Q1 2022 Editas Medicine Inc Earnings Call

Good morning, and welcome to the EBITA Medicine first quarter 2022 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.

Ron Moldaver: I would now like to turn the call over to Ron Moldaver, Investor Relations at Editas. Thank you, Paul. Good morning, everyone.

Request.

I would now like to turn the call over to Ron <unk> Investor Relations at EBIT thoughts medicine.

Unknown Executive: And welcome to our first quarter 2022 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate updates. A replay of today's call will be available on the investor section of our website approximately two hours after its completion.

Thank you Paul Good morning, everyone and welcome to our first quarter 2022 conference calls 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 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.

Unknown Executive: 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 10k, which is on file with the SEC and updated by our subsequent filings.

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.

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.

Ron Moldaver: 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.

All over to our Chief Executive Officer, Jim Mullen.

Thanks, Ron and good morning, everyone.

Jim Mullen: I'm joined today by several members of the Editas executive team, including Mark Sherman, our Chief Scientific Officer, Michelle Robertson, our Chief Financial Officer, and Charlene Stern, our General Counsel. We made excellent progress this quarter. I look forward to more meaningful milestones. In the Brilliance trial for LCA10, we dosed the first pediatric patient with EDIT101. This marks the first time ever a child was dosed using in vivo CRISPR gene editing, an incredible accomplishment. Given that LCA-10 is one of the leading causes of inherited childhood blindness, pursuing the dosing of younger patients is potentially a critical step forward to treating this disease.

I'm joined today by several members of the other types of executive team, including Mark Sherman, Our Chief Scientific Officer, Michelle Robertson, our Chief Financial Officer, and Charlene Stern, Our general counsel.

We made excellent progress this quarter look forward a more meaningful milestones this year.

And the brilliance trial for LCA time, we dose the first pediatric patient with edit 101.

This marks the first time ever the trial was dosed using in vivo CRISPR gene editing and incredible accomplish.

Given the LCA 10 is one of the leading causes of inherited childhood blindness pursuing the dosing of younger patients with potentially a critical step forward to treating this disease.

Jim Mullen: And yesterday at the ARVO conference, we presented data further supporting the Favorable Safety and Immunogenicity Profile Edit 101. We expect to complete testing of our pediatric mid-dose cohort in the first half of 2022 and initiate our pediatric high-dose cohort later this year. We're also planning on providing clinical updates for EDIT101 in the second half of the year. Later today at the Arvo conference, we'll present non-human primate data with edit 103 for retinitis pigmentosa, demonstrating the unique design of our in vivo knockout and replace candidates preserve retinal function. That program is advancing towards IND-enabled studies, which we expect to start by the end of the year.

And yesterday at the ARVO Conference, we presented data further supporting the favorable safety Immunogenicity profile of edit 101.

We expect to complete dosing of our pediatric mid dose cohort in the first half of 2022 and initiate our pediatric high dose cohort later this year.

We're also planning on providing clinical update for edit 101 in the second half of the year.

Later today at the ARVO conference, we will present non human primate data with edit one of three for retinitis pigmentosa demonstrating the unique design of our in vivo knockout and replace candidates reserve retinal function.

That program is advancing toward IND, enabling studies, which we expect to start by the end of the year alright.

Jim Mullen: Our Edit 301 program for sickle cell disease and beta thalassemia continues to screen and enroll trial patients. For sickle cell, we've successfully edited several patients' cells ex vivo and are on track to begin dosing before the end of next month and for beta thalassemia later this year. Our cellular therapy programs are advancing. We showed impressive INK preclinical data.

Alright at 301 program for sickle cell disease, and beta thalassemia continues to screen and enroll trial patients for sickle cell. We've successfully added several patients cells ex vivo and are on track to begin dosing before the end of next month and for beta Thalassemia later this year.

Our cellular therapy programs are advancing we showed impressive I NK preclinical data.

Jim Mullen: We'll have new data on Addit202 later this month at ASGCT, and we're pleased to have our longstanding partner, BMS, opt into a seventh Alpha Beta T cell program. The U.S. Patent and Trademark Office recently issued a favorable patent interference decision to the Broad Institute, affirming our foundational CRISPR-Cas9 intellectual property position. Charlene's joining us today, and she'll discuss the implications of that decision in more detail in a few minutes.

We will have new data on attitude or two later this month at <unk> and we're pleased to have our longstanding partner BMS opt into a seven alpha beta T cell program.

The U S patent and trademark office recently issued a favorable patent interference decision to the broad Institute affirming our foundational CRISPR.

Intellectual property position.

<unk> is joining us today and she will discuss the implications of the decision in more detail in a few minutes.

Jim Mullen: And finally, we're excited to announce a new leader for our organization, Gilmore ONeill, and I'll comment on that in a few moments, but first, I'd like to briefly review our clinical program. As mentioned, we dosed our first pediatric patients in the Brilliant Study for EDIT101 for LCA10. It was the first time that CRISPR gene editing medicine was administered to a child.

Finally, we're excited to announce a new leader for our organization Gilmore O'neill and I'll comment on that in a few moments, but first I'd like to briefly review our clinical progress.

As mentioned, we dosed, our first pediatric patients and brilliance study for edit 101 for LCA.

It's the first time that in vivo CRISPR gene editing medicine has been administered to a child. This is a significant milestone for many young individuals living with disease their families as well as for the medical and scientific field.

Jim Mullen: This is a significant milestone for many young individuals living with the disease, their families, as well as for the medical and scientific fields. The interest and support we've received from the entire patient community has been overwhelming, and it gives us an enormous sense of enthusiasm as we continue to apply our gene editing capabilities to other genetic diseases. This is the first of four planned pediatric patients in the mid-dose cohort, which we expect to complete before the second half of the year.

The interest and support we've received from the entire patient community has been overwhelming and it gives us enormous sense of enthusiasm as we continue to apply our gene editing capabilities to other genetic diseases.

This is the first of four planned pediatric patients in the mid dose cohort, which we expect to complete before the second half of the year.

Jim Mullen: Then, following an independent data monitoring committee assessment of the safety data, we will begin dosing the pediatric high-dose cohort, which we expect to initiate later this year. To date, EDIT101 has been safe and well-tolerated in treated patients. The viral shedding data presented yesterday at the ongoing ARVO conference supported the program's favorable safety profile. The clinical data demonstrated that EDIT101 viral shedding was transient, indicating no systemic viral persistence following administration.

Then following an independent data monitoring committee assessment of the safety data, we will begin dosing the pediatric high dose cohort, which we expect to initiate later this year.

To date edit 101 has been safe and well tolerated in treated patients the viral shedding data presented yesterday at the ongoing ARVO conference supported the programs favorable safety profile.

The clinical data demonstrating the edit 101 viral shedding was transient indicating no systemic viral persistence following the administration.

Jim Mullen: There was also no correlation between edit 101 dose levels and the levels of viral shedding, as we expected, based on other ocular gene therapies, including those using AAV5. A more comprehensive clinical update on the BRILLIANCE trial will be provided in the second half of the year. This update will include safety and efficacy assessments for all patients who have had at least six months of follow-up evaluations, including at least 12 months of data on the adult mid-dose cohort and at least six months of data on the adult high-dose cohort.

There is also no correlation between edit 101 dose level and the level of viral shedding as we expected based on other ocular gene therapies, including those using AAV five.

A more comprehensive clinical updating the brilliance trial will be provided in the second half of the year. This update will include safety and efficacy assessments on all patients who have had at least six months of follow up evaluations, including at least 12 months of data on the adult mid dose cohort and at least six months of data on the adult high dose cohort.

Jim Mullen: We anticipate these data will lay the foundation for the registrational trial of EDIT101. And as we've said in the past, we're exploring the most relevant and sensitive endpoints to support the development of the registrational trial, continuing to evaluate how we can most effectively interpret trial information while always considering what is most meaningful to the patient. In addition to the trial data, we're also looking at our natural history study data to identify the most reproducible measures.

We anticipate these data will lay the foundation for the Registrational trial of edit 101, and as we've said in the past we're exploring the most relevant insensitive endpoints to support the Registrational trial development continuing to evaluate how we can most effectively interpret trial information while always considering what is most meaningful to the patients.

In addition to the trial data. We're also looking at our natural history study data to identify the most reproducible measures will present some data on that study at the upcoming tides conference with additional findings later in the year.

Jim Mullen: We'll present some data on that study at the upcoming TIDES conference, with additional findings later in the year. Moving to Edit 301 on our ex vivo platform, the Phase 1-2 RUBY trial for sickle cell disease is enrolling study patients, and we are on track to begin dosing in the first half of 2022, with initial top-line clinical results expected by year-end. We have completed apheresis cycles in multiple patients to collect enough cells to edit and restore a healthy level of fetal hemoglobin.

Moving to edit 301 at our steel platform. The phase one two Ruby trial for sickle cell disease is enrolling study patients and we're on track to begin dosing in the first half of 2022 with initial topline clinical results expected by year end.

We have completed a recent cycles in multiple patients to collect enough. So the edit and restore a healthy level of fetal hemoglobin. These patients have already had their cells extracted.

Jim Mullen: These patients have already had their cells extracted, their extracted cells edited, and we're in the process of scheduling their actual dosing where we re-infuse their edited cells. This requires an extended hospital stay so that each patient can undergo the required preconditioning regimen necessary to have their edited CD34 cells successfully administered back to them. We're also preparing to initiate the Phase 1-2 trial of EDIT-301 for the treatment of transfusion-dependent beta thalassemia, or TDT.

Extract itself edited and we're in the process of scheduling their actual dosing, where we re infuse their edited cells. This requires an extended hospital stays so that each patient can.

So the required pre conditioning regimen necessary to have their edited CD 34, so successfully administered back to them.

We're also preparing to initiate the phase one two trial of edit 301 for the treatment of transfusion dependent beta thalassemia or T V P.

Jim Mullen: Edit 301 recently received a rare pediatric disease designation for beta thalassemia, which it has for sickle cell disease as well, and we remain on track to dose the first TDT patient this year. We're very excited as we approach the first patient dosing at trial one. We believe this program can be a one-time treatment for both sickle cell disease and TDT. Our unique approach recreates the same protective mutations that result in hereditary persistence of fetal hemoglobin.

Edit 301 recently received a rare pediatric disease designation for beta thalassemia, which it has for sickle cell disease as well and we remain on track to dose the first patient this year.

We're very excited as we approach the first patient dosing of edit 301. We believe this program can be a one time treatment for both sickle cell disease and T. D G.

Our unique approach recreate the same protective mutations that result in hereditary persistence of fetal hemoglobin patients with these protective mutations are essentially asymptomatic.

Jim Mullen: Patients with these protective mutations are essentially asymptomatic. We're also utilizing our Editas-engineered ASCAS12A enzyme, one of the most specific enzymes in the gene editing field, to make these precise, complex edits. Because of the natural validation underlying the approach grounded in human genetics, we believe EDIT301 will be a safe and durable approach to treating both of these indications. Finally, I want to mention the upcoming management change we announced a few weeks ago. Starting June 1st, Gilmore ONeill will take over as CEO, and I will assume the role of Executive Chairman.

We're also utilizing our edit toss engineered Aes test 12, eight enzyme one of the most specific enzymes in the gene editing field to make these precise complex edits.

Because of the natural validation underlying the approach grounded in human genetics, we believe edit 301 will be a safe and durable approach to treating both of these indications.

Jim Mullen: Gilmore brings an incredible breadth of experience to Editas, including 20 years in genetic medicine clinical development, both as a physician and a scientist. He has overseen the development of numerous successful products, many addressing rare disease indications, as they made their way from early discovery to launch and are now accessible to patients worldwide. As Executive Chairman, I'll be working closely with Gilmore and the rest of the executive team to drive long-term value. When the announcement was made, one frequently asked question we received was, why now?

Finally, I want to mention the upcoming management change, we announced a few weeks ago, starting June 1st Gilmore O'neill will take over as CEO and I will assume the role of executive Chairman Guillermo brings an incredible breadth of experience, including 20 years in genetic medicine clinical equivalent both as a physician and.

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He has overseen the development of numerous successful products, many addressing rare disease indications as they made their way from early discovery to launch and now accessible to patients worldwide.

Exactly the chairman I'll be working closely with <unk> and the rest of the executive team to drive long term value.

When the announcement was made one frequently asked question. We received was why now.

Jim Mullen: The simple answer is that Gilmore is the right person for the job and this is the right time. His creative experience in drug development, including preclinical and medical, is exactly what Editas needs today. Not in a year or two, but now.

The simple answer is that Gilmore is the right person for the job and it's the right time his.

His creative experience of drug development, including preclinical and medical is exactly what edit tests needs today.

In a year or two but now.

Charlene Stern: We're in an excellent position with two early stage clinical programs making good progress, with several preclinical programs, and we're continuing to enhance our technology and capabilities to address other clinically significant indications. This is exactly the right moment in time to bring in Gilmore, where we can leverage his expertise to address later stage clinical trial design, prepare the next several clinical programs, and select the next clinically relevant targets to pursue. His experience and passion for creating genetic medicine will add depth and vision to our team for years to come.

We're in excellent position with two early stage clinical programs, making good progress with several preclinical programs and we're continuing to enhance our technology and capabilities to address other clinically significant indications.

This is exactly the right moment in time to bring in Gilmore, where we can leverage his expertise to address later stage clinical trial design prepare the next several clinical programs and select the next clinically relevant targets to pursue.

His experience and passion for creating genetic medicine will add depth and vision to our team for years to come.

Charlene Stern: Now I'd like to turn the call over to Charlene to update everyone on the recent patent decision regarding the foundational IP surrounding Cas9. For some background, Charlene was one of the first people to join Editas to launch the company in 2013, and she was and continues to be instrumental in developing the company's IP strategy. I'm thrilled to have her join us. Good morning, Charlene.

Now I'd like to turn the call over to Charlotte to update everyone on the recent patent decision regarding the foundational IP surrounding cast nine <unk>.

For some background Charlene was one of the first people to join other tasks. The launch the company in 2013, and she was and continues to be instrumental in developing the company's IP strategy I'm thrilled to have her join US This morning shortly.

Charlene Stern: Thank you, Jim. And good morning, everyone. Since the founding of Editas, we have placed substantial importance on securing robust intellectual property protections covering our scientific discovery. We were pleased with the recently issued favorable patent interference decision from the U.S. Patent and Trademark Office, reinforcing Editas's foundational intellectual property position. This was the second favorable ruling determining that Broad Institute was the first to invent the use of CRISPR-Cas9 editing in eukaryotic cells. Those patents are owned by Broad and exclusively licensed to Editas Medicine for the development of medicines for people living with serious diseases.

Thank you Jim and good morning, everyone. Since the founding of that attack, we have placed substantial importance.

Charlene Stern: This decision means that Editas is uniquely positioned to make licenses available to those companies interested in using Cas9 for developing human therapeutics. Given the size of the U.S. patient market and the number of companies vying to develop CRISPR-Cas9 medicine, the decision supports Editas to engage in broader licensing discussions regarding future CRISPR-based medicine. As anticipated, the University of California group, known as CBC, filed its appeal of the USPTO's decision in the federal circuit.

Carrying robust intellectual property protection covering our scientific discoveries we were pleased with the recently issued favorable patent interference decision from the U S patent and trademark office reinforcing editors as foundational intellectual property position. This was the second favorable ruling.

In determining that broad institute like the first to invent the use of CRISPR Cas nine editing and eukaryote itself.

Those patents are owned by broad and exclusively licensed to edit talked medicine to the development of medicines for people living with serious diseases.

This decision means that at a task is uniquely positioned to make licenses available to those companies interested in using cash sign for developing human therapeutics given.

Given the size of the U S patient market and the number of companies buying to develop CRISPR Cas nine medicine. It decision support at a task to engage in broader licensing discussion regarding future CRISPR based medicines.

As anticipated the University of California group known as CVC filed its appeal of the U S. PTO this decision to the federal circuit.

Charlene Stern: That appeal will focus on whether the USPTO decision was factually supported and whether it correctly applied the law to those facts. Those facts were thoroughly reviewed by the USPTO, and we believe it correctly applied the law.

That appeal will focus on whether the U S. PTO decision with factually supported and whether it correctly applied the law to those facts.

These facts, what's thoroughly reviewed by the U S. P T O and we believe incorrectly applied the law.

Charlene Stern: Thus, we believe that the Federal Circuit will affirm the Patent Office's decision. We remain confident that the validity of Broad's patent will continue to be maintained, further strengthening Editas' IP position. Regardless of the appeal outcome or potential settlement between Broad and CBC, our exclusivity agreement means that we are the party responsible for any licensing discussions as CRISPR-Cas9 products enter the market. Looking ahead, Editas will continue to play this important role as the CRISPR gene editing market matures.

Thus, we believe that the federal circuit will affirm the patent office's decision.

We remain confident that the validity of growth pattern will continue to be maintained further strengthening at a Texas IP position.

Regardless of the appeal outcome or potential settlement between broad and C V C.

Our exclusivity agreement means that we are the party responsible for any licensing discussion as CRISPR Cas nine products enter the market.

Looking at the next several years at his hospital continue to play this important role as the CRISPR gene editing market matures.

Charlene Stern: Although the interference focused on Broad's Cas9 portfolio, importantly, Editas is the exclusive licensee of both the Cas9 and the Cas12a patent estates for making human medicine. As such, we are able to issue exclusive and non-exclusive sub-licenses for Cas9, Cas12a, as well as Editas' own patents in the field of human therapeutics. This includes in vivo and ex vivo therapeutic uses.

Although the interference focused on broadcast nine portfolio importantly at its heart is the exclusive licensee of both the cat nine and the cast 12, eight patent estate for making human medicine.

As such we are able to issue exclusive and nonexclusive Sublicense says our Caf nine Casco Bay as well as at a tarsus owned patents in the field of human Therapeutics. This includes in vivo and ex vivo therapeutic uses.

Mark Sherman: Again, our intellectual property is one of the most important facets of the company. We've always believed that our cutting-edge science is one of the ways we attract world-class scientists. Their research subsequently builds on top of our existing platforms and capabilities for which we seek new patent protection. That is why, at every step of the way, we try to protect the intellectual properties surrounding our gene-editing advancements while bringing novel medicines to patients in need of them.

Again, our intellectual property is one of the most important facets of the company.

We've always believed that our cutting edge science is one of the ways, we attract world class scientists.

Their research subsequently built on top of our existing platforms and capabilities for which we seek new patent protection.

That is why at every step of the way we try to protect the intellectual property surrounding our gene editing advancement, while bringing novel medicines to patients in need of them.

Mark Sherman: With that, I will turn the call over to Mark to review our preclinical program. Thank you, Charlene. We're making strong progress with our preclinical pipeline, and we've just announced compelling data for several of our programs. For example, First Edit 103 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 the onset of symptoms in their early years.

With that let me turn the call over to Marc to review our preclinical programs.

Thank you Charlene.

We're making strong progress with our preclinical pipeline and we've just announced compelling data for several of our programs.

First edit 103 for rhodopsin associated autosomal dominant retinitis pigmentosa.

<unk> is a disease of the retina, leading to blindness typically later in life, although a significant number of patient experience onset of symptoms in the early years.

Mark Sherman: There are currently no approved treatments. Edit 103 uses two adeno-associated virus vectors, or AAVs, to knock out the disease-causing mutant rhodopsin gene while simultaneously replacing that aberrant gene with a functional one. However, the knockout of the gene in the retinal photoreceptor cell can only occur if the components for the replacement gene are also delivered to that same cell.

There are currently no approved treatments.

That is one of the three uses two <unk> associated virus vectors or AAV.

To knock out the disease, causing rhodopsin gene, while simultaneously, replacing that aberrant gene with a functional one.

In all cases, the gene in the retinal photoreceptor cells only occur if the components for the replacement Gina also delivered to that same Sal.

Mark Sherman: This approach can potentially address more than 150 gene mutations that cause rho-ADRP. As Jim mentioned, we'll be presenting preclinical data on EDIT103 at ARVO later today. That data reports that EDIT103 achieved nearly 100% productive editing in non-human primates, generating over 30% functional rhodopsin gene replacement, resulting in corrected protein levels, which in this study proved to be a therapeutically effective level. The program is moving rapidly toward the clinic, and we expect to initiate IND-enabling studies before the end of 2022.

This approach can potentially address more than 150 gene mutations that cause ROE a DRP.

As Jim mentioned, we'll be presenting preclinical data on edit one O three at ARVO later today.

That data reported at one of the three achieved nearly 100% productive editing and nonhuman primates generating over 30% functional rhodopsin gene replacement, resulting in corrected protein levels, which in this study proved to be a therapeutically effective level.

The program is moving rapidly towards the clinic and we expect to initiate IND, enabling studies before the end of 2022.

Mark Sherman: We're especially excited about this program because it serves as a proof of concept for the treatment of other autosomal dominant disease indications where a gain of negative function needs to be corrected. We're also very pleased with the progress we're making with our IPSC-derived NK-Cell medicine program for solid tumors. Using our proprietary engineered ASCAS-12A Nuclease and SLEEK technology, we've developed engineered NK cells that we believe have potent anti-tumor activity and substantially increased persistence, an important limitation with many existing NK cell approaches.

We are especially excited for this program because it serves as a proof of concept for the treatment of <unk>.

Thermal dominant disease indications, where again of negative function needs to be corrected.

We're also very pleased with the progress, we're making with our Ips derived NK cell medicine program for solid tumors.

Using our proprietary engineered <unk> 12, a nuclease slick technology, we've developed engineered NK cells that we believe have potent antitumor activity and substantially increased persistence and important limitation with many existing NK cell approaches.

Mark Sherman: At the American Association for Cancer Research Conference in April, we reported in vitro and in vivo preclinical data on the enhanced tumor killing capacity of a double knock-in INK cell. A cleavable CD16 and membrane-bound IL-15 were knocked into cells, increasing antibody-dependent cellular cytotoxicity, or ADCC, while prolonging INK cell persistence in vivo.

At the American Association for Cancer Research Conference in April we reported in vitro and in vivo preclinical data on the enhanced Jim carrying capacity.

Knocking I NK cell.

A favorable <unk> 16, a membrane bound IL 15 were knocked into south increasing antibody dependent cellular cytotoxicity or ADC.

While prolonging NK cell persistence in vivo.

Mark Sherman: These two knock-in edits have thus far produced tremendous preclinical results. And as many of you are aware, our Edit 202 construct incorporates these edits, left a knockout of cytokine-inducible SH2-containing protein or fish, and TGF Beta Receptor 2. These two knockouts are designed to enhance the function of the INK cells with the two knock-ins, supporting our belief that EDIT202 will be a differentiated allogeneic cell therapy.

These two knocking edits thus far produced tremendous preclinical results and as many of you are aware edit 200 to construct incorporate speech at its lesser knockout of cytokine inducible <unk> containing protein or fish.

TGF beta receptor two.

These two knockouts are designed to enhance the function of the NK cells with the two knock ins supporting our belief that <unk> will be a differentiated allogeneic cell therapy.

Mark Sherman: To our knowledge, this is the only program that incorporates these four edits in a single engineered NK cell. New preclinical data on EDIT202 will be presented at the upcoming American Society for Gene and Cell Therapy, or ASGCT, conference, will show in vitro and in vivo data demonstrating significantly augmented AGCC activity against multiple solid tumor cell life and prolonged in vitro persistence in the absence of exogenous cytokines. Edit 202 combined with trituzumab resulted in a greater reduction in tumor burden and prolonged survival in an ovarian cancer mouse model when compared against the antibody plus wild-type INK cells.

Our knowledge. This is the only program that incorporates these four edits in a single engineered NK cell.

New preclinical data on edit 202 will be presented at the upcoming American Society for gene and cell therapy or <unk> TCT conference.

We'll show in vitro and in vivo data demonstrating significantly augmented AGC against multiple solid tumor cell lines and prolonged in vitro persistence and the absence of exogenous cytokines.

And at 202, combined with Trastuzumab resulted in greater reduction in tumor burden and prolonged survival in an ovarian cancer mass model when compared against the antibody plus a wild type <unk> NK cells.

Mark Sherman: An important element of our INK products is the actual cell editing and clone selection process, which allows Editas scientists to identify single clones having the precise combination of edits desired while eliminating those having unwanted editing results. It's an exquisite approach to limit the risk associated with a complex gene editing process because we can characterize a single clone extensively and know that we have exactly what we want with no off-target edits or chromosomal abnormalities, for example.

An important element of our NK products is the actual cell editing and client selection process, which allows editors scientists to identify single clients, having the precise combination combination of edits desired.

While eliminating those having unwanted editing results, it's an exquisite approach to limit the risk associated with the complex gene editing process, because we can characterize a single clone extensively and know that we have exactly what we want is no off target edits for chromosomal abnormalities for example.

Mark Sherman: We believe our cell therapy platform 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. In addition to our in-house oncology programs, our productive partnership with Bristol Myers Squibb around alpha beta T cells continues to advance, with BMS opting into a seventh program. We believe that these programs could result in novel, potent T-cell therapy approaches for cancer.

We believe our cell therapy platform 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.

In addition to our in house oncology programs, a productive partnership with Bristol Myers Squibb around Alpha Beta T cells continues to advance with BMS opting into a seven program.

We believe that these programs could result in novel potent T cell therapy approaches for cancer the.

Mark Sherman: The BMS programs leverage several of our unique platform technologies, including the proprietary Cas9 and AsCas12a nucleases and our guide RNA design to create autologous and allogeneic approaches in immuno-oncology. The most advanced program from this collaboration is in our IND-enabling studies, and we look forward to continuing our collaboration with BMS to develop important new medicines for cancer. Finally, I'd like to say a few words on the recently issued FDA guidance for industry on human gene therapy products incorporating human genome editing. The safe development of gene editing therapies is, as you would expect, of foremost importance to editors.

The BMS programs leveraged several of our unique platform technologies, including the proprietary test on Ias 12, Nucleases and our guide RNA design to create autologous and allogeneic approaches in immuno oncology.

The most advanced program from this collaboration is in IND, enabling studies and we look forward to continuing our collaboration with BMS to develop important new medicines for cancer.

Finally, I'd like to say a few words on the recently issued FDA guidance for industry on human gene therapy products, incorporating chairman gene editing.

The safe development of gene editing therapies is as you would expect our foremost important to <unk>.

Michelle Robertson: We were very pleased to see that the FDA guidance is highly consistent with the steps that we've already taken to ensure the safety of our products. We rigorously characterize on- and off-target editing as part of our preclinical development activities, and we see ourselves as being at the vanguard of gene-editing computational biology and bioinformatics software development. We also pay particular attention to the stringency and quality required to design, manufacture, and test genome editing components being considered for our product development.

We were very pleased to see that the FDA guidance is highly consistent with the steps that we've already taken to ensure the safety of our products.

We rigorously characterized on and off target editing as part of our preclinical development activities and we see ourselves as being at the bank out of gene editing computational biology, and bioinformatics software development.

We also pay particular attention to the stringency and quality required to design manufacture and test genome editing components being considered for our product development.

Michelle Robertson: We've always placed the highest priority on ensuring patient safety and closely review and follow the FDA's recommendations and guidance in our development plan. With that, I'll turn the call over to Michel to review our financial updates. Thank you, Mark, and good morning, everyone.

We've always place the highest priority on ensuring patient safety and closely reviewing followed the fda's recommendations and guidance and our development plans.

With that I'll turn the call over to Michelle to review our financial updates.

Thank you Mark and good morning, everyone.

Michelle Robertson: I'd like to refer you to our press release issued earlier today for a summary of our financial results for the first quarter of 2022. I'll take this opportunity to briefly review a few items. Our cash, cash equivalents, and marketable securities as of March 31st were $566 million compared to $620 million as of December 31st, 2021. We continue to be disciplined with our expense management, and our cash runway extends into early

To refer you to our press release issued earlier today for a summary of our financial results for the first quarter of 2022.

This opportunity to briefly review a few items.

Our cash cash equivalents and marketable securities as of March 31 were $566 million compared to $620 million as of December 31, 2021.

We continue to be disciplined with our expense management and our cash runway extends into early 2024.

Michelle Robertson: Revenue and operating expenses were relatively flat year over year. Revenue for the first quarter was $6.8 million compared to $6.5 million for the same period last year, and that slight increase was mostly driven by our collaboration with BMF. G&A expenses for the quarter were $20 million, compared with $21 million for the first quarter of 2021.

Revenue and operating expenses were relatively flat year over year revenue for the first quarter was $6 8 million compared to $6 5 million for the same period last year and that slight increase was mostly driven by our collaboration with BMS.

G&A expenses for the quarter were $20 million compared with $21 million for the first quarter of 2021.

Michelle Robertson: And R&D expenses were $38 million this quarter, compared with $42 million for the same period last year. This decrease was driven by success payments triggered during the first quarter of 2021, but there was no similar activity in the first quarter of this year, slightly offset by increased manufacturing and clinical investment. Overall, Editas remains in a strong financial position as we advance our program. With that, I will hand it back. Thank you, Michelle.

R&D expenses were $38 million this quarter compared with $42 million for the same period last year.

Increase was driven by success payments triggered during the first quarter of 2021, which there was no similar activity in the first quarter. This year slightly offset by increased manufacturing and clinical and message.

Overall antitrust remained strong financial position as we advance our programs with that I will hand, it back to Jim.

Michelle Robertson: We're looking forward to an exciting set of milestones for our programs and company in 2022. For example, we expect to complete dosing the pediatric mid-dose cohort for ED101 in the first half of the year. In the second half of the year, we'll initiate dosing for the pediatric high-dose cohort and provide a clinical update on the program. For EDIT 301 for sickle cell disease, we anticipate dosing the first patient in the first half of 2022 and providing top-line data by year-end.

Thank you Michelle we're.

We're looking forward to an exciting set of milestones for our programs and company in 2022, we expect to complete dosing in pediatric mid dose cohort for <unk> 101 in the first half of the year.

Half of the year, we will initiate dosing for pediatric high dose cohort and provide a clinical update on the program.

We've added 301 for sickle cell disease, we anticipate dosing our first patient in the first half of 2022 and provide topline data by year end. We also expect to have the first CBT patient dose as well.

Michelle Robertson: And we also expect to have the first TDT patient dose as well. We're advancing our EDIT 202 INK cell therapy program towards IND-enabling studies, and we expect to release additional preclinical data as we move toward that goal.

We're advancing our edit to I N T cell therapy program towards IND, enabling studies and we expect to release additional preclinical data as we move towards that goal, we'll continue supporting BMS as they advance through Alpha beta T cell programs towards the clinic clinics will further advance our innovative platform technologies, such as our innovative sleep.

Jim Mullen: We'll continue supporting BMS as they advance their alpha-beta T cell programs toward the clinic. Additionally, we'll further advance our innovative platform technologies, such as our innovative SLEEK platform that enables our cell therapy programs. And on top of our internal objectives, we anticipate business development efforts for future development and commercialization opportunities. We have a robust pipeline and technology platform secured by a broad foundation of intellectual property that was recently affirmed by a USPTO ruling.

<unk> platform that enables our cell therapy programs and on the top of our internal objectives, we anticipate business development efforts for future development and commercialization opportunities.

We have a robust pipeline and technology platform secured by a broad foundation of intellectual property.

Was recently affirmed by the U S. PTO ruling we're excited by the advances across our pipeline and we aimed to bring these programs to patients. So they can benefit from the tremendous potential of gene editing.

Jim Mullen: We're excited by the advances across our pipeline, and we aim to bring these programs to patients so they can benefit from the tremendous potential of gene editing. And finally, I'll once again welcome Gilmore to the company.

Jim Mullen: I still plan on engaging with many of our stakeholders, including our investors, and look forward to maintaining a productive dialogue. We thank all of you for your interest and support. And with that, we'll open it up to questions and answers. Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone. The confirmation tone when you create your line is in the question. You may press star two if you'd like to remove your question. For participants, please use speaker equipment. It may be necessary to pick up your handset before pressing the start button.

And finally once again welcome to go more to the company still plan on engaging with many of our stakeholders, including our investors and look forward to maintaining a productive dialogue.

We thank all of you for your interest and support.

That will open it up to questions and answers.

Yeah.

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

I'd like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue. You May press star two if you'd like to remove your question from the queue for participants using speaker equipment and may be necessary to pick up your handset before pressing the historically.

Operator: One moment, please, while we pull for questions. Thank you. Our first question comes from Joon Lee with Truist.

One moment, please while we poll for questions.

Yes.

Thank you. Our first question comes from Joon Lee with <unk>. Please proceed with your question.

Joon Lee: Hi, thanks for taking our questions and for the updates. We're getting a lot of questions from investors on sickle cell disease recently. So as you discuss your trial with the FDA and what sort of trial, the study size, and the duration, follow-up, the FDA is asking to get a 301 approved. Can you share any information around that?

Hi, Thanks for taking our questions for the updates.

We're getting a lot of questions from investors on sickle cell disease recently.

As you've discussed your trial with the FDA and what sort of trough the study size and the duration.

A follow up the FDA is asking for three years.

301 approved.

Certainly any information around and I have a follow up.

Jim Mullen: And I have a follow-up. Well, I mean, we probably haven't probably our next engagement with the FDA will be after we have completed dosing of the first few patients in the trial. At this point, we don't have any reason to believe that our pathway to through clinical trials is any different than what we've seen from the competitors. So I still anticipate that we're probably looking for, you know, 40 to 60 patients, plus or minus, and the same efficacy outcomes that they're looking for and durability outcomes that they're looking for, whether it's Bluebird or CRISPR or anybody else. Great

Well I mean, we haven't.

Our next engagement the FDA will be after we have completed dosing of the first few patients in the trial.

At this point, we don't have any reason to believe that our pathway to.

Through clinical trials is any different than what we've seen from the competitors. So I would still anticipate that were probably looking for.

Uh huh.

40% to 60 patients plus or minus.

And the same efficacy outcomes.

They are looking and durability of outcomes that they're looking for whether it's bluebird or christopher or anybody else.

Great.

Jim Mullen: So the second most common question is around your BD and licensing strategy given your favorable IP position in the U.S. So, you know, what types of BD and licensing deal do you have in mind for the foreseeable future?

For the second most important question is around your BD and licensing strategy, giving you a favorable IP position in the U S.

What types of BD in licensing deal do you have in mind.

For the foreseeable future. Thank you.

Jim Mullen: Thank you. So we anticipate doing a wide range of licensing deals. We're going to continue to do both exclusive and non-exclusive licensing. You know, this would be true for both Cas9 as well as Cas12a.

So we envision doing a wide range of licensing deals we're going to continue to do both exclusive and nonexclusive licensing this would be true for both cost line as well as <unk>.

Jim Mullen: You know, you know, I would expect that some of these arrangements may be strategic licenses, partnerships, and collaborations, where others, you know, I would expect will be straight licenses. And a quick one if I can, you know, since you dosed the first pediatric patient in April for EDIT101 and there is a requirement of six-month follow-up prior to data disclosure, can we expect something around October or is your data disclosure strategy such that you're going to wait until all four pediatric patients have been dosed by the end of the first half, which would put data disclosure towards the end of the year?

I would expect that some of these arrangements may be strategic licensing partnerships and collaborations where others I would expect it will be straight licenses.

Okay, and then a quick one if I can.

Since we dosed our first pediatric patient in April for edit 101.

Requirement of six month follow up prior to data disclosure.

Can we expect something around October or is your data disclosure strategy, such that youre going to wait until all for pediatric patients had been dose.

By by the end of the first half, which would put data this quarter towards the end of the year. Thank you.

Jim Mullen: Thank you. Yeah, so the data disclosure we've talked about, We've talked about the adult mid-dose, the adult high-dose, and then previously we said we would have, we would expect that we would update on sort of the safety outcomes from the first pediatric patients at that readout, which, you know, October, you know, that's probably, October, November, probably a reasonable timeframe to be thinking about, but unlikely that we'll have, We'll try to actually have complete cohorts of data going forward before we try to report out on the efficacy part, but the safety, obviously, is a little bit more of a rolling information.

Yes.

Data disclosure we've talked about.

We've talked about the adult mid dose the adult high dose and then previously we said we would have we would expect that we would update on sort of the safety.

Outcomes from the first pediatric patients at that readout, which.

October .

<unk>.

November probably a reasonable time frame to be thinking about.

But unlikely that we'll have.

We will try to actually have complete cohorts of data.

Going forward before we started to report out on the efficacy and safety.

Obviously, there's a little bit more of a rolling.

<unk>.

Jim Mullen: Thank you. Our next question comes from Joel Beatty with Baird. Please proceed with your, Hi, thanks for taking the questions. For potential BD, do you see that happening for some of your lead agents that are in the clinic or entering the clinic within the next year? And if so, are there certain time points or catalysts that you'd like to have before, you know, that could make more sense?

Thank you. Our next question comes from Joel Beatty with Baird. Please proceed with your question.

Alright, thanks for taking the questions.

Four potential BD do you see that happening for some of your lead agents that are in the clinic or entering the clinic within the next year.

If so are there certain time points are.

Catalyst.

I heard before that could make more sense.

Joel Beatty: Yeah, Joel, good question. And, you know, I've, in the past tried to address this a bit so Yeah, so let's start with, 3.0.1, the sickle cell disease beta thalassemia, you know, it's always been my view that over the longer term, we would want a commercial partner for that product, particularly for outside the US, but potentially to share some of that inside the US inevitably that comes with probably become a bit of a development partner in the late stage.

Yes, Joe good question.

Yes.

In the past tried to address this a bit so.

So let's start with.

Joel Beatty: I have, you know, we thought about that probably a couple of years ago and concluded that the better time to engage in those conversations was once we start to get some clinical data. Because, in my view, that's what the bigger partners are always going to look at.

301, the sickle cell disease beta thalassemia.

It's always been my view that over the longer term, we would want a commercial partner for that product, particularly for outside the U S, but potentially to share.

Some of that inside the U S and inevitably that comes with probably.

<unk> come a bit of a development partner in the late stage.

I have.

We thought about that probably a couple of years ago and concluded that the better time to engage on those conversations was once we start to get some clinical data because in my view, that's what the bigger partners are always going to look to and Thats, where we can create the maximum value for ourselves.

Jim Mullen: And that's where we can create sort of the maximum value for ourselves. So that's one, I would say a second area that we look at is with the INK platform, the IO spaces, particularly as you know, it's complex, and it's expensive. And there we would look to partnerships to enhance both our depth of expertise, as well as, you know, just the ability to finance and run clinical trials over a longer period of time, and ultimately commercialize. That's not an area where I think we're likely to play any time soon, as far as I can see.

So that's one I would say the second area that we'd look to us.

With the pay platform.

The Io spaces, particularly as you know it's complex.

It's expensive.

There we would look to.

For partnerships to enhance both our depth of expertise as well as just the ability to finance and run clinical trials over a longer period of time at.

And ultimately commercialize that's not an area where I think.

We're likely to deploy any time that I can see in the ocular space.

Jim Mullen: In the ocular space, we like those programs. There's a suite of those programs and some programs that we have not yet disclosed. We'll start to talk about those later in the year. But those are small enough clinical trials and targeted enough in what I'll call the high unmet need but not hypercompetitive space. Our current thinking is we should continue to just own those.

We like those programs, there's a suite of those programs.

And some programs that we have not yet disclosed.

Let's talk about those later in the year.

But those are small enough.

Clinical trials and targeted enough and what I'll call high unmet need, but not hyper competitive space.

Well, our current thinking as we continue.

Just one of those and then maybe lastly to expand a little bit on what Charlene.

Jim Mullen: And then lastly, to expand a little bit on what Charlene said, there's certainly some areas that we have thought about and done some work in. But it's a question of, could we accelerate and create more value for everybody by partnering those up sooner rather than later? And I'm in particular thinking about potentially in vivo targets.

There are certainly some areas that we have thought about and done some work in.

But it's the question of could we accelerate in crude.

More value for everybody by partnering those up sooner rather than later in particular thinking about.

Potentially in vivo targets.

Jim Mullen: Great, thank you. Thank you. Our next question comes from Dagon Hopp with Steeple.

Great. Thank you.

Thank you. Our next question comes from Dae Gon Ha with Stifel. Please proceed with your question.

Dagon Hopp: Please proceed with your question. Yeah, good morning. Thanks for taking our questions and congratulations on all the progress. Two questions for me, one on one-on-one and one on three-on-one.

Yes. Good morning, Thanks for taking our questions and congrats on all the progress two questions for me one on one on one and one on 301, so looking at one O. One your recent competitor not in the gene editing space, but using a ASO read out sort of their comprehensive analysis following their phase II III disappointment.

Jim Mullen: So, looking one-on-one, your recent competitor, not in the gene editing space but using ASO, read out sort of their comprehensive analysis following their phase two, three disappointment and couldn't really find anything in terms of trial misconduct. And so, just wanted to get your take on what your thought process is when it comes to de-risking your trial. And when you commented, Jim, in your prepared remarks on looking at additional endpoints through the natural history study, I think so far we've only seen the BCVA, FST, and navigation.

Couldnt really find anything in terms of trial misconduct almond. So just wanted to get your take on what's your thought process is when it comes to de risking of your trial.

And when you commented on Jim in your prepared remarks on looking at additional endpoints through the natural history study I think so far we've only seen the BCA F. S. T. A navigation so any additional endpoints that you've collected that hasnt been presented that you're kind of leaning towards based on the natural history analysis. That's question one.

Jim Mullen: So, any additional endpoints that you've collected that haven't been presented that you're kind of leaning towards based on the natural history analysis, that's question one. On three-on-one, just curious, since you seem to be following the rubric of a competitor that's about to file by the end of the year, recognizing there are some points of differentiation here, but can you set some expectations for the year-end And specifically, is it HBF content that's going to be the point of differentiation or VOC, since we've already seen some pretty compelling data from your competitor? Thanks. Yes,

On 301, just curious since you seem to be following the rubric of a competitor that's about to file by the end of the year recognizing there are some point of differentiation here, but can you set some expectations for the year end data and specifically is it hbf content, that's going to be the point of differentiation or <unk>.

Since we've already seen some pretty compelling data from your competitor. Thanks.

Yes.

Jim Mullen: Okay, so let's see, ProQR, so the first question was really 101 and endpoints and what, if anything, do we learn from the ProQR? So, yeah, we have, as you know, we've talked about visual acuity, we've talked about retinal sensitivity with FST, and we've talked about mobility. There are other measurements that we have used in that trial, such as pupillometry and OCT and other things. What we haven't spent time talking about is also patient-reported outcomes, so that would probably be the other element that we're interested in making sure we match up what the patients and physicians are reporting to connect to the more objective data, which would be the maze, visual acuity, retinal performance sensitivity, etc.

Okay. So lets see <unk>. So the first question was really 101 and endpoints.

What if anything do we made from the pro QR. So.

Yes, we have as you know we've talked about visual acuity, we've talked about our retinal sensitivity with FSC and we've talked about mobility. There are other measurements that we have used in the trial.

Such as Pupillometer tree.

OCC and other things what we haven't spent time talking about is also patient reported outcomes. So that would probably be the other element that we're interested in making sure we match up what the patients and physicians reporting.

To connect to the more objective data, which would be Mays visual acuity.

No performance sensitivity et cetera.

So those would be the kinds of things that we're thinking of looking at and probably the ones that we've not spoken about much or the patient reported outcomes. What are we doing is we're trying to learn as we go for us to use the information from the natural history study.

Jim Mullen: So those would be the kinds of things that we're thinking of looking at. And probably the ones that we've not spoken about much are patient-reported outcomes. What we're doing is we're trying to learn as we go, plus use the information from the natural history study to ensure that after we get past the sentinel patient, so remember the sentinel patient for each one of our dose groups is always light perception only, so very, very poor incoming vision, and to make sure that we select patients after that who are most likely to be able to show a response with those endpoints that we're using But in particular, it's visual acuity, retinal sensitivity, and mobility measurements.

To ensure that after we get past the Sentinel patient so remember the sentinel patients for each one of our dose groups.

It is always light perception, only so very very poor incoming vision.

To make sure that we do.

Select patients after that that are most likely to be to be able to show a response with those endpoints that we're using.

And particularly the visual acuity retinal sensitivity ability mobility measurements.

Jim Mullen: So that's actually the logic for extending the cohorts that we've talked about before. So we'll add at least another four patients, probably in the high dose adult cohort. So did I answer all your questions Mark? Did I get all your questions on that one?

So that's so thats actually the logic for extending the cohorts that we've talked about before so we will add at least another four patients.

And the high dose adult cohort.

So did I answer Mark did I get all the questions on that one I'm looking over at <unk>.

Jim Mullen: I'm looking over at Mark to make sure I answered the question correctly. I think the other thing, you know, the ProQR data is a valuable data set for us to track, right? So it was very unfortunate for the patients and for them that they got the surprise they did with phase two, three.

I think the other thing the <unk> date.

<unk> is a valuable data set for us to track right. So it was very unfortunate for the patient and then that take up that surprised me Dave.

It's two to three so we know that we have to focus on.

Jim Mullen: So we know that we have to focus on, you know, response rate and true performance against the end points before we make the decision on the registrational trial. So I think that's going to be helpful. Yeah, I'd say, you know, unfortunately, I think ProCR got pushed into this, I'm guessing, I'm speculating, probably got pushed into this. You know, sham procedure as the control. I don't think that's something that we could do in any event.

Response rate and true performance against the endpoints before we make the decision on the Registrational trials. So I think that's going to be out there.

And I'd say.

Fortunately I think procure got pushed into this im guessing.

Im speculating probably got pushed into this.

Sham procedure as the control.

I don't think Thats something that we could do any in any event, but I also don't think it's.

Based on everything we've seen through the natural history study that's actually warranted.

Or you could even get it pass through the IRB. So thats just editorial comment.

Jim Mullen: But I also don't think it's, You know, based on everything we've seen for the natural history study, that it's actually warranted, or you'd even get a test in IRB. So that's just an editorial comment. 301. If I remember Jay, your question is, well, what are our expectations for data by year end? And what will we have that will start to point to differentiation?

301.

Remember J. Your question is whats our expectation for data by year end.

Jim Mullen: So expectations for data by year end are really going to be for the patients that we will have dosed by then, and engraftment, and we'll start to see the fetal hemoglobin levels. There will not be sufficient data to make any conclusions on VOCs or anything until, you know, sometime next year. So from that perspective, then you'll have to look at how people want to extrapolate, if you will, preclinical data and actual data in the clinic to decide whether to think about differentiation on either efficacy or durability.

And what will we have that will start to point to differentiation. So expectations for data by year end is really going to be.

For the patients that we will have dose by then.

<unk>.

We will start to see the fetal hemoglobin levels.

Not be sufficient data set to make any conclusions on vlccs or anything until.

Sometime next year. So from that perspective, then youll have to look at how people want to extrapolate if you will preclinical data and actual data in the clinic to decide whether to.

To think about differentiation on either efficacy or durability.

Mark Sherman: Mark, do you have any thoughts that we should add to that? only that we're making very good progress on generating the data set to respond to the FDA on the questions that they had about the study. So that's going really well. Yeah.

Mark do you have anything else that.

We should add to that.

Tony that we're making very good progress on generating that data set to respond to the FDA on the question for a hedge on our study so that's going very well.

Jim Mullen: So if I may add just one quick follow-up to the 101 questions on the press release, and you said this previously, your goal here as for next steps would be to expand one or more dose levels in the adult cohort. So would it make sense to expedite that process by at least starting on the mid dose, since you've already dosed low and mid, and we might be seeing some kind of dose response at the mid level, and then, depending on the high, decide on whether to pursue that second dose expansion, whether low or high? I hope that makes sense. Thanks again. So now that you have given me a really difficult question, Jay, I'm looking over to Mark. It's a good question.

So if I may add just one quick follow up to the one on one question on the press release and you said. This previously your call here at the as of next steps would be to expand one or more dose levels in the adult cohort. So would it make sense to expedite that process by at least starting on the mid dose since you've already.

Dose blow and med and we might be seeing some kind of a dose response in the mid level and then depending on the high decide on whether to pursue that second dose expansion, whether low or high I hope that makes sense. Thanks Scott.

Yes.

So now that you gave me a really difficult question, Jay I'm looking over to Mark.

Jim Mullen: So, you know, we're looking at the date. We're going to look at the data as it rolls out. As you heard, we've dosed the first pediatric patient in the mid-dose cohort too. So I think we really want to make sure that we have, Taking a close look at the data, both the safety data as well as any emerging information that comes from the efficacy assessments, I use that to drive the final decision on whether we expand in one or both of the available cohorts for the adults.

It's a good question. So we're looking at the data we're going to look at the data the wells.

Could we have dosed the first pediatric patient at the mid dose cohort two so I think we really want to make sure that we have.

Taking a closer look at the data both the safety data as well as any emerging information that comes from the efficacy assessments and use that to drive.

Final decision on whether we expanding one or both of the available cohorts for vehicles.

Jim Mullen: Yeah, the preclinical data would say the high dose is most likely to have the best effect. But as Mark said, we just have to react to the data as we see it roll in. I mean, we will have six months.

The preclinical data would say the high dose is most likely to have.

The best effect, but as Mark said, we just have to react to the data as we see it roll in.

I mean, we will have six months.

Jim Mullen: Data on the mid-dose and 12-month data on the low dose that we'll report next. And then, as you recall, we finished dosing the initial four adult patients in December of last year. So that data will come through in the third quarter as well.

Data on the.

Mid dose and 12 month data on the low dose that we'll report next and then as you recall, we finished dosing of the initial four adult patients in December of last year, So that data will come through in the third quarter as well.

Jim Mullen: Thank you. Our next question comes from Deb Chodopadhyay with Guggenheim. Please proceed with your question. Hi, this is Ry Forseth. I'm on behalf of Debjit.

Thank you. Our next question comes from Doug.

So part of it with Guggenheim. Please proceed with your question.

Hi, This is Ryan for Seth on for that CIT.

For edit 301 could you walk us through the timing between subject dosing and how you account for the necessary in Grafman time and safety evaluations.

Ry Forseth: For EDIT 301, could you walk us through the timing between subject dosing and how you account for the necessary engraftment time and safety evaluations? Sure. So, you know, once the patient has their cells re-infused, we expect approximately a 40-day period over which we are going to monitor neutral-fetal engraftment, that's the first step, followed by patient engraftment with general safety evaluations and clinical chemistry. So at that point, when we have proof of engraftment, that will be the trigger for the second patient to be dosed, and then they That's it.

Sure so.

Once the patient has the sales we infused we expect approximately 40 day period over which we're going to monitor neutral failing <unk>. That's the first step followed by patient <unk> with general safety evaluations and clinical chemistry. So at that point when we have proof within grasp that will be the trigger.

For the second patient to be dosed and then they will go through a similar evaluation.

Got it thank you.

Mark Sherman: Thank you. Thank you. Our next question comes from Steven Seedhouse with Raymond James. Please proceed with your question. Hi, good morning.

Thank you. Our next question comes from Steven <unk> with Raymond James. Please proceed with your question.

Steven Seedhouse: Thanks for taking the time to answer the question. I had one on sickle cell and one first on LCA-10. Just looking at the viral shedding data from ARVO, the, You know, as you look across the patients, there's like six, six or seven orders of magnitude difference in the virus copies, and it doesn't look like it's related to dose. And then on the x axis, you know, most patients have viral shedding below the limit of detection, but there's one that is detected out to week six. So I just wanted to ask, what are the drivers, I guess, of just the heterogeneity here and what are the implications?

Yeah.

Hi, good morning, Thanks for taking the question I had one on.

Sickle cell and one first on LCA 10, just looking at the viral shedding data from.

<unk> <unk>.

B.

As you look across the patients that was like six six or seven orders of magnitude difference.

And the virus copies and it doesn't look like it's related to dose and then on the X axis most patients have.

Below the limit of detection viral shedding, but theres one that.

Is detected out to week six so I just wanted to ask what are the drivers I guess of just the heterogeneity here and what are the implications does it tell you anything about pharmacodynamic.

Mark Sherman: Does it tell you anything about pharmacodynamics? Uh... expectations or safety expectations. And then the question on sickle cell is just, you know, appreciating that your hypothesis sort of lends to an expected difference in safety long-term. But I'm curious if around the time of transplant, whether it's engraftment time or, you know, early safety events, if your preclinical data suggests you'd expect to see differentiation versus the BCL11A approach. Thanks for taking the question.

Expectations are safety expectations.

And then the question on sickle cell is just.

Appreciating that your hypothesis.

A lens to an expected difference in safety long term, but I'm curious if around the time of transplant, whether it's <unk> time or or.

Or.

Early safety events. It's your preclinical data suggest you'd expect to see differentiation versus the Bcl M&A approach. Thanks for taking the questions.

Mark Sherman: So I'll take the first one on viral shedding. You're correct, you know, the data is somewhat variable. I would say, based on my prior experience, this is exactly what you expect with subrational administration of AV viral vectors; there is variability in the way that the virus is administered, meaning sometimes the volume of the blood may be slightly different. Occasionally, you get, Reflexome runs the retinal to me.

So I'll take the first one on viral shedding so.

Youre correct. The data is somewhat variable I would say based on my prior experience. This is exactly what you expect with the sub retinal administration of AAV viral vectors there.

Their ability in the way that the virus is administered meaning sometimes that volume at that flat maybe slightly different occasionally you get.

We flex and run the rest of the alchemy. So just generally this is a kind of a messy procedure to get tight data on viral shedding I think the overall message is it's in line with what we would expect from an AAV based therapy, if no clear dose response relationship to the administration and its just a general.

Mark Sherman: So just generally, this is a kind of a messy procedure to get data on viral shedding, but I think the overall message is it's in line with what we would expect from an AAV-based therapy. There's no clear dose response or relationship to the administration, and it's just a general, pretty benign response.

<unk> pretty benign.

Mark Sherman: The expectation is, you know, given subretinal administration, that the vector really doesn't get much beyond the eye in any appreciable amounts. And I think that's essentially what we're finding, albeit on occasion, you'll get somatic lies, but in general, that's what we would expect. And so your question on 301 was about engraftment and anything about our product that is likely to point to early differentiation. That's, you know, a question of, you know, watching the data, which is what we're going to do, and, you know, seeing how it in fact mimics what we've seen in preclinical.

Response, the expectation is given sub retinal administration that activity doesn't get much beyond the eye in any appreciable amongst I think that's essentially what we're finding.

On occasion, you'll get some added lives, but in general that's probably been expense.

And so your question on 301 was about and dressed in anything about our product that is likely to point too early differentiation.

That's.

A question of.

Mark Sherman: So if it indeed mimics what we've seen in the preclinical, we'd expect to have, you know, quite high accuracy. We'd expect the graph to be what we've seen with other programs similar to this, and that we have very high editing levels, etc.

Watching the data, which is what we're going to do.

Seeing how.

<unk> mimics what we've seen in the preclinical.

So if it indeed mimics what we've seen in the preclinical we'd expect to have quite high.

We'd expect the <unk> to be what we've seen with other programs similar to this.

And that we have very high editing levels.

Et cetera, So I don't.

Mark Sherman: So I don't, you know, and hopefully, that will also correspond to clinically relevant production of HPF. And we'll see how high that is. I don't know that once you get beyond a certain threshold, anybody actually knows how much higher is better.

And hopefully that will also correspond to.

Clinically relevant.

Production of Hbf, and we'll see how high that is I don't know that once you get beyond a certain threshold anybody actually knows.

How much higher is better.

Mark.

Mark Sherman: Mark, I don't know if you have any data to support that. No, I think you're correct. We think the high editing efficiency of the AS-Cas12a nucleate is really important here.

No I think you're correct, we think that high editing efficiency of the AD cost 12 annual cases really important here, we know from the preclinical data that we are getting very good editing at the progenitor cells, which could be a determinant of the durability of hbf or general.

Mark Sherman: We know from the preclinical data that we are getting very good editing of the progenitor cells, which could be a determinant of the durability of HPF or general Response. And that with the mechanism that we are pursuing, we don't get any lineage spillage following editing. I think that could be an important factor that plays out over the longer term.

Response.

And that we know with the mechanism that we are pursuing we don't get any lineage skewing following editing.

That could be an important factor that plays out over the longer term.

Steven Seedhouse: All right, thank you. Thank you. Our next question comes from Jay Olson with Oppenheimer and Company. Please proceed with your question. Hi, this is Cho on the line for Jay.

Alright, thank you.

Thank you. Our next question comes from Jay Olson with Oppenheimer and company. Please proceed with your question.

Cho: Thanks for taking the question. I guess for Edit 101, you mentioned you're looking for more sensitive endpoints and also maybe patients that are more responsive to the treatment. Just wondering if the same applies to the pediatric patients and also if you're collecting patient-reported outcomes from those pediatric patients.

Hi, This is chung lines R. J, thanks for taking the question.

I guess for added well one you mentioned you are looking for more sensitive endpoints that also may be patients that are more responsive to the treatment. Just wondering if the same applies to the pediatric patients and also through our <unk> patient reported outcome.

Pediatric patients. Thank you.

Jim Mullen: Thank you. So, yes, the same logic would apply to pediatric patients going forward, and I just want to be careful about how we describe, you know, how we're selecting patients. So it's less about whether we think the product works or doesn't work, and it's probably more about over what range are these endpoints sensitive enough to actually pick up a difference, right? So that's really more what we're trying to target here is to ensure that the incoming baseline site for the patients is in a range where these endpoints will work.

So yes, the same logic would apply to the pediatric patients.

Moving forward.

Okay.

Just want to be careful about how we.

How we describe.

How we're selecting patients so.

Less about do we think the product works or doesn't work and it's probably more about over what range are these endpoints sensitive enough to actually pick up a difference right.

So that's really more of what we're trying to target here is to ensure that the incoming.

The baseline so for the patients using a range, where these endpoints will work and as you can appreciate.

Jim Mullen: And as you can appreciate, you know, BCVA, and even Berkeley, if they have very, very low vision coming in, it's not very useful, you know; there's not too much information you're going to get from that. And by the same token, if they have very good eyesight coming in, their ability to maneuver through the maze is already at sort of the top of the scale, right?

<unk>.

The Berkeley.

They have very very low vision coming in it's not a very useful.

Too much information, you're going to get from that.

And by the same token if they have very good I'd say coming in their ability to maneuver through the maze.

He is already at sort of the top of the scale right. So I just use those as kind of examples of Av.

No.

How we think about.

Adjusting the incoming.

The inclusion criteria if you will.

Do we have more questions.

Okay.

Jim Mullen: So I just use those as kind of examples of how we think about adjusting the incoming inclusion criteria. Do we have more questions? Thank you. Our next question comes from Rick Bienkowski with SVB Security. Please proceed with your question. Good morning.

Thank you. Our next question comes from Rick Ian Koski with SBB Securities. Please proceed with your question.

Rick Bienkowski: Congratulations on all the progress and thanks for taking our questions. First, I was hoping you could clarify exactly where the Edit202 program is in development. I know a lot of your recent scientific presentations have highlighted this program, but I don't believe we have any guidance for an IMD filing. Could you maybe discuss some of the work that's ongoing for EDIT202 and what steps need to be completed before an IND filing? And then I have a second question.

Hey, good morning, Congrats on all the progress and thanks for taking our questions.

First I was hoping you could clarify exactly where and developments at its <unk> program and as I know a lot of your recent scientific presentations have highlighted this program, but I don't believe we have any guidance for an IND filing could.

Could you maybe discuss some of the work that's ongoing for editorial too and what steps need to be completed before an IND filing.

Mark Sherman: The press release guided for cash runway into early 2024. Could you also just dive into some of the major assumptions around this number, including maybe how many clinical programs you'd expect to advance in parallel and whether or not this is dependent on any incoming milestone? Maybe I'll, this is Mark. I'll take the 202 question.

And then I have a second question the press release guidance for cash runway into early 2024.

Could you also just dive into some of our major assumptions around this number including maybe how many clinical programs, we would expect to advance in parallel and whether or not this is dependent on any incoming milestones.

Michelle Robertson: So you're correct; we haven't yet given specific guidance on the date of the IND filing. But as you can imagine, all of our efforts are directed towards completing the data package that will be necessary to file an IND, which includes all of the pharmacology and toxicology work, preparations for an IND-enabling GLP toxicology study, which includes both the pharmacology side and the preparation of the Cell, you know, we did clinical clone selection, and then I finally developed this framework for my first evidence-based study.

Maybe I'll. This is mark I'll take the <unk> question. So you are correct, we haven't yet given specific guidance on the date of the IND filing, but as you can imagine all of our efforts are directed towards completing the data package that will be necessary to file an IND.

Which includes order the pharmacology and toxicology work preparations for an IND, enabling <unk> toxicology study, which includes both.

The pharmacology side, but also the preparation of the.

South.

Clinical claims selection and then expansion and differentiation of that that you have sufficient sales to conduct all of these studies, so that's where we're going right now.

Michelle Robertson: Thanks to them all, I can also trust that I have turned out and shown what I hope will stay effective. And I'll take the second question, Rick. So our cash runway is based on and includes our current plan for our current clinical programs, as well as our preclinical programs that we've spoken about. And it does not assume any incoming cash from milestones or BD.

Our plans solidify will.

Maybe later in the year give more guidance on narrowing.

<unk> a date as to why we think it could be available.

And I'll take the second question <unk>. So our cash runway is based on it includes our current plan. So our current clinical programs as well as our preclinical programs that we've spoken about and it does not assume any incoming cash from milestones or <unk>.

<unk>.

Mark Sherman: So it essentially assumes everything that we've discussed and talked about in our clinical or preclinical pipeline moves forward at a pace. Great. I just wanted to follow up on the Edit202 program, which mentioned advancing internal and external manufacturing capabilities in tandem. Is that perceived to be a bottleneck for the IND filing as well? Or is that just, you know, work that's ongoing in parallel with other preclinical work? It's the

So it essentially assumes everything that we invest.

<unk> talked about in our clinical or preclinical pipeline.

Moves forward at pace.

Hi, Great I, just wanted to follow up on that <unk> program.

The press release mentioned.

I had mentioned advancing internal and external manufacturing capabilities in tandem is that perceive to be a bottleneck for the R&D filing as well or is that just work that's ongoing in parallel with the.

Other preclinical work.

Mark Sherman: It's just the approach we're taking to develop a methodology for the expansion and differentiation and then the transfer of that methodology to an external CDMR. But we don't view that as a normal business, and we don't view that as rate-limiting to moving this program to the class. Thank you. Our next question comes from Madhu Kumar with Goldman. Please proceed with your questions. Hey guys, this is Rob One from MADU.

It's the latter it's just the approach we're taking to develop and methodology for the expansion and differentiation and then the transfer of that methodology to external CMO.

Well, we don't do that.

Normal business and we don't view those rate limiting to moving this program for the quarter.

Thank you. Our next question comes from <unk> Kumar with Goldman Sachs. Please proceed with your question.

Rob ONe: Thanks for taking our question. I was just wondering whether the high dose cohort of brilliance includes any homozygous, IVF-26 patients. I don't believe so at this point in time. Yeah, we haven't.

Okay.

Hey, guys. This is rob on for <unk>. Thanks for taking our question I was just wondering does the high dose cohort of brilliance include any homozygous.

<unk> 26 patients.

I don't believe so at this point in time, yes, we haven't we haven't released the specific sets of patients included in that cohort.

Mark Sherman: We haven't released the specifics of the patients included in that cohort, but as you know, homozygous patients constitute probably about 10% of the population. And so we're focusing on the entire population, not just the. Thank you. Thank you. Our next question comes from Luca Issi with RBC Capital. Oh, great. Thanks so much for taking my questions. Congratulations on all the progress. Just a few ones here.

As you know homozygous patients constitute probably about 10%.

Population is that we're focusing on the entire population not just.

Yes.

Thank you.

Thank you. Our next question comes from Luca <unk> with RBC capital. Please proceed with your question.

Oh, great. Thanks, so much for taking my questions. Congrats on all the progress.

Luca Issi: So, on LCA-10, you know, maybe circling back on a few prior questions, maybe ask a little bit more directly, and I understand lots of moving parts as the data is still evolving, but what will be the endpoint that you will pitch to the FDA today as the primary endpoint for LCA-10? And then, on the IEP, can you just talk about how we should think about the long-term implications, given you now have the upper end in the U.S., but my understanding is that CDC is in a stronger position in the EU. Would it be fair to assume that this will all come down to a cross-licensing agreement between the parties where the economics depends on geography?

Q1 here so on LCA.

Maybe circling back on a few prior question, maybe ask a little bit more directly and I understand a lot of moving part is the data is still evolving but what will be the endpoint that you pitched the SBA today as the primary endpoint for LCA 10.

And then the second on the IP can you just talk about how we should think about the long term implications. Given you now have the upper end in the U S. But my understanding is the CVC is in a stronger position in the EU would it be fair to assume that this will all come down to cross licensing agreement between the parties, where the economics of it depends on the gene.

Charlene Stern: And then lastly, can you just give us any update on the chief medical officer search and maybe remind us who the ideal candidate here is in the breadth of the pipeline, which obviously spans ophthalmology, hematology, and oncology? Thanks so much. Luca, you're assuming that we can remember a compound question. Do you want to start with us? Yeah, with 101.

And then lastly can you just give us any update on the Chief Medical Officer search and maybe remind US who is the ideal candidate given the breadth of the pipeline, which obviously spans ophthalmology hematology oncology.

So much.

Look a year assuming that we can remember a compound question.

<unk> will answer the latter yes with one on one.

Mark Sherman: Yeah, we haven't made that decision yet. As we've indicated, there's a lot of data coming in, and the decision will be data-driven based on what that looks like in both the adults and, hopefully, you know, in the pediatric patients. And that will guide our final choice. But right now, it's still under evaluation. Carleen, do you want to take that?

Yes, we haven't made that decision yet as we've indicated there is a lot of data coming in and the decision will be data driven based on what that looks like in both the adult hopefully in the pediatric patients and that will guide our final choice, but right now.

Still under evaluation.

Charlie you want to take that sure. So we see tremendous value in our IP and we think that we have a significant longer term opportunity to think about how we license the technology.

Charlene Stern: Sure. So we see tremendous value in our IP, and we think that we have a significant longer-term opportunity to think about how we license the technology. The USPTO decision is very favorable to Editas and Broad.

The U S. PTO decision is very favorable to edit Thompson, Brian and we believe that that decision will be upheld on appeal. We also believe that the majority of drug development and commercial sales will play out here in the U S and so that really underscores the importance and value of the IP that we have.

Jim Mullen: And, you know, we believe that the decision will be upheld on appeal. We also believe that the majority of drug development and commercial sales will take place here in the US. And so that really underscores the importance and value of the IP that we have. Yeah, I mean, I've looked at all of the models that everybody's put together for Cas9 programs that might get commercialized. And, you know, it always looks like it always did, which is that two-thirds or more of the revenue is going to come out of the US market.

Yes, I mean I've looked at.

All of the models.

Everybody has put together a forecast nine programs that Mike.

Get commercialized.

It always looks like it always did which is two thirds or more of the revenue is going to come out of the U S market.

Charlene Stern: And then there's also an underlying presumption in what some of the companies are saying is that we actually need anything for FTO in Europe, and that's by no means clear at all. So, and particularly for our sickle cell program, remember, we're using Cas12, and so that's... The CAF 9 question is completely irrelevant to our sickle cell program. And it's not clear that we need anything else at this point in time for FTO, for any of our other programs outside the U.S., and for the two of you. Great. Thank you. Yeah, no, go ahead.

And then there is also an underlying presumption and what some of the companies are saying is that we actually need anything for FCO.

In Europe .

That's by no means clear at all.

So and particularly for our Silicon software and were remember we're using test well.

So thats.

The cat nine question is completely irrelevant for our sickle cell program.

It's not clear that we need anything else at this point in time for Fgo for any of our other programs.

Yes.

And as Greg said on the call.

Okay.

Oh, yes, yes.

Go ahead.

Jim Mullen: Mark was just adding that the 202 program uses the ASCAS-12 as well, so anyway, you had another I'm sorry, You know, got it. Super helpful. Last one on the chief medical officer search. Thank you. Oh, chief medical officer. See, I told you if you asked me a compound question, I wouldn't understand it. So we're in the process of interviewing people. What's the perfect candidate?

Mark was just adding the 202 program uses the <unk> 12 as well so.

So you had another I am sorry.

Got it Super helpful last one on the Chief Medical Officer search. Thank you Oh, Chief Medical Officer I told you if you have any.

Final question I wouldn't get it.

So we're in the process of interviewing people, what's the perfect candidate needs.

Jim Mullen: You know, it needs to be somebody that is a clinician scientist. You know, and why that's important here is, obviously, they need to know how to develop a program. And they have to see that they have to have been part of and overseen successful clinical development from sort of the beginning of the end. Because, as I've said before, you know.

It needs to be somebody that is a clinician scientist.

No.

And why that's important here.

Obviously, they need to know how to develop a program and they have had to see they have to have been part of and overseen successful clinical development from sort of the beginning of the yen.

Because as.

I've said before.

Jim Mullen: A-A-A-A-A-A, real clinical development starts in phase four, right after you get your initial approval. And then the reason they need to be the scientist part is this is a highly technical area that's moving fairly quickly, they need to be able to partner very closely with Mark's team as they think about what are the next targets, right, so that we make sure we match up not only targets that are technically doable, but that are clinically relevant, and that we that we can foresee a pathway develop. Yeah, so that's a second.

Real clinical development starts in phase four right.

After you get your initial approval and then the reason they need to be the sciences part of this is a highly technical.

Area, that's moving fairly quickly they need to be able to partner very closely with.

Mark's team as they think about what are the next targets right. So that we make sure we match up.

Not only targets that are technically doable, but better clinically relevant.

And that we that we can foresee a pathway to develop.

Jim Mullen: And lastly, you know, it has to be somebody that sort of knows and has overseen the building and the expansion of a high-functioning medical organization and has had to have that experience. So, you know, I think those are the profiles we're looking for. And for sure, from the people that we're interviewing, we're getting those. So I'm very optimistic; we're going to get a very high-quality candidate here. That is, you know, going to be a real addition to what's now a nicely building team.

So that's the second and lastly has to be somebody that.

That sort of knows and has overseen the building and the expansion of our high function medical organization.

And has had to have that experience. So I think those are the profiles we're looking for.

And for sure from the people that we're interviewing we're getting those so.

I'm very optimistic we're going to get a very high quality.

Canada here.

That is.

Going to be a real addition here to what's now a nicely building team so remember.

Jim Mullen: So remember, you know, Mark has done a great job in not even 12 months, right, Mark, not 12 months yet, of really getting the research focused and getting all of these programs moving, the preclinical and the technology development. The price, the clinical part of it is starting to move much better than it was. And I think we should have had a CMO added to Gilmore's experience, you know, not now that we've really got the team necessary to drive this business for years to come.

Mark has done a great job.

Even 12 months.

Mark not 12 months yet.

Really getting the research focused and getting all of these programs moving to the preclinical and the technology development.

But.

The clinical part of it is start is moving much.

Much better than it was.

I think we had a CMO that into.

Gilmore has experience.

Now, we've really got the team necessary to drive this business for years to come.

Gina Wong: Thank you. Our next question comes from Gina Wong with Barclays. Please present your question. Thank you. This is Tom on behalf of Gina Wong.

Thank you. Our next question comes from Gena Wang with Barclays. Please proceed with your question.

Tom: We have two questions, one for 301 about sickle cell disease and one for 101. Grafton Evaluation, https://www.kenhub.com, O.Y.O.Y.O.Y. No, it's earlier, and, Summation of... Editio Nol, Pediatric Corridor, selection, The number of patients by year end was the first question on 301. Yes, our expectation will be that by year end, we will have dosed two patients. As I indicated earlier, the start of the trial is very carefully monitored, so the first patient has to get at least out to week six before we will be able to confirm that the edited product has engrafted in that patient.

Thank you. This is Tom for Gina on we have two questions. One for spring of one for the sickle cell disease in the windfall one one so for sickle cell disease, given the dosing interval for the safety and engraft and valuation.

<unk> patients can we expect for the year end.

Right and.

101, I know, it's earlier and everything should be data driven but just wanted to get your own assumption.

Sure.

Need additional pediatric cohort expansion to further guide.

The dose selection and trial design for the pivotal trial.

The number of patients by year end with first question on 301.

Yes, our expectation will be that by year end, we will have dose two patients.

As I indicated earlier.

The start of that trial is very carefully monitored the first patient has to get at least add too.

<unk> six before we will be able to confirm that the FSA product I think grasp that patients.

Tom: The immune system is being reconstituted. So that takes us, you know, we've indicated that the first patient will get it by the first half of the year. So that takes us into sort of the third quarter. And then we hope to get at least one more patient dose before the end of the year. And we may have more than that.

Immune system is being reconstituted so that takes us.

We've indicated that the first patient we will get those by the first half of the year. So that takes us into sort of the third quarter and then we hoped together at least one more patient dosed before the end of the year.

Mark Sherman: But what Mark's referring to is what we will have for data that we've discussed is really, I think people can expect to fish, and then your question on 101. Yes, so I think it was the cadence of the additional dosing. So I think we're sticking with the guidance we've given that we expect the pediatric mid-dose cohort to complete dosing by mid-year, and that we will initiate the dosing of the high-dose pediatric patient cohort by year-end.

And we may have more than that.

What Mark's referring to is what we will have for data.

We've discussed is really I think people can expect to finish.

And then your question on 101.

Yes, so I think it with the cadence of the additional dosing we're sticking with the guidance we have given that we expect a pediatric mid dose cohort to complete dosing by mid year and that we will initiate dosing at the high dose pediatric coach.

Patient cohort by year end.

Mark Sherman: And similarly, with the adult expansion cohort, one of those to be initiated and hopefully completed by year-end. Thank you. Our next question comes from Liisa Bayko with Evercore ISI. Please proceed with your question. Hi, I think most of my questions have been answered. I guess just one outstanding question: for Edit 103, you know, as we're thinking about endpoints, and it's, you know, obviously very complex in these ocular diseases, what kind of endpoints make sense to kind of track this disease?

And similarly, with the adult expansion cohort one of those to be initiated hopefully completed by year end.

Thank you. Our next question comes from Lisa <unk> with Evercore ISI. Please proceed with your question.

Mark Sherman: I know, you know, vision loss tends to occur later in life. Is this something that's, you know, you think more easily measured by some of the endpoints that are commonly used or might require some other kind of metrics? Just curious how you're thinking about the regulatory approach here.

Hi, I think most of my questions have been answered I guess, just one outstanding for edit one O three.

As we're thinking about endpoints and it's.

Obviously very complex and these ocular diseases, what kind of endpoints makes.

It makes sense to kind of track this disease I know.

Vision loss tends to occur later in life.

Yes.

When you think more easily measured in by some of the endpoints that are commonly used or might require some.

Some other kind of metrics just curious how you're thinking about that.

Regulatory approach here.

Mark Sherman: Yeah, so it will be our intention to use most of the same exploratory endpoints for the rhodopsin indication as we do for 101. As you probably know, this is a rod photoreceptor disease. The initial decline occurs in peripheral vision, so perimetry will be an ideal way of looking at that. And so right now, we will do all of the things that we've been doing with 2-info-101, which includes monitoring retinal sensitivity, this anatomical evaluation by OCT, and so on, patient-reported outcomes.

Yes, so it will be our intention to use most of the same exploratory endpoints for rhodopsin indication as we did it for 101 as you probably know this is a rod photoreceptor diseases. So the initial decline occurred in peripheral vision.

A predatory will be an ideal way of looking at that and so right now we will do all the things that we've been.

To them for 101, which include monitoring retinal sensitivity this of anatomical evaluation by OCC and so on patient reported outcomes.

Mark Sherman: But all of those types of typical measures we'll take a look at because this is not an indication for which there is an existing therapy. So in this patient population, we'll have to see which of the endpoints is the most responsive to treatment. And some of these endpoints will be a little easier to conduct on these patients because they are coming in with, you know, good eyesight, at least central vision. And you don't have any stigmas and things that make some of the data hard to collect with certain groups of patients that want to learn.

All of those types of typical measures we will take a look at because this is not an indication for which there is a <unk>.

So in this patient population will have to see.

Which of the end places the most responsive to the treatment.

And some of these endpoints will be a little easier to conduct on these patients because they are coming in with.

Yeah.

Good eyesight at.

At least a central vision.

And you don't have the stigmas in things that make some of the data hard to collect with certain groups of patients.

Liisa Bayko: Thank you. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Goodbye. BF-WATCH TV 2021

Thank you ladies and gentlemen, this concludes today's presentation.

Thank you once again for your participation you may now disconnect.

Goodbye.

Okay.

[music].

Yes.

Yes.

And then.

[music].