ruby trying to edit 301 data.
We.
We will be reading out the data in December .
And we believe that we will be.
To be able to share data and plan to share data that would show that we are our competitors as I've said in my in my previous remarks.
We believe that the sickle cell and TVT spaces require and have the potential.
To accept multiple therapeutics, using CRISPR technology, and we believe that we can actually have and provide a very competitive product for patients with regard to the 101 data.
We will actually be able to share our plans to share that stages assessed.
Later this month.
This month November .
And actually we'll be able to talk about our next steps forward.
Based on deals, it's just that about the Ruby study.
Matthew and also related to Chinas question earlier, so in my comments about 30% of hemoglobin bubble is really based on the hypothesis of the clinical observation of the H B F. H and is not our target up a fetal hemoglobin expression level as <unk>.
Neil mentioned, we believe we have a differentiated and competitive products and we will we're looking forward to share that data with you.
Later this year.
Yes.
Okay. Thanks.
Our next question is from.
With Stifel. Please proceed with your question.
Hey, good morning, Thanks for taking our questions and congrats on all the progress.
Quick clarification on Ruby before I go to brilliance on Ruby I thought I heard two patient data by end of year, but I think I heard <unk> Zhong say efficacy data from one. So if you can clarify that that would be great in terms of brilliance I guess, it's more of a two part question. So Joe more when you say commercially viable what.
Kind of number of range are we talking about when it comes to prevalence.
And as it pertains to the efficacy signal that we might see at the presentation. Later. This month you know earlier this year of procure had data.
That turned out to be completely opposite of what they thought would be considered enriched.
Population for efficacy. So how do you think about sort of handicapping. What you see later this month and how that could be predictive of future outcomes.
And edit 101 slash LCA 10 population. Thank you.
Thanks very much.
So.
Let me clarify the Ruby.
We will be presenting safety data from two patients and efficacy data from one patients based on that you may want to expand yes, yes.
Just clarify on that.
We have the first we reported the first patient dose during the last updated in August .
Then these patients we recently updated we have dose the second patient. So the first patient and we will have a longer duration of observation.
Given that these.
<unk> gene editing ITT.
Gene therapy program, we expect it will take time to see meaningful efficacy data, where we will share all of that available for the two patients that we feel the first patients that may be more meaningful from an efficacy perspective.
Okay that helps.
Thanks, very much based on that let me turn to the <unk>.
Brexit question I think the first question is around the definition of viable.
Essentially when we actually look at these data.
<unk>.
With regard to determining the commercial viability of a segment that we're actually of the patient population that will be determined by a number of factors and essentially at the highest level an intersection of the magnitude and clinical meaningfulness of the effect size. In addition to.
Population segment size.
With regard to your second question around <unk>, obviously that was a very unfortunate outcome.
For patients.
In that we are using an AAV delivered at genome editing tool.
We're using a <unk>.
<unk> as a service based chemistry.
But I think we are very conscious of the importance.
Robustly being able to segment.
Patient population and predictive manner, and we as we look at our data and share. It with you will be able actually to go into more detail around that.
Thank you.
Excellent look forward to it thanks.
Our next question comes from Phil Nadeau with Cowen <unk> Co. Please proceed with your question.
Good morning, Thanks for taking my questions just two from US first on Ruby on that first patient that you've mentioned that you're gonna have succeeded from I don't believe I heard you say anything about a crises events being part of the efficacy measures will you be able to.
Present, any data on that or releasing data on that or is it too early in that patients with valuation and then second on the 202, just what remains before you can you can enter the clinic with that program.
So im going to ask at based songs to answer the first question and marks the second question.
Thanks, Phil.
For the will be efficacy data as I mentioned, we bought.
To provide a safety as well as key Hematological parameters, we certainly will report boc, but as I mentioned earlier.
Short term duration of observation may not be most meaningful but it was 60, we reported data on that.
Yes, Phil this is mark.
I think as we.
Perhaps it discussed it last.
Earnings call.
Completing the any animal pharmacology data that's necessary to support the IND, enabling Tox study design and conduct and as we mentioned in the script that is planning for some time next year.
Perfect. Thank you.
Our next question is from Jay Olson with Oppenheimer. Please proceed with your question.
Oh, hey, thanks for taking the questions.
Two questions from us for edit one O. One can you remind us if you started dosing of pediatric high dose group I think you had previously mentioned.
There was a <unk> review of pediatric mid dose cohort cohort last year and is there any update you can provide on that and then for edit two O. Two can you just talk about the data that you'll be presenting at city. Thank you.
Yeah.
Alright, thanks, very much Jay so with regard to one on one I'll have based song answer that question and the 200 to Cynthia Alaska Mark to address yes.
Yeah. Thanks, Thanks for the question.
Yes, as I mentioned, we did have a DMC meeting.
As planned.
We previously scheduled a normal meeting and at that meeting the <unk> reviewed all of the clinical data.
<unk>.
And they.
They see a satisfactory safety profile and regarding your question about how those pediatric cohort you will discuss the IBM Z and although they are satisfactory with a safety profile will become and to continue the study as planned but they recommended to review additional three months.
Data from the existing patients before starting the high dose cohort in pediatrics.
This will not impact our plan to release that data of these months as we just PV some mentioned and it will also will not impact our.
<unk> decision.
Program, we feel we have.
Adequate data to make a decision about this program.
Yeah, Hi, it's a market okay.
Yes, we're not really in a position to give specifics about the <unk> data yet given that it's under embargo.
As I mentioned in the script, we did present, an update at ESG, ICT, which gave some pretty interesting data on the in vivo <unk> model.
And.
Tumor killing.
Two examples so will the data will continue on that track.
Thank you Mark.
Thank you very much.
Our next question is from Joel Beatty with Baird. Please proceed with your question.
Thanks for 103 of the presentation last month described 100% gene editing and nacco and 30% replacement levels could you discuss why 100% editing when it.
To lead to a 100% protein levels and almost 30% enough.
Thank you Mark I'm going to ask Mark tasks.
So.
Can you just clarify the second part of that so the 100% editing.
Is necessary to remove the mutant rhodopsin. So this is oklahoma dominant disease. The 30% replacement. So this is 30% of the codon optimized smokehouse sandwich in a disease setting would be essentially 60% of the endogenous rhodopsin since it's only one aneel.
In the HP model you May recall, we had reported data showing that we had a knockout only arm as well as a noncash and replace.
And we were able to correct. The phenotype that occurred in that market only arm, which is basically lots at Rockford receptors with the 30% rhodopsin replacement. So we felt in that particular.
<unk> system that was very encouraging data to show that you could overcome loss of rhodopsin. There are as you may know some published data.
I'm thinking of a dog muscles from the <unk> group, which arrived at a somewhat similar conclusion that around 50%. We've got sitting in that particular market with sufficient to correct the phenotype.
So thanks, very much Mark Joe just to be absolutely clear.
Sure there is no room for any confusion or misunderstanding in contrast to LCA 10.
The 103 or 101 of the LCA 10.
103 program is addressing an RFP for.
Disease, which is a dominantly inherited toxic gain of function, which is why mark makes the point that you want to have the highest possible efficiency in knocking down that.
Gene that's generating that.
Owing to the nature.
Of the approach.
We are knocking down both the mutant toxic.
Ali as well as the healthy allele and therefore, we're replacing that with a.
Codon optimized.
Replacement, a reduction and I think you heard mark if the rationale why we believe that that replacement is sufficient.
Maybe just one other comment I think one reason why.
We are getting such high productive editing for the <unk> program is its a single guy So we're simply introducing in Dallas, which to which cost frame shifts in the transcription and therefore loss of the endogenous rhodopsin that's different to the 101 program, while you have a cool guy.
Neither team, which in this case the installation or the ocean is a low percentage.
Alright, thank you.
Our next question is from Luca <unk> with RBC. Please proceed with your question.
Excellent. Thanks for taking our questions. This is Lisa on for Luka.
I have two questions one.
One is on the NK cell platform.
We have seen some press lately, suggesting that you are at the one yard lines pardon me oncology pipeline here for the NK program.
Just wondering if you have any updates there.
And number two on the sickle cell you know given the.
This is very competitive.
Was just wondering if you could comment on any additional endpoints youre thinking about besides crises.
Also I want to welcome measures like stroke heart failure renal failure.
In order to help differentiate your product for them from others.
Taking the questions.
Thanks, very much Ivan with regards to the NK platform.
Have at 12 and has been very open.
Yeah.
Over the past year or so that we are keen to unlock the full potential of our NK platform.
Through partnerships and with regard to you know sharing.
Updates, we will look forward to sharing updates, but only when we have any kind of partnership.
Signed and executed.
With regard to 301 and our approach differentiation.
R R.
Ah Readouts.
Later this year will be that initial our data from the <unk>.
Ruby study.
Going forward.
We are actually considering a number of approaches to determining the potential for differentiation of our product I think you've touched on some of them there are many others.
We're actually considering.
And obviously.
Those considerations.
Considerations those outcomes.
We're in discussions with our key opinion leaders experts and ultimately with regulators in the future and we'll share more details in the future.
Great. Thanks for taking our questions.
Our next question comes from Ian <unk> with Wells Fargo Securities. Please proceed with your question.
Hi, Thanks for taking my questions. So first on the.
The sickle cell program.
I think by so you mentioned.
That the minimum H B F. A level of 30%, which is considered clinically meaningful is not necessarily a.
The target hbf level could you elaborate.
A bit more on that.
Target hbf level and secondarily for this program.
Where could you talk about the venue for the sickle cell data update and also in terms of the length of the follow up for the first patient.
Where do you plan to make the data cut.
Turning from the mouse mouse a follow up thanks.
Thanks.
Okay.
Thank you for the question for the wholesale.
Patients regarding the fetal hemoglobin level as I just mentioned that.
Our.
Hypothesis of design the commodity Q was based on the B.
Clinical observation.
That about etch F P patient with CCAR sale. So that's how we get to these.
30 30.
30% of patients right. So that's kind of what we have is certainly not our clinical targets. We're fully aware of this field and we will looking forward to share our data with you later this year.
Thanks, very much based on.
With regard to the value for the update.
We are <unk>.
Planning to share these data before the end of the year and we will be less.
Laughing at you know the.
The venue.
Later on.
Then with regard to the length of follow up on the cut for the data for our 301.
For the two patients we will have the safety data as based on has outlined and with regard to efficacy data hematologic parameters that data cut would be occurring close to the disclosure, but certainly should be in the early <unk>.
Faith that we would anticipate based on experience in this space.
Great. Thanks for.
The color.
And on the LCA 10 program.
I think I heard for the pediatric meet those patients the data will be safety only.
So two questions.
When would you expect to have at least three months data from the pediatric cohort.
And also for the measurement of.
B C D E and F S T and perhaps also navigation.
Could the pediatric patients.
Produced could those patients perform these tests and provide.
Reliable results.
<unk>.
Yes, thanks, very much and for those follow up questions. Yes, you are correct. Our plan is to share safety from the pediatric at mid dose cohort and we will give.
Clarity on the duration of follow up at the time of the disclosure and specifics and with regard to <unk> and I may have based on comment a bit on that but it is important to note that one of the reasons that we actually carried at the natural history study was amongst other things not just to deter.
Well the the.
Long term our progression of the disease was but it was actually also understand the behavior of those outcomes that we are using including PCV a visual navigation courses.
In the context of that disease and across multiple age groups based on I don't know if you want.
Sure.
Good question about the endpoints right.
Guillermo mentioned earlier about the purpose of the <unk> study as well as why we actually conduct can be natural history study. So we will be able to use the data from natural history study to contextualize as you pointed out for FSP or visual navigation cost. The challenge is that you.
And not only for the pediatric patient could it be for other adult patient too. So we fully understand that so we are analyzing testing and retesting variability in all of those reliability of the endpoints.
Great. Thanks by so many thanks Gilmore for all the color.
Our next question comes from Madhu Kumar with Goldman Sachs. Please proceed with your question.
Hi, This is Mario for module, we have two questions. So first how should we think about the internal pipeline development versus external partnering for X ocular or hemoglobin apathy programs, particularly for oncology cell therapy programs.
And then second what impact because the inflation reduction or IRI have one indication expansion on pipeline candidates.
Thanks, very much for your questions.
With regard to the internal pipeline.
As I said a little earlier.
In my prepared remarks.
We are continuing we have and I've been very excited and happy with the work I've done with the executive team and actually looking across our portfolio as we evaluate our strategy and looking forward to sharing that in the coming months.
<unk>.
But I think the one thing I can say that has been said consistently is that we believe we have a very exciting technology and we want to find ways to unlock its full potential by appropriate focusing of the pipeline internally as well as seeking.
Powerful.
And robust partnerships too.
Enable us to expand our bandwidth to fully realize the potential of our technology, but as I say, we will be able to share more about that in the coming months.
And.
With.
Archie IRA.
Thank you for that.
We actually I know that there has been a bit of press and some companies have actually talked about IRA restricting.
There are approaches I think it's important to be approved certainly looked at that legislation and the regulation around it and we believe that there is an issue.
It is designed to.
To enable us to develop.
New technologies to target.
Difficult and challenging human diseases that have struggled with a very unmatched in the high unmet need and so we actually feel very optimistic that our technology can operate and innovate continue to innovate within the context of the IRA owing to the way the regulation is written.
Thank you. Thank you.
Our next question comes from Lisa <unk> with Evercore ISI. Please proceed with your question.
Hi, Thanks for taking my question.
Be curious about any retailer insights you're getting from them.
Instead of the progression of X and sell through the regulatory.
Process, and then as that as that kind of a.
Fast follower maybe.
Maybe you can describe here how you see positioning.
The marketplace there.
Yes. Thank you very much Lisa for your question, obviously, we're very excited.
Along with everyone, who is developing therapeutics in this space.
And very specifically.
Has this will be an important pathfinder for genome editing as it moves through the regulatory approval process.
In addition, it's worth pointing out.
That with regard to our exclusive license holding forecast nine.
There is an additional upside potential to us beyond just the information that we learn as the.
Regulators.
Sure.
Evolution of our thinking for this space.
With regards to positioning.
We believe that the.
<unk> space.
Because it's new.
And because of the very high unmet need.
Tempered by the what we would anticipate over the next couple of years might be some hesitancy in uptake.
Importantly, the evolution of the payer landscape.
That we will actually been a very good position with the timing and progression and progress, we're making with <unk> 301 program that the majority of the president patients will actually still be awaiting therapy at the time of our launch.
And so with the differences in our approach and our potential to differentiate this additional upside as we see so we believe that we have competitive product and that is to say there is space for our product and it will be spaced substantial space for our product at to meet the significant unmet need of pace.
<unk> with both sickle cell and TVT with our three in one product.
Okay. Thank you.
We have reached the end of our question and answer session.
Okay.
Okay.
Thank you for joining the conference you may disconnect and you disconnect your lines at this time.
Goodbye.
Okay.
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