Q4 2021 Editas Medicine Inc Earnings Call
Good morning, and welcome to Eddie talked medicines fourth quarter and full year 'twenty 'twenty. One conference call. All participants are now in a listen only mode. There will be a question and answer session. At the end of this call. Please be advised that this call is being recorded at the company's request I would now like to turn the call over to Rob All day bread and butter.
Your relationship that I, just talked about isn't thank you may begin.
Thank you Laura and good morning, everyone 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 the call for Q&A as a reminder, various remarks that we make during this call.
All 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 forward looking statements as a result of various important factors, including those did.
And 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 spin.
Typically 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 Chief Executive Officer, Jim Mullen.
Thanks, Ron and good morning, everyone.
I'm joined today by several members of the.
The executive team, including Mark Shearman, our Chief Scientific Officer, and Michelle Robertson, our Chief Financial Officer.
I want to start off by providing a few highlights from last year and some important upcoming milestones for editors.
We achieved clinical proof of concept with edit 101 for LCA 10, a leading cause of inherited blindness in children.
Initial trial data demonstrated successful delivery in vivo editing with improvements in vision.
We're on track to complete dosing of the pediatric mid dose cohort in the first half of 2022, we expect to initiate dosing of pediatric.
High dose cohort later this year.
Analyze the cost for edit 103, or four form of autosomal dominant retinitis pigmentosa another diseases of the retina.
Which leads to blindness and has no approved treatments for this program is progressing towards IND, enabling studies, we plan on sharing additional preclinical data at ARVO conference. This spring.
Our pipeline of in vivo products is expanding quickly. We now have four wholly owned ocular programs and more ocular opportunities. We're also well positioned to explore additional indications outside of the ongoing preclinical work.
Where they're edit 301 program for sickle cell disease, we've successfully edited cells ex vivo are on track to dose the first patient in the first half of this year.
And we're also pleased to obtain IND clearance for edit 301 in transfusion dependent beta thalassemia and we're in the process of setting up the clinical sites and beginning to screen potential study subjects.
Back to dose the first beta thalassemia patient sometime this year.
We announced it at 202, a highly differentiated Ips derived NK cell investigational medicine with four gene edits, we presented data demonstrating how our approach has the potential to accretive allogeneic off the shelf NK cell therapy medicine with enhanced activity against solid tumors and.
And finally, we advanced our collaboration with Bristol Myers, Squibb, and Alpha Beta T cells.
<unk> has opted into six programs with one declared a development candidate into IND, enabling studies to date, we have received over $125 million in payments plus have potential for further milestones and royalties in the future.
Now I'd like to spend a few minutes reviewing our clinical programs.
Last year, we treat the important in vivo clinical proof of concept with edit 101 for LCA 10.
The initial brilliance trial data demonstrated successful delivering editing with meaningful improvements in vision. These improvements were quantified by several assessments, including a patient's ability to maneuver through mazes at different light levels.
Improvements in full field light sensitivity testing and best corrected visual acuity, we're very excited by these results and our progress on edit 101 was highlighted as one of the top breakthroughs last year by the American Association for the advancement of Science.
At the end of last year, we completed dosing of the adult high dose cohort and thus far we have not seen any dose limiting toxicities or serious adverse events.
Any reported adverse events have been attributed surgical procedure and have subsequently been resolved the.
The strong safety profile across all three dose levels is very encouraging as we advanced the trial in pediatric patients.
Our next milestone is complete dosing of the pediatric mid dose cohort in the first half of the year review of the safety with the IBM Z and initiate dosing of the pediatric high dose cohort.
We're also expanding patient enrollment in one or more of the previously completed adult cohorts that expansion will help further explore the dose responses and provide us with additional data as we design, a registrational trial and select appropriate endpoints.
Clinical update for edit 101 will be provided in the latter half of the year, which will include 12 month data at the mid dose cohort six month data of the high dose cohort.
Thus far we've received very encouraging feedback on this trial from investigators clinicians and most importantly, the patients.
One of the study participants who reported meaningful improvement upon their daily lives, including simple things like being able to walk through doorways or walking around outside a bit more independently.
We are exploring the most relevant and sensitive endpoints to support further development of the trial continuing to evaluate how we can most effectively interpret trial information and considering what is most meaningful to patients.
In addition to the trial data. We're also looking at our natural history study data to identify the most reproducible measures and we expect to have that data available later this year.
Moving on to edit 301, and our ex vivo platform.
We've developed potentially onetime treatment for both sickle cell disease and transfusion dependent beta thalassemia are.
Our unique approach disrupts the binding site of Bcl 11, a consistent with what we what is seen for naturally carry mutations that result in hereditary persistence of fetal hemoglobin or HP FH pay.
Patients, who co inherit one or more of these protective mutations generally don't exhibit pain crises experienced fewer hospitalizations and Oregon damage that have longer life spans because of the natural validation of this approach in human genetics. We believe edit 301 is likely to be a safe and durable approach to treating both.
These indications.
As a reminder, we are editing debated equivalent promoter in patients generate protected changes that increase fetal hemoglobin similar HP FH this should reduce or potentially even eliminate disease symptoms in individuals with sickle cell disease or TVT.
Edit 301 also utilizes our highly efficient and specific proprietary aaas cast 12 day enzyme.
We believe the choices editing site combined with the editing specificity and efficiency afforded by our unique enzyme could lead to a safer and more durable therapy.
And the Ruby trial that at 301 for sickle cell disease, we've successfully added patient cells ex vivo and our track for dosing in the first half of 2022 with initial clinical data.
<unk> by year end.
The beta thalassemia IND was cleared by the FDA last December and one of the process of setting up the clinical site IRB approvals and patient screening and expect to dose the first PDT patients by year end.
And finally I wanted to update everyone on our clinical operations, while the CMO searches underway. Our current clinical operations team, which has extensive ophthalmology and hematology experience is continue to advance our clinical trials. The top tier agency has been retained to assist us in the search and we plan on reviewing initial candidates in the coming.
<unk>.
Our objective is to bring in someone with a proven track record of regulatory approvals for complex medicines, and organizational leader, who could spearhead multiple clinical trials and someone who will work closely with Mark's team as we strategically build out our pipeline.
We do not anticipate any direct any disruption in our clinical programs or upcoming milestones and I look forward to updating you. Once a decision is made.
With that let me turn the call over to Mark to review, our preclinical programs and platform technologies.
Thank you Jim.
Im very excited by all of the progress we've been making in advancing our early stage pipeline, including two new development candidates that we announced this year.
First.
One of the three well rhodopsin associated autosomal dominant retinitis pigmentosa.
ROE a DRP is a disease of the restaurant leading to blindness. Typically later in life, although a significant number of patients experienced onset of symptoms.
Yes.
There are currently no approved treatments.
To treat rotator at APLP, it's necessary to knock out a disease, causing rhodopsin gene and then replace that gene with a functioning one.
Based on our preclinical data we have been able to accomplish this with a unique dual AAV nutcase and replace approach.
The knockout of the gene in the retinal cell can only occur if the components for the replacement gene I'll also delivered to that same cell.
The replacement gene corrected the primary light sensitive protein necessary for proper rod photoreceptor function.
Very importantly, we expect edit 103 to address more than 150 mutations in this gene that causes the disease.
We tested this therapy in nonhuman primates and showed that we achieve virtually 100% productive that chain, which in this case means not cadence achieved.
The corresponding gene replacement resulted in production of approximately 37% of human ROE approaching the optimal tests, which we expect to be a therapeutically effective level.
As Jim mentioned, we plan to present these and additional data at the medical conference.
The program is moving towards the clinic rapidly and by the end of 2022, we expect that we will be well advanced in IND, enabling studies.
Notably the queue AAV gene editing approach that we are using for ROE. AARP also provides a pathway and initial proof of concept for the treatment of other autosomal dominant disease indications.
If negative function needs to be corrected.
With Usher syndrome Iia program, we've refined the construct for edit 102 and significantly increase productive editing by using a different tools that can approach with an optimized <unk> cost 12, a and an improved diet RNA configuration.
This potentially alternative construct resulted in a 350% increase in productive editing compared to our earlier construct.
This is also the first time to our knowledge that anyone has eased and as cash 12, a enzyme packaged in an AAV for delivery.
We're also working on other large indications and taking advantage of our experience in ocular diseases and a range of delivery solutions.
We expect to declare an additional new development candidate for an in vivo ocular indication later this year.
Moving onto our cell therapy programs, we've announced a new development candidate <unk> 200, <unk> a highly differentiated.
<unk> derived NK cell medicines for solid tumors.
Our overall objective is to develop engineered NK cells with potent antitumor activity and substantially increased persistence and important limitation with many existing NK cell approaches.
For this construct we make four edits.
One to improve antibody dependent cellular cytotoxicity.
Once <unk> become tumor microenvironment resistance.
One to improve activation proliferation in such analytic activity and one to improve persistence.
To the best of our knowledge. We are currently the only company that has this specific combination of edits.
And in engineered allogeneic cell.
We believe this approach has the potential to create highly active off the shelf NK cell therapy medicines that could be used for the treatment of multiple types of solid tumors.
We expect to advance this program to IND, enabling studies. This year earlier. This year, we presented initial edit 202 preclinical data demonstrating improved persistence with adding such as cytokine support.
<unk> antibody dependent cellular cytotoxicity and significant tumor reduction or even clearance in less than one week.
We continue additional in vitro in endeavour experiments, some of which will be presented at the upcoming AACE meeting this spring.
After adding two we selected a number of potential edits that may further increase NK antitumor activity.
Such as introducing a chimeric antigen receptor or car.
We anticipate that there will be follow on product configurations that can be customizable or specific solid tumor indications.
With GMP closed selection for the first program well underway and the process for expansion and differentiation advancing we anticipate the development to follow on programs to be significantly more streamlined.
Briefly going back to add it to two I wanted to highlight the utilization of snake technologies from a knockin editing.
Sleep is short for selection by essential Exxon Knockin, which many of you may have heard as described last year.
Technology that utilizes the <unk> 12, a nuclease to selectively and at high efficiency integrate trans genes into a specific Lucas SM.
Essentially a technique allows us to get high efficiency knock in with a number of different cell types, while also ensuring robust and controls transgene expression.
We view sleek as a key tool to accelerate the development of gene edited engineered cell therapies.
We have demonstrated more than 95% knock inefficiencies using the ask cost 12, a nuclease.
Various clinically relevant target cells, including IPF fees.
T cells and NK cells.
We also anticipate using sleep to fine tune the expression levels of transgene cargos, an important attribute of next generation cell therapy medicines.
I would also point out that once we've exited the south we select a single cell clone for further development that has the exact intended edits.
Cloud that extensively characterized and showing the elimination of any clones with chromosomal abnormalities for example, and allows us to derive the final population of precisely edited cells no off target editing.
This important safety attribute is another reason why we've invested so heavily in our cell therapy platform.
Finally, with continuing to make good progress with our ongoing partnership with Bristol Myers Squibb around Alpha Beta T cells.
BMS has opted into six programs and one development candidate is in IND, enabling studies.
Leveraging many of our technologies, including our proprietary cast nine at Ash, Castorama Nucleases and our guide RNA design to create autologous and allogeneic approaches in immuno oncology.
We look forward to continuing to work closely with our colleagues at BMS to develop important new medicines for cancer.
With that I'll turn it over to Michelle to review our financial results.
Thank you Mark and good morning, everyone.
Like to refer you to our press release issued earlier today for a summary of our financial results for the fourth quarter and full year of 2021 I will take this opportunity to briefly review a few items.
At a cost remains in strong financial position.
Our portfolio, we're well positioned for continued execution supporting the manufacturing and clinical objective about trial and.
Also enabling.
Our preclinical pipeline.
Our cash cash equivalents and marketable securities as of December 31 was $620 million compared to $512 million as of December 31, 2020, our cash runway to extend through 2023.
Revenue for 2021 with $26 million compared to $91 million. In 2020. This decrease is mostly driven by over $70 million in recognized revenue from the Allergan collaboration termination in 2020 slightly offset by revenue from our collaboration agreement with <unk>, which is now part of BMO.
G&A expenses were consistent with our expectations and increased from $67 million in 2000 $20 million to $76 million in 2021.
R&D expenses decreased from $168 million in 2000 $20 million to $143 million in 2021.
The $15 million decrease was driven by the termination of our agreement with Allergan handheld as well as a decrease in success payment expense related to our license agreement factor.
Factoring those out we did see an increase in manufacturing and clinical related costs last year as we advance edit 101, and edit 301, we expect clinical and manufacturing expenses to be the primary driver of spending growth in 2022.
We ended last year with approximately 216 <unk> unexpected.
And expect to have just under 300 full time in place, but we ended this year most of the Onboarding will be focused on supporting our clinical programs developing new technology and building out our CMC capabilities.
With that I will hand, it back to Jim.
Thank you Michele 2021 was a transformative year for edit to us and we expect 2022 to be another exciting year.
101, we will initiate dosing in pediatric high dose cohort expand one or more of the previously completed adult cohorts and provide a clinical data update in the second half of the year.
We also expect that at 103 to be well into IND, enabling studies and finalize the product construct of rush to a program and declare a new development candidate for our in vivo ocular indications.
<unk> 301 for sickle cell disease, and beta thalassemia will have the initial patient dosing for both indications with initial sickle cell disease clinical data by year end.
So therapy platform, we will begin IND, enabling studies edit 202, our first of a series of <unk> programs, and we're continuing to supporting BMS and their T cell programs as they advance first program towards the clinic.
For our platform development and technology innovation, we plan.
<unk>, enhancing and developing new and improved technologies as well as techniques for gene editing and delivery.
And finally I've always believed in the business development is an important facet of long term value creation, when we expect to leverage our technologies and capabilities with partners, where it will be mutually beneficial.
Addition to our internal efforts, we plan to pursue future development and commercialization opportunities in areas outside of our core strategic focus through partnerships.
We thank all of you for your interest and support with that we'll open it up to Q&A.
At this time, we'll be conducting a question and answer session I would like to ask a question. Please press star one on your telephone keypad a confirmation.
Your line is in the question queue, you might start to move your question from the queue for participants using speaker equipment. It may be necessary for you to pick up your handset before pressing the Starkey one moment please poll for questions.
First question comes from the line of Dae Gon Ha with Stifel. You May proceed with your question.
Hi, good morning, guys.
Just a couple from US this is Jack on for Dagon.
Just what is your general thoughts I guess on the discrepancy and BCBS measures in the LCA 10, and what steps are you or slash strategies are you taking to me.
Minimise such a gap in your program.
Mark do you.
Do you want to take that I'm not sure I completely understand the question, but maybe you do.
Okay My understanding yes so.
The FCA patient population has quite a range of CVA.
CVA measurements at the time that we get to see them and this is obviously based on the trajectory and the time course of disease.
We've instituted in addition to the standard.
<unk> chart additional ways of measuring that visual function in acuity.
In addition to the.
<unk>.
Sensitivity of the retina and as gene mentioned, the mace and so I think our approach really is to try to use all of those measurements to assess the function of the patients in that response to treatment.
Great. Thanks, that's helpful and then in Europe , and your PR, you mentioned expanding enrollment.
And your adult cohorts.
And Youre contemplating and what will drive the determination.
Between one or more.
So the goal with the expansion is to really generate more data on one or more doses.
Already tested in the adults.
Think as we had indicated there is some variability across patients and so we want to be able to make the best decision on the optimal dose.
And the response profile of patients and so that's the driver for expanding the patient numbers, we want to give ourselves flexibility into what those numbers actually end up being.
Just on the data as it comes through.
Great. Thanks.
Taking the questions.
Our next question comes from the line of June Lee with True Securities. You May proceed with your question.
Hi, good morning.
Maybe on slide.
June our question relates to powerful asleep.
Technology.
We would like to understand if you could elaborate please on.
Internal programs, but are using.
Click technology and if there is any.
Potential for collaboration or sub licensing of this technology out and at the end.
This is Barry.
Interesting technology.
Any potential for in vivo applications.
Sneak better.
Genes or tissue specific.
James.
Yes.
Yes. Thanks for the question I'll take that so right now we've highlighted its use in two areas one.
Internally for the ICSC editing for the Iron K program, where we've used to sneak technology to knock in the CD 16 membrane bound IL 15 constructs.
And then in addition, we've utilize that technology in our collaboration on Alpha Beta T cells with Bristol Myers Squibb.
We continue to look for ways in which to advance the technology itself.
<unk> in its current guys, but we continue to look for additional fleet types for example in ways in which we can.
<unk> expression <unk> transgene into different systems one of the.
Properties that makes.
<unk> technology so powerful.
Is that you essentially enrich for those sales which have successfully in <unk>.
Each homology directed repair and have reconstituted the essential Exxon.
And that is a portion of the total SaaS and those that do not do that.
We'll die because of knocking into an essential theme.
So that property is really powerful in many settings, but it does provide potential limitation to its using vivo because of that aspect of the technology. So we don't see this as a cure all for everything in terms of knocking invalid is very powerful in the situations in which we are using it.
And then lastly, yes, we are open to possibility of licensing the technology Thats a lot of proprietary know how as well as the use of the <unk> nuclease and so yes, we would entertain potential licensing opportunities.
Thank you very much thanks for taking our questions.
Our next question comes from the line of Phil Nadeau with Cowen <unk> Company. You May proceed with your question.
Good morning, Thanks for taking my questions a couple from US first on edit 301, we're curious if theres any update on the efficacy assays any.
Any new.
The new timelines as to when this could be completed.
Ill start that Mark and maybe you want to finish it so the efficacy.
Theres a few different efficacy slash potency assays I think you may be referring to the potency assay. So.
<unk>.
That is well developed ultimately it needs to be qualified using patient samples.
So that'll be a process.
Undergo over the course of the next couple of quarters is to qualify that assay with actual patient samples.
Mark I don't know if theres anything you want to elaborate on.
The only thing I would add is that with confidence of the performance of those assays.
<unk> put a lot of effort internally to make them as good as they can be.
So as Jim mentioned ready now its getting the patient samples to be able to confirm their specifications.
And can you remind us of the process of getting the clinical hold lifted do you have to.
Presumably you have to submit your findings to the FDA and I have to verify that they agree that the.
The assays have been qualified.
That's correct, we were very encouraged by the fact that the beta thalassemia IMD got cleared so.
Relatively easily I should say because that contains.
Essentially the same information on how these assays will be run on the FDA liked what they saw that so I think it's a matter of us.
Providing that information to them.
Getting that response.
Great.
The second question from US is an LCD.
<unk> in your prepared remarks, some of the challenges of conducting studies in the condition did you learn anything from the recent results from the illuminate trial.
Notable there that informs here.
Designs on future I'll say 10 studies.
So I think the outcome of that data was very unfortunate for the FCA and patient community community I mean, right now we don't have any more insight than Youtube intensive the information that <unk> currently released which is essentially the top line.
The primary and secondary so we can't comment any further at this point.
Great. Thanks for taking my questions.
Our next question comes from the line of Gena Wang with Barclays. You May proceed with your question.
Thanks for taking my question I'm, calling in for Gena.
Just one from us with multiple program.
<unk> clinical program.
Late stage.
How should we think about the pipeline prioritization.
In the long term.
Interesting question.
How should we think about pipeline prioritization.
I think the answer to that is probably we are going to be following the data and so those.
Areas.
Platforms.
Start to see the strongest data.
That leads to actual drugs meaningful drugs.
That's where we will.
Double down on the investments.
So it's probably well it is premature because we just don't have data sufficient data the ocular programs or for that matter sufficient data.
Don't have clinical data yet on the sickle cell and beta thalassemia.
Probably a great question as we proceed into sort of second half of 2023.
But we will follow the data.
Thank you.
Our next question comes from the line of Luke.
With RBC you May proceed with your question.
Perfect. Thanks for taking my question. This is Lisa one for Luka.
Just a couple from me I will I'll see a pen.
Got it looks like Youre going to provide a safety update and I will be open at ARVO, which is going to look at viral shedding.
Just wondering if you can provide more color on the rationale behind that.
Viral shedding something the FDA has been asking for and also how how will the CSF, where you're going to look at the fluid and aqueous of die.
And another question about expanding enrollment.
Adult cohort.
Just wondering does that mean, possibly that.
The highest doses will not most efficacious dose or is this the session also partly based on safety as well. Thank you.
So I can take those two questions. So the viral shedding assay is a standard requirement.
For AAV based therapies.
Yes.
It relies on collection of tears in bladder necessity assessing it and based on that.
The data that I've seen from similar studies. This is of no concern it's a standard.
Saturday to the FDA requires and we know that sub retinal injection is a very precise way of introducing the virus.
Into the to the retina.
It really doesn't go beyond that.
That question.
Yes, just to reiterate my previous answer I mean, we.
Are still in the phase one dose escalation and we have a limited number of patients.
<unk> enrolled and so we just want to the opportunity to acquire more data. So that we can make the best decision as to which of the two doses may be more effective and as Jim mentioned in his earlier remarks. This is important both the dose and any other insight into the different efficacy measurements.
And we use that information to plan for the pivotal Registrational trial.
Yes, and just to add.
Some time perspective, so we did complete the high dose cohort in Q4, but it's too early to have any really meaningful readout from that so we just keep our options open as we see the data from that plus the more extensive data from the mid dose to decide where we're going to.
Expand.
And is that thanks for taking my questions.
Yes.
Our next question comes from the line of Madhu Kumar with Goldman Sachs. You May proceed with your question.
Hey, guys. Thanks for taking my question, it's Rob on for Madhu I was just wondering what are you looking to see from the initial clinical data.
Sickle cell patients and the Ruby trial at year end.
Okay.
Well it'll be first it'll be basic safety and graft meant.
In the beginning and the expression profile of fetal hemoglobin.
Mark.
Its probably about all we will have at that point in time, Mark do you want to add anything to that.
Key factors neutrophil and government later in platelet and graph went in potential early signs of Hbf production.
Alright, thank goodness.
One other question is like how should we think about the Bristol Alpha Beta T cell collaboration in terms of milestones path to the clinic.
Okay.
Milestone.
It would be pretty classical milestone payments and royalties.
Once they became commercial.
I don't know Ron how much guidance specific guidance that we've given in the past.
Minimal we can just talk about the current progress.
Yes.
Alright. Thanks.
Our next question comes from the line of Jim Lee with True Securities. You May proceed with your question.
Hi, This is Matthew again.
I wanted to ask a question.
Related to AARP, Mark you said that it is necessary to reintroduce.
A functional copy based on my understanding of.
<unk>, removing the mutant and Neil should be sufficient.
There are.
<unk> like this.
<unk> nine.
That is a retrofit.
And Neil So what is the necessity of reintroducing the wildfire.
In these patients.
Yes.
So the approach actually knock stand both the mutant and the endogenous rhodopsin because the guide with.
With mutation is not the <unk>.
<unk> to discriminate between mutant and wild type.
So you're going to get enough data and.
And so thats why you require that replacement set the replacement rhodopsin will it be in Episome will help.
<unk> generated from the second AAV.
It will serve to provide a functional copy of rhodopsin in those cells.
Thank you.
Our next question comes from the line of Jay Olson with Oppenheimer. You May proceed with your question.
Hey, Good morning. This is Sharon on the line for J. Thanks for taking the question.
<unk>.
While ongoing pediatric cohort I'm just wondering.
With you.
So we will have to happen.
And separately any chance that we could see data from Pwc pediatric cohort this year. Thank you.
So short answer yes, there will be an it DMC review following the.
Enrollment of the mid dose pediatric cohort.
<unk> as has and we will see further data from the agile hydro's cohort as well as the pediatric mid dose cohort.
Our guidance is that we are hoping to complete enrollment of the mid dose by the middle of the year and hopefully if all goes well completion of the high dose pediatric patients by year end.
That's the guidance we've given.
Okay, Thanks, and any chance, we can see the data from the pediatric cohort this year.
We have not yet committed to a timeline for presenting that information.
Okay. Okay. Thank you.
Our next question comes from the line of Joe.
Betty with Baird you May proceed with your question.
Hi, Thanks for taking the question.
With the.
Editing enhancements to one or two that have been made that increased.
Editing back 250% is that type of approach something that could be applied to.
On one end and how does the editing a point I want to compare to the older and newer versions.
Two.
Okay. So the.
101.
<unk> added 103.
For approaching the editing a little differently in terms of whether it's an exon intron a single guide or a dual guide. So I don't know that Thats, a generalization that I can make across all three programs one in too.
Comparing the numbers.
As a consequence is not really the right thing to do because you're looking at different processes.
But what I would say is while we've essentially focused on with edit 102 is going back to.
Advance.
Technology to really maximize the.
The editing that we think is possible with both <unk> and potentially <unk> cast 12, a in a single or dual AAV format. So that involved a lot of.
Hardcore molecular biology around.
The design of the gene cassette.
Introduction of the features that may enhance expression of the guy the stability of the guys in patent, especially the nuclease and then looking at that in all different configurations.
But thats kind of how we arrived at the 350% improvement.
A plasmid based system by.
Spending a lot of time looking at all of its configurations.
And those rules some of them may be generalizable bet.
Given that the approaches are quite different from an editing perspective.
Each system is it kind of.
Alf contained system that would meet optimization.
Thank you.
Our last question comes from the line of Rick of Jankovskis with SBB Leerink. You May proceed with your question.
Hey, good morning, and thanks for taking our questions. So my first question really just focuses around clinical trial execution, while the company is searching for a CMO a.
Could you elaborate a bit on who is currently in charge of clinical trial execution and planning while the search is ongoing and also it looks like either CMO transition hasnt disrupted any of the projected timings around clinical trial starts or Readouts. So could you maybe clarify what are the current base case assumptions around when our new CMO would need to <unk>.
In order to hit all of those projected timing.
While the project.
I'll start with the last question first so the projected timing.
We have really nothing to do with when a CMO search.
<unk> because those are all.
If you will.
Balls in motion.
We have <unk>.
Yes.
On staff.
Biologists she's overseeing the 101 programs and of course.
Collaborating with Mark's team as we look at the preclinical programs.
<unk> space and the sickle cell disease beta thalassemia, we have a second physician who is the hematologist.
We experienced in this area overseeing those trials in addition to that there is.
Senior executive with.
Several decades of experience of running overseeing managing.
Multiple clinical trials that overseas sort of the clinical trial operations. We also have.
Clinical sciences.
In the organization as well.
Look and think about the data analysis data management some of the clinical trial design.
Activities.
So.
So the clinical operations piece of it or I'll call. It the blocking and tackling pieces of it in the short term we will report to me.
The more medical scientific pieces are reporting to mark.
Or just collaborating together with that whole team.
As we move forward and as we look for a new CMO.
Alright got it that's helpful.
I have a second question Thats, a little off topic, but if we look to some competitors in gene editing. There are a few companies that have been embracing LNP technology to deliver editors for ex vivo in vivo applications, while it looks like most of edits houses programs are really focused on electroporation and AAV vectors for delivery.
I was just hoping to get some of your thoughts around LNP delivery and gene editing and why or why not this technology would be appropriate to incorporate into editorialist pipeline.
Let me give that one to mark Thats, a perfect one for Murray.
Thanks, Jim.
Great question and yes, we do have an interest in the deployment of LNP technology across a number of different programs we have not.
Publicized reveal the details of that yet.
This is an area that we have an interesting chart.
Alright got it thanks for taking the questions.
Ladies and gentlemen. This concludes today's presentation. Thank you once again for your participation you may now disconnect your lines at this time.
Goodbye.
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