Q2 2022 Editas Medicine Inc Earnings Call

[music].

Good morning, and welcome to edit tossed medicine second quarter 2022 conference call. All participants are now in a listen only mode. There will be a question and answer session. At the end of this call. Please be advised that this call is being recorded at the company's request.

Unknown Executive: Good morning and welcome to Editas Medicine's second quarter 2022 conference call.

Operator: 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.

Operator: So we are expecting to and planning to share clinical data from one and possibly two patients, at the end of this year. That patient data will include safety, as well as engraftment and hematological parameters.

Operator: I would now like to turn the call over to Ron Moldover, Investor Relations at Editas Medicine.

Operator: With regard to the unmet need, we believe that the differentiation, given by our product.

I would now like to turn the call over to Rod Mill dollar Investor relations at the top.

Thank you Paul Good morning, everyone and welcome to our second quarter 2022 Conference call earlier. This morning, we issued a press release, providing our financial results and recent corporate updates a replay of today's call will be available on the investors section of our website approximately two hours. After its completion after our prepared remarks, we will open the.

Ron Moldover: Thank you, Paul.

Operator: And there are two elements of the differentiation.

Ron Moldover: Good morning, everyone, and welcome to our second quarter 2022 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate updates.

Ron Moldover: A replay of today's call will be available on the investor section of our website approximately two hours after its completion.

Ron Moldover: After our prepared remarks, we will open the call for Q&A.

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 provision under the private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by these.

Ron Moldover: 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 provision under the Private Securities Litigation Reform Act, of 1995.

Operator: I've highlighted the fact that we anticipate durable, a very durable expression of fetal hemoglobin owing to the promoter of the gamma globin genes that we've targeted.

Ron Moldover: 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 FTC as updated by our subsequent filings.

Forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC as updated by our subsequent filings. In addition, any forward looking statements represent our views only as of today and should not be relied.

Ron Moldover: 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.

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 executive Chairman Jim Mullen.

Ron Moldover: Now I will turn the call over to our Executive Chairman, Jim Mullen.

Jim Mullen: Thanks, Ron, and good morning, everyone.

Operator: But in addition, we're using a high fidelity, highly efficient editing nuclease, in the form of AF-Cas12A.

Thanks, Ron and good morning, everyone.

Jim Mullen: I'm joined today by several members of the Editas executive team, including Gilmore O'Neill, our Chief Executive Officer, Mark Sherman, our Chief Scientific Officer, Michelle Robertson, our Chief Financial Officer, and Baesong May.

I'm joined today by several members of the editors executive team, including Gilmore O'neill, Our Chief Executive Officer, Mark Sherman, Our Chief Scientific Officer, Michelle Robertson, our Chief Financial Officer, and based on my right.

Jim Mullen: who I am thrilled to welcome as our new Chief Medical Officer.

Who I am thrilled to welcome as our new Chief Medical Officer.

Jim Mullen: As you know, on June 1st, Gilmore assumed the role of CEO, and I became Executive Chairman of the Board. Over the past two months, I've partnered closely with Gilmore and the executive team to ensure the seamless changeover of the CEO role.

As you know on June 1st Gilmore assumed the role of CEO and I became executive chairman of the board over the past two months I've partnered closely with Joe Moore, and the executive team to ensure the seamless changeover of the CEO role.

Jim Mullen: We are very fortunate to appoint a leader of Gilmore's caliber as CEO. During his nearly 20 years of experience in genetic medicine and clinical development, including senior leadership positions at Sarepta and Biogen, he has led some of Biotech's most successful clinical programs. Gilmore's drug development experience, proven leadership, passion for genetic medicine, and focus on patients are exactly the right skill set and experience to lever the foundation we've built over the past several years and lead the company toward commercialization.

We are very fortunate to appoint a leader Gilmore caliber as CEO .

During his nearly 20 years of experience in genetic medicine in clinical development, including senior leadership positions at <unk> and Biogen.

Some of biotechs, most successful clinical programs.

Morris drug development experience proven leadership.

And for genetic medicine and focus on patients are exactly the right skill set and experience deliver the foundation, we've built over the past several years and lead the company towards commercialization.

Jim Mullen: If his first few months are any indication of his leadership abilities, Editas' next few years are undoubtedly poised for success.

This is the first few months or any indication of his leadership abilities.

The next few years are undoubtedly poised for success.

With that I am very pleased to turn the call over to our new CEO Gilmore O'neill.

Jim Mullen: With that, I'm very pleased to turn the call over to our new CEO, Gilmore O'Neill.

Operator: And what we believe is that that durable benefit is actually, has the potential to be an important differentiator simply because it is independent.

Thank you Jim and good morning, everyone.

Let me first say that I am delighted to be here today.

As you know any past as a forerunner in the development of CRISPR gene editing technology, and I am very happy to have the opportunity to lead the company to create potentially life changing medicine I.

I also want to thank Jim for continuing to strengthen the editors leadership team over the past few years and I'm honored to work alongside such a talented and dedicated group of people.

With the addition of our new Chief Medical Officer, we now have a complete and even stronger leadership team in place.

Gilmore O'neill: Thank you, Jim, and good morning, everyone.

Operator: It drives expression independent of stress or atheropoiesis, which is something that could actually become increasingly mitigated over time.

Let me start off by giving you my initial two months.

The Companys technology is what drew me to Eddie.

Gilmore O'neill: Let me first say that I am delighted to be here today.

But I have seen since my arrival has reinforced my enthusiasm and gives me even more confidence in the companys potential.

Gilmore O'neill: As you know, Editas is a forerunner in the development of CRISPR gene editing technology, and I am very happy to have the opportunity to lead the company to create potentially life-changing medicine.

Gilmore O'neill: I also want to thank Jim for continuing to strengthen the Editas leadership team over the past few years, and I am honored to work alongside such a talented and dedicated group of people.

Eddie has is transforming from a technology platform company into a therapeutics company and will continue to create develop and will commercialize new therapeutic assets to treat previously untreatable serious diseases.

It has.

As in numerous areas of differentiation a truly distinct expertise in nuclease enhancements and bioinformatics to drive lead discovery.

These enhanced enzymes, then coupled with proprietary RNA chemistry to make efficient high precision.

And overall the foundational science that has led to the current pipeline of potential projects is impressive.

In addition, I found a very creative team of innovators in our discovery group.

<unk> CMC expertise and promising clinical assets supported by a robust R&D pipeline.

With these pieces in place to support our therapeutic pipeline. We now have to focus on clinical execution, which is why I'm. So happy to welcome Dr. Based on <unk> as our new Chief Medical Officer to Eddie Testaments.

Gilmore O'neill: With the addition of our new chief medical officer, we now have a complete and even stronger leadership team in place.

Gilmore O'neill: Let me start off by giving you my initial two-month assessment.

Based on brings substantial translational and registrational trial experiences across several therapeutic areas, including hematology, where specific he oversaw the global approvals of two drugs for non malignant blood disorders.

His extensive and more importantly, a proven track record of both incentives and advancing therapeutics from the bench through clinical development, leading to multiple global drug approvals.

Based on joins us from Sanofi, where he served as senior global project hedge in rare disease and rare blood disorders.

Prior to Sanofi based on worked at Biogen, where I had the privilege of working with them and I can personally attest to his breadth of knowledge and effective leadership skills.

Officially started about two weeks ago, and we very much support for his contribution to the months and years ahead now.

Now I would like to provide my initial thoughts on our lead pipeline products, starting with our edit 301, autologous Brooklyn for sickle cell disease, and transfusion dependent beta thalassemia.

Operator: And so it would be important to maintain that durable expression, of fetal hemoglobin and doing it independently of stress or atheropoiesis confers a significant differentiated advantage in the long term.

As many of you know edit 301 utilizes a unique mechanism of action.

It's the promoter of the gamma globin genes to disrupt binding of the Bcl <unk> pressure.

Operator: And then with regard to our confidence around the expression of fetal hemoglobin, I'm going to ask Mark to talk a little bit about our preclinical data.

In turn this provides high and durable levels of fetal hemoglobin or hbf in a manner that is independent of the original budget stress, resulting in reduced particularly and basically just events of sickle cell patients and resulting anemia and transfusion dependent beta thalassemia patients. In addition, this is the first time doesn't autologous.

Operator: Yeah.

Z for drug product has been edited using our high fidelity Aes has 12 engineered nuclease.

We have continued to build momentum with edit 301 in the past quarter, we dosed the first patient in the Ruby trial for sickle cell disease and that patient has successfully engrafted.

Partial clinical hold was lifted by the FDA, which will allow us to include efficacy data from all patients in a future registration package and we are successfully collected in essence sales of additional sickle cell disease patients with.

We continue to expand trial sites to help create a steady cadence of patients rolling.

And we remain on track to provide top line clinical data before year end.

Additionally, we received orphan drug designation for <unk> in May and we remain on track to dose the first GDT patient by year end.

Moving now to our lead in vivo program edit 101 for LCA 10, which is a devastating inherited retinal dystrophy caused by autosomal recessive CET 90 mutations.

Our ongoing phase one brilliant study has been designed to achieve several objectives.

<unk> at dose Optimizes, the benefit risk balance of edit 101 and that can advance to registration.

To identify segments LCA 10 patients most likely to benefit from therapy in a registrational study using based on clinical and physiologic characteristics and to identify the optimal endpoints for UC registration study.

The safety profile has thus far been very encouraging and has allowed us to move up to a high dose and into pediatric patients and the efficacy data generated to date support proof of concept of gene editing is occurring in retinal photo receptors.

This morning, we announced that we have the dose to pediatric patients in the mid dose cohort.

As of today, we remain on track by the clinical update on the brilliance trial later this year, which.

Which we expect to include safety and efficacy assessments on all patients who have had at least six months follow up evaluations.

These data will help identify the most relevant and sensitive endpoints to support Registrational trials.

Beyond developing a treatment for LTA can be edit 101 program lays the foundation for subsequent popular drug development programs with in our in vivo platform.

The proven safety of the capsid success administration of the editing machinery through sub retinal injection and the delivery of the CRISPR Cas nine enzyme to the photo receptors have demonstrated that we can effectively retinal cells in vivo.

For example, our 103, our edit 103 program for adoption.

So on the dominant RP leverages all of these elements.

In addition has demonstrated much higher preclinical editing efficiency and edit 101 with nearly 100%.

So even though both the edit 101 and edit one of the three programs use the same AAV vector.

Nine enzyme the editing efficiency of the edit 102 program is substantially greater.

Moving to our intellectual property portfolio as a reminder, roads patents covering past nine are exclusively licensed to editors for therapeutic development.

Earlier this year the broad Institute prevailed for the third time against the University of California, along with his corners collectively referred to a CPC in protecting these patents when the patent trial and appeal board or <unk> rules in the broad safer.

Anticipated CDC file an appeal to the federal circuit, and we remain confident road and by extension to Eddie past when once again prevail.

If that is indeed, the case, Eddie task will retain the rights to issue either exclusively or non exclusively licenses for bros. CRISPR Cas nine IP for human therapeutics in the United States, which is the dominant market for innovative medicines.

And as a reminder, both our ex vivo cell therapy <unk> pro platforms use our proprietary E. S. Castro, there, which is not encumbered by any intellectual property disputes.

We believe this strong IP position, coupled with our exclusive right to brown future IP licenses to companies desiring to commercialize CRISPR past nine medicines is a significant value driver for our stakeholders and with that I will turn it over to our new Chief Medical officer based on that thank.

Thank you. Thank you Guillermo and good morning.

Operator: Hi, Jan.

Operator: So early in the program, the preclinical team conducted sort of direct comparisons of the different editing mechanisms, whether the HPG promoter region or the BCL11A itself. And we found that the promoter region editing gave slightly higher HPS levels, at least in a preclinical model, but also importantly, that we maintain the fidelity of the lineages derived from those cells, whereas with the BCL11A approach, there was some lineage skewing. So I think efficacy-wise, we believe there could be an advantage.

I'm very excited to be speaking with everyone today, and we will start off by sharing what drew me to Adidas.

Gilmore O'neill: The company's technology is what drew me to Editas. What I have seen since my arrival has reinforced my enthusiasm and given me even more confidence, in the company's potential.

Operator: And then long-term safety-wise, also, we have some concerns with BCL11A, you know, editing a transcription factor which has more than one function.

Gilmore O'neill: Editas is transforming from a technology platform company into a therapeutic company that will, continue to create, develop, and will commercialize new therapeutic assets to treat previously untreatable serious diseases.

Operator: But, you know, at this point in time, the differentiation will be determined by the clinical data, and that is the data that's emerging.

Firstly I was impressed by the quality of the company's time and its leadership in gene editing field.

Operator: Thank you.

Operator: Our next question is from Steve Seedhouse with Raymond James.

And in the last several years working gene therapy, and RNA medicines, So always closely monitoring the evolution of gene therapy, and an emergence of CRISPR based gene editing.

Operator: Please proceed with your question.

Operator: Good morning.

That would be triggered by Adidas work and it's a unique approach to address E genetic diseases.

Additionally, what inspires me.

And I think what in fact, most people do need industry is the opportunity to create a new medicine and make a difference for people suffering serious.

Gilmore O'neill: Editas has in numerous areas of differentiation, including distinct expertise in nucleate enhancements, and bioinformatics to drive lead discovery. These enhanced enzymes then coupled with proprietary RNA chemistry to make efficient, high-precision, edits.

And it has to work is highly differentiated from other players in the field.

Gilmore O'neill: And overall, the foundational science that has led to the current pipeline of potential, products is impressive.

The opportunity to be a part of a gene editing pioneer is why I'm here.

Over the course of my career I have had the privilege to work in all segments of drug development lifecycle.

Gilmore O'neill: In addition, I found a very creative team of innovators in our discovery group, strong, CMC expertise, and promising clinical assets supported by a robust R&D pipeline.

Operator: This is Brian Deschner, Dr. Steve.

<unk> pharmaceutical industry at the CDC kind gift over 20 years ago.

Looking at CMC.

It was the leading discovery research team.

After transitioning to discovery research I also had the opportunity to assist in clinical development, we should that we should the way I have to state it.

Gilmore O'neill: With these pieces in place to support our therapeutic pipeline, we now have to focus, on clinical execution, which is why I'm so happy to welcome Dr. Baesong Lai as our new chief medical officer to Editas Medicine. Baesong brings substantial translational and registrational trial experiences across several, therapeutic areas, including hematology, where specifically he oversaw the global approvals of two drugs for non-malignant blood disorders.

Took a leadership role in clinical development with end to end responsibility from first in human clinical study to global approval.

Gilmore O'neill: He has extensive and, more importantly, a proven track record of both inventing and investing, therapeutics from the bench through clinical development, also leading to multiple global drug approvals.

My experience in E&C in discovery research has been among the value and has impacted me my work in clinical development.

In general I consider myself to be attractive at heart and.

Michael.

Editors.

Bringing vital medicines through approval for patients who need treatment.

I look forward to updating you on our clinical progress on subsequent calls.

Operator: I wanted to ask, what is your general expectation for neutrophil, and platelet engraftment for patients in the sickle cell study?

With that I will turn the call over to our Chief Scientific Officer, Marc who will provide an update on our R&D efforts.

Gilmore O'neill: Baesong joins us from Sanofi, where he served as senior global project head in rare disease, and rare blood disorders.

Gilmore O'neill: Prior to Sanofi, Baesong worked at Biogen, where I had the privilege of working with, him, and I can personally attest to his breadth of knowledge and effective leadership skills.

Thank you best film Husky.

Gilmore O'neill: He officially started about two weeks ago, and we very much look forward to his contributions, in the months and years ahead.

Gilmore O'neill: Now I would like to provide my initial thoughts on our lead pipeline product, starting with

Operator: And have there been any SAEs of note, in particular associated with the cell product?

Our scale MAU has provided updates on edit 101, and edit 301 I'd like to begin with edit 103 for ROE ADR P.

Gilmore O'neill: our EDIT-301 autologous program for sickle cell disease and transfusion-dependent beta thalassemia. As many of you know, EDIT-301 utilizes a unique mechanism of action that edits the promoter, of the gamma-globin genes to disrupt binding of the BCL11A suppressor. In turn, this provides high and durable levels of fetal hemoglobin, or HPF, in a manner that, is independent of erythropoietic stress, resulting in reduced sickling and vaso-occlusive events in sickle cell patients, and resolving anemia and transfusion dependence in beta thalassemia patients.

Operator: Thank you.

Gilmore O'neill: In addition, this is the first time that an autologous ex-zivo drug product has been edited, using our high-fidelity AS-Cas12A engineered nuclease.

Operator: Thanks, Brian.

As a reminder, one of three is highly differentiated from edit 101 with a different approach and superior preclinical data.

Gilmore O'neill: We have continued to build momentum with EDIT-301 in the past quarter. We dosed the first patient in the RUBY trial for sickle cell disease, and that patient, has successfully engrafted. The partial clinical hold was lifted by the FDA, which will allow us to include efficacy, data from all treated patients in a future registration package. And we have successfully collected and edited cells of additional sickle cell disease patients.

Operator: Good to meet you.

Operator: So our expectation for engraftment of platelets in neutrophils, we actually designed our protocol to capture it around day 30 to 40.

I think one of the three use it to <unk> associated virus vectors to locate the mutant rhodopsin in order to correct the toxic gain of function.

Gilmore O'neill: We continue to expand trial sites to help create a steady cadence of patient enrollment, and we remain on track to provide top-line clinical data before year-end.

Operator: Obviously, it varies across patients, and that has been the experience for both autologous and in our genetic experience in general.

Gilmore O'neill: Additionally, we received orphan drug designation for base thalassemia in May, and we remain on track to dose the first TDT patient by year-end.

Operator: But we will be able to share more specifics of that near the end of the, year and as the program progresses.

Gilmore O'neill: Moving now to our lead in vivo program, EDIT101 for LCA10, which is a devastating inherited, retinal dystrophy caused by autosomal recessive CEP290 mutations. Our ongoing phase one brilliant study has been designed to achieve several objectives.

Operator: The second question, SAEs, we've not actually seen.

While simultaneously, replacing that aberrant gene with a function of what.

The knockout of the gene in the rest of the photoreceptor cells can only occur if the components for the replacement gene I'll also delivered two and active in that same sale.

This mutation agnostic approach and potentially address more than 150, <unk> mutations that cause ROE a DRP.

At the Alco meeting in May we presented preclinical data that demonstrated nearly 100% productive editing in nonhuman primates and generated over 30% functional rhodopsin gene replacement, which proved to be therapeutically effective and that NH Pea study.

Gilmore O'neill: To identify a dose that optimizes the benefit and risk balance of EDIT101, and that can advance to registration.

Operator: We've not actually seen SAEs in this experience to date.

Gilmore O'neill: To identify a segment of LCA10 patients most likely to benefit from therapy in a registrational study using baseline clinical and physiologic characteristics, and to identify the optimal endpoints for use in a registration study.

Operator: But obviously, we are aware that the procedure itself, beyond the editing but in general for engraftment, does carry identified risks.

Gilmore O'neill: The safety profile has thus far been very encouraging and has allowed us to move up in to our high dose and into pediatric patients, and the efficacy data generated to date support proof of concept that gene editing is occurring in retinal photoreceptors. This morning, we announced that we have a dose to pediatric patients in the mid-dose cohort.

Gilmore O'neill: As of today, we remain on track to provide a clinical update on the brilliance trial later, this year, which we expect to include safety and efficacy assessment on all patients who have had at least six months of follow-up evaluations. These data will help identify the most relevant and sensitive endpoints to support registrational trial development.

The data also showed improved photoreceptor organization and improve restaurant morphology and in no case and replace treated group.

Gilmore O'neill: Beyond developing a treatment for LCA10, the EDIT101 program lays the foundation for subsequent, ocular drug development programs within our in vivo platform. The proven safety of the capsid, success administration of the editing machinery through subretinal injection, and the delivery of the CRISPR-Cas9 enzyme to the photoreceptors have demonstrated that we can effectively edit retinal cells in vivo.

As we continue to optimize the product. We also think there is potential for further improvement upon that data that we've already presented.

We also recently received encouraging FDA feedback on edit 103, and its expectations as we approach an IND filing.

Gilmore O'neill: For example, our EDIT103 program for rhodopsin autosomal dominant RP leverages all of these elements and, in addition, has demonstrated much higher, preclinical editing efficiency than EDIT101 with nearly 100% editing. So, even though both the EDIT101 and EDIT103 programs use the same AV vector and Cas9 enzyme, the editing efficiency of the EDIT103 program is substantially greater.

Just on the FDA input and our ongoing work on the program we remain on track to initiate IND, enabling studies later this year.

Moving now to our cell therapy programs.

Gilmore O'neill: Moving to our intellectual property portfolio as a reminder, Broad's patents covering Cas9, are exclusively licensed to EDITAS for therapeutic development. Earlier this year, the Broad Institute prevailed for the third time against the University of California, along with its co-owners, collectively referred to as CBC, in protecting these patents when the Patent Trial and Appeal Board, or PTAB, ruled in the Broad's favor.

Operator: And obviously, we monitor that very closely.

Gilmore O'neill: As anticipated, CBC filed an, appeal with the Federal Circuit, and we remain confident Broad, and by extension EDITAS, will once again prevail.

Gilmore O'neill: If that is indeed the case, EDITAS will retain the sole right to issue either exclusively or nonexclusively licenses for Broad's CRISPR-Cas9 IP for human therapeutics in the United States, which is the dominant market for innovative medicine.

In June we announced a collaboration with the metrics related to our strategic research collaboration and licensing agreement with <unk>.

Gilmore O'neill: And as a reminder, both our ex vivo and cell therapy pro platforms use our proprietary AS-Cas12A, enzyme, which is not encumbered by any intellectual property disputes.

Operator: But I think very importantly, we have not seen SAEs at all, and more specifically have not seen adverse events that would give us concern about the product.

Operator: Thank you very much.

Seven two which we will apply our gene editing technology to gamma Delta T cell adoptive cell therapies and area, where in metrics has world class expertise.

Operator: Thank you.

We believe that this collaboration will give us the opportunities to develop novel T cell based therapeutics for enhanced tumor recognition.

Gilmore O'neill: We believe this strong IP position, coupled with our exclusive right to grant future IP, licenses to companies desiring to commercialize CRISPR-Cas9 medicine, is a significant value driver for our stakeholders.

Operator: Our next question comes from Madhu Kamal with Goldman Sachs.

Gilmore O'neill: And with that, I will turn over to our new Chief Medical Officer, Baisong Mei.

Operator: Please proceed with your question.

Yes that is a therapy collaboration with Bristol Myers Squibb, we were pleased to announce earlier. This morning that BMS adopted into an eight editing program for Alpha Beta T cell therapeutics.

Baisong Mei: Thank you.

Operator: This is Omari from Madhu.

Baisong Mei: Thank you, Gilmore.

Operator: For the first question, could you give us a sense of what kind of efficacy profile do, you need to see at a given one-on-one dose to pursue a registration or trial?

Baisong Mei: And good morning.

Operator: And then what venue do you plan to present one-on-one update at, a medical meeting or, separately?

Operator: So with regard to our success criteria, what we would want to see is an extension of the, POC that we've seen with stability and potentially improvement in some of the adult patients.

This was the fifth opt in over the last 12 months and we have collectively optimistic about continuing the momentum of that partnership.

Operator: I think the other determinant of success for the study will be identifying a segment of, the patient population that maximizes or has a maximum probability of responding to the therapy and also interacting with a select set of endpoints that will actually also be determined by the phase one study and our interaction or our analysis of that co-analysis of the natural history study.

Operator: And with regard to selection of the dose, the phase one study will actually obviously, be part of selecting that dose.

Operator: And as you say, the success criteria for selecting that dose would be determined by seeing maintained, stability and improvement in a segment of the patient.

Operator: And we don't actually have a, we are currently evaluating where we would share that data, but we would anticipate that it's likely to be at a webinar later this year.

Operator: Thank you guys for your questions.

Operator: Thank you.

CMS has multiple early programs covering both solid and heme tumors that incorporate edit touchless technology.

Operator: There are no further questions at this time.

And use multiple edits.

Similarly engineered T cells.

Both autologous and allogeneic platforms.

The most advanced program from this collaboration is currently in IND, enabling studies.

The engineered cell demonstrates improved tumor, killing and antitumor efficacy compared to wild type cells, both in vitro and in vivo.

We believe that these improved pharmacodynamic and phenotypic characteristics and engineered T cells open the door for numerous potential clinical applications.

For our in house cellular therapy programs. We are very pleased with the progress we are making with our Ips derived NK cell medicine program for solid tumors.

Baisong Mei: I'm very excited to be speaking with everyone today.

Baisong Mei: And we'll start off by sharing what drew me to Editas. Firstly, I was impressed by the quality of company's science and its leadership in gene, editing field.

With a focus on edit sure too with our lead program in this area.

Baisong Mei: I spent the last several years working in gene therapy and RNA medicines, so I was closely, monitoring the evolution of gene therapy and the emergence of CRISPR-based gene editing. I was intrigued by Editas' work and its unique approach to address genetic diseases.

Baisong Mei: Additionally, what inspired me, and I think what inspires most people in this industry, is the opportunity to create a new medicine and make a difference for people suffering from serious diseases.

Currently in preclinical development.

Using our proprietary engineered <unk> nuclease and snakes technology, we have developed engineered NK cells that have potent antitumor activity and substantially increased persistence in preclinical models, which we believe could lead to lower frequency dosing and important potential advantage for patients compared to many.

Baisong Mei: Editas' work is highly differentiated from other players in the field.

Existing NK cell approaches.

At the <unk> annual meeting in May we presented data demonstrating that today in vivo solid tumor model added two or two in combination with an antibody induced significant tumor <unk>.

Reduction tumor burden reduction.

<unk> and complete tumor clearance and 40% of mice over the course of the experiment.

The edit to dramatically improve mess survival over wild type of NK cells in the same muscle.

Is that all <unk> remained alive at the end of the 120 day study period.

These impressive data support the development of edit 202, as a potential allogeneic cell based medicine for treating solid tumors.

One of the key Differentiators in this program as I use of Athena cell free system to expand and differentiate the edited Ips C into mature NK cells.

Most approaches that facilitate the differentiation of <unk> immune cells involved platforms that typically use feed yourselves, introducing inherent risks and exemption of south fragments getting into the final drug product.

In contrast, I NK platform developed using a feeder cell free system with defined components for GMP I NK cell production and we are currently in the process of scaling the manufacturing.

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

Operator: This does conclude today's conference call.

Operator: Thank you for your participation.

Operator: You may now disconnect.

Thank you Mark 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 2020.

Operator: Goodbye.

This opportunity.

A few items.

Our cash cash equivalents marketable securities as of June 3500, 28 million compared to $566 million in the prior quarters, we continue to be disciplined with our expense management and our cash runway.

And into 2020.

Revenue for the first half of the year was $13 7 million for the same period last year. The increase was primarily attributable to additional programs licensed under our collaboration with BMS.

G&A expenses for the first half of the year $36 million compared to 44 3 million for same period in 2021.

The decrease was primarily driven by performance awards granted.

That were recognized in the second quarter 2021.

R&D expenses for the first half year were $82 million.

6 million same period last year. This increase was primarily driven by increased manufacturing.

Employee related.

Yeah.

And lastly, as Mark mentioned, we recently announced the collaboration.

As part of these collaborations <unk> received an upfront cash payment.

For additional payments based on development regulatory and commercial milestones.

<unk> will also receive royalties on future net sales on any products that may result from this collaboration.

Overall <unk> remains in strong financial position.

Our program.

I'll turn the call back to Joe Moore.

Thank you Michelle.

Baisong Mei: And the opportunity to be a part of a gene editing pioneer is why I'm here.

Again, I want to reiterate how excited I am for the future of outages why do we have exponentially enhanced our technology capabilities. We are no longer simply a technology platform company.

Over the past several years, we have focused on building out our operations and manufacturing teams and have our sights on the end goal, which is commercialization of life changing medicines for patients and it's a very thoughtful clinical development. We are rapidly transitioning with therapeutics company, while remaining on the cutting edge of innovation.

Baisong Mei: Over the course of my career, I have had the privilege to work in all segments of drug, development lifecycle.

Baisong Mei: I entered pharmaceutical industry as a CNC scientist over 20 years ago.

Baisong Mei: While working in CNC, I was leading discovery research team.

Baisong Mei: After transitioning to discovery research, I also had an opportunity to assist in clinical, development, which is where I have stayed. I took a leadership role in clinical development with end-to-end responsibility on first-in-human, clinical study to global approval.

Underpinning this transition are further advancements to our innovative technologies, such as our proprietary sleep knock in gene editing platform.

We also continued to be active with business development activity and look forward to advancing discussions related to our foundational intellectual property.

Moving forward, we will prioritize assets that maximize the probability of technical regulatory and commercial success. This includes current and future programs in our pipeline.

Baisong Mei: My experience in CNC and discovery research has been profoundly valuable and has impacted, me in my work in clinical development.

So what is in store for aggressive this year on the in vivo side, we will be providing a more comprehensive clinical update on our brilliance trial of edit 101 later this year.

Baisong Mei: In general, I consider myself to be a drug developer at heart, and my goal is to help, clinical editors to develop and bring the right medicine through approval for patients who need treatment.

Baisong Mei: I look forward to updating you on our clinical progress on subsequent calls.

That update will focus on safety data additional POC data set to 90 as seen in the retinal sort receptors and the identification of the optimal patient segment.

<unk> functional visual outcomes for use in future Registrational studies.

Following feedback from the FDA, we plan on initiating IND, enabling studies for edit 103 for row ERP later this year.

Baisong Mei: With that, I will turn the call over to our chief scientific officer, Mark, who will provide an update on our R&D efforts.

And moving to ex vivo, we expect to have initial top line clinical data for our <unk> study in sickle cell disease. Later this year, which will include data from the first patient of potentially second patient.

And finally, we have begun screening based Palestinian patients for the study of edit 301 for beta thalassemia and anticipate a resist editing of product is the first patient dosing or before the end of the year.

We thank all of you for your interest and support.

And with that we're ready to open up the call for Q&A.

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

Mark Sherman: Thank you, Baishong.

Mark Sherman: As Gilmore has provided updates on EDIT101 and EDIT301, I'd like to begin with EDIT103, for Rho-ADRP.

Like to ask a question. Please press star one on your telephone keypad. The confirmation tone will indicate your line is in the question queue.

Mark Sherman: As a reminder, EDIT103 is highly differentiated from EDIT101 with a different approach and, superior preclinical data. EDIT103 uses two adeno-associated virus vectors to knock out the mutant rhodopsin in order, to correct the toxic gain of function while simultaneously replacing that aberrant gene with a functional one. The knockout of the gene in the retinal photoreceptor cell can only occur if the components for, the replacement gene are also delivered to and active in that same cell.

Mark Sherman: This mutation-agnostic approach can potentially address more than 150 gene mutations that cause, Rho-ADRP.

Mark Sherman: At the ALBO meeting in May, we presented preclinical data that demonstrated nearly 100% productive, editing in non-human primates and generated over 30% functional rhodopsin gene replacement, which proved to be therapeutically effective in that NHP study. The data also showed improved photoreceptor organization and improved retinal morphology, in the knockout and replace treated group.

Mark Sherman: As we continue to optimize the product, we also think there is potential for further, improvement upon that data that we've already presented.

Mark Sherman: We also recently received encouraging FDA feedback on EDIT103 and its expectations as, we approach an IND filing. Based on the FDA's input and our ongoing work on the program, we remain on track to initiate, IND-enabling studies later this year.

You May press star two if you'd like to remove your question from Nokia for participants using speaker equipment and that would be necessary to pick up your handset before pressing the star keys.

Mark Sherman: Moving now to our cell therapy programs.

One moment, please while we poll for questions.

Mark Sherman: In June, we announced a collaboration with EMATICS related to a strategic research collaboration, and licensing agreement, pursuant to which we will apply our gene editing technology to gamma delta T-cell adoptive cell therapies, an area where EMATICS has world-class expertise.

Mark Sherman: We believe that this collaboration will give us the opportunity to develop novel T-cell-based, therapeutics for enhanced tumor recognition.

Mark Sherman: In our cellular therapy collaboration with Bristol Myers Squibb, we were pleased to announce, earlier this morning that BMS has opted into an eight editing program for alpha beta T-cell therapeutics. This was their fifth opt-in over the last 12 months, and we are collectively optimistic, about continuing the momentum of that partnership.

Yeah.

Mark Sherman: BMS has multiple early programs covering both solid and heme tumors that incorporate edit, assay technology and use multiple edits to optimally engineer T-cells, both in autologous and allogeneic platforms.

Mark Sherman: The most advanced program from this collaboration is currently in ING-enabling studies. The engineered cells demonstrate improved tumor killing and anti-tumor efficacy compared, to wild-type cells, both in vitro and in vivo. We believe that these improved pharmacodynamic and phenotypic characteristics in engineered, T-cells open the door for numerous potential clinical applications.

Yeah.

Mark Sherman: For our in-house cellular therapy programs, we are very pleased with the progress we are, making with our iPSC-derived NK cell medicine program for solid tumors, with a focus on, EDIT202 as our lead program in this area and currently in preclinical development. Using our proprietary engineered ASCAS12A nuclease and SLEEK technology, we have developed, engineered NK cells that have potent anti-tumor activity and substantially increased persistence in preclinical models, which we believe could lead to lower frequency dosing, an important potential advantage for patients compared to many existing NK cell approaches.

Mark Sherman: At the ASGCT annual meeting in May, we presented data demonstrating that an in vivo solid tumor, model, EDIT202 in combination with an antibody-induced significant tumor reduction, tumor burden reduction, resulting in complete tumor clearance in 40% of mice over the course of the experiment.

Michelle Robertson: Thank you, Mark.

Thank you. Our first question is from Gena Wang with Barclays. Please proceed with your question.

Mark Sherman: Further, EDIT202 dramatically improved mouse survival over wild-type INK cells in the same, model such that all mice remained alive at the end of the 120-day study period.

Mark Sherman: These impressive data support the development of EDIT202 as a potential alginaic cell-based, medicine for treating solid tumors.

Mark Sherman: One of the key differentiators of this program is our use of a seed-cell-free system to expand, and differentiate the edited iPSC into mature NK cells.

Mark Sherman: Most approaches that facilitate the differentiation of iPSC into immune cells involve platforms, that typically use fetal cells, introducing inherent risk of exogenous cell fragments getting into the final drug product.

Mark Sherman: In contrast, our INK platform is developed using a fetal-cell-free system with defined, components for GMP INK cell production, and we are currently in the process of scaling the manufacturing.

Michelle Robertson: With that, I'll turn the call over to our Chief Financial Officer, Michelle, to review our financial updates.

We're taking our question this is Tom.

I have two questions for sickle.

Sickle cell disease.

<unk> seen a female so first I understand maybe earlier, but do you have a rough estimate.

Quiet following purity and trial size for both indications given the ftes experience with either a more advanced part outs and secondly on the trial.

And side would you be able to dose the next patient in parallel or when would you be able to do that.

Thank you I am afraid I couldn't catch your name.

But I propose the size of the study.

We are at.

Closely monitoring.

While at the FDA and other regulatory authorities are guiding to us.

And to our peers in this space.

But we have designed this study to enable us to recruit the <unk>.

<unk> is necessary and we have the manufacturing capacity to ensure that absolute supply will be available after those numbers.

With regards to enrollments.

We have in our current protocol a.

Set of criteria.

For the first couple of patients where we follow them.

For approximately 40 days, rather specifically 40 days and hold an independent data monitoring review of safety data to initiate the second and at <unk>.

Third patients after that our intention is to move as quickly as feasible and this is one of the reasons why I'm. So happy that we have our new Chief Medical officer based on my with his experience.

In this space to help us really doubled down on clinical execution.

Thank you.

Thank you. Our next question is from Joon Lee with tourists Securities. Please proceed with your question.

Alright, thanks for taking thanks for the updates and taking our questions and looking forward to the progress with the new additions to the management.

I have two questions on edit 301 are you able to disclose how quickly the cells and graph that also I'd presume bypassing the need for buyer, let look at it for edit 301 with promoter edits could lead to better efficacy compared to using enhancer edits do you think that will show up as a clinical benefit or is that more.

Have a manufacturer manufacturing consideration and lastly.

How are you looking to differentiate from ex itself and I have a quick follow up.

Okay. Thank you very much at June .

So.

We have not yet just because we will be planning to disclose our clinical data at the end of the year. When we will actually be able to give outcomes around and grassman as well does a hematological parameters.

With regards to the differentiation, we believe that as you say.

You are saying the promoter of the gamma globin actually does.

Increase the durability of expression of fetal hemoglobin.

That may be displayed.

In the Hematological parameters over time.

But I think as we have.

Set in previous discussions.

Discussions.

We anticipate that the clinical benefits of which we believe there will be important wells will declare themselves are over a longer term follow up after.

For patients.

I actually could not hear your third question I'm afraid.

Oh, no I think you answered it.

So a quick follow up on the Gamma Delta what drew you to gamma Delta and are you applying your sleek method for the gamma <unk> Alpha program I might have missed that side once out of multitasking and thank you so much.

Mark Hey, John its Mark here I can certainly answer that so.

We really like the opportunity of Gamma Delta T cell program with the matrix provides us many of the technologies that we have used to support the MS program can be equally applied to the <unk> program.

As we had indicated in the earlier press release.

They have the opportunity to nominate.

Up to a number of targets for that program.

We're looking forward to getting that initial lift from them, but short answer is yes, we can apply <unk> nuclease basic technology to that program.

Fantastic. Thank you so much.

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

Great. Good morning, Thanks for taking our questions and congrats on all the progress on our work come on Board del Mar Nice to speak to you again two questions from US just wanted to follow up on June's question about differentiation. So if gilmore when you were talking about.

Michelle Robertson: And good morning, everyone.

Michelle Robertson: I'd like to refer you to our press release issued earlier today for a summary of our, financial results for the second quarter of 2022.

Michelle Robertson: I'll take this opportunity to briefly review a few items.

Michelle Robertson: G&A expenses for the first half of the year were $36 million, compared to $43 million, for the same period in 2021. The decrease was primarily driven by performance awards granted in 2021 that were recognized, in the second quarter of 2021.

Michelle Robertson: And lastly, as Mark mentioned, we recently announced a collaboration with Enatics. As part of this collaboration, Etitas received an upfront cash payment and is eligible for, additional payments based on development, regulatory, and commercial milestones. Etitas will also receive royalties on future net sales on any products that may result, in this collaboration.

Michelle Robertson: R&D expenses for the first half of the year were $82 million, compared to $76 million, for the same period last year. This increase was primarily driven by increased manufacturing and clinical investments in, wage-related services.

Michelle Robertson: Overall, Etitas remains in a strong financial position as we continue to advance our program.

Michelle Robertson: With that, I'll hand the call back to Dilbar.

Gilmore O'neill: Thank you, Michelle.

Differentiation between edit 301, and C T X or y and potentially declaring itself sort of over the longer term.

How long of a follow up would we anticipate before we differentiate or see that differentiation play out.

Given that the market dynamics at that point would be presumably see checks all one being marketed and then secondly on edit 301, Mark just looking back at the strategy you have youre using the dual vector I guess can you walk us through sort of the idea or why it would be a superior compared to a single vector.

<unk> utilizing edit 101, and perhaps as we anticipate the second half update from brilliance is there anything that you would be looking to that could be potentially seen as a read through with two out of three are what is the IND, enabling studies get underway. Thanks, so much.

Thanks, very much and take on good to talk again, let me address the first question.

Around 301 differentiation and add the read through on the clinic.

That would be something that we will actually have to determine a over the long term. However, we do see the potential.

We're of persistence and durable feeding homeowners expression, that's something that we could see a based on a hematological parameters in the near term in the medium to long term.

Could see and would anticipate reading those true on the clinical side too.

Two.

Entailing.

Hemoglobin levels.

At a very favorable levels to ensure long term benefits to patients with regard to end organ health.

And we would see that reading through in both sickle cell and basic palestinia and the long term.

We'll say your addressed market dynamics, I think I'd like to address that too wild CTX 001 may actually be first to market based on our experience and observation of recent gene therapeutics, our so called one and done therapy launches, we anticipate that the the pulled.

True from that <unk> zero, one approval will.

We will not actually leads to a large number of treated patients remain a large number of untreated patients remain at the time of our launch and commercialization because of the challenges are outside capacity and again. This is what we've seen with other gene or one of them therapies as well as the.

The challenges are around negotiating access and reimbursement.

So for those reasons, we do believe that that market is there for our product and then with our differentiation of <unk> hundred one we believe that this could be the treatment of choice.

And then I'm happy to answer your question on edit one O three.

The similarities with one O one really the AAV five capsid and the S. A cast nine and so we know that with sub retinal injection, we can effectively transduce human photo receptors, both without data as well as from other gene therapy programs, but I think pretty much that's where the similarities are.

And with edit one O three the reason why we are using a <unk> vector system is because it is an autosomal dominant disease with a dominant kind of negative function of the mutated rhodopsin.

Any therapy has to stop by removing that mutant <unk>.

Dobson and then replacing it with a codon optimized wild type human rhodopsin and the only way you can do that.

Just on the size of the components is with a dual vector system and as you probably remember we split the components.

Rationally between the two vectors, so that only those foot receptors, which take up both Texas, which actually by the way, it's probably all of them anyway, but only those photoreceptor should take up both Texas can actually.

Executing the two step process of knocking down the endogenous and replacing it.

And lastly for this particular for edit one of the three were targeting rod photoreceptor as opposed to a cone photoreceptor Saturday.

Yeah.

Great. Thanks, so much.

Thanks.

Thank you. Our next question is from Jay Olson with Oppenheimer. Please proceed with your question.

Gilmore O'neill: Again, I want to reiterate how excited I am for the future of Etitas.

Gilmore O'neill: While we have exponentially enhanced our technology capabilities, we are no longer simply a technology, platform company.

Oh, Hey, everybody I want to also have a new management team and thank you for the introduction.

Gilmore O'neill: Over the past several years, we have focused on building out our operations and manufacturing, teams and have our sights on the end goal, which is commercialization of life-changing medicines for our patients.

Gilmore O'neill: Through very thoughtful clinical development, we are rapidly transitioning to a therapeutics, company while remaining on the cutting edge of innovation. Underpinning this transition are further advancements to our innovative technologies, such as our, proprietary sleek knock-in gene editing platform.

Gilmore O'neill: We also continue to be active with business development activity and look forward to advancing, discussions related to our foundational intellectual property.

Thanks for taking the question.

Maybe just on one on one.

Gilmore O'neill: Moving forward, we will prioritize assets that maximize the probability of technical, regulatory and commercial success. This includes current and future programs in our pipeline.

Can you just comment on the pace of enrollment in the pediatric cohort and any color you can provide there in terms of when you expect to complete dosing in a mid dose cohort.

And when is the next Ah I D. M. C safety review and also any color you can provide on the dosing and expanded cohorts how many patients.

And when we should expect to see a data or clinical update in the second half of the year. Thank you.

Gilmore O'neill: So what is in store for the rest of this year?

And thanks very much Jay.

So let me start at the end and just say that we will be on track to provide clinical data updates.

Gilmore O'neill: On the In Vivo side, we will be providing, a more comprehensive clinical update on our brilliance trial of EDIT101 later this year. That update will focus on safety data, additional POC data for CEP290 editing in the retinal, photoreceptors, and the identification of the optimal patient segment and functional visual outcomes for use in future registrational studies.

Gilmore O'neill: Following feedback from the FDA, we plan on initiating IND-enabling studies for EDIT103 for Rho ADRP later this year.

At the end of the year or before the end of the year. Prior guidance has been around the October November timeframe.

Gilmore O'neill: And moving to Ex Vivo, we expect to have initial top-line clinical data for our Ruby study in, sickle cell disease later this year, which will include data from the first patient and potentially second patient.

And in that data set we will provide efficacy data from the completed mid and high Adult's dose cohorts from an efficacy point of view from a CIT for safety, we will actually have a data cut from all dose patients as would be good practice.

Gilmore O'neill: And finally, we have begun screening beta-thalassemia patients for the EDIT-thal study of EDIT301 for beta-thalassemia and anticipate apheresis editing of product and, first patient dosing all before the end of the year.

Gilmore O'neill: We thank all of you for your interest and support, Editas.

With regard to the <unk>. The IBM Z is scheduled to meet measure that is the independent data monitoring committee is scheduled to meet later this quarter at which point you would evaluate data, including the two pediatric mid dose patients and that meeting a wood.

Can you give a decision to enable us to start enrolling in the high dose cohort and then with regards to the timing of pediatric enrollment.

Gilmore O'neill: And with that, we are ready to open up the call for Q&A.

The approach we initially used was slower than we expected.

Operator: Thank you.

One of the reasons that I'm here and Thats based song has joined US is to really double down our efforts on clinical execution.

We have amended and are actively amending the approach and anticipate that we will be enrolling a faster I do have to say that I don't have complete line of sight, yes.

Share that with you in the near future.

Maybe to add one comment on the agile as you recall, we gave ourselves the option to expand into the mid and high dose adults.

And you know that.

It used to be a possibility obviously reliant upon evaluation of the data as it emerges.

Great. Thanks for taking the question.

Okay.

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

Operator: We will now be conducting a question and answer session.

Hi, This is Ranga Patel Entre Luke AUC. Thank you for taking my question I just wanted to ask Mr. O'neill. Given this is your first earnings call can you talk about the top three reasons why you decided to join the organization and maybe what was the biggest hesitation or concern.

Operator: If you would like to ask a question, please press star 1 on your telephone keypad.

Operator: The confirmation tone will indicate your line is in the question queue.

And just another on sickle cell, assuming vertex and CRISPR and possibly Blue got approved ahead of you. How are you thinking about the likelihood of getting approved on a single arm trial can back da asking you would have on a head to head trial.

Operator: You may press star 2 if you'd like to remove your question from the queue.

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

So I just I'm sorry at Reno. Thanks for your question. This is Gilmore here.

Clarify it I am the one who has just joined the company and based on that just in a company that Michelle I'm happy to say has been with the company for some time as she met cheapened out. So forgive me I just wanted to be sure that maybe you were addressing the question to me and what I would say is that what drew me to the company, where a number of things not just the <unk>.

Operator: One moment, please, while we pull for questions.

Operator: Thank you.

Operator: Our first question is from Gina Long with Barclays.

Operator: Please proceed with your question.

And the history of its foundational CRISPR technology.

But <unk>.

Very importantly, the strength of the science that I saw here and particularly the.

Our differentiated core expertise in nuclear as design and engineering. One Nice example is 12 eight.

<unk> evolution.

Which is a high fidelity high efficiency enzyme that we've actually now have in the clinic.

In addition, the guide RNA there is substantial expertise in both chemistry and designed for a guide or to name other important capabilities also sits within our discovery.

Group.

Particularly around our our quantitative.

Biology, which AIDS us in our design of a guide Rnas finally, the CMC capabilities switch.

Which are actually impressive.

With both scale and quality and you are more important to concrete examples that we have so little supply.

Both for delivery of an EV as well.

Autologous editor itself I did see finally about CMC, but there are other things that drew me as well. The fact that the technology is in the clinic using two platforms and quite frankly, the cash position, which should be self described our strong and well it's actually importantly, enjoying it.

So then the other question was around vertex and CRISPR in both the impact of those approvals might have.

Our design.

Yes.

You know, how we talk to the FDA and the outcomes of our discussions the FCA are some things that I would not want to speculate on but I will tell you that.

Our trial currently is designed in a way that enables us to look at both hematological parameters as well as clinical Congresses booked for the sickle cell patient population that we are treating on recruiting as well as the basic trial patient population and the press.

Surgeons that were seeing SaaS gives us some confidence about our approach and obviously as the field.

<unk> evolves.

We will be more confidence, but I think currently we are very well positioned.

In our design approach to developing a 301.

The only other thing I do actually want to remind everyone off is that our partial clinical hold.

Was removed by the FCA why does that matter it matters because it enables us to use all of the efficacy data.

In the ongoing trials as part of a marketing application.

Operator: We're taking our question.

Great. Thank you.

Operator: This is Tom for Gina.

Yeah.

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

Operator: I have two questions for the sickle cell disease, and beta-thalassemia.

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

Operator: So first, I understand it might be earlier, but do you have a rough estimate on the required following-up period and trial size for both indications, given the FDA's experience with other more advanced products?

So my first question is regarding the development of edit 301 in beta Thal given that there is an upcoming could do for date for computing gene therapy candidate.

For beta cell in the U S can you speak to the opportunity along with some of the challenges in starting phase one trials in a treatment setting isn't approved gene therapy product.

And for my second question, what's the Alpha beta and Gamma Delta T cell programs have license agreements with outside partners.

I NK cell program is currently being developed in house.

Thank you Omar I was hoping to get your thoughts on the rationale for keeping this program, where we owned and what's the right stage of development would be for thinking about whether or not a partnership here would make sense.

Okay. Thanks, very much rich.

So with regard to edit 301.

The change, but based on solid team here and indeed sickle cell remains strong we believe.

We believe that it has value.

On its own right. We believe it's a differentiated product, but actually very important we believe that.

At the time that we both initiation or were there as we continue I should say to recruit patients into our ongoing trials and.

When we look at the commercial space when we would launch.

We believe that owing to.

The number of the challenges I outlined.

The uptake and the number of treated patients will actually to be relatively slow certainly for that first approval because of challenges around.

Access and reimbursement.

We have actually confidence that there is value to this program for those reasons and also that we will be able to execute on enrolled in our ongoing Eddie.

As well as Ruby studies.

With regard to the partnering.

You pointed out our partnerships in some immuno oncology spaces.

As Mark has said.

The <unk> program.

Is has moved well.

We are always interested in.

We're looking at the potential for partnerships.

One of the great opportunities and challenges that I have seen with epipen.

Is the broad applicability of its technology and I think I said, when I joined the organization and and maintained the position that one very good way to maximize the value of that technology for patients as well as for our other stakeholders is to maximize and broaden our bandwidth rich.

<unk> through partnership.

We are open to looking at partnerships and have said before that we are open to partnerships across a number of our platforms, including the <unk> platform.

Thank you. Our next question is Phil Nadeau with Cowen <unk>.

Company. Please proceed with your question.

Operator: And secondly, on the trial, on the enrollment side, would you be able to now to dose the next few patients in parallel, or when would you be able to do that?

Good morning, Thanks for taking our questions a couple on the ocular programs from US first on edit 101, I think you're guiding to.

Finding the Registrational trial design by the end of the year seems like you're you only have a pretty modest experience with the pediatric high dose a.

By that time, so how can you.

Does that in the Registrational trial without without that hydro stayed at when when the Idose data provide important information on the dose necessary to patients and possibly the efficacy endpoint.

So we have not guided to.

Defining a final registration study about a year for the very simple reason that.

One would have to do that in discussions with regulatory authorities, including the FDA.

Operator: Thank you.

I should have said by the way Phil. Thank you for your question Nishu.

But we have not given that guidance.

What we anticipate doing is looking at that data, we would have a large datasets.

From our mid and high dose a dose.

Patients and we'll be able to look at a segment of the patient population.

Because we have seen proof of concepts in adult subjects.

And we will be also looking ash and evaluation and selecting potential endpoints and we will bring that entire datasets to regulatory.

Engagements. It is important to note that we also have a natural history data set that we'll be looking at that actually also helps us in selecting designing and understanding performance of interaction off those two at the end.

Points with a broad population that spans the pediatric and adult population.

That's very helpful. And then second question on edit one of three.

You disclosed non human primate data that shows 95% editing and about 37% human protein production in nonhuman primates.

What data is there to suggest whether that couple of protein production is sufficient to rescue them.

To rescue the disease.

Yes, Thanks, Phil I mean, we're basing that well there are two factors that led us to make that statement. One is in the study itself.

And the rate in the market only.

We're able to demonstrate a loss of photo receptors that could be corrected with a nutcase and replace approach and so in that particular experiment that 30 ish percent rhodopsin were sufficient to rescue those cells, which would otherwise.

Be eliminated.

You know from the retina. That's one the second is that they said well published.

Published.

<unk> model from the <unk> group.

C N and William Beltran.

They did a nutcase and replace experiment with E. S. H RNA in rhodopsin in their hands. They showed that the bank's 30% rhodopsin expression with sufficient to rescue.

Receptors in that model system. So those two pieces of information together, we believe guide us to an approximate level of rhodopsin expression that will be sufficient what we've also said, though is that that was the level in that particular experiment. There are still some things that we can change in the <unk>.

That those experiments are conducting to modify the editing versus replacement levels.

That work is ongoing in the lead up to the DNA.

That's very helpful. Thanks for taking our questions.

Yeah.

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

Operator: Thank you.

Operator: I'm afraid I couldn't catch your name, but I propose the size of the study.

Hi, Thanks for taking the question for edit 101.

Operator: We are closely monitoring what the FDA and other regulatory authorities are guiding to us and to our peers in this space.

Have you gotten any FDA feedback on their thoughts of a use of the.

First street cohort as opposed to using a control arm in a registrational trial.

Thanks, very much Joel.

Clearly.

Operator: But we have designed a study to enable us to recruit the patients necessary, and we have the manufacturing capacity to ensure that clinic supply would be available for those numbers. With regards to enrollment, we have in our current protocol a set of criteria for the first couple of patients, where we follow them for approximately 40 days, or rather specifically 40 days, and hold an independent data monitoring review of safety data to initiate the second and third patients.

Operator: After that, our intention is to move as quickly as is feasible, and this is one of the reasons, why I'm so happy that we have our new chief medical officer, Baselang Lai, with his experience in this space to help us really double down on clinical execution.

The fact that we have a natural history cohort.

Has been a very important point in our discussions.

Operator: Thank you, our next question is from Joon Lee with Truist Securities, please proceed with your question.

Within internally around our strategy for clinical development, we have not yet had such discussions with the regulatory authorities.

But.

We will be using both our clinical.

Interventional experienced in the brilliance trial as well as natural history study as we consider the optimal design and prepare for those discussions with the authorities, including the FDA.

Great. Thank you.

Yeah.

Yeah.

Thank you. Our next question comes from non shoe with Wells Fargo Securities. Please proceed with your question.

Operator: Hi, thanks for taking, thanks for the updates and taking our questions, I'm looking forward, to the progress with the new additions to the management.

Hi, Thanks for taking my questions and I wanted to I wanted to add my congratulations to go more in Python for your new appointment.

So.

Operator: I have two questions, on EDIT301, are you able to disclose how quickly the cells engrafted?

First question is related to 301, I think you touched upon the differentiation from CTX or won earlier in the call I just want to follow up more.

More specifically, whether you expect to see a greater hemoglobin fetal hemoglobin induction with your promoter editing approach.

Compared with CTX, Oh, one and also when you review our currently available clinical data for CTX or one where do you see.

The potential unmet need.

Are you in that in those dataset and perhaps your perhaps 301 could further improve in those areas.

And also.

301, how many patients have you pay for east and our manufactured the product for Ruby study and how what are at the year end data update are we should we expect just the first patients data or could we expect.

More patients data at year end. Thank you.

So thanks very much.

Nice to meet you, let me start with the end and that'll work back and also site and ask Mark to address some of the preclinical data.

Operator: Also, I presume bypassing the need for biallelic EDIT for EDIT301 with promoter EDITs could, lead to better efficacy compared to using enhancer EDITs, do you think that will show up as a clinical benefit or is that more of a manufacturing consideration?

Operator: And lastly, how are you looking to differentiate from exocell and I have a quick follow-up.

So we.

Operator: Thank you very much, Joon, so we have not, we will be planning to disclose our clinical, data at the end of the year when we will actually be able to give outcomes around engraftment as well as hematological parameters.

We are expecting to and planning to share clinical data from.

One and possibly two Ah patients at the end of this year that patient data will include safety as well as in grasslands and Hematological parameters.

With regard to the unmet need.

Operator: With regard to the differentiation, we believe that, as you say, editing the promoter of, the gamma globin actually does increase the durability of expression of fetal hemoglobin.

We believe that the differentiation.

<unk>.

Given by our product and there are two elements of differentiation I've highlighted the.

Operator: That may be displayed in the hematological parameters over time, but I think as we have, said in previous discussions, we anticipate that the clinical benefits of which we believe there will be important ones will declare themselves over a longer term follow-up for patients.

Baxter, we anticipate durable a very durable expression of fetal hemoglobin, owing to the promoter of the gamma globin.

Operator: I actually could not hear your third question, I'm afraid.

Genes that we've targeted but in addition, we're using a high fidelity highly efficient editing nuclease.

Sure.

Cash at 12 eight.

And what we believe is that that durable benefit is actually has the potential to be an important differentiator or.

Simply because.

It is independence it drives expression independent office, Christopher with leases, which is something that could actually.

Become increasingly mitigated over time, and so it would be important to maintain.

That durable expression of fetal hemoglobin and doing it independently of Crestwood squeezes.

First a significant differentiation advantage in the long term and then with regard to our our confidence around the expression of fetal hemoglobin I'm going to ask Mark just to talk about our preclinical data, yes, hi, Anna.

So early in the program the preclinical team conducted to the direct comparison.

Editing mechanisms, whether the HBK promoter region or the PCL M&A itself and we find that the.

The promoter region editing gave a slightly higher H b S levels at least in a preclinical model, but also importantly that we remain we maintain the fidelity of the lineage lineages derived from those cells, whereas with the T cell <unk> approach there was some skewing so.

Efficacy wise, we believe that could be an advantage and then long term safety wise also we have some concerns with T cell.

Editing, a transcription factor, which has more than one.

Function.

At this point in time, the differentiation will be determined by the clinical data that is the data that's emerging.

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

Operator: Oh, no, I think you answered it.

Good morning, This is Ryan Deschner on for Steve.

Operator: So a quick follow-up on the gamma delta, you know, what drew you to gamma delta and are, you applying your SWEAK method for the gamma delta program?

Operator: I might have missed that as I was multitasking.

I wanted to ask what is your general expectation for neutrophil and platelet and graph meant for patients in the sickle cell study.

There been any.

Of note in particular associated with the sell product. Thank you.

Operator: Thank you so much.

Thanks, Brian good to meet you so our expectation for in Grassman, a place of neutrophils.

Operator: Mark.

Operator: Hey, Joon, it's Mark here, I can certainly answer that.

Operator: So you know, we really like the opportunity that the gamma delta T-cell program with hematics, provides us. Many of the technologies that we have used to support the DMS program can be equally, applied to the hematics program.

Operator: As we had indicated in the earlier press release, you know, they have the opportunity to nominate, up to, you know, a number of targets for that program, and we're looking forward to getting that initial list from them.

We actually designed our protocols to capture around day 30.

240.

Obviously, it varies across patients and that has been the experience.

For both autologous and allogeneic.

Our generic experience in general.

But we will be able to share more specifics of that are.

Near the end of the year and as the program progresses.

The second question.

Secondly, we have not actually seen not actually seen its.

S Aes.

And.

Spirit to date, but obviously.

We are aware of that.

The procedure itself.

Beyond the interesting, but in general for Grassman does carry identified risks and obviously, we monitor that very closely but I think very importantly, we have not seen sce's at all and more specifically has not seen adverse events.

And that would give us concern about the product.

Got it thank you very much.

Thank you. Our next question comes from Matt who come on with Goldman Sachs. Please proceed with your question.

Operator: But short answer is yes, we can apply the S-Cas12a nuclease SWEAK technology to that, program.

Operator: Fantastic.

Operator: Thank you so much.

This is omar or for module for the <unk>.

Operator: Thank you.

Operator: Our next question is from Dagon Ha with Stiefel.

First question could you give us a sense of what kind of efficacy profile do you need to see given what our dose to pursue a registrational trial and then what do you pay it presents.

Operator: Please proceed with your question.

Operator: Great.

Operator: Good morning.

Update at a medical meeting or separately.

So with regard to our success criteria well.

Operator: Thanks for taking our questions and congrats on all the progress and welcome on board, Gilmore.

Operator: Nice to speak to you again.

We would want to see is an extension of the POC that we've seen with stability and essentially improvement.

Operator: Two questions from us.

Operator: Just wanted to follow up on Joon's question about differentiation.

In some of the adult patients.

Operator: So Gilmore, when you were talking about differentiation between EDIT301 and CTX001 potentially declaring, itself sort of over the longer term, I guess how long of a follow-up would we anticipate before we differentiate or see that differentiation play out given that the market dynamics at that point would be presumably CTX001 being marketed?

The other determinants of success for the study will be identifying a segment of the patient population that maximizes or has the maximum probability of.

Operator: And then secondly, on EDIT301, Mark, just looking back at the strategy you have here, using the dual vector, I guess can you walk us through sort of the idea or why it would be superior compared to a single vector utilizing EDIT101?

Operator: And perhaps as we anticipate the second half update from Brilliant, is there anything that, you would be looking to that could be potentially seen as a read-through to EDIT301 as the IND-enabling studies get underway?

Operator: Thanks so much.

Operator: Thanks very much, Dagon.

Responding to the therapy and also interacting.

Operator: Good to talk again.

Operator: Let me address the first question around 301, differentiation and the read-through on the clinic.

Operator: That would be something that we will actually have to determine over the long term.

Operator: However, we do see the potential of persistence and durable fetal homologous expression as something that we could see based on hematological parameters in the near term.

Operator: In the medium to long term, we could see and would anticipate reading those through on the clinical side to maintaining hemoglobin levels at a very favorable level to ensure long-term benefits to patients with regard to end-organ health.

With a select set of endpoints that would actually also be determined by the phase one study and our interaction.

Operator: And we would see that reading through in both sickle cell and basic thalassemia in the long, term.

Operator: I will say you addressed market dynamics.

Our analysis of that.

Right.

Co analysis of the natural history study.

Operator: I think I'd like to address that too.

Operator: While CCX001 may actually be first to market, you know, based on our experience and observation, of recent gene therapeutics or so-called one-on-done therapy launches, we anticipate that the pull through from that CCX001 approval will not actually lead to a large number of treated patients remain, a large number of untreated patients remain at the time of our launch and commercialization because of the challenges around site capacity.

Operator: And again, this is what we've seen with other gene or one-on-done therapies, as well as the challenges around negotiating access and reimbursement.

And with regard to selection of the dose.

Operator: So for those reasons, we do believe that that market is there for our product.

Operator: And then I'm happy to answer your question on edit 103.

Operator: And then with our differentiation of 301, we believe that this could be the treatment of choice.

Operator: The similarities with 101 are really, the AAV5 capsid and the SA-Cas9.

<unk> phase one study will actually obviously be partial selection that dose.

Operator: And so we know that with subretinal injection, we can effectively transduce human photoreceptors both with our data, as well as from other gene therapy programs.

As you say the success criteria for selecting that dose would be determined by <unk>.

Operator: But I think pretty much that's where the similarities end.

Operator: With edit 103, the reason why we're using a, dual vector system is because it's an autosomal dominant disease with a dominant gain of negative function of the mutated rhodopsin.

Operator: Any therapy has to start by removing that mutant rhodopsin and then replacing it with a codon-optimized wild-type tumor rhodopsin.

Operator: And the only way you can do that based on the size of the components is with a dual vector system.

Operator: And as you probably remember, we split the components rationally between the two vectors so that only those photoreceptors which take up both vectors, which actually, by the way, is probably all of them anyway, but only those photoreceptors who take up both vectors can actually execute the two-step process of knocking down the endogenous and replacing it.

Operator: And, you know, lastly, for this particular, for edit 103, we're targeting rod photoreceptors as opposed to cone photoreceptors.

Seeing a maintained stability and improvement in a segment of patients.

Operator: Great.

Operator: Thanks so much.

Operator: Thanks.

Operator: Thank you.

Operator: Our next question is from Jay Olson with Oppenheimer.

Operator: Please proceed with your question.

Operator: Oh, hey, everybody.

Operator: I want to also welcome the new management team.

Operator: Thank you for the introduction, and thanks for taking the question.

And we will we don't actually have a we are currently evaluating where we would share that data, but anticipate that is likely to be at a webinar later this year.

Operator: Maybe just on Edit 101, can you just comment on the pace of enrollment in the pediatric cohort and any color you can provide there in terms of when you expect to complete dosing in the mid-dose cohort, and when is the next IDMC safety review, and also any color you can provide on the dosing and expanded cohorts, how many patients, and when we should expect to see data or clinical update in the second half of the year?

Okay.

Alright, Thank you guys for questions.

Thank you there are no further questions at this time.

Operator: Thank you.

Operator: Thanks very much, Jay.

Operator: So let me start at the end and just say that we will be on track, to provide clinical data updates at the end of the year or before the end of the year.

Operator: Our guidance has been around the October-November timeframe, and in that data set, we will provide, efficacy data from the completed mid- and high-adult-dose cohorts from an efficacy point of view.

It does conclude today's conference call. Thank you for your participation you may now disconnect.

Operator: For safety, we will actually have a data cut from all those patients, as would be good practice.

Operator: With regard to the IDMC, the IDMC is scheduled to meet later. That is, the Independent Data Monitor Committee is scheduled to meet later this quarter, at which point it will evaluate data, including the two pediatric mid-dose patients. And that meeting would give a decision to enable us to start enrolling in the high-dose cohort.

Operator: And then with regard to the timing of pediatric enrollment, the approach we initially used, was slower than we expected. One of the reasons that I'm here and that Baesong has joined us is to really double down our efforts on clinical execution. We have amended and are actively amending the approach and anticipate that we will be enrolling faster.

Operator: I do have to say that I don't have a complete line of sight yet, but we'll share that with you in the near future.

Operator: And maybe to add one comment on the adult, as you recall, we gave ourselves the option, to expand into the mid- and high-dose adults.

Operator: And, you know, that continues to be a possibility.

Operator: Obviously, it's reliant upon evaluation of the data as it emerges as well.

Operator: Let me start at the end, and then I'll work back and also cite and ask Mark to address, some of the preclinical data.

Operator: Great.

Operator: Thanks for taking the question.

Operator: Thank you.

Goodbye.

Operator: Our next question is from Luca Issy with RBC Capital Markets.

Operator: Please proceed with your question.

Operator: Hi, this is Reena Patel on for Luca Issy.

Operator: Thank you for taking my question.

Operator: I just wanted to ask, Mr. O'Neill, given this is your first earnings call, can you talk about the top three reasons why you decided to join the organization and maybe what was the biggest hesitation or concern?

Operator: And just another on sickle cell, assuming Vertex and CRISPR and possibly Blue get approved ahead, of you, how are you thinking about the likelihood of getting approved on a single-arm trial?

Operator: Can the FDA ask you to run a head-to-head trial?

Operator: So, I'm sorry, Reena, thanks for your question.

Operator: This is Gilmore here.

Operator: I just want to clarify, I am the one who has just joined the company, and Baisong has just joined the company.

Operator: Michelle, I have to say, has been with the company for some time, as she found out about it.

Operator: So forgive, me, I just want to be sure that maybe you were addressing the question to me.

Operator: And what I would say is that what drew me to the company were a number of things, not just the fact, and the history of its foundational CRISPR technology, but very importantly, the strength of the science that I saw here, and particularly the differentiated core expertise in nuclease design and engineering.

Operator: One nice example of the ASCAS12A evolution, which is a high-fidelity, high-efficiency enzyme that we have actually now have in the clinic.

Operator: In addition, the guide RNA, there is a substantial expertise in both chemistry and design for a guide RNA.

Operator: Other important capabilities also sit within our discovery group, particularly around our, quantitative biology, which aids us in our design of guide RNAs.

Operator: Finally, the CNC capabilities, which are actually impressive with both scale and quality, and more importantly, the concrete examples that we have clinical supply, both for delivery of AAV, as well as autologous edited cells.

Operator: I did say finally about CNC, but there are other things that drew me as well.

Operator: The fact that the technology is in the clinic, using two platforms, and quite frankly, the hash position, which Michelle described as strong and was actually importantly in joining.

Operator: So then the other question was around Vertex and CRISPR and what the impact, of those approvals might have on our design.

Operator: How we talk to the FDA and the outcomes of our discussion with the FDA are some things that I would not want to speculate on, but I will tell you that our trial currently is designed in a way that enables us to look at both hematological parameters as well as clinical parameters, both for the sickle cell patient population that we are treating and recruiting as well as the beta cell patient population.

Operator: And the big precedent that we're seeing set gives us some confidence about our approach.

Operator: And obviously, as the field evolves, we will be more confident.

Operator: But I think currently we are very well positioned in our design approach to developing 301.

Operator: The other thing I do actually want to remind everyone of is that our partial clinical hold was removed by the FDA.

Operator: Why does that matter?

Operator: It matters because it enables us to use all the efficacy data in the ongoing trials as part of a marketing application.

Operator: Great.

Operator: Thank you.

Operator: Thank you.

Operator: Our next question comes from Rick Bienkowski with SVB Security.

Operator: Please proceed with your question.

Operator: Hey, good morning.

Operator: Congrats on all the progress and thanks for taking our questions.

Operator: Just two from us.

Operator: So my first question is regarding the development of EDIT301 and BetaFowl.

Operator: Given that there is an upcoming PDUFA date for a competing gene therapy candidate for BetaFowl in the U.S., can you speak to the opportunity along with some of the challenges in starting Phase I trials in a treatment setting with an approved gene therapy product?

Operator: And for my second question, both the Alpha, Beta, and Gamma Delta T cell programs have, license agreements with outside partners and the INK cell program is currently being developed in-house.

Operator: Gilmore, I was hoping to get your thoughts on the rationale for keeping this program wholly owned and what the right stage of development would be for thinking about whether or not a partnership here would make sense.

Operator: Thanks very much, Rick.

Operator: So with regard to EDIT301, the opportunity for basal thalassemia and indeed sickle cell remains strong, we believe.

Operator: We believe that it has value on its own right. We believe it's a differentiated product.

Operator: But actually, very importantly, we believe that at the time that we both initiate or as we continue, I should say, to recruit patients into our ongoing trials and when we look at the commercial space when we would launch, we believe that owing to a number of the challenges that I've outlined, the uptake and the number of treated patients will actually be relatively slow, certainly for that first approval because of challenges around access and reimbursement.

Operator: So we're actually confident that there is value to this program for those reasons and also that we will be able to execute and enroll in our ongoing EDITAL as well as RUBY studies.

Operator: With regard to the partnering, as you've pointed out, our partnerships in some immuno-oncology spaces, as Mark has said, the INK program has moved well.

Operator: We are always interested in partnering or looking at the, potential for partnerships.

Operator: One of the great opportunities and challenges that I have seen with EDITAL is the broad applicability of its technology.

Operator: And I think I said when I joined the organization and maintained the position that one very good way to maximize the value of that technology for patients as well as for our other stakeholders is to maximize and broaden our bandwidth for execution through partnership.

Operator: And so we are open to looking at partnerships and have said before that we are open to partnerships across a number of our platforms, including the INK platform.

Operator: Thank you.

Operator: Our next question is from Phil Nadeau

Operator: with Cowan and Company.

Operator: Please proceed with your question.

Operator: Morning.

Operator: Thanks for taking our questions.

Operator: A couple on the ICLR programs from us.

Operator: First, on Edit 101, I think you're guiding to defining the registrational trial design by the end of the year.

Operator: It seems to us like you only have pretty modest experience with the pediatric high dose by that time.

Operator: So how can you design the registrational trial without that high dose data?

Operator: Wouldn't that high dose data provide important information on the dose necessary?

Operator: The patients and possibly the efficacy endpoints.

Operator: So, we have not guided to defining a final registration study by the end of the year for the very simple reason that one would have to do that in discussions with regulatory authorities, including the FDA.

Operator: I should have said, by the way, Phil, thanks for your question.

Operator: Good to meet you.

Operator: But we have not given that guidance.

Operator: What we anticipate doing is looking at that data.

Operator: We would have a large data set from our mid and high dose adult patients, and we'll be able to look at a segment of the patient population.

Operator: It is important to note that we also have a natural history data set that we'll be looking at that actually also helps us in selecting, designing, and understanding performance and interaction of those clinical endpoints with a broad population that spans the pediatric and adult population.

Operator: That's very helpful.

Operator: And then, second question on Edit 103.

Operator: You've disclosed non-human primate data that shows 95% editing and about 37% human protein production in non-human primates.

Operator: What data is there to suggest whether that level of protein production is sufficient to rescue the disease?

Operator: Yeah, thanks, Phil.

Operator: I mean, we're basing that, well, there are two factors that led us to make that statement. One is that in the study itself, in the knockout only arm, we were able to demonstrate a loss of photoreceptors that could be corrected with the knockout, and replace approach.

Operator: And so, in that particular experiment, that 38% rhodopsin was sufficient to rescue those cells, which would otherwise be eliminated in that, you know, from the retina.

Operator: That's one.

Operator: The second is that there's a well-published dog model from the UPenn group, Art Tadician and William Beltram, where they did a knockout and replace experiment with the shRNA and rhodopsin.

Operator: And in their hands, they showed that about 30% rhodopsin expression was sufficient to rescue photoreceptors in that model system. So those two pieces of information together, we believe, guide us to an approximate level of rhodopsin expression that will be sufficient.

Operator: What we've also said, though, is that that was the level in that particular experiment.

Operator: There are still some things that we can change in the way that those experiments are conducted to modify the editing versus replacement levels.

Operator: And that work is ongoing in the lead up to the IND and APEN studies.

Operator: Thanks for taking our questions.

Operator: Thank you.

Operator: Our next question is from Joel Beatty with Baird.

Operator: Please proceed with your question.

Operator: Hi.

Operator: Thanks for taking the question.

Operator: For Edit 101, have you gotten any FDA feedback on the thought of the use of the natural history, cohort as opposed to using a control arm in a registrational trial?

Operator: Thanks very much, Joel.

Operator: Clearly, the fact that we have a natural history cohort has been a very important point in, our discussions internally around our strategy for clinical development.

Operator: We have not yet had such discussions with the regular authorities, but we will be using, both our clinical intervention experience in the brilliance trial as well as a natural history study as we consider the optimal design and prepare for those discussions with the authorities and through the FDA.

Operator: Great.

Operator: Thank you.

Operator: Our next question comes from Yanan Xu with Wells Fargo Security.

Operator: Please proceed with your question.

Operator: Hi.

Operator: Thanks for taking my questions, and I wanted to add my congratulations to Gilmore and Bison, for your new appointments.

Operator: So first question is related to 301.

Operator: I think you touched upon the differentiation from CTX-001 earlier in the call.

Operator: I just want to follow up more specifically whether you expect to see a greater fetal, hemoglobin induction with your promoter editing approach compared with CTX-001.

Operator: And also, when you review currently available clinical data for CTX-001, where do you see, the potential unmet need in those data sets?

Operator: And perhaps 301 could further improve in those areas.

Operator: And also, 301, how many patients have you aphorized and or manufactured the product, for in the Ruby study?

Operator: And at the year-end data update, should we expect just the first patient's data, or could, we expect more patient's data at year-end?

Operator: Thank you.

Operator: So thanks very much, Yanan.

Operator: Nice to meet you.