Editas Medicine, Inc.

Ladies and gentlemen, good morning and welcome to EDITAS Medicine fourth quarter and full year 2020 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, Operator.

Good morning, everyone, and welcome to our fourth quarter and full year 2020 conference call. Earlier this morning, we issued a press release providing our financial results and corporate updates for the fourth quarter and full year 2020. 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 about the company's future expectations, plans, and prospects constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. 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 quarterly report on Form 10Q, which is on file with the SEC. 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.

Thank you, Ron. Good morning, everyone, and thank you for joining us today. With me this morning are several members of the Editas executive team, including Lisa Michaels, our new chief medical officer, and Michelle Robertson, our chief financial officer. I would like to start off by saying how thrilled I am to speak with everyone today on the first earnings call as Editas CEO. As many of you already know, I've been chairman of Editas board since 2018. Since assuming the role of CEO earlier this month, the most common question I've received, other than what this means for the company, is, Why do this now? The reason I was drawn to Editas originally was because of the remarkable gene editing technology and the promise of potentially curing diseases that were once thought to be uncurable. Over the last three years, my enthusiasm for the company grew as quickly as the company itself. The chance to step in as CEO at this stage of the company is an incredible opportunity. When I started working at Biogen in 1989, The company was smaller than Editas is today. The success and growth of Biogen is directly related to the people and components that were in place at each phase of that company. As Editas transitions from preclinical to clinical to development and commercialization, I look forward to strategically leading the company through each of these stages. The editing technology that is the foundation of Editas is fantastic. As this technology continues to advance, along with all the downstream technologies, we need to make sure the company is strategically positioned to maximize these capabilities and bring medicine to patients. Now I'd like to discuss 2020. But before I do that, I'd like to just acknowledge all of the hard work that all of the associates did during 2020, working through COVID, as everyone else in the world has had to do as well. But we enter 2021 as the global leader in in vivo gene editing and are posed to bring our first ex vivo medicine to the clinic. So let's begin with some of the accomplishments of Editas over the past year. We made history one year ago by initiating and advancing the first ever clinical trial of an in vivo gene edited medicine with edit 101 for LCA 10. We regained full operating control and rights of our ocular programs to renew agree with the AbbVie and transitioned to clinical contracts, IND for EDIT 101, and manufacturing to EDITOS in the second half of the year. We presented preclinical data demonstrating the best-in-class potential of EDIT 301 for sickle cell disease, filed the IND, and received approval by the FDA to begin patient enrollment in the Ruby clinical trial. We expanded our manufacturing capabilities through relationships with Azure and Catalan, And we extended our cash run rate at year end with more than $500 million of cash and raised approximately $250 million in net proceeds earlier this year, enabling us to fund our operations well into 2023. And lastly, we added outstanding executive leadership with the appointments of Lisa Michaels as Chief Medical Officer and muted Charity to the Board of Directors. I'm pleased to have Lisa join me on the call today. The momentum of these accomplishments puts EDITAS in a very good position to achieve a number of value-creating milestones in 2021. Our key goals for 2021 are first, to continue dosing patients in the brilliance trial for EDIT 101. I'm pleased to announce we've already dosed the first patient in cohort two. We also plan to share initial clinical trial data from the phase one to brilliance trial of EDIT 101 before the end of the year. We'll advance our ocular programs by declaring a development candidate for RP4, which is retinosis pigmentosus. Initiate dosing in the Phase I-II Ruby clinical trial of EDIT301 for the treatment of sickle cell disease. And we expect to file an IND application for EDIT301 for the treatment of beta thalassemia. We want to continue the development of our engineered iPSC-derived NK cell medicines for the treatment of solid tumor cancers and present new preclinical data at medical meetings later this year. And finally, we will progress the company's collaboration with Prista Meyers Squibb to advance alpha-beta T cell medicines. Now, let me turn the call over to Lisa Michaels, our new chief medical officer, to introduce herself. discuss EDIT 101 and EDIT 301 clinical trials, and to review our broader pipeline. Lisa?

Thank you, Jim. Thank you both for your introduction, and thank you for being with all of you for being with us on the call today. I'm very pleased to have joined EDITUS and to have the opportunity to lead an extremely experienced and dedicated group of clinical trial professionals who are focused on bringing treatments to patients with debilitating diseases resulting from genetic causes. By training and in my early career, I was a pediatric hematologist oncologist. My interest during my academic practice was on finding and creating treatment solutions for rare diseases across the spectrum of immunology, blood and bone marrow disorders, and malignancies. And as such, I have been involved with clinical research and drug development for both industry and academia for more than 25 years. I joined Editas from Bayer Pharmaceuticals, where in my most recent position, I was the head of clinical development of the rare diseases cell and gene therapy therapeutic area. I'm very excited about the transformative potential of EDItoss' premier gene editing platform, and I'm excited to drive development of these potentially curative treatments into the clinic and onto approval with the goal of transforming the future standard of care. I'll begin today's update with our in vivo gene edited medicine pipeline, which constitutes the first pillar of our therapeutic strategy. As Jim mentioned, last year the first patients ever to receive an in vivo gene editing product were dosed in the BRILLIANCE trial. Now, this is a Phase 1-2 safety study of EDIT-101 for the treatment of Leber's congenital amaurosis type 10, or LCA10. The goal of the development program is to demonstrate a cure of this genetic retinal disease that results in blindness, usually in childhood. At the recent JP Morgan conference, we shared the very important finding that there were no dose-limiting adverse events in the first two patients that were treated. This result has allowed us to escalate to the next planned dose cohort. Additionally, the observed safety allowed us to modify the inclusion criteria to allow enrollment of sentinel patients with visual acuity better than just light perception. The feedback from our investigators is that this change will facilitate enrollment and is expected to help the study regain momentum. As such, we're pleased to report that we have already dosed the first patient in the adult mid-dose cohort. We continue to follow all the treated patients for the primary endpoint of safety every three months for the first year and concurrently collect data to confirm the expected beneficial effects of the edits. We expect to share clinical data from the BRILLIANCE trial by the end of this year. Now, following 101, Our next in vivo ocular program is Edit 102 for the treatment of Usher syndrome 2A. Usher 2A is a different inherited retinal disease that results in progressive loss of vision in childhood or later in life. This program follows on our work on Edit 101 as Edit 102 uses much of the same editing machinery and delivery system as Edit 101. As we reported also at the recent J.P. Morgan meeting, we have completed the transfer of manufacturing materials of Edit 102 from AbbVie to our CDMO, and we are progressing the program forward. Our third ocular program is aimed at another progressive cause of blindness, autosomal dominant retinitis pigmentosa type 4, or RP4. RP4 is a more complex target, as mutations are found throughout the gene. Consequently, we are exploiting the strengths of our editing approach to replace the abnormal gene with a wild-type version, and we've made excellent progress on this program and plan to identify a development candidate by year end. Our program's targeting treatments for blindness aim to solve a significant need around the globe. Looking to the future, we plan to further expand our in vivo pipeline and aim to leverage the curative potential of gene editing to address other inherited causes or predispositions to blindness across all age groups. So now transitioning to our ex vivo gene-edited medicine programs, which is our second area of focus. Our most advanced ex vivo cell medicine program is EDIT301. This is a potentially best-in-class, durable, autologous cell medicine for sickle cell disease and beta thalassemia. With the FDA approving the start of the Phase I-II Ruby study in sickle cell disease, we expect to enroll our first patient later this year. In addition, we will be moving EDIT301 forward into beta thalassemia the goal to follow the IND by year end. Preclinical data that was presented at the recent American Society of Hematology Conference, or ASH meeting in December, showed that the editing of CD34 cells from healthy donors and from sickle cell patients using 301 was greater than 90% efficient and was specific. Off-target effects were not detected. Predictive of the expected clinical benefit, the red cells derived from patients with sickle cell disease and edited with EDIT301 showed effective switching of hemoglobin production in favor of fetal hemoglobin. And in the same presentation, EDITAS demonstrated the development of a successful large-scale manufacturing system for EDIT301 that will be used in the processing of patient cells as part of our clinical program. Ultimately, we believe that EDIT301 will provide a durable and differentiated treatment with the potential to transform the lives of patients living with sickle cell disease and transfusion-dependent beta thalassemia. Moving next to oncology, the other major focus of our gene-edited cell medicines programs. Well, at the end of last year, we decided to discontinue our healthy donor-edited NK cell program, Edit 201, in order to focus our resources on advancing iPSC-derived NK cell medicines. The learnings from non-clinical studies completed on the HDNK program are directly relevant to the development of iPSC-derived NK cells, which we believe have potentially superior benefits as a homogeneous, fully characterized therapeutic, which is off the shelf for the treatment of a variety of tumor types. By targeting use of INK cells, we hope to avoid the toxicities associated with other immunotherapies, such as graft-versus-host disease and cytokine relief syndrome. Editas also shared data at last December's ASH meeting showing that INK cells, which have the CISH NTGF beta double knockout, were more effective in killing tumor cells than control INK cells in a model mimicking the in vivo tumor microenvironment. And these data support the potential of our INK program as a treatment for solid tumors. Our INK program is complemented by our partnership with Bristol-Myers Squibb. This collaboration recently generated a milestone payment for Editas, resulting from our alpha-beta T-cell medicines program, providing an important part of validation for our editing technology and expertise. Overall, the progress we've made across both in vivo and ex vivo gene editing has advanced our goals of developing differentiated, transformational medicines for people living with serious diseases. And we look forward to building our momentum in 2021, and we'll provide updates on our progress along the way. And now I'd like to turn the call over to our Chief Financial Officer, Michelle Robertson.

Thank you, Lisa, and good morning, everyone. Editas remains in a strong financial position as we advance our portfolio forward. As Jim mentioned, our recent financing resulted in net proceeds of approximately $250 million, substantially strengthening our balance sheet. Combined with the capital raised from last year, we are well positioned for continued execution, supporting the manufacturing and clinical objectives of the Brilliance and Ruby clinical trials, and also enabling the advancement of our preclinical in vivo and ex vivo candidates. Our cash equivalents and marketable securities as of December 31st were $512 million compared to $457 million as of December 31st, 2019. This does not include the approximately $250 million in net proceeds raised earlier this year, which extends our cash runway well into 2023. Now turning to revenue and expenses, which we have also summarized in our financial results for the fourth quarter and full year 2020 in the press release that was issued earlier today. Revenue was $91 million compared to $21 million for the same period last year. This increase was mostly attributed to previously deferred revenue of $57 million from the termination of our alliance with Allergan, as well as revenue received from our other collaborations and out-licensing agreements. While our G&A expenses remained relatively flat in 2020 at $68 million compared to $65 million in 2019, R&D expenses for the full year 2020 were up $61 million to $158 million. This increase was primarily driven by our ramp-up in manufacturing and clinical-related costs for Edit 101 and Edit 301, as well as non-recurring charges related to collaborations and success payments to our licensors. These expenses combined with our expanding and maturing pipeline and advances in our platform were the primary drivers of growth in our spending in 2020. We expect that these will continue to be the primary drivers of spending growth in 2021. Over the course of the year, we grew the size of our organization by approximately 23%, increasing to over 240 full-time employees from 195 employees at the end of 2019. At this time, we don't expect any material negative financial impact for COVID-19. In fact, as Lisa alluded to, our Brilliance and Ruby trials are both progressing, and we are excited to be part of these potentially life-changing solutions to patients. And with that, I will hand it back to Jim.

Thank you, Michelle. The company is incredibly proud of what it achieved over the last year. These accomplishments have solidified our position as a global leader in in vivo gene editing and leave us poised to expand our clinical pipeline. That these accomplishments were achieved amidst a global pandemic is a testament to the hard work and unwavering commitment of our employees and partners. Over the last three years, and especially over the last three weeks, I've learned a tremendous amount about the diseases Editas is trying to cure, the patients suffering from them, and the capabilities that this company has to potentially change these patients' lives. I'm both humbled and excited to serve as Editas' permanent CEO. We look forward to our progress in 2021 and the momentum it will generate towards the ultimate goal of developing differentiated, transformative medicines across a range of serious diseases. We thank all of you for your continued interest and support. And with that, we will open up the call for Q&A. Operator?

Thank you. And as a reminder, ladies and gentlemen, to ask a question, just press star 1 on your telephone. To withdraw your question, press the pound or hash key. Please stand by while we compile the Q&A roster. And our first question comes from Gina Wang with Barclays. Your question, please.

Hi, this is Sheldon for Gina. Thanks for taking our question. I have two, if I may. So first on edit 101, could you remind us how much waiting period is required for the cohort two and beyond? And implicitly, how many patients could we expect in the updates before year end? And my second question is on edit 301, So given the recent adverse events reported by Bluebirds, how are you thinking about the conditioning regimen and the overall approach in sickle cell disease?

Thanks. All right. I guess that's me. That's Lisa Michaels. And I will jump in for those two questions. So to the first one regarding LCA10, you asked, I think, starting with what was the waiting period. By the protocol, there is a four to six week waiting period that occurs after each first two patients are dosed in that protocol. So we're actually very happy to let everybody know that we were able to dose our first patient in the mid-dose cohort actually back in January. And so that patient will be coming back in for one of the major safety follow-up periods of time in order to determine if it's safe to move on to the second patient in the cohort. That patient then would be dosed sometime in the next several weeks if we have the approval or we see no safety concerns. And then we have a second waiting period on that patient before we can enroll the next two. So we're looking at four patients being dosed in the mid-dose cohort based upon that timeline at the moment. We also have the follow-up visits being planned for the first two patients in cohort one. Both of those patients are also scheduled for return visits in the next several weeks. We continue to follow those patients on an every three-month basis after the initial safety follow-up, where we're looking both for mid- and long-term safety, as well as additional efficacy. And so we're looking, as we move forward with the second cohort of patients in combination with the first one, to have a significant amount of robust enough data set regarding both safety and hopefully early signs of efficacy in combination, where we'll be able to give some nice results some nice conclusions. So that's why we've pretty much targeted the second half of the year in order to share more data. For the second question, I think we're all watching Bluebird very, very carefully and very cautiously at the moment. I feel very sympathetic to my colleagues and friends who've not only participated in the treatment of patients in part of that study, as well as also Bluebird, which has a substantial amount of data, as well as a number of patients treated, to suddenly have this setback several years into their program. As much as we're watching them at the moment, I think an important part to keep clear here is that the Bloomberg as well as our program are not really interchangeable. They actually, even though it's the same patient population, similar procedures to treat the patients and also overlapping and very similar clinical endpoints, the laboratory endpoints as well as the approach to treating those patients are distinctly different approaches. The Bluebird program is based on lentil virus injection of a gene therapy, basically putting in the normal functioning beta-globin gene. And so between lentil virus and also being a gene therapy program, it actually is a very distinctly and different approach than what we're doing with doing non-viral delivery programs. And also doing gene editing. So it's not really clear at the moment that the risks that they have encountered will be the same as we move into a gene editing program. But we are watching very closely and very carefully because any outcomes from this do have the potential to affect our approach moving forward.

Thank you. Maybe just a quick clarification. On the waiting period, you mentioned the four to six weeks, and then later you mentioned the second waiting period. So is the four to six weeks the two waiting periods combined, or is each one?

So each patient is treated sequentially. So we have to do one patient first, wait for follow-up, second patient, wait for follow-up, and then we have the ability to treat the subsequent patients.

Got it. Thank you so much. Thank you. Our next question is from Corey Kasimov with JP Morgan. Your question, please.

Hey, good morning. This is Turner on for Corey. Thanks for taking my question. So just with respect to the Ruby trial, where are you with the improved potency assay that the FDA requested just prior to enrolling the efficacy portion? And how do you see those timelines intersecting so that it won't cause any future delays?

So it's helpful to at least understand that the protocol basically is divided into basically a roll-in, very similar to what I just described actually for LC10. The first couple of patients who were treated in that study are part of the quote-unquote safety cohort, and that allows us to be able to provide long enough observation times between patients to ensure that what we're doing is actually both safe but also efficacious. So that's really kind of the period of time that the FDA has allowed us to just move forward exactly as planned, and in the same timeframe that we'll continue to work through the potency assay. In the meantime, we have a little bit more clarity from the agency regarding the type of questions that they actually had, and so we are planning to go back actually sometime mid this year with a clearly defined plan, so hopefully that the FDA will agree with our progress moving forward. But it's not interfering with our timelines. It's something that can easily be done in parallel to the work that we're already starting.

Great. That's helpful. Thank you. Okay.

Thank you. Our next question is from Phil Nadeau with a Cowan & Company. Your question, please.

Good morning. Thanks for taking my question. First, a question on Edit 102 for USH2A. Can you talk a bit more about the program and what is necessary to get it into the clinic?

So anyway, we're basically moving forward with a clinical candidate in that particular space. And I think largely what we're really doing is just trying to get more of the non-clinical confirmation of effect in various different models before we declare that clear candidate. And we're hoping to have that progress done later this year.

Got it. And then second on 301, in light of the prior question on Bluebird and maybe the concerns around the approach generally plus the competition, can you talk about what will be the bar to moving that forward. What type of proof-of-concept data do you need to see to advance that into a pivotal trial?

I'm a little confused. Are we talking about what we've seen with lentil bar or what we're seeing in our clinical trial?

Well, so I think the concern is also about the preconditioning regimen. So there's concern about the preconditioning regimen, plus it's a relatively crowded field. So can you talk about the bar that you're... you're holding to 301 to move it into a pivotal study and continue to invest in the program?

You know, I told a lot of people during J.P. Morgan that basically I see each one of these plans as a sequential improvement on the one prior to it. And we had talked even at that time about the theoretical concerns of safety. And at the time, they were more theoretical concerns of safety related to using both the lentil virus and a gene therapy approach versus gene editing. In consequence, the next level of proof here is really, is gene editing going to be a sequential improvement over safety in that particular setting? And also the particular targets that we're looking at, such as, are you going after BCL11A, which I remind people means B-cell leukemia, you know, it was defined as part of a known problem in other clinical settings. versus targeting a more physiologic point such as the gamma globulin locus, which mimics physiologic changes that take place for hemoglobin F. So I think one of the things that will differentiate with all of these over the long term actually is going to be the potential related to safety. In the short term, I think a lot of people are looking at the conditioning regimen, which has always been one of the biggest hurdles in even treating patients with what was considered the standard of care for cures, a bone marrow transplant. Many patients did not go for it because of the concerns related to the conditioning regimen. And the advantage of the autologous programs, of course, is that you're able to use much less conditioning. Obviously, the concerns that have come up recently with the lentil viral program have also a little bit to do with whether or not these are effects that are associated with alkalinating agents such as busulfan. So I think we're still kind of waiting and watching with all of that, but I do think that as we move all these programs forward, the main focus and goal is not only getting excellent clinical outcomes, but also being able to improve on safety long-term.

Great. That's very helpful. Thank you.

Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your question, please.

Hello, everyone. This is Costa Son for Matthew. A quick question from us on the NK sales program. When do you think you will be ready to file an IND for this program and what steps are needed to be ready for the IND filing? Thank you.

I guess I'll jump in by the fact that we were making a huge amount of progress and we're actually moving forward to an IND filing for our HDNK program with the Edit 201 program. But I think as we began to become much more familiar with the process of doing the edits as well as the benefits of using iPSC cells versus human-derived NK cells, we began to be much more aware of the advantages of moving forward with an iPSC off-the-shelf type program. So for right now, what we're doing is that we're now taking that deep dive into our INK program with those learnings and looking at what would be our best clinical candidates or the first approach to a proof-of-concept study. So I think we'll probably provide a little bit more information on those specific targets before I'm able to give you a clear timeline for the IND.

Great. Thank you.

Thank you. Our next question is from June Lee with Truett Securities. Your question, please.

Hello. This is Miguel Coelho filling in for June Lee. Thank you for taking our questions. Regarding Edit 101, how will the BCVA baseline influence the efficacy readout, and how close do you think we can get to near normal vision? And also, according to your predictions, 10% editing might be sufficient in the fovea, But more conservative estimates based on adaptive optics publications suggest 20% editing might be required to restore near normal vision. What is your perspective here? Thank you.

Okay. So I think there's two questions there. One is related to the 10% threshold for quality edits. And the other one was what? I'm sorry?

The other one is related to the BCVA baseline, so basically how well the patients can see before they enroll in a trial and are treated, because one idea is that you'll see higher improvements in lower BCVA, but how will this influence the efficacy readout?

Okay, so we're actually keeping a very open mind related to what would be defined as a primary efficacy readout for these patients. BCVA is only one of several different measurements that we're looking at. We're also looking at whether or not we can get some improvement in terms of these patients look down a gun barrel. So we're also looking at any potential improvements in visual fields as can be measured with perimeter free. And we're also looking at mobility and function very similar to LuxTernative through the use of a maze. I think each one of those in themselves provides a potential real quality improvement for these patients' vision. And as of today, as we're collecting information on our patients, I think we'll have a better chance to see where we're going to fall in terms of the true benefits of vision, which are the real benefits that the patients are having. It may be across more than one measure. So another reason why I'd like to be able to provide more of a robust efficacy readout on these patients as opposed to just focusing on just one endpoint. To the second question related to the amount of editing, I think everybody is aware that the original modeling data was based upon how much vision could be lost and still maintain really good optical vision. And those are the datas where if you're coming out with 10% versus 20%. What I can tell you, however, is that 10% was only considered to be a threshold response, and that is what we chose for the first two patients treated in the trial. With our mid-dose response, we're actually expecting editing frequencies greater than 20%.

Excellent. Thank you so much.

Thank you.

Thank you. Our next question is from Jay Olson with Oppenheimer. Your question, please.

Oh, hi. Thank you for taking the questions. Maybe on capital allocation, can you talk about your strategy for allocating resources across the ocular hemoglobinopathy and IO franchises and how you prioritize those And then are there any gaps that you'd like to fill with inline sitting or acquisition in your technology or delivery platforms? And then finally, maybe a question for Jim. Congrats on all the new leadership. Can you maybe talk about any changes that you're making or planning to make in the direction of the company? Thank you.

Okay. Jay, thanks. This is Jim. Let me... try on all three of those and probably get a little bit of help from Michelle on the first part. So I think part one was capital allocation. As we go into 2021, it's against those three big platforms, in vivo, ex vivo, and the IPSC, the INK platform. It's roughly a third, a third, a third. It's not exactly that because we're also doing some investments in the platform technologies, which probably bears a little bit on your second question. Let me finish the first question. The way we think about that is uh you know just looking at the kind of progress we're making and how well though each one of those platforms is unfolding and so you know obviously as we recapture the all the rights for ocular that's a nice space if as edit 101 hopefully continues to move forward smoothly you have actually quite a bit of synergy as you go to the future programs When you look at the HSC or the sickle cell, obviously there's another opportunity that we're planning on there with beta thalassemia. It'll be a different trial, but the same product. And then the INK is really a platform, and the way I think about that platform is is starting from IPSCs, being able to successfully edit them, clone them, differentiate them, and expand them into whatever cell type we'd like. In this particular case, INK. That's a nice platform, and we're focused on reducing that really to practice. I think Lisa touched on you know thinking through and how we're addressing which edits we will start with there um so i don't think that's that's probably not that is not settled yet but it's a platform right so once we start with a few edits we can continue on to add additional edits or change the edits to address different segments of the disease or different tumor profiles if you will um things that we you know want to fill in around look i think we're always attentive to questions on advancement of the platform technology always trying to think about how we can improve the delivery aspects you saw beam do a deal i think it was earlier this week sort of on delivery We probably are not going to chew off LNPs right now because I think we've got plenty on our plate. So interesting deal for them, but probably not one that we would have been excited about at this moment in time. Certainly the manufacturing area is very complex for us with those three big platforms. We have a couple of partnerships there, one with Catalan, one with Azure, which is really us performing the activities the manufacturing activities within their uh controlled spaces and then of course we're also making the guides and the rmps for ourselves in boulder as well as doing insourcing some or outsourcing some of that um So, you know, those are some of the specific, as you think about these programs more broadly, I've been around this business a long time, you know, we're going to need more partnerships, and whether those be manufacturing, academic, development partnerships, or commercial partnerships, we will for sure be active in that space. It's really a question of timing around the different programs and when is the best time to engage in those conversations. For the near term, to progress the INK, to progress the sickle cell disease, and for that matter to progress the ocular programs, we have access to the things we need in the near term. It's sort of the medium and long term that I'm thinking about. In terms of direction to the company, I probably just described how I'm thinking about that. It's early days, so I'm really trying to dig into each one of these platform areas. But broadly speaking, I'm thinking about these as three very broad platforms, which we need to, if you will, reduce the science to products and practice. If we can do that successfully, then not only do we have some initial very exciting product prospects, but it really opens up the world to the other applications for gene editing technology. you know, to sort of circle all the way back, you know, business development and partnerships, it's clear everybody needs them in this business. You just have to be thoughtful about when you do them and who your partners are. You know, even Pfizer needed one to make a vaccine. So, you know, you just have to be very open to filling in those gaps and bringing in additional expertise and capabilities. Hope that answers the question.

It's super helpful. Thanks for taking the question.

Thank you. And our last question is from Steve Seedhouse with Raymond James. Your question, please.

Hi, this is Ryan Deschner on for Steve Seedhouse. In LCA10, could you talk a little bit more about the data review protocol in that study specifically? At what time points you'll be taking visual acuity or the gun barrel assessment and other measurements? And then also, how do you see R&D spend increasing over 2021? Thank you.

All right, so I'll take the first one, and then I'll hand off the second one. So for the first one, actually, the patients come in for routine visits every three months. Once we get past that first four- to six-week period of time where we're primarily focusing on safety, the key question in that period of time, of course, is some of the questions that were raised actually with the very first patients treated was on the potential to actually have the Cas9 apparatus result in a very damaging or potentially not easily managed inflammatory state. We have not seen that, which for me is a huge and positive finding and really has allowed us to be able to be a little bit more flexible in the type of patients that we're enrolling in the study. And as a consequence, what I'm just reminding folks is that because of that safety concern, the first two patients were treated at a low dose, and they were also with patients who don't have the ability to actually discern vision. They can only tell the difference between light and dark and whether or not there's a light flashing in front of their eyes. So the ability to be able to measure changes in those may be very much physiologic measurements, such as changes in pupil responses to light, whether or not they can actually discern flashes of light in different parts of the eye, whether or not we can see anatomical changes. But we're also continuing to follow these patients both through routine walks through mazes, visual, various different methods of seeing whether or not they concern shapes and sizes. as well as also these physiologic measurements. And like I think I said walking through the maze, I want to make sure I got everything. So basically every three months consistently over time we are continuing to measure these things moving forward. Does that answer the question? Yes, thank you. Okay, so I'll hand off the second one.

Yes, so I'll handle the second one, the R&D expense. So, you know, as you know, we've got the rights back to the Ocular program, so we're fully responsible for those programs. So you'll see increased investment, obviously, in Ocular, as well as continued investment in the INK programs and sickle cell, particularly, as Jim mentioned, in manufacturing. So we'll continue to make significant investments in our manufacturing, both internally and externally. as well as continuing to hire key positions in our clinical operations and regulatory departments.

Okay. Thank you very much.

Thank you. And ladies and gentlemen, this concludes our Q&A session. I would like to turn the call back to James Mullen for his final remarks.

Thank you all for sitting through the call this morning. Appreciate all the questions. Pretty clear what people are focused on. And we look forward to continuing the dialogue as the year goes on and talking about clinical data and progress on the other programs. So appreciate it. Thank you very much. Everyone have a great weekend.

And ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.