Q2 2021 Editas Medicine Inc Earnings Call

Good morning, and welcome to advertise medicine second quarter, 2 down from 21 conference call.

Operator: Good morning, and welcome to Editas Medicine's second quarter 2021 conference call. All participants are now in a listen-only mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded at the company's request.

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 Companys request.

I would now like to turn the call over to Ron Wall neighbor Investor Relations at the top.

Ron Woldaber: I would now like to turn the call over to Ron Woldaber, Investor Relations at Editas Medicine. Thank you, Daryl.

Thank you Daryl and good morning, everyone and welcome to our second quarter 2021 Conference call earlier. This morning, we issued a press release, providing our financial results and corporate updates for the second quarter of 2021.

Ron Woldaber: Good morning, everyone, and welcome to our second quarter 2021 conference call. Earlier this morning, we issued a press release providing our financial results and corporate updates for the second quarter of 2021. A replay of today's call will be available on the investors section of our website approximately two hours after its completion.

Today's call will be available on the investors section of our website approximately 2 hours. After its completion after our prepared remarks, we will open the call for Q&A as a reminder, various remarks that we make during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the safe.

Ron Woldaber: After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC.

Harbor provisions under the private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on form 10-K, which is on file with the.

SEC. 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 <unk>.

Ron Woldaber: 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.

Our Chief Executive Officer, Jim Mullen.

Thanks, Ron and good morning, everyone on.

Jim Mullen: Thanks Ron, and good morning everyone. I'm joined today by several members of the Editas executive team, including Mark Sherman, our new Chief Scientific Officer, Lisa Michaels, our Chief Medical Officer, and Michelle Robertson, our Chief Financial Officer. I want to start off by providing some highlights from the second quarter and reviewing our upcoming milestones. Editas has had a strong first half of the year with excellent momentum across our platforms and lead programs.

I'm joined today by several members of the edit tests executive team, including Mark Sherman, Our new Chief Scientific Officer, Lisa Michaels, our Chief Medical Officer, and Michelle Robertson, our Chief Financial Officer.

I wanted to start off by providing some highlights from the second quarter and reviewing our upcoming milestones.

Texas had a strong first half of the year with excellent momentum across our platforms and lead programs.

Jim Mullen: The EDIT 101 brilliance trial for LCA-10 is proceeding very well, with the Independent Data Monitoring Committee recently endorsing enrollment of the first of two planned pediatric cohorts, and we've also started enrolling patients in the adult high-dose cohort. We are also expected to share initial clinical data from the EDIT 101 trial this September. This will mark the company's first ever clinical data readout. The ruby study of edit 301 for sickle cell disease is screening patients, and we remain on track to begin dosing by the end of the year.

Edit 1 on 1 brilliance trial for LCA 10 is proceeding very well with the independent data monitoring Committee recently endorsing enrollment from the first of 2 planned pediatric cohorts and we've also started enrolling patients in the adult high dose cohort.

We are also expected to share initial clinical data from the other 1 on 1 trial. This September this will mark the company's first ever clinical data readout.

The Ruby study of edit 301 for sickle cell disease is screening patients and we remain on track to begin dosing by the end of the year.

In the pre I N D work for edit 301 in beta thalassemia is progressing and we remain on track to file the R&D before year end.

Jim Mullen: And the pre-IND work for EDIT 301 and beta thalassemia is progressing, and we remain on track to file the IND before year F. Additionally, additional data supporting the unique properties of our proprietary Cas12a enzyme were recently published in Nature Communications, and we plan to present new data on our multi-transgene knock-in proficiency at upcoming Cold Spring Harbor meetings.

Additional data supporting the unique properties of our proprietary cash 12, a M zone was recently published in nature Communications.

<unk> planned to present, new data on our multi transgene, Nokia and proficiency upcoming Cold Spring Harbor meeting.

These accomplishments further support the incredible potential of our gene editing platform.

Jim Mullen: These accomplishments further support the incredible potential of our gene editing platform. Our manufacturing capabilities for LEAD programs have advanced nicely, and we're ready to manufacture all clinical supplies for the RUBY trial. We continue to progress our oncology programs, including our iPSC-derived NK cell program that we are advancing in preclinical studies. And finally, we continue to make headway on our remaining preclinical programs, including ocular diseases. Additional updates on those programs will be provided later this year.

Our manufacturing capability for our lead programs have advanced nicely and we are ready to manufacture all from suppliers for the Ruby trial.

We continue to progress our oncology programs, including our Ips derived NK cell program that we're advancing in preclinical studies.

And finally, we continue to make headway on our remaining preclinical programs, including ocular diseases additional updates on those programs will be provided later this year.

On the leadership side, we had several important announcements last quarter, Dr. Mark Shearman joined the company as our new Chief Scientific Officer, Mark is an experienced executive who has brought multiple programs from aviation into and through the clinic and has led numerous successful partnerships. He brings an extensive track record of achievements.

Jim Mullen: On the leadership side, we had several important announcements last quarter. Dr. Mark Sherman joined the company as our new chief scientific officer. Mark is an experienced executive who has brought multiple programs from ideation into and through the clinic and has led numerous successful partners. He brings an extensive track record of achievements in drug discovery and clinical development across multiple therapeutic modalities. Mark is two months into his new position, and I'm pleased to have him on the call with us today. We're also delighted that Dr. Qi Li joined us as Chief Regulatory Officer. Qi brings an extensive resume guiding over 30 development programs through the regulatory process.

In drug discovery and clinical development across multiple therapeutic modalities.

Mark is 2 months into his new position on we're pleased to have him on the call with us today.

We're also delighted that Dr. Qi Li joined US as Chief regulatory officer. She brings an extensive resume guiding over 30 development programs through regulatory processes, including multiple U S and global submissions and he will be a critical part of our leadership team as we advance our pipeline.

Jim Mullen: Including multiple US and global submissions, and he will be a critical part of our leadership team as we advance our pipeline. And finally, we're pleased to announce the promotion of Bruce Eaton to our executive team as chief business officer. Bruce has been involved with Editas in various capacities since 2015, starting as a consultant, then a research collaborator, and as a full-time leader of our Boulder site. He brings a successful track record, including more than 30 years of scientific operations, business development, and corporate strategy experience in both public and private companies.

And finally, we're pleased to announce the promotion of Bruce eating to our executive team as Chief business Officer, Bruce has been involved with edit to us in various capacities since 2015, starting as a consultant than a research collaboration collaborator and as a full time leader of our Boulder site.

He brings a successful track record, including more than 30 years of scientific operations business development and corporate strategy experience in both public and private companies.

Jim Mullen: He has a deep understanding of biochemistry and biophysics for the innovation and development of medicines. Bruce's expertise at the executive table will have a critical impact on how Editas continues to evolve. So overall, I'm extremely happy with the progress through the first half of the year, and with our expanded executive team, I have the utmost confidence that we have the right people in place to lead Editas to the next phases of the company's growth and towards long-term success. With that, let me turn the call over to Mark for his first earnings call as Editas Chief Scientific Officer. Mark.

Deep understanding of biochemistry and biophysics for the innovation and development of medicines Bruce expertise from the executive table will have a critical impact on how out of tests continues to evolve.

So overall I'm extremely happy with the progress through through the first half of the year and with our expanded executive team I have utmost confidence we have the right people in place fleet at a test of the next phases of the company's growth and towards long term success.

With that let me turn the call over to Mark for his first earnings call with editor editor as Chief Scientific Officer Mark.

Thank you Kim and thank each and everyone dialing in.

Mark Sherman: Thank you, Jim, and thank you to everyone dialing in. So I'm thrilled to have joined Editas and to have the opportunity to lead an extremely experienced and dedicated group of researchers and scientists. My short time at the company has only reinforced my excitement about working with Jim, the rest of the leadership team, and the exceptional people throughout the organization. To give you a bit of background on myself, I have almost 30 years of drug discovery and development experience.

I'm joined at a test and to have the opportunity to lead an extremely experienced and dedicated group of researchers and scientists.

In my short time at the company has only reinforced my excitement and working with him the rest of the leadership team on the exceptional people throughout the organization.

To give you a brief background about myself I have almost 30 years from discovery and development experience.

Mark Sherman: I've been fortunate enough to be a part of advancing around 15 drugs into clinical development. I began my career in academia and then moved to the corporate R&D side, where I conducted research into Alzheimer's disease and other neurodegenerative disorders as well as autoimmune diseases.

Fortunate enough to be a part of advancing Ryan 15 drugs into clinical development.

I began my career in Academia, and then move to the corporate R&D side, where I conducted research into Alzheimers disease.

The neuro degenerative disorders, as well as autoimmune diseases.

So the last 6 years I was the CFO applied genetic technologies Corporation, developing AAV gene therapy, mostly for orphan diseases.

Mark Sherman: For the last six years, I was the CSO at Applied Genetic Technology Corporation, developing AAV gene therapy, mostly for ocular diseases. The impressive technology platform and the potential breakthrough capability of gene editing technology in the regenerative medicine space are what brought me to Editas. Most of my scientific work revolves around ophthalmology, immunology, and neurology, all key areas of development for this company.

The impressive technology platform and the potential breakthrough capability of gene editing technology in the regenerative medicine space is what brought me to IHS.

Of my scientific work as it revolves around ophthalmology immunology and neurology.

All key areas of development for this company.

You'll be able to apply it just has to be the best technological breadth towards my skills and expertise is truly a remarkable opportunity.

Mark Sherman: To be able to apply Editas' vast technological breadth to my fields of expertise was truly a remarkable opportunity. I've always been intrigued by new aspects of science or technology that can improve the likelihood of being successful in drug development or which open new treatment avenues for patients who otherwise might not have other options. Editas' gene editing platform has the potential to do both of those things. It allows us to address certain diseases not easily addressed with other treatments while also developing differentiated new medicines. This company has what I believe to be an unparalleled capability to edit the human genome, and I'm excited to be part of its mission to transform medicine. So, two examples illustrate this point.

I've always been intrigued by new aspects of sides of technology that can improve the likelihood of being successful in from development, well, which opened new treatments avenues for patients who otherwise might not have other options.

That is tested gene editing platform has the potential from both of those.

That is to address certain diseases.

On the addressed with other treatments, while also developing differentiated new medicine.

This company has what I believe to be on unparalleled capabilities to edit the human genome and I'm excited to be part of its mission to transform medicine.

So 2 examples illustrate this point firstly.

Mark Sherman: Firstly, the recent publication in Nature Communications that Jim mentioned earlier, detailing an engineered AS-Cas12a nuclease, which we believe to be a significantly advanced enzyme, with editing efficiency approaching 100% across sites in multiple cell lines and high on-target specificity. This engineered nuclease alleviates many off-targeted editing concerns often observed with Cas9 enzymes, consequently leading to an improved safety profile and making it This also greatly reduces the process chemistry challenges associated with the manufacturing of high quality guide RNAs.

Publication in nature Communications that Tim mentioned earlier can you tailing in engineered a S counts 12 day, new P. A which we believe to be a significantly advanced enzyme with editing efficiency are approaching 100% across sites in multiple cell lines and high on target specificity.

This engineered nuclease alleviate many off target in Edison concerns often observed with past 9 enzymes, Consequently, leading to an improved safety profile and making it ideal for complex therapeutic gene editing applications.

It also greatly reduces the process chemistry challenges associated with the manufacturing of high quality Guide Rnas.

This proprietary true could be an important step forward in the development of novel therapies.

Mark Sherman: This proprietary tool could be an important step forward in the development of novel therapies for serious genetic diseases such as sickle cell disease, as well as provide a significant opportunity to create engineered cell therapies for cancer. Secondly, the development of SLEEK technology, which stands for Selection by Essential Gene Exon Knock-In. We're excited to announce that this new gene editing strategy enables us to achieve nearly 100% knock-in of functional transgene cargoes at specific locations in the genome.

Genetic diseases, such as sickle cell disease as.

As well as providing significant opportunities to create engineered cell therapies for cancer.

Secondly, the development of Snake technology, which stands for selection by essential gene Exxon knock him well.

We're excited to announce that this new gene editing strategy enables us to achieve nearly 100% knock in a functional transgene cargos specific location in the genome.

We believe that this has broad applications not only for substantially improving current gene editing cell medicine like car T and car NK cell therapies.

Mark Sherman: We believe that this has broad applications not only for substantially improving current gene editing cell medicines like CAR-T and CAR-NK cell therapies, but beyond those applications, it could have immense potential in protein replacement strategies, for example. Details of this exciting technology will be shared later this month in an oral presentation at the Cold Spring Harbor Laboratories conference. So, having been with Editas for about two months now, I've outlined my high-level priorities as CFO, which are, firstly, to continue to advance our current in vivo, ex vivo, and cell-based therapy platforms; we progress our in vivo gene editing ophthalmology programs and further strengthen our existing preclinical pipeline; and, expand our world-class gene editing capabilities and the delivery technologies they rely upon

On those applications it could have immense potential in protein replacement strategies for example.

Details on this exciting technology will be shipped later this month in an oral presentation at the Cold Spring Harbor Laboratory conference.

So having been with other tests for about 2 months now I pipeline my high level proxies as CFO.

Chop Circinate continue to advance our current in vivo ex vivo in cell based therapy platforms.

She progressed in vivo gene editing and loyalty programs and further strength in our existing preclinical pipeline.

Expand our world class gene editing capabilities and the delivery technologies they rely upon.

And finally to continue to grow and develop the scientific base and builds upon our research and development team that is second to none.

Mark Sherman: And finally, to continue to grow and develop the scientific base and build upon a research and development team that is second to none. With this impressive technology and world-class talent at Editas, I'm excited to discover and develop revolutionary new medicines to help people living with serious diseases. With that, I'd like to turn it over to Lisa.

With this impressive technology and World class talent and other tests I'm excited to discover and develop revolution, new medicines to help people living with serious diseases.

With that I'd like to turn it over to Lisa.

Thank you Martin I wanted to just simply say I am excited to have you join us as part of our team.

Lisa Michaels: Thank you, Mark, and I wanted to simply say I'm excited to have you join us as part of our team. As part of that, I'd like to start with an update on the BRILLIANCE trial for EDIT 101 for the treatment of LCA10. Last quarter, we completed dosing of the adult mid-dose cohort, and as Jim mentioned, we met with the study's independent data monitoring committee to review the safety data from the adult low-dose and mid-dose cohorts. The IDMC agreed with EDITAS that we could begin enrolling the first of the two planned pediatric cohorts.

Okay. That's part of it I'd like to start with an update on the brilliance trial for edit 1 on 1 for the treatment of LCA 10 last quarter, we completed dosing of the adult net dose cohort and as Jim mentioned, we met with the study's independent data monitoring Committee to review the safety data from the adult low dose and that dose cohorts. The I D. M. C agreed with that a task that we could begin a whole linked the first of the 2.

<unk> pediatric cohorts.

Lisa Michaels: This is an important step in the trial since LCA-10 is an early-onset retinal degenerative disease that results in vision loss and blindness at an early age. We believe that younger participants in the study could provide the best opportunity to achieve the greatest magnitude of clinical benefit. As a reminder, LCA-10 is the most common cause of inherited childhood blindness, and it affects three out of every 100,000 children around the world, so new therapeutic options are urgently needed.

It is an important step in the trials LCA 10 is an early onset retinal degenerative disease, which results in vision loss and blindness, adding early age and we believe that younger participants on this study could provide the best opportunity to achieve the greatest magnitude of clinical benefit.

As a reminder, L. T E. Com is the most common cause of inherited childhood blindness and in fact 3 out of every 100000 children around the world. So new therapeutic options are urgently needed and we continue to believe that a single administration would be preferred over a chronic dosing regimen by clinicians parents and the patient community.

Lisa Michaels: We continue to believe that a single administration would be preferred over a chronic dosing regimen by clinicians, parents, and the patient community. In addition to enrolling patients in the pediatric mid-dose cohort, we're also enrolling patients in the adult high-dose cohort. Those cohorts are planned to have four patients each, and we expect a complete dosing of the two-dose groups in the first half of next year. We intend to present initial clinical data from EDIT 101 at the International Symposium on Retinal Degeneration in September.

In addition to enrolling patients in the pediatric mid dose cohort. We're also enrolling patients in the adult high dose cohort those cohorts are planned to have for patients each and we expect to complete dosing of the 2 dose groups in the first half of next year.

We intend to present initial clinical data from edit 101 at the international Symposium at retinal degeneration. In September now. This is an exciting milestone as it will be the first time that edit touchwood presented clinical data at a meeting the data will include safety and evaluation of the measures of biological activity from the 6 adult patients that have been treated in the first.

Lisa Michaels: This is an exciting milestone, as it will be the first time that EDITAS will present clinical data at a meeting. The data will include safety and evaluation of the measures of biological activity from the six adult patients that have been treated in the first two-dose cohort. Now, the primary objective of the study is safety. Our goal is to develop a safe treatment that is not limited by dose-limiting inflammatory reactions, does not induce abnormal changes in retinal anatomy, and most importantly, does not result in loss of vision that the patient may experience. Our analysis of this early data set will consider all the observations across the multiple measurements that have been collected and are currently being collected, which will be shown at this symposium.

2 dose cohorts.

Now the primary objective of this study is safety our goal is to develop a safe treatment. That's not limited by dose limiting inflammatory reactions does not induce abnormal changes retinal anatomy and most importantly does not result in loss of vision that the patient may have.

Our analysis of this early dataset will consider all the observations across the multiple measurements that have been collected and are currently being collected which will be shown at the suppose young representative endpoints could impart would provide evidence of productive editing may include measurement on from Atmel responses to light as well as clinically relevant outcomes such as reproducible improves.

Lisa Michaels: Representative endpoints that could provide evidence of productive editing may include measurement of retinal responses to light, as well as clinically relevant outcomes such as reproducible improvement in patient-reported visual acuity or in the ability to maneuver around objects at different levels of illumination. Following the main study protocol, we will monitor patients for both safety and for secondary clinical endpoints every three months for a year and continue follow-up for two additional years. Collectively, observing patient trends at each planned dose level over time will validate EDIT101 as a viable medicine for LCA-10 and also help de-risk our subsequent ocular programs.

Net and patient reported initial acuity or in the ability to maneuver around objects at different levels of elimination.

Following the main study protocol, we will monitor patients for both safety and for secondary clinical endpoints every 3 months free year and continue follow up for 2 additional years.

Collectively observing patient trends at each plant dose level over time will validate edit 1 on 1 as a viable medicine for LCA 10, and also help derisk. Our subsequently get my programs.

Very happy with how this trial's progress during this year and we aim to maintain the same pace for enrolling and dosing patients in the next 2 cohorts.

Now moving to our ex vivo programs, specifically edit 301.

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As we've said before we believe that edit 301 has the potential to be a differentiated and important medicine for sickle cell disease and beta thalassemia patients. Our phase <unk> study is that it's been on 1 is active in screening patients and we continue to add 12 sites.

Lisa Michaels: I'm very happy with how this trial has progressed during this year, and we aim to maintain the same pace for enrolling and dosing patients in the next two cohorts. Now, moving to our ex vivo programs, specifically EDIT 301, as we've said before, we believe that EDIT 301 has the potential to be a differentiated and important medicine for sickle cell disease and beta thalassemia patients. Our Phase 1-2 Ruby study of EDIT 301 is active in screening patients, and we continue to add trial sites.

Our CMC group is ready to support us with all clinical manufacturing require for this phase of the study.

We also have received an approved clinical trial application from health, Canada, which will expand the number of potential study sites and we remain on track to begin patient dosing by the end of 'twenty 'twenty 1.

Additionally, we also remain on track to follow on investigational new drug application for edit 301, and beta thalassemia by the year end.

Providing further preclinical support of the potential benefits of edit 301, we presented additional data at the European Hematology Association Congress in June.

Lisa Michaels: Our CMC group is ready to support us with all clinical manufacturing required for this phase of the study. We have also received an approved clinical trial application from Health Canada, which will expand the number of potential study sites, and we remain on track to begin patient dosing by the end of 2021. Additionally, we also remain on track to file our investigational new drug application for EDIT 301 in beta thalassemia by year end.

This data shows that editing at the beta globin locus using our proprietary cash 12 day enzyme results in a highly robust fetal hemoglobin induction erythroid progenitor cells.

Importantly, this occurred at a high level of specificity and no detection of off target editing.

And at 3 O..1 mimics a naturally occurring mutation associated with hereditary persistence of fetal hemoglobin as opposed to other approaches to target B C. L 11 day.

Lisa Michaels: Providing further preclinical support of the potential benefits of EDIT 301, we presented additional data at the European Hematology Association Congress in June. This data shows that editing at the beta-globin locus using our proprietary Cas12a enzyme results in highly robust fetal hemoglobin induction in erythroid progenity cells. Importantly, this occurred at a high level of specificity and with no detection of off-target editing. EDIT 301 mimics a naturally occurring mutation associated with hereditary persistence of fetal hemoglobin, as opposed to other approaches that target BCL11A.

This approach in the present day to support our view that edit 301 differentiates itself from other programs through its highly efficient editing and specificity, which we anticipate will result in optimal safety and efficacy.

By demonstrating robust and sustained fetal hemoglobin expression with those short and long term safety. We aim to have a best in class medicine to treat sickle cell disease, and beta thalassemia that will hopefully lead to longer lifespan for these patients.

Our clinical operations teams for edit 1 on 1 or 301 have already been working very tiresome to move these programs forward and I truly believe that the sooner we can get on medicines to patients sooner, we can deliver on our promise to transform people's lives.

Lisa Michaels: This approach and the presented data support our view that EDIT 301 differentiates itself from other programs through its highly efficient editing and specificity, which we anticipate will result in optimal safety and efficacy. And by demonstrating robust and sustained fetal hemoglobin expression with both short and long-term safety, we aim to have a best-in-class medicine to treat sickle cell disease and beta thalassemia that will hopefully lead to longer lifespans for these Our clinical operations teams for EDIT101 and EDIT301 have already been working very tirelessly to move these programs forward.

And with that I'd like to turn things over to Michelle to briefly run through the financial results Michelle.

Thanks, Lisa and good morning, everyone.

I'd like to refer you to our press release issued earlier today for a summary of our financial results for the second quarter and I'll take this opportunity to briefly review a few highlights from.

During the first half of this year. So last year total operating expense increased by approximately $25 million.

This was primarily related to an increase in stock based compensation of $14 million as well on the $9 million success payment due under 1 of our institutional license that was expense neutral during the first quarter of this year.

The remaining increase is driven by our expanding clinical regulatory and manufacturing efforts to support both our brilliant and Ruby trial and the pre I N D work for edit 301 for beta thalassemia.

Lisa Michaels: And I truly believe that the sooner we can get our medicines to patients, the sooner we can deliver on our promise to transform people's lives. And with that, I'd like to turn things over to Michelle to briefly run through the financial results.

Quarter over quarter total operating expenses were 56 million in the second quarter compared to 63 million for Q1, excluding stock based compensation of 12 million balance in Q1 and $14 million in Q2, and the $9 million cash payment in Q1 operating expenses were essentially flat in the first 2 quarters of this year.

Michelle Robertson: Thanks Lisa and good morning everyone. I'd like to refer you to our press release issued earlier today for a summary of our financial results for the second quarter, and I'll take this opportunity to briefly review a few highlights. Comparing the first half of this year to last year, total operating expenses increased by approximately $25 million. This was primarily related to an increase in stock-based compensation of $14 million as well as a $9 million success payment due under one of our institutional licenses that was extensively full during the first quarter of this year.

It helps us balance sheet and cash position remains very strong our cash balance as of June 30th $698 million compared to $723 million at the end of Q1.

Capital will allow us to execute on our strategy to progress our clinical programs and further develop our pipeline and continue to build our internal manufacturing capability. We anticipate that this cash position will fund our operations well into 2023.

With that I'll hand, it back to Jim.

Yeah.

Thank you Michelle the first half of this year has been very productive per editors and the gene editing community. We continue to see important accomplishments from the field, including the successful demonstration of in vivo gene editing. This milestone reflects ongoing maturation of this novel therapeutic modality immense potential for the technology.

Michelle Robertson: The remaining increase is driven by our expanding clinical, regulatory, and manufacturing efforts to support both our Brilliance and Ruby trials and the pre-IND work for EDIT301 for beta thalassemia. Quarter over quarter, total operating expenses were $56 million in the second quarter compared to $63 million in Q1. Excluding stock-based compensation of $12 million in Q1 and $14 million in Q2, and the $9 million success payment in Q1, operating expenses were essentially flat in the first two quarters of this year.

It supports the fundamental notion that the gene editing medicine administered directly to people, who can have a clinical benefit and more importantly, this marks a monumental milestone for patients living with genetic diseases.

The potential power of CRISPR gene editing is a major stride forward from the genomic field on people who were trying to help.

I've said on a previous call. It's truly a remarkable time to be involved in gene editing I believe we have an obligation to utilize this once in a generation technology to develop the best possible true treatments for patients and promote progress within the scientific and medical communities.

Michelle Robertson: Editas' balance sheet and cash position remain very strong. Our cash balance as of June 30th was $698 million, compared to $723 million at the end of Q1. This capital will allow us to execute on our strategy to progress our clinical programs, further develop our pipeline, and continue to build our internal manufacturing capabilities. We anticipate that this cash position will fund our operations well into 2023. With that, I'll hand it back to Jim.

We thank all of you for your support and interest from the company and with that we'll open it up to questions and answers operator.

Thank you we will now be conducting a question and answer session. If you would like to ask a question. Please press star 1 on your telephone keypad.

A confirmation tone will indicate your line is in the question queue. You May press star 2 if he would like to remove your question from next year for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star keys, 1 moment. Please while we poll for your questions.

Jim Mullen: Thank you, Michelle. The first half of this year has been very productive for Editas and the gene editing community. We continue to see important accomplishments in the field, including the successful demonstration of in vivo gene editing. This milestone reflects ongoing maturation of this novel therapeutic modality and immense potential for the technology. This supports the fundamental notion that a gene-editing medicine administered directly to people can have a clinical benefit. And, more importantly, this marks a monumental milestone for patients living with genetic disease.

Yeah.

Our first questions come from the line of Gena Wang with Barclays. Please proceed with your question.

Thank you for taking my questions.

I have 2 questions. The first 1 is regarding the LCA.

Program on.

I think you mentioned the primary endpoint on like maybe a clinical imagine you were a share just wondering Mike you mentioned visual acuity wondering first of all could you also share mobility course score and then how should we look at those in the context of natural history, when you share the data.

Jim Mullen: Validating the Potential Power of CRISPR Gene Editing is a major stride forward for the genomic field and people who we are trying to help. As I've said on previous calls, it's truly a remarkable time to be involved in gene editing. I believe we have an obligation to utilize this once-in-a-generation technology to develop the best possible treatments for patients and promote progress within the scientific and medical communities. We thank all of you for your support and interest in the company. And with that, we'll open it up to questions and answers. Operator.

And the second question is regarding box wheel, 1 for sickle cell disease, just wondering a hamster the partial clinical hold already resolved them on.

When you see on the on track dosing, our first patients do you expect that wont be giving yourself the pie before yeah.

Lisa are you there.

Hi, pardon I'm, Jean I apologize I was on mute I was trying not to cough into my microphone.

Operator: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question.

So to your first question Gena regarding what's going to be reported in Rd.

Added for the edit 1 on 1 program moving into the RT 2021 meeting so I've already summarized the meeting is that the primary outcome on this study really remains safety and dose limiting toxicity. So the data on the cumulative safety data of the patients had been dosed in the first 2 whole courts will definitely be presented at that meeting.

Operator: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Operator: Please be sure to pick up your handset before pressing the star keys. One moment, please, while we poll for your questions. Our first questions come from the line of Gina Wang with Barclays. Please proceed.

But I want to remind people is that this is still on ongoing study moving forward over time and that we collect a quite large number of observations with 2 primary goals. The first 1 is for the purposes of being able to demonstrate that editing has actually occurred in the ice and that would be a very interesting proof of concept for us to share regarding any potential change instead of <unk>.

Huidong Wang: Thank you for taking my questions. I have two questions.

Huidong Wang: The first one is regarding the ALCA 10 program. I think you mentioned the primary endpoint, or the clinical measurement you will share. Just wondering, you mentioned visual acuity. Wondering, first, will you also share the mobility core score? And then, how should we look at this in the context of a natural history when you share the data?

<unk> either in the anatomy of the retina, where also reflections of responses from the retina to light.

The second 1 regarding the efficacy outcomes that you're that you've.

Huidong Wang: And the second question is regarding the 3.0.1 for sickle cell disease. Just wondering, has the FDA partial clinical hold already been resolved? When you say on-track for those in the first patient, do you expect that will be resolved by before year end?

2 such as B C V. A and also for being able to maneuver in the base I want to remind everybody. It's still quite early in the trial on the longest patient at the mid dose cohort was only does to January so we're still collecting data prospectively. It's certainly our intent to look across the entire range of measurements in each individual.

Huidong Wang: You expect that to be resolved by the four-year end.

Lisa Michaels: Liisa, are you there? I pardon myself. I'm.

Lisa Michaels: I pardon, Gina, I apologize. I was on mute. I was trying not to cough into my microphone.

Lisa Michaels: So to your first question, Gina, regarding what's going to be reported in RD-301 for the EDIT-101 program moving into the RD-2021 meeting. So I've already summarized the meeting, and the primary outcome of the study really remains safety and dose-limiting toxicity. So the data and the cumulative safety data of the patients who've been dosed in the first two cohorts will definitely be presented at that meeting. But what I want to remind people is that this is still an ongoing study moving forward over time and that we collect quite a large number of observations with two primary goals.

Patients moving forward and that we will be sharing a at least on data that will be comprehensively looking at the possibility of being able to show both the efficacy as well as clinical outcomes at the study beyond that I'm not yet prepared to give you more detail.

To the second question.

With 301.

Just kind of remind everybody it's not a it's not a complete clinical hold it as a partial hold basically in order to be able to validate the clinical assays that we're using to correlate dosing to clinical efficacy. It does not interfere at all with our ability to move forward, we are able to dose patients in the trial in an ongoing fashion as is already out.

Lisa Michaels: The first one is for the purposes of being able to demonstrate that editing has actually occurred in the eyes, and that would be a very interesting proof of concept for us to share regarding any potential changes that have occurred either in the anatomy of the retina or also reflections of responses of the retina to light.

Did the protocol and so it's actually having no impact on our ability to move forward, we will need to have some patient data to correlate on in order to be able to lift the hold with the agency later on.

Thank you.

Yeah.

Lisa Michaels: The second one regarding the efficacy outcomes that you've alluded to, such as BCVA and also for being able to maneuver in the maze. I want to remind everybody that it's still quite early in the trial. The longest patient in the mid-dose cohort was only dosed in January, so we're still collecting data prospectively. It's certainly our intent to look across the entire range of measurements in each individual patient moving forward, and we will be sharing at least data that will be comprehensively looking at the possibility of being able to show both efficacy as well as clinical outcomes in the study.

Thank you. Our next question comes from the line of Matthew Harrison with Morgan Stanley. Please proceed with your questions.

Good morning give you on this has cost us on for Matthew 1 question from Boston and D..2 on no..1 can you please remind us what the stopping type pediatric the high dose cohort.

So the stopping so the stopping criteria is very clear across all different dose cohorts and that is basically the dose limiting toxicity. This would include inflammatory responses that cannot be controlled with the use of steroids and would also include any potential loss of visual acuity on any patient that's something that's measured.

Yeah.

Thank you.

Okay.

Thank you. Our next question will come from the line of Phil Nadeau with Cowen <unk> Company. Please proceed with your questions.

Lisa Michaels: Beyond that, I'm not yet prepared to give you more detail. On the second question about 301, I just kind of remind everybody that it's not a complete clinical hold; it is a partial hold, basically, in order to be able to validate the clinical assays that we're using to correlate dosing to clinical efficacy. It does not interfere at all with our ability to move forward. We are able to dose the patients in the trial in an ongoing fashion as already outlined in the protocol, and so it's actually having no impact on our ability to move forward. We will need to have some patient data to correlate in order to be able to list the agency later on.

Good morning, Congrats on the progress on follow up question from me on on 1 on 1 in the in your corporate presentation, you mentioned secondary efficacy endpoints and 1 on ones trial, including Mac with thickness Electroretinogram and put people on a true it.

It sounds like you're going to use those to figure out if there's sufficient anything going on in the retina.

Not all that familiar with those measures can you give us some idea of what changes you'd need to see to have confidence that there's a sufficient amount of editing.

In vivo.

There could be ultimately improvements in visual acuity I know youre going to a patient population.

Gregory Allen Harrison: Thank you. Our next questions come from the line of Matthew Harrison with Morgan Stanley. Please proceed with your question. Good morning, everyone. This is Kostas Son on behalf of Matthew.

Okay. So that's basically the way I have been dividing it up is and I think you summarized it actually quite well. The first 1 is a lot of electrophysiological measurements as well as merit physiological responses to either different colors of light pupil every responses to light being shined in the eyes. Because these patients do tend to have either reduced or very sluggish respond.

Gregory Allen Harrison: One question from us on Edit 101. Can you please remind us what the stopping criteria are in the high-dose cohort? So the stopping, so the stopping criteria.

Lisa Michaels: So the stopping criteria are very clear across all different dose courts, and that is basically the dose-limiting toxicity. This would include inflammatory responses that cannot be controlled with the use of steroids and would also include any potential loss in visual acuity in any patient who has something that's lost.

If we were to see consistent changes moving forward in any of those measures that at least would be a signal to us that editing is taking place in the back of the eye.

This is sort of my indirect way of measuring it without the ability to actually measure the protein that's being created on the I'm moving forward as to the clinically relevant end points I would agree with those that say that basically are definitely those things that impact the patient's ability to function such as visual acuity or also the ability to maneuver around the mace would be.

Philip M. Nadeau: Thank you. Our next questions come from the line of Phil Nadeau with Coway & Company. Please proceed with your questions.

Philip M. Nadeau: Good morning, and congratulations on the progress. A follow-up question for me on 101. In your corporate presentation, you mentioned secondary efficacy endpoints in 101's trial, including macula thickness, electroretinogram, and pupillometry. It sounds like you're going to use those to figure out if there's sufficient editing going on in the retina. I guess I'm not all that familiar with those measures. Can you give us some idea of what changes you'd need to see to have confidence that there's a sufficient amount of editing? In vivo, could there ultimately be improvements in visual acuity in a young enough patient population?

The approvable endpoints on the ones that we bring most value to the patient perf.

Perfect and then.

Another follow up question on 301, and that's to the last question. It sounds like you'll need some clinical data to validate the assay is necessary to remove the clinical hold do you have a definitive agreement with FDA on that.

Amount.

Clinical data that's necessary for the number of patients or or duration.

So at the moment, we have at least proposed a matrix in order to be able to show how that across multiple different measures to show consistency is the product being given to the patients on.

Plan is to actually be able to present that to the agency. Once we have data to support it perfect. Thanks for taking our questions.

Okay.

Thank you. Our next question will come from the line of yarn and Xu with Wells Fargo. Please proceed with your question.

Lisa Michaels: Okay, so basically, the way I've been dividing it up is, and I think you summarized it actually quite well, the first one is a lot of electrophysiologic measurements as well as, you know, using physiologic responses to either different colors of light or pupillary responses to light being shined in the eyes because these patients do tend to have either reduced or very sluggish responses. If we were to see consistent changes moving forward in any of those measures, that would at least be a signal to us that editing is taking place in the back of the eye.

Thanks for taking my questions. So on the Biomarkers for lack of from better worse on.

The the several measures that you will.

Investigate to see to understand whether there's editing do we know that those measures are do they.

Range by simply by sub retinal injection.

Injection for example, or do.

Do they change based on a placebo type response do we have some understanding of how reliable are those the biomarkers are.

Lisa Michaels: This is sort of my indirect way of measuring it without the ability to actually measure the protein that's being created in the eye moving forward. As to the clinically relevant endpoints, I would agree with those that say that basically those things that impact a patient's ability to function, such as visual acuity or also the ability to maneuver around the maze, would be the approvable endpoints and the ones that would bring the most value to the patient.

I think so.

And I invite mark to jump in if he feels like he wants to add color to it but I think 1 of the most important things for US is first of all the biologic markers are basically physiologic responses. So these are purely objective measures that we can actually measure physiologic changes that can take place.

CERN about placebo is that it is on blinded both to treat her invitation those snow, which I has been treated and this is the primary reason why we're actually focusing on reproducibility of onetime measurement that shows a significant change in vision is not going to be enough for us it really needs to be able to be sustained across multiple different measures over time.

Philip M. Nadeau: Perfect. And then another follow-up question on 301. And the answer to the last question, it sounds like you'll need some clinical data to validate the assays necessary to remove the clinical hold. Do you have a definitive agreement with the FDA on the amount of clinical data that's necessary, the number of patients, or duration?

Yeah, and if I could add thanks for the question Yaron.

Lisa Michaels: So at the moment, we have at least proposed a matrix in order to be able to show how the product across multiple different measures to show consistency of the product being given to the patients. The plan is to actually be able to present that to the agency once we have data to Perfect. Thanks for taking our questions.

No from covering other companies that are administering sub retinal a b.

There is a possibility of slight changes in and around the surgical procedures that lesson and reestablish it attaches.

I, usually tracked by comparing the untreated eye and interestingly as I pointed out overtime. They generally settle down within a couple of weeks and so.

Yanan Zhu: Thank you. Our next questions come from the line of Yanan Zhu with Wells Fargo. Please proceed with your question.

All of that day that gets collected on track and you know the intention is to.

Yanan Zhu: Thanks for taking my questions. So on the biomarkers, for lack of better words, the several measures that you will investigate to see whether there's editing, do we know that those measures change simply by subretinal injection, for example, or do they change based on a placebo-type response? Do we have some understanding of how reliable those biomarkers are?

Show over time, a real treatment effect, that's separate from a surgical or any other intervention on related change.

Got it that's very helpful and for you.

You mentioned the longest a photo op Inc.

Net those cohort is since January.

What about their shortest a photo of a it does that has that patient finished well that patients have finished on the 3 months efficacy evaluation by the time of presentation.

Lisa Michaels: So, and I invite Mark to jump in if he feels like he wants to add color to it, but I think one of the most important things for us is, first of all, the biological markers are basically physiologic responses. So these are purely objective measures that we can actually measure physiologic changes that can take place. The concern about placebo is that it is unblinded; both the treater and the patient both know which eye has been treated, and this is the primary reason why we're actually focusing on reproducibility. A one-time measurement that shows a significant change in vision is not going to be enough for us. It really needs to be able to be sustained across multiple different measures over time.

I can tell you, where we're coming down to the wire on that 1 so I'm not I I need to be able to see what the timing of that visit is going to be.

Great. Thank you.

Yeah.

Thank you. Our next question comes from the line of Corey caused them off with J P. Morgan. Please proceed with your question.

Hey, good morning, guys. Thanks for taking the question.

My questions on 1 on 1 and 301 recovered. So I wanted to ask you about the I P. S C and K program and if you could just update us on on the progress Youre, making there and upcoming milestones we should be on the lookout for thank you.

Okay.

Mark do you want to handle that 1.

Okay.

Yeah. So.

We've indicated in the corporate presentation some of the chain.

Changes that are being made and.

Mark Sherman: Yeah, and if I could add, thanks for the question, Yanan. As you know, from covering other companies that are administering subretinal AAV, there is a possibility of slight changes in and around the surgical procedure as the retina reestablishes, and reattaches. Those are usually tracked by comparison to the untreated out, and as Lisa pointed out, over time, they generally settle down within a couple of weeks or so. You know, all of that data gets collected and tracked, and the intention is to show over time a real treatment effect that's separate from any surgical or any other intervention related change. Thank you very much; the mid-dose cohort has been since January. What about the shortest follow-up? Does that, has that patient finished, will that patient have finished the three-month efficacy evaluation by the time...

We continue to develop the necessary editing for the final construct and also the differentiation profile and process for that and so right now.

That's really what we're focused on.

And we'll be providing updates you know again later in the year on the progress.

Okay.

Thank you. Our next question will come from the line of Joon Lee with true Securities. Please proceed with your questions.

Alright, thanks for taking our questions on sort of cohort 2 or the patients enrolled also light perception only like cohort 1 or are they able to perceive hand motion or better and in the court to and I have a follow up on 3 on.

Okay. So for 1 on 1 the way the protocol is basically written as we were able to Inc. Based upon the safety that was seen in the first cohort we were able to modify the protocol. So that we could proceed beyond just like perception patients. However at each dose level, we do have 1 sentinel patient who's in gold price.

Yanan Zhu: I can tell you we're coming down to the wire on that one, so I need to be able to see what the timing of that visit is going to be.

Lisa Michaels: Great, thank you.

Corey Cosimoff: Thank you. Our next question comes from the line of Corey Cosimoff with J.P. Morgan. Please proceed with your question. Hey, good morning, guys. Thanks for taking the question. My questions on 101 and 301 were covered.

For the purposes of evaluating safety and making sure there's no inflammatory reactions that would limit on treatment of further patients. So the first patient is light perception, but each additional on patient enrolled can have a better visual acuity.

Corey Cosimoff: If you could just update us on the progress,

Mark Sherman: And if you could just update us on the progress you're making there and upcoming milestones, we should be on the lookout for. Thank you.

Okay.

Just following up on that if you look at the stuff so far some data on their visual improvements, including D. C. D E and mobility evident as early as month wanted to know is there.

Joon So Lee: Mark, do you want to handle that one?

Mark Sherman: Yeah, so we've indicated in the corporate presentations some of the, Transcribed by https://otter.ai We continue to develop the necessary editing for the final construct and also the differentiation profile and process for that. And so right now, that's really what we're focused on, and we'll be providing updates again later in the year on the progress. Thank you. Our next questions come from the line of Joon Lee with Truist Securities. Please proceed with your questions.

Any reason to believe that the effects of 1 on 1 would be any slower than the interest that's mediated exon skipping and I'm curious if you have any thoughts on the genetics of the onset of clinical effect between genome editing versus that supports all of them.

So I guess the way if you're thinking in terms of the absolute timing, we do know that from our non clinical data that the optimal editing has occurred by about 6 weeks after injection.

As Mark has alluded to there I'll set the cost of the procedure needs to be some healing that needs to take place in the back of the eye. So the first measurement that we would expect to see some change would be at 3 months, however, because appropriately looking for consistent responses as well as potential improvement following it out to at least 6 months or longer is going to be what we're gonna.

Joon So Lee: Hi, thanks for taking our questions. For Cohort 2, are the patients enrolled also like?

Joon So Lee: perception only, like cohort one, or are they able to perceive?

Joon So Lee: to proceed with a hand motion or better in the court to and have a follow up on three.

Lisa Michaels: Okay, so for 101, the way the protocol is basically written is that based upon the safety that was seen in the first cohort, we were able to modify the protocol so that we could proceed beyond just light perception patients. However, at each dose level, we do have one sentinel patient who's enrolled primarily for the purposes of evaluating safety and making sure there are no inflammatory reactions that would limit treatment of further patients. So the first patient has light perception, but each additional patient enrolled can have better visual acuity.

Looking at but is there any it's hard to compare the 2 different modalities since a very different approaches.

And just for clarification, the cohort 2 will be for patients worth of data.

So as each cohort is planned to be for patients and then we'll evaluate.

Okay. Thank you.

No.

Thank you our next questions come from the line of Thiago felt with credit Suisse. Please proceed with your questions.

Hi, This is Jonathan on for Keith Thanks for taking on a question.

Joon So Lee: And so, you know, following up on that, you know, if you look at the cephalofarcin data, there are visual improvements, including BCDA and mobility evident as early as months one and two. You know, is there any reason to believe that the effect of edit one-on-one would be any slower than the antisense-mediated exon skipping? You know, I'm curious if you have any thoughts on the kinetics of the onset of clinical applications between genome editing versus exonsology.

For edit 1 on 1 in light of the upcoming readout from the low and mid dose cohorts for the adults how should we be thinking about how these results may translate to the respective doses and the pediatric cohorts.

What are the key differences, we should be thinking about that thanks.

I think we still have yet to kind of learn that in terms of the observations in.

In general the maturity of the human eye. After you get about 3.3 years of age the at least the anatomy and the size of the iron relatively simpler most of the changes that occur on the iron more or less completed by about 6 to 8 years of age. So I'm not I don't know that we're going to see a difference in terms of clinical response or safety.

Lisa Michaels: So I guess the way, if you're thinking in terms of absolute timing, we do know from our non-clinical data that optimal editing has occurred by about six weeks after injection. But, as Mark has alluded to, there also, because of the procedure, needs to be some healing that needs to take place in the back of the eye. So the first measurement that we would expect to see some change would be at three months.

Lisa Michaels: However, because we're really looking for consistent responses as well as potential improvement, following it out to at least six months or longer is going to be what we're going to be looking at. But is there any, It's hard to compare the two different modalities since they're very different approaches.

We'll have a chance to evaluate that as we move forward.

Gotcha. Thank you very much.

Yeah.

Yeah.

Thank you. Our next question is coming from the line of Steve seat House with Raymond James. Please proceed with your questions.

Good morning.

301, I'm, just curious beyond editing efficiency, what advantages you might anticipate from using the S test flow.

Joon So Lee: And just for clarification, cohort two will be four patients worth. So each cohort is planned to be.

In sickle cell specifically like.

So viability doubling time manufacturing success rate things like this compared to legacy on.

Lisa Michaels: So each cohort is planned to be four patients, and then we'll evaluate them.

Nucleases.

Obviously correspond to improve clinical outcomes and then also on the that the ultra nuclease. It looks like it's small enough to package into a flow any thought on.

Tiago Feltz: Thank you. Our next questions come from the line of Tiago Feltz with Credit Suisse. Please proceed with your questions. Hi Jonathan Onford-Kiago, thank you for taking our question. For Edit 101, in light of the upcoming readout for the low and mid-dose cohorts, for adults, how should we be thinking about how these results may translate to the respective dose?

Advancing that anyways into LCA 10, or.

Or and future ocular disorders nuclear as you pointed out do you think that.

So maybe I can take those questions. So as you saw in the nature Communications paper.

Past 12, engineered cash 12 day or cost while they altura.

A lot of very favorable properties, you mentioned some of them specificity.

Tiago Feltz: The key differences between the respective doses and the pediatric cohorts, what are the key differences we should be thinking about there? I think we still have yet to kind of learn that in terms of

The.

On target.

Editing efficiency potency.

All of that 1 other factor which is <unk>.

Lisa Michaels: I think we still have yet to kind of learn that in terms of observations. In general, the maturity of the human eye after you get about three years of age, at least the anatomy and the size of the eye are relatively similar. Most of the changes that occur in the eye are more or less completed by about six to eight years of age. So I don't know that we're going to see a difference in terms of clinical response or safety. We'll have a chance to evaluate that as we move forward.

Important for US also with the guide on a size tends to be quite a bit smaller than the cash 9 guidance and that's important when you're on manufacturing. He's a guide RNA because the fidelity decreases the longer length of the.

Guidance. So we feel that that is definitely an advantage for <unk>.

Lindsey.

On target editing.

And the second part of your question of course, yes, we can set a cash 12, a into an AAV and so we're looking to deploy that in some of the in vivo gene editing.

Steven James Seedhouse: Thank you. Our next questions come from the line of Steve Seedhouse with Raymond James. Please proceed with your question.

Steven James Seedhouse: Good morning. First on Edit 301, I'm just curious, beyond editing efficiency, what advantages you might anticipate from using the ASCAS-12A in sickle cell, specifically things like Cell Viability, Doubling Time, Manufacturing Success Rate, things like this, compared to legacy nucleases. That may obviously correspond to improved clinical outcomes. And then also, on that ultra nuclease, it looks like it's small enough to package into AAV5. Any thoughts on advancing that nuclease into LCA10 or, or in future ocular disorders? Is this the nuclease you're planning on using? Thank you. So maybe I can.

Programs that we have on going on potential future ones and actively working on optimizing the potential.

Potential configurations that you could use with respect to the guidance so all of that.

In progress.

Thank you our next questions come from the line of Joel Beatty with Citi. Please proceed with your questions.

Hi, This is Jonathan Barrett on thanks for taking the questions.

The LCA 10 program in the pediatric mid dose cohort ages.

Ages, and what status of disease course, and the children do you anticipate in enrolling and what could that mean for the ability to interpret clinical results compared to the first cohorts that will be reading out in September.

Mark Sherman: So maybe I can take those questions. As you saw in the Nature Communications paper, the CAS-12, Engineered CAS-12A, or CAS-12A-Ultra has a lot of very favorable properties. You mentioned some of them, specificity, and on target.

So we've got a little bit of a balancing act and all of this because the protocol does allow us to go as young as 3 years of age in the treatment of the patients, but I think 1 of the key outcomes that we want out of this is just not it's not just safety, but it's also the ability of the patient to be able to cooperate with the various different observations because what we're looking for at the end of the day.

Mark Sherman: Editing, efficiency, potency, all of that. One other factor which is important for us also is that the guide RNA size tends to be quite a bit smaller than the Cas9 guides, and that's important when you're manufacturing these guide RNAs because the fidelity decreases the longer the length of the guide. Guidance. So we feel that that is definitely an advantage for, you know, intrinsic, on target editing. And the second part of your question: of course, yes, we can fit a Cas12a into an AAV.

It's a clear signal of efficacy. So the selection of the first patients will be treated on the cohort are being considered about their ability to participate in the observations and I think you know there's no solid draw on mining here, but you know what if you think about your 5 or 6 year old whether they can sit through a long day of observations and walking through day uses I think as part of our consideration.

Joel Beattie: And so we're looking to deploy that in some of the in vivo gene editing programs that we have ongoing and potential future ones, and actively working on optimizing the potential configurations that you could use with respect to the guides. So all of that is in progress. Thank you. Our next questions come from the line of Joel Beattie with Citi. Please proceed with your question. Hi, this is Joel from Baird. Thanks for taking the questions. For the LCA-10 program,

Yes.

Great I appreciate that yeah.

Yeah.

Thank you our next questions come from the line of Jay Olson with Oppenheimer. Please proceed with your question.

Oh, Hey, congrats on the progress on thank you for taking our questions.

On the edit 101 data coming in September can.

Can you talk about whether or not we should expect to see the clinical measurements fluctuate over the follow up period or remained relatively consistent.

Joel Beattie: What ages and what stage of the disease course in the children do you anticipate enrolling in?

Consistent and then.

Joel Beattie: What could that mean for the ability to interpret clinical results compared to...

For any safety signals are there ways to tell whether a potential side effects are coming from the administration procedure day.

Joel Beattie: compared to the first cohorts that we'll be reading out in September.

The vehicle or the gene editing and then I had a follow up on the C. D. If I could.

Lisa Michaels: So we've got a little bit of a balancing act to do with all of this because the protocol does allow us to go as young as three years of age in the treatment of the patients. But I think one of the key outcomes that we want out of this is not just safety, but it's also the ability of the patient to be able to cooperate with the various different observations because what we're looking for at the end of the day is a clear signal of efficacy.

Okay. So I guess the first 1 is the consistency of measures I just wanted to remind everybody. It's still relatively young days for that middle dose cohort.

Because like I said the first patient was started in June and the next 3 patients were on a hold over the following 5 months. So for some of these patients we wont have that much reproducible data just yet.

Lisa Michaels: So the selection of the first patients who will be treated in the cohort is being considered on their ability to participate in the observations. And I think there's no solid drawn line here, but if you think about your five or six-year-old child, whether they can sit through a long day of observations and walking through mazes, I think is part of our consideration.

As for the safety observations. It is 1 of the more important observations on the trial not just short term toxicity related to inflammation or our problems related to the administration of the product, but also any changes that might occur in the high moving forward. So that data is being collected prospectively.

Lisa Michaels: We really appreciate that. Thanks. Thank you. Our next questions come from the line of Jay Olson with Oppenheimer. Please proceed with your question. Oh hey, congratulations on the progress, and thank you for taking our questions.

Great. Thank you and then.

For 301 in S. E. T study can you just talk about your timeline.

For completing the target enrollment in that study and then maybe comment on what.

Jay Olson: On the EDIT-101 data coming in September, can you talk about whether or not we should

What the FDA might want to see in terms of a follow up period and S. E D. Given some potential safety concerns from other companies using gene therapy.

Jay Olson: Do you expect to see clinical measurements fluctuate over the follow-up period or remain stable?

Jay Olson: Consistent, and then.

So so the second half of the question is we are expecting and in fact, it's sort of standard across the entire gene therapy and gene editing space that long term follow up for safety will be a requirement. So pharmacovigilance is going to be something that all of us have to be addressing moving forward.

Jay Olson: For any safety signals,

Lisa Michaels: Are there ways to tell whether potential side effects are coming from the administration procedure?

Jay Olson: AAV Vehicle or Gene Editing, and then I had to follow up on SED if I could.

Lisa Michaels: Okay, so I guess the first one is the consistency of measures. I just want to remind everybody it's still relatively young days for that middle dose cohort because, like I said, the first patient was started in June, and the next three patients were enrolled over the following five months. So for some of these patients, we won't have that much reproducible data just yet. As for the safety observations, this is one of the more important safety observations of the trial, not just short-term toxicity related to inflammation or problems related to the administration of the product but also any changes that might occur in the eye moving forward. So that data is being collected prospectively.

Our timeline on it still again early days.

We actually are actively opening up sites, we have a number of patients who are undergoing screening and I'm I'm focusing mostly on getting my first patient dose by the interest this year.

Great. Thanks for taking the questions.

Yeah.

Thank you our next questions come from the line of Matthew Kumar with Goldman Sachs. Please proceed with your questions.

Oh, great. Thanks for taking our question so.

Think about any 1 on 1 the high dose versus the Midland logos frame those doses relative to the preclinical with boost range. You described in your previous studies and then kind of following from that confidence.

Jay Olson: Great. Thank you. And then,

Jay Olson: or 301 in the SED study. Can you just talk about that?

Confidence that a higher dose.

Lisa Michaels: Your timeline for completing the target enrollment in that study and then maybe comment on what the SEA might want to see in terms of a follow-up period in SED, given some potential safety concerns from other companies using gene therapy.

1 could achieve better outcomes for LTA on patients. Thanks.

Mark do you want to try that 1 or you want me to bite.

No.

So.

The doses.

I'm sure you've already asked a similar question before the doses chosen for the clinical study, where obviously guided by the preclinical pharmacology and toxicology work that was done in mice and nonhuman primate.

Jay Olson: So the second half of the question is, we are expecting, and it's sort of standard across the entire gene therapy and gene editing space, that long-term follow-up for safety will be a requirement, and so pharmacovigilance is going to be something that all of us have to be addressing moving forward. As for our timeline, it's still, again, early days. We are actually actively opening up sites. We have a number of patients who are undergoing screening, and I'm focusing mostly on getting my first patient dosed by the end of this year.

<unk>.

To address the question about whether we think a higher dose will lead to better editing we have evidence, particularly in the humanized mice muscle at that would be the case I think in non human primates. There is.

Jay Olson: Great. Thanks for taking the questions.

Madhu Sudhan Kumar: Thank you. Our next questions come from the line of Madhu Kumar with Goldman Sachs. Please proceed with your answer. Great, thanks for taking our question.

Some indication that that could also occur the data was I would say less clear in terms of the fact that the NH P guides we're not.

Madhu Sudhan Kumar: Edited by: https://otter.ai

Madhu Sudhan Kumar: [inaudible]

Performing as effectively at the human ones, but in principle, yes, the expression of the nuclease components and the editing productive editing increase with dose and so going from the mid to high dose, which is a factor of 3.

Mark Sherman: Mark, do you want to try that one, or do you want me to bite?

Mark Sherman: The doses, as I'm sure you've already asked a similar question before, the doses chosen for the clinical study were obviously guided by the preclinical pharmacology and toxicology work that was done in mouse and non-human primate. To address the question about whether we think a higher dose will lead to better editing, we have evidence, particularly in the humanized mouse model, that that would be the case. I think in non-human prima

You know going into it.

Have an expectation that that could yield better results, but obviously the clinical data will have to bear that out.

Yeah.

Thank you. Our next question is coming from the line of at least a banker with Evercore. Please proceed with your question.

Mark Sherman: There is some indication that that could also occur. The data was, I would say, less clear in terms of the fact that the NHP guides were not performing as effectively as the human ones. But in principle, yes, the expression of the nuclease components and the editing, productive editing, increased the dose. And so going from the mid to high dose, which is a factor of three, going into it, we would have an expectation that that could yield better results. But obviously, the clinical data will have to bear that out. Thank you. Our next question has come from the line of Liisa Bayko with Evercore. Please proceed with your

Hi, Thanks for taking my question I'm on.

As you think about the kind of available visual field for these patients for AR at it.

1 O..1 can you maybe describe kind of with the way you're administering how much how much kind of I don't know on away surface area would be available for editing and is there anything you can do to kind of expand that further.

Okay.

I guess I'll start with you.

Go ahead, Marty we can fight each other for this what if you want.

Thank you.

Across different fields, where companies are introduced up lab up to for example, 300 my pleasure covering about a 20 degree.

Liisa Ann Bayko: Hi, thanks for taking the question. I'm wondering, as you think about the kind of available visual field for these patients for Edit 101, can you maybe describe, kind of, in the way you're administering it, how much of the surface area would be available for editing, and is there anything you can do to kind of expand that further?

Area, so a completely covering the macula, which is the important component here for.

Our ability to restore cone function. So I think I hope that answers your question, but that's the.

The intent, but with the current testing paradigm.

Liisa Ann Bayko: I guess I'll start with you. Go ahead, Mark. We can fight each other for this one if you want.

Okay. So what you're saying is you can cover the entire macula with that with a bleb and so that should be sufficient in terms of like kind of covering the visual field in a way.

Mark Sherman: across different fields where companies have introduced a BLEB up to, for example, 300 microliters, you are covering about a 20-degree area, so completely covering the macula, which is the important component here for the ability to restore cone function. So I hope that answers your question, but that's the intent with the current dosing paradigm.

Well, that's covering the majority if not all of the cones, especially on which are obviously content in the Mexican fovea region.

The rods, which are also expressed most positive expressed in that area. So again. This is I would say the day.

Liisa Ann Bayko: Okay, so what you're saying is you can cover the entire macula with that.

Standard approach to covering central retina.

Liisa Ann Bayko: Transcribed by https://otter.ai

A b treatments.

Okay and then.

And I would say the LCA LCA 10 is somewhat of a central retina basically what's happened in many of these patients is there is a preserved area of selling off on normal cells, where there hasnt been degeneration and actually that's in the central retina itself. So these are the cells that are most likely the ones that we're going to have the best effect from.

Mark Sherman: Well, that's covering the majority, if not all, of the cones expression which is obviously concentrated in the maculophobia region plus the rods which are also expressed, you know, more sparsely but expressed in that area. So again, this is, I would say, a tricky Standard Approach to Covering Central Retinitis A and B Treatment.

Yep.

Just with rates I mean companies have attempted to put the bleb.

Liisa Ann Bayko: LCA10 is somewhat of a central retina. Basically, what's happened in many of these patients is that there is a preserved area of normal cells where there hasn't been degeneration. And actually, that's in the central retina itself. So these are the cells that are most likely the ones that we're going to have the best effect from. Yeah.

The outside the mid periphery or in some cases multiple blabs for the.

Former approach.

Disease quite often is heterogeneous in the periphery, so it's not that straightforward, especially.

Mark Sherman: And maybe just to illustrate, I mean, companies have attempted to put the BLEB either outside the mid-periphery or, in some cases, multiple BLEBs for the former approach. You know, the disease quite often is heterogeneous in the periphery, so it's not that straightforward to actually carefully cover the degenerative rod area if that's what you are attempting to do. And then the challenge with the multiple BLEB approaches, on the one hand, yes, you can cover a greater area, but then you're introducing multiple retinotomies, and one of the things you absolutely want to avoid is reflux of the product because, as you may be aware, individual dosing, which is essentially what's then happening, leads to a greater likelihood of ocular inflammation. And so those are the trade-offs that you're considering.

Carefully cover the guarantee Lord area. If that's what you are attempting to do.

And then the challenge with the multiple bleb approaches on the 1 hand, yes, you can cover a greater area, but then.

Introducing multiple rats, and automates and 1 of the things you absolutely want to avoid is reflective of the product because as you may be aware, you know interdigital dosing, which essentially what's been happening leads to a greater likelihood of.

Inflammation.

And so those are the trade offs that you're considering.

Okay.

Okay. That's helpful. Thank you.

And then for for edit 301.

As you kind of look at the data the clinical data coming out you know from companies like vertex CRISPR.

Liisa Ann Bayko: Okay, that's helpful. Thank you.

Edit 301: For Edit 301, as you look at the clinical data coming out from companies like Virtex,

And where where do you see the opportunity I know theoretically that kind of advantages you're describing.

Edit 301: Vortex CRISPR and where where do you go

And those makes sense, but sort of in a practical form as you as you kind of look at the data that's evolving where do you see the opportunity to make a difference with edit 301. Thank you.

Edit 301: And where do you see the opportunity? I know theoretically the kind of advantages you're describing, and those make sense, but sort of in a practical form, as you kind of look at the data that's evolving, where do you see the opportunity to make a difference with EDIT 301?

Yes.

Jeremy Lisa.

Well, you always answered it well I'm actually.

Really answer it really well so.

Edit 301: Thank you.

Edit 301: Well, you always answer it so well. I'm happy to let you use it.

Well, yeah, so I'll take that went on for Jim.

You have to you have to take a little bit longer view what trials.

Edit 301: I think you have to take a little bit longer view of what trials in sickle cell and beta thalassemia are attempting to accomplish, which is ultimately long-term morbidity and mortality, so organ damage and extension of life, which is a big issue for these patients. So I think as you see things unfold, yes, the initial data coming out of the other companies is actually impressive. And that's great for the patient, but I think we have to see how this unfolds over a longer period of time.

In sickle cell and beta thalassemia are attempting to accomplish which is ultimately the long term morbidity and mortality organ damage.

Extension of life, which is a big issue for these patients so I think.

As you see things on pool, yes.

Initial data coming out of the other companies is actually impressive and that's great for the patients.

But I think we have to see how this on pools over a longer period of time.

Edit 301: And so I would expect that in this field, there'll be long-term efficacy and safety studies used in this field. And that's how things will differentiate, and then ultimately, as efficacy is demonstrated and safety is demonstrated, the companies are going to go to work, and some have already begun, on what are the conditioning strategies or basically how to make the treatment burden as light as possible for patients, and that may also relate to the drug, the simplicity of the drug, how much drug you have to deliver, how many cells you have to collect, et cetera, e So I think there are a number of other variables that will come into play as things unfold.

And so I would expect that this field will be long term efficacy and safety studies.

Used in this field.

Yes.

How things will differentiate and then ultimately as efficacy as demonstrated in the safety has demonstrated the cash.

Companies are going to go to work and some already are.

What are the conditioning strategies or basically how to make good.

The treatment burden.

As late as possible for patients.

And.

That may also relate to.

The drug the simplicity the drug how much drug you have to deliver how many sales you have to collect etcetera etcetera. So I think there's a number of other variables that will come into play as things unfold.

Luca Issi: Thank you. Our next questions come from the line of Luca Issi with RBC. Please proceed with your questions.

Thank you our next questions come from the line of Luca, Let's see with RBC. Please proceed with your questions.

Luca Issi: Oh terrific, thanks so much for taking my question, congrats on all the progress, two quick ones, one for Liisa and Mark and the other one for Jim, so for Liisa and Mark, your

Terrific. Thanks, so much for taking my question Congrats on a on the progress 2 quick 1 on 1 from for Lisa Mark and get them on for Jim So for Lisa Mark.

Luca Issi: Liisa Mark. You're obviously using AAV to deliver your construct. And I think the FDA is having an advisory committee meeting on September 2nd and 3rd to talk about the safety of AAV. So I'm wondering, one, if you're planning to participate in that adcom, and two, what are your expectations going into that event? And maybe Jim, for you, bigger picture, you know, what's the latest thinking in business development? When you think about the three kind of big dimensions of your pipeline, which are obviously the eye, hemoglobinopathies, and oncology, which of them do you think are going to be core to edit a story going forward? Versus which one maybe you're willing to partner? And maybe on the in-licensing side, do you have any appetite to actually bolster your pipeline via BD? Thanks so much.

You're obviously using AAV to deliver your construct and I think the FDA is having an advisory Committee meeting September 2nd and third to talk about the safety of AAV. So I'm wondering 1 if you plan to participate in that AD com and 2 what are your expectation getting into that event and maybe Jim for you a bigger picture you know what's the latest thinking on business development. What do you think about the 3 kind of.

Big dimension of your pipeline, which is obviously the eye haemoglobinopathy that oncology, which of them you think going to be core to I think the story going forward versus which 1 may be you're willing to partner and maybe on the licensing side do you have any appetite to actually bolster your pipeline <unk>. Thanks, so much.

Mark Sherman: So maybe I can take the first question. Yes, we will be participating in the FDA. They were meeting to discuss, you know, some emerging issues with AAV. What I would say to answer kind of the second part of that is, you know, people are using AAV for multiple very different purposes and at significantly different amounts. And so I think the Oculus space, one of the reasons why this was one of the first areas that people used AAV as a delivery vehicle is because you can, you know, there's a very defined anatomy; you can deliver the product very carefully to the right place.

Okay. So maybe I can take the first question, yes, we will be participating in the F. D. A.

Meeting to discuss.

Some emerging issues with a b it what I would say to answer the second part of that is.

People are using a vehicle multiple very different approaches and at <unk>.

Significantly different amounts and so I think the oculus space 1 of the reasons. Why this was 1 of the first areas that people use AAV as a delivery vehicle is because you can you know there's.

Very defined anatomy, you can deliver the product very carefully to the right place on it relatively low on match you know 100 to 1000 of the dose that somebody.

Mark Sherman: And it's at relatively low amounts, you know, 100 to 1000 times the dose that some of the other systemic administrations are using. So I think that meeting will be important. I think some aspects of it around viral integration or immunogenicity are probably more relevant for the DMD and the, you know, the hemophilia folks where they're using much higher levels and you do clearly have an immune-related response. But, you know, The meeting will result in some guidelines and some further direction, and that's obviously important to be aware of, and if it becomes relevant for Editas, we'll fully participate and be part of

Stomach administration, but he was so I think that meeting will be important I think some aspects of it around.

Bartlett integration or Immunogenicity of probably more relevant for the D. M D and the the hemophilia folks where they used to think much higher levels than you do plenty have immune related response, but.

The meeting will read it will result in some guidelines on some further direction and that's obviously important to be aware off and if it becomes relevant for interest as well.

Do you participate and be part of that.

Jim Mullen: So, Luca, let me take the second part of that, which is sort of the BD strategy overall. So, in addition to building the leadership group that I talked about early in this call, we have also been building depth below that leadership group. And so, you know, for the first time, and now that Mark's here, I'm thrilled to have Mark, Lisa's getting a little bit of bandwidth to start thinking about sort of the broader strategy.

Yeah.

So let me take the second part of that which is a which is sort of BD strategy. Overall. So in addition to building the leadership group that I talked about early on this call. We have also been building depths below that leadership group and so.

For the first time and now in our remarks here I'm thrilled to have mark leases, giving a little bit of a bandwidth.

To start thinking about.

Sort of the broader strategy and we've appointed Bruce eaten that we've really got the team together now to really rigorously sort of think about strategy no.

Jim Mullen: And we've appointed Bruce Eaton, and we've really got the team together now to really rigorously sort of think about strategy. Now, let me take you to the sort of how we're thinking about BD. I have, you know, I've been in the industry a long time.

Now, let me take you to the sort of how we're thinking about BD.

I have.

I've been in the industry, a long time, and so on I'm fairly pragmatic about.

Jim Mullen: And so I'm fairly pragmatic about, What do we think we can execute, and what do we think we will ultimately need help with? So we've got a nice productive relationship with BMS on the T-cell side of oncology. We've made, I think, pretty significant advancements on our IPSC-derived NK platform, but there's an area where I think going into clinical development and, certainly, further into clinical development and commercialization, we will be best served if we have a partner in that.

What do we think we can execute well.

And what do we think we will ultimately need help with so we've got a nice productive relationship with B M. S.

T cell side of oncology.

We've made.

Pretty significant advancements on our Ips derived NK platform, but there is an area, where I think I'm going into clinical development and certainly no.

Further into clinical development and commercial.

That we will be best served if we have a partner in books.

Jim Mullen: So that will be something that we will look to. It's always hard to judge exactly what the right moment in time is to do that, but that will be a high priority. Similarly, with the 301 program, I feel very comfortable that we can advance that one clinically, but ultimately, we would want a commercial partner, particularly a U.S. one. And certainly, I also know that that means if you get a commercial partner, they're going to want to participate at some meaningful level in late stage development, right?

That will be something that we will look to its always hard to judge exactly what the right moment in time as do that but that will be a high priority.

With the 301 program.

Feel very comfortable that we can advance that 1 clinically, but ultimately we would want a commercial partner, particularly ex U S. M.

And.

Certainly I also know that that means that you get a commercial partner, they're going to want to participate at some meaningful level in the late stage development right. So those would be sort of 2 bigger pieces with respect to thinking about in licensing things. We are actively talking about that because that can come in.

Jim Mullen: So, those would be sort of two bigger pieces. With respect to thinking about licensing things, we are actively talking about that. I think that can come in different flavors and forms. We can edit. We know that.

Different flavors and forms we have.

As you know what I consider the.

The biggest challenge in gene editing.

As we on a weekend edits and we know that it's can you get the editing machinery to the right, Oregon on the road so pipe.

Jim Mullen: It's, can you get the editing machinery to the right organ or the right cell type at the right efficiency? [inaudible] And then lastly, things that potentially complement either our technology or a therapeutic area where we have an interest, for example, Ocular, where we have a number of programs. We'd certainly look to think about augmenting the depth of our pipeline. Hopefully, that, Fantastic!

Efficiency.

With a with an appropriate safety profile and so you know when you think about our 3 programs right. They are in some ways 3 different ways of delivering editing therapy.

Reputed, but we'll look at additional ones. So AAV as good as it is has its own limitations, we've seen other people with a L. M P's.

For the right indications <unk> and or other different delivery modalities is certainly something we'd look at it and then lastly, you know things that potentially complement either our technology or a therapeutic area, where we have an interest for example, ocular where we have a number of programs, we'd certainly work too.

Jim Mullen: Fantastic. Yes.

Operator: Thanks so much. I appreciate it. Thank you. There are no further questions at this time.

Let's think about augmenting the depth of book over a pipeline there hopefully that helps.

Fantastic. Thanks, so much I appreciate it.

Yeah.

Thank you there are no further questions at this time I would like to turn the call back over to management for any closing remarks.

Jim Mullen: I would like to turn the call back over to management for any closing remarks.

Well, thank you very much everyone.

Jim Mullen: Well, thank you very much, everyone. A lot of great questions today. Really appreciate all the interest. We will have, I know, a number of conversations here over the coming days. I greatly look forward to talking with all of you in the future. Thanks again, and I think we will call it a day. Appreciate your time. Take care.

A lot of great questions today really appreciate all the interest rate, we will have I know a number of conversations here over the upcoming days.

Greatly look forward to.

Talking with all of you in the future. Thanks, again, and I think we will call. It a day I appreciate your time take care.

Operator: Thank you for your participation. This does conclude today's teleconference. You may disconnect your lines at this time.

Thank you for your participation. This does conclude today's teleconference. You may disconnect your lines at this time.

Have a great day.

Yeah.