Good morning and welcome to the Editas Medicine’s Fourth Quarter and Full Year 2021 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 Ron Moldaver, Investor Relations at Editas Medicine. Thank you. 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 2 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 constitute forward-looking statements for 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 Chief Executive Officer, Jim Mullen..

Thanks, Ron and good morning, everyone. I am joined today by several members of the Editas 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 Editas.

We achieve clinical proof-of-concept with EDIT-101 for LCA10, a leading cause of inherited blindness in children. The initial trial data demonstrates successful delivery in in vivo editing with improvements in vision.

We are on track to complete dosing of the pediatric mid-dose cohort in the first half of 2022 and expect to initiate dosing of the pediatric high-dose cohort later this year. We finalized the construct for EDIT-103 form of autosomal dominant retinitis pigmentosa, another disease of the retina, which leads to blindness and has no approved treatments.

This program is progressing towards IND-enabling studies. We plan on sharing additional preclinical data at the ARVO conference this spring. Our pipeline of in vivo products is expanding quickly. We now have 4 wholly-owned ocular programs and more ocular opportunities.

We are also well-positioned to explore additional indications outside of the eye, with ongoing preclinical work. With our EDIT-301 program for sickle cell disease, we have successfully edited cells ex vivo, are on track to dose first patient in the first half of this year.

And we are also pleased to obtain IND clearance for EDIT-301 in transfusion-dependent beta thalassemia and we are in the process of setting up the clinical sites and beginning to screen potential study subjects. We expect to dose first beta thalassemia patient sometime this year.

We announced EDIT-202, a highly differentiated IPSC-derived NK-cell investigational medicine with 4 gene edits. We presented data demonstrating how our approach has the potential to create an allogenic off-the-shelf NK cell therapy medicine, with enhanced activity against solid tumors.

And finally, we advanced our collaboration with Bristol Myers Squibb in alpha beta T-cells. BMS has opted into 6 programs with one declared development candidate in 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 LCA10. The initial BRILLIANCE trial data demonstrates successful delivery in 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 are 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 to surgical procedure and has subsequently been resolved. 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 the safety with the IDMC and initiate dosing of the pediatric high-dose cohort. We are 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 the registrational trial and select appropriate endpoints. The clinical update for EDIT-101 will be provided in the latter half of the year, which will include 12-month data in the mid-dose cohort and 6-month data of the high-dose cohort.

Thus far, we have received very encouraging feedback on this trial from investigators, clinicians, and most importantly, the patients. Some of the study participants have 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 are 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 in our ex vivo platform, we have developed a potentially one-time treatment for both sickle cell disease and transfusion-dependent beta thalassemia.

Our unique approach disrupts the binding site of BCL11A consistent with what is seen for naturally occurring mutations that result in hereditary persistence of fetal hemoglobin, or HPFH.

Patients who co-inherit one or more of these protected mutations generally don’t exhibit pain crises, experience fewer hospitalizations and organ damage and 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 of these indications. As a reminder, we are editing the beta globin promoter in patients generate protective changes that increase fetal hemoglobin, similar HPFH.

This should reduce or potentially even eliminate disease symptoms in individuals with sickle cell disease or TDT. EDIT-301 also utilizes our highly efficient and specific proprietary AsCas12a enzyme.

We believe that choice of editing site, combined with the editing specificity and efficiency afforded by our unique enzyme, could lead to a safer and more durable therapy.

In the RUBY trial of EDIT-301, for sickle cell disease, we have successfully added patient cells ex vivo and are tracked for dosing in the first half of 2022, with initial clinical data expected by year end.

The beta thalassemia IND was cleared by the FDA last December and we are in the process of setting up the clinical sites, IRB approvals and patient screening and expect to dose the first TDT patients by year. And finally, I wanted to update everyone on our clinical operations, while a CMO search is underway.

Our current clinical operations team, which has extensive ophthalmology and hematology experience, is continuing 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 months.

Our objective is to bring in someone with a proven track record of regulatory approvals for complex medicines, an organizational leader who can 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 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 program and platform technology..

Thank you, Jim. I am very excited by all the progress we have been making in advancing our early stage pipeline, including two new development candidates that we announced this year.

First, EDIT-1034 for rhodopsin-associated autosomal dominant retinitis pigmentosa, RHO adRP is a disease of the retina leading to blindness typically later in life although a significant number of patients experience onset of symptoms in their early years. There are currently no approved treatments.

To treat RHO adRP, it’s necessary to knock out the disease causing mutant 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 knockout and replace approach.

The knockout of the gene in the retinal cell can only occur if the components for the replacement gene are also delivered to that same cell. The replacement gene corrects the primary light sensitive protein necessary for proper rod photoreceptor function.

And very importantly, we expect EDIT-103 to address more than 150 mutations in this gene that caused the disease. We tested this therapy in non-human primates and showed that we achieved virtually 100% productive editing, which in this case means knockout of the gene.

The corresponding gene replacement resulted in production of approximately 37% of human RHO protein at the optimal dose, which we expect to be a therapeutically effective level. As Jim mentioned, we plan to present these and additional data at the ARVO 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 dual AAV gene editing approach that we are using for RHO adRP also provides a pathway and initial proof-of-concept with a treatment of other autosomal dominant disease indications, where a gain of negative function needs to be corrected.

With our Usher Syndrome 2A program, we have refined the construct for EDIT-102 and significantly increased productive editing by using a different dual vector approach with an optimized AsCas12a under the improved guided 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 used an AsCas12a enzyme packaged in an AAV for delivery.

We are also working on other large indications in the eye taking advantage of our experience in ocular diseases and our range of delivery solutions. We expect to declare an additional new development candidate for an in vivo ocular indication later this year.

Moving on to our cellular therapy programs, we have announced a new development candidate EDIT-202, a highly differentiated iPSC-derived NK-cell medicine for solid tumors.

Our overall objective is to develop engineered NK cells with potent anti-tumor activity and substantially increased persistence, an important limitation with many existing NK cell approaches.

For this construct, we make 4 edits, one to improve antibody dependent cellular cytotoxicity, one to overcome tumor microenvironment resistance, one to improve activation, proliferation and cytolytic activity, and one to improve the systems.

To the best of our knowledge, we are currently the only company that has this specific combination of edits in an 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 without exogenous cytokine support, strong antibody-dependent cellular cytotoxicity and significant tumor reduction or even clearance in less than one week.

We continue additional in vitro and in vivo experiments, some of which will be presented at the upcoming AACR meeting this spring. After EDIT-202, we have selected a number of potential edits that may further increase NK anti-tumor 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 clone selection for the first program well underway and the process for expansion and differentiation advancing, we anticipate the development of follow-on programs to be significantly more streamlined.

Briefly going back to EDIT-202, I wanted to highlight the utilization of SLEEK technologies for the knock-in editing. SLEEK is short for SeLection by Essential-gene Exon Knock-In which many of you may have heard us describe last year.

It’s a technology that utilizes the AsCas12a nuclease to selectively and at high efficiency integrate transgenes into a specific locus. Essentially, the technique allows us to get high efficiency knock-in with a number of different cell types, while also ensuring robust and controlled 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-in efficiencies using the AsCas12a nuclease in various clinically relevant target cells, including iPSCs, T-cells and NK cells.

We also anticipate using SLEEK to fine-tune the expression levels of transgene cargos, an important attribute of next generation cell therapy medicines. I’d also point out that once we have edited the cells, we select a single cell clone for further development that has the exact intended edits.

That clone gets extensively characterized ensuring the elimination of any clones with chromosomal abnormalities, for example, and delays us to derive a final population of precisely edited cells with no off-target editing. This important safety attribute is another reason why we have invested so heavily in our cell therapy platform.

Finally, we are continuing to make good progress with our ongoing partnership with Bristol Myers Squibb around alpha-beta T-cells. BMS has opted into 6 programs and one development candidate is in IND-enabling studies.

They are leveraging many of our technologies, including our proprietary Cas9 and AsCas12a nucleases and our guide RNA design to create autologous and allogeneic approaches in immunooncology. We look forward to continuing to work closely with our colleagues at BMS to develop important new medicines for cancer.

With that, I will turn it over to Michelle to review our financial results..

Thank you, Mark and good morning everyone. I would like to refer you to our press release issued earlier today for summary of our financial results for the fourth quarter and full year of 2021. I will take this opportunity to briefly review few items. Editas remains in a strong financial position as we advance our portfolio forward.

We are well-positioned to continued execution supporting the manufacturing and clinical objectives of our trials and also enabling the advancement of 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 extends through 2023.

Revenue for 2021 was $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 Juno, which is now part of BMS.

G&A expenses were consistent with our expectations and increased from $67 million in 2020 to $76 million in 2021. R&D expenses decreased from $158 million in 2020 to $143 million in 2021.

The $15 million decrease was driven by the terminations of our agreements with Allergan and Sandhill as well as a decrease in success payment expense related to our license agreements. Factoring those out, we did see an increase in manufacturing and clinical related costs last year as we advanced EDIT-101 and EDIT-301.

We expect clinical and manufacturing expenses to be the primary drivers of spending growth in 2022. We ended last year with approximately 260 employees and expect to have just under 300 full-time employees by the end of this year.

Most of the on-boarding will be focused on supporting our clinical programs, developing new technologies and building out our CMC capabilities. With that, I will hand it back to Jim..

Thank you, Michelle. 2021 was a transformative year for Editas and we expect 2022 to be another exciting year. For EDIT-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 EDIT-103 to be well into IND-enabling studies and finalize the product construct of USH2A program and declare a new development candidate for our fourth in vivo ocular indication.

EDIT-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. In our cell therapy platform, we will begin IND-enabling studies in EDIT-202, our first of a series of iNK programs.

And we will continue supporting BMS in their T-cell programs as they advanced the first program towards the clinic. For platform development and technology innovation, we plan on continuing, enhancing and developing new and improved technologies as well as techniques for gene editing and delivery.

And finally, I have always believed in the business development as an important facet of long-term value creation when we expect to leverage our technology capabilities with partners, where it will be mutually beneficial.

In addition to our internal efforts, we plan to pursue future development 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 will open it up to Q&A..

[Operator Instructions] Our 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 Dae Gon.

Just what is your general thought, I guess on the discrepancy and BCVA measures in the LCA10 and what steps are you or/strategies are you taking to minimize such a gap in your program?.

I am not – Mark, do you want to take that? I am not sure I completely understand that question, but maybe you do..

Okay. At least my understanding, yes, so the LCA patient population has quite a range of BCVA measurements at the time that we get to see them. And this is obviously based on the trajectory and the time course of the disease.

We have instituted in addition to the standard ETDRS chart, additional ways of measuring their visual function and acuity in addition to the BCVA self-sensitivity of the retina and as you mentioned the maze.

And so I think our approach really is to try to use all of those measurements to assess the function of the patients and their response to treatment?.

Great, thanks. That’s helpful.

And then in your PR, you mentioned expanding enrollment in your adult cohorts, what is the end you are 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 of the doses that we have already tested in the adults. I 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 based on the data as it comes through..

Great. Thanks. Appreciate taking the questions..

Our next question comes from a line of Joon Lee with Truist Securities. You may proceed with your question..

Hi, good morning. This is Mehdi on for Joon. Our question relates to powerful SLEEK technique technology. And we would like to understand if you could elaborate these on internal programs that are using SLEEK technology and if there is any potential for collaboration or sublicensing of this technology out.

And at the end, this is very interesting technology do you see any potential for in vivo application of SLEEK method for different genes or tissue specific genes? Thanks..

one, internally for the iPSC editing for the iNK program, where we have used the SLEEK technology to knock-in the CD16 membrane bound IL-15 constructs. And then in addition, we have utilized that technology in our collaboration on alpha-beta T-cell with Bristol Myers Squibb. We continue to look for ways in which to advance the technology itself.

It’s powerful in its current guys that we continue to look for additional SLEEK sites, for example and ways in which we can control expression and transgenes into different systems.

One of the properties that makes SLEEK technology so powerful is that you essentially enrich for those cells, which have successfully conducted homology directed repair and have reconstituted the Essential Exon. And that is a proportion of the total cells and those cells that do not do that will die, because you are knocking into an essential theme.

So, that property is really powerful in many settings, but it does provide potential limitation to its use in vivo, because of that aspect of the technology. So, we don’t see this as a cure all for everything in terms of knocking in, but it 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. There is a lot of proprietary know-how as well as the use of the AsCas12a 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 & Company. You may proceed with your question..

Good morning. Thanks for taking our questions. Couple from us.

First, on EDIT-301, we are curious if there is any update on the efficacy essays, any new timelines as to when this could be completed?.

I will start that, Mark and maybe you want to finish it. So the efficacy, there is a few different efficacy/potency assays, I think you maybe referring to the potency assay, Phil and that is well developed. Ultimately, it needs to be qualified using patient samples.

So that will be a process that we 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 there is anything you want to elaborate on?.

The only thing I would add is that we are confident of the performance of those assays. We have put a lot of effort internally to make them as good as they can be. And so as Jim mentioned really now it’s getting the patient samples to be able to confirm the specifications..

And can you remind us of the process of getting the clinical uplift is do you have to presumably you have to submit your findings to the FDA and you have to verify that they agree that the essays have been qualified?.

That’s correct. We were very encouraged by the fact that the beta thalassemia IND got cleared so relatively easily, I should say because that contains essentially the same information on how these assays will be run and the FDA liked what they saw there. So I think it’s a matter of providing that information to them and getting their response..

Great.

And then second question from us is in LCA10 you discussed 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, anything notable there that informs your designs on future LCA10 studies?.

So, I think the outcome of that data was very unfortunate for the LCA10 patient community. I mean, right now, we don’t have anymore insight than you do in terms of the information that ProQR is currently released, which is essentially the top line later on 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 the question. I am [indiscernible] for Gena.

Just one from us with multiple program preclinical program in late stage, how should we think about the pipeline prioritization in the mid to 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 or platforms that we 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, a sufficient data on the ocular programs or for that matter, sufficient data – we don’t have clinical data yet on the sickle cell and beta thalassemia. Probably a great question as we proceed into sort of the second half of 2023. But we will follow the data..

Thank you..

Our next question comes from the line of Luca Issi with RBC. You may proceed with your question..

Perfect. Thanks for taking my question. This is [indiscernible] for Luca. Just a couple for me on LCA10. And I noticed that it looks like you are going to present a safety update on LCA10 or low, which is going to look at viral shedding.

Just wondering if you can provide more color on the rationale behind this, is viral shedding something the FDA has been asking for? And also how will this be assessed? Are you going to look at the fluid in the aqueous of the eye? Then another question about expanding enrollment in the adult cohort, just wondering, does this mean possibly that the highest dose is maybe not the most efficacious dose, or is this decision also partly based around safety as well? Thank you..

So, I can take those two questions. So, the viral shedding assay is a standard requirement for AV based therapies. And it relies on collection of tears and blood and assessing it and based on the data that I have seen from similar studies, this is of no concern.

It’s a standard set of data the FDA requires and we know that subretinal injection is a very precise way of introducing the virus into the retina. And it really doesn’t go anywhere beyond that. So, that’s that question. And yes just to reiterate my previous answer, I mean we are still in the Phase 1 dose escalation.

And we have a limited number of patients at this point 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 with the dose and any other insight into the different efficacy measurements as to we use that information to plan for the pivotal registrational trial..

Yes. And just to add, just 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 data from that, plus the more extensive data from the mid-dose to decide where we are going to expand..

And with that, thanks for taking the questions..

Our next question comes from 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 from sickle cell patients in the RUBY trial at year end?.

Well, it will be – first it will be basic safety engraftment and the beginning – and the expression profile, fetal hemoglobin. Mark – if that’s probably about all we will have at that point in time.

Mark, do you want to add anything to that?.

They are the key factors neutrophil engraftment later in platelet engraftment, and potential early signs of HbF production..

Alright, thanks.

And just one other question is like how should we think about the Bristol activated T-cell collaboration in terms of milestones adds to the clinic?.

Milestones, I mean they would be pretty classical milestone payments and royalties if once they became commercial. I don’t know Ron, how much guidance that specific guidance that we have given in the past..

We can just talk about the current progress..

Alright. Thanks..

Our next question comes to line of Joon Lee with Truist Securities. You may proceed with your question..

Hi, this is Mehdi again. I wanted to ask a question related to adRP. Mark, you said that it is necessary to reintroduce the functional copy. Based on my understanding of adRP removing the mutant allele should be sufficient as they are mutant like this e249 stop that is a recessive allele.

So, what is the necessity of reintroducing the wild type allele in these patients?.

So, the approach actually knocks down both the mutants and the endogenous rhodopsin and because the guide – the mutation is not sufficient to discriminate between mutant and wild type. So, you are going to get a knockdown of both. And so that’s why you require the replacements.

So, the replacement rhodopsin will be an epithermal copy generated from the second AV and that 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 Chuck on the line for Jay. Thanks for taking the question. Just for adding 101 ongoing pediatric cohort, just wondering if there is IDMC safety review? And if so, when will that happen? And separately, any chance that we could see data from pediatric cohort this year? Thank you..

So, short answer is yes, there will be an IDMC review following the enrollment of the mid-dose pediatric cohort. The IDMC has and we will see further data from the adult high-dose cohort as well as the pediatric mid-dose cohort. And 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 have 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. Thank you..

Our next question comes from the line of Joel Beatty with Baird. You may proceed with your question..

Thanks for taking the question.

With the editing enhancements to EDIT-102 that have been made that increased editing by 250%? Is that type of approach something that could be applied to EDIT-101? And how does the editing of 101 compared to the older and newer versions of EDIT-102?.

Okay. So, the EDIT-101, EDIT-102 and EDIT-103 are all approaching the editing a little differently in terms of whether it’s an Exon and Intron, a single guide or a dual guide. So, I don’t know that there is a generalization that I can make across all three programs one and two.

Comparing the numbers, as a consequence is not really the right thing to do, because you are looking at different processes.

But what I would say is what we have essentially focused on with EDIT-102 is going back to advance technology to really maximize the editing that we think is possible with both Cas9 and potentially AsCas12a, in a single or dual AAV format.

So, that is involved a lot of molecular biology around the design of the gene cassette, the introduction of other features that may enhance expression of the guide, the stability of the guide, sometimes expression of the nucleus, and then looking at that in all different configurations.

So, that’s kind of how we arrived at 350% in movement in a plasmid based system by spending a lot of time looking at all of these configurations. And those rules, some of them maybe generalizable, but as I have said given that the approaches are quite different from an editing perspective.

Each system is kind of a self contained system that would need optimization..

Thank you..

Our last question comes from the line of Rick Bienkowski with SVB 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.

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 the CMO transition hasn’t 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 a new CMO would need to join in order to hit all of those projected timings?.

Projected, so I will start with the last question first. So, the projected timing may have really nothing to do with when a CMO search concludes, because those are all if you will, balls in motion. We have an MD on staff that’s hematologist.

She is overseeing the 101 programs, and of course, collaborating with Mark’s team, as we look at the preclinical programs and the ocular space. And the sickle cell disease, beta thalassemia, we have a second physician who is a hematologist with experience in this area, overseeing those trials.

And in addition to that there is a senior executive with several decades of experience of running, overseeing, managing multiple clinical trials that oversee sort of the clinical trial operations.

We also have some clinical scientists in the organization as well that that look and think about the data analysis, data management and some of the clinical trial design activities. And so the clinical operations piece of it, I will call it the blocking and tackling pieces of it in the short-term will report to me.

The more medical scientific pieces are reporting to Mark and he and I are 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. That’s 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 and in-vivo applications.

While it looks like most of Editas’ programs are really focused on electroporation and AAV vectors delivery. I was just hoping to get some of your thoughts around LNP delivery in gene editing and why or why not this technology would be appropriate to incorporate into Editas’ pipeline..

I am going to give that one to Mark, that’s a perfect one for Mark..

Alright. 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, revealed the details of that yet, but this is an area that we have an interest in for sure..

Okay, 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..