Q3 2019 Earnings Call

Good morning, and welcome to Editas Medicine third quarter 2019 conference call.

Operator: Editas Medicine's third quarter 2019 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 has been recorded at the company's request. I would now like to turn the call over to Mark Mulliken, Vice President of Finance and Investor Relations at Editas Medicine.

All participants are now when I listen only mode. There will be a question and answer session. At the end of this call. Please be advised said this cost being recorded at the company's request I would now like to turn the call over to Mark Mullikin, Vice President Finance and Investor Relations at Editas Medicine.

Thank you operator, good morning, everyone and welcome to our third quarter 2019 conference call.

Mark Mulliken: Thank you, operator. Good morning, everyone.

Mark Mulliken: And welcome to our third quarter 2019 conference call. Earlier this morning, we issued two press releases that will be discussed on this call. The first announces an amendment to our longstanding collaboration with CELG. The second press release provides our financial results and corporate updates for the third quarter of 2019. A replay of today's call will be available on the investors and media section of our website approximately two hours after its completion.

Earlier. This morning, we asked you to press releases that will be discussed on this call.

The first announced as an amendment to our longstanding collaboration with Celgene.

Second press release provides our financial results and corporate updates for the third quarter 2019.

A replay of today's call will be available on the investors and media section of our website approximately two hours after its completion.

Mark Mulliken: After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent quarterly report on Form 10-Q, which is on file with the FCC. 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. We specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. Now, I will turn the call over to our Chief Executive Officer, Cindy Collins.

After our prepared remarks, we will open the call for killing.

That's a reminder, various remarks that we make during this call about the company's future expectations plans and prospects.

Constitute forward looking statements for purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward looking statements as a result, the various important factors, including those discussed in the risk factor section of our most recent quarterly report on Form 10-Q , which is on file with the FCC.

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.

We specifically disclaim any obligation to update or revise any forward looking statements. Even if our views change now I will turn the call over to our Chief Executive Officer, Cindy Collins.

Cindy Collins: Thank you, Mark. Good morning, and thank you, everyone, for joining us for our third quarter 2019 corporate update. In addition to Mark, I'm joined by several members of the Editas executive team, including Charlie Albright, our chief scientific officer; Judith Abrams, our new chief medical officer; and Eric Eck, our interim chief financial officer. Editas has had a productive quarter, and we are excited to share some of the highlights with you today. First and foremost, I am pleased to welcome Dr. Judith Abrams as our new Chief Medical Officer. Judith has tremendous experience and an outstanding reputation.

Thank you Mark good morning, and thank you everyone for joining us for third quarter 2019 corporate update.

In addition to Mark I'm joined by several members of the Editas executive team, including Charlie Albright, Our Chief Scientific Officer, Judith Abrams, our new Chief Medical Officer, and Eric Eric Our interim Chief Financial Officer.

At a child has had a productive quarter and we're excited to share some of the highlights with you today.

First and foremost I am pleased to welcome Dr. Judas Abrams as our new Chief Medical Officer, Judith has tremendous experience and an outstanding reputation. She is a valued addition to our executive team and her arrival is ideal as we prepare to just the first patient in the brilliance phase one too.

Cindy Collins: She is a valued addition to our executive team, and her arrival is ideal as we prepare to dose the first patient in the Brilliance Phase I-II clinical trial. Second, we announced this morning an amendment to our longstanding collaboration with Celgene to develop engineered T-cell medicines for cancer. As you may recall, our original collaboration spanned the entire field of engineered T-cells. The amended collaboration will focus on alpha-beta T-cells, freeing up Editas to develop its own medicines using non-alpha-beta T-cells. As a result of this amendment, we are entitled to receive a payment of $70 million with the potential for future milestones and royalties on alpha-beta T-cell medicines developed by Celgene using our technology. Third, we are making solid progress with EDIT301, our preclinical candidate to treat sickle cell disease and beta thalassemia.

Clinical trial.

Second we announced this morning and amendment to our long standing collaboration with Celgene to develop engineered T cell medicines for cancer as you may recall, our original quick collaboration spanned the entire field of engineered T cells. The amended collaboration will focus on Alpha beta.

He sells freeing up out of China to develop its own medicines using non alpha beta T cells.

As a result of this amendment we are in titles.

You receive a payment and $70 million with the potential for future milestones and royalties on Alpha Beta T cell medicines developed by Celgene using our technology.

Third we are making solid progress with added three a one our preclinical candidate to treat sickle cell disease and beta thalassemia, we look forward to sharing nvvault data at the upcoming Ash meeting demonstrating why we believe it has the potential to be a best in class medicine for.

Cindy Collins: We look forward to sharing in vivo data at the upcoming ASH meeting, demonstrating why we believe it has the potential to be a best-in-class medicine. Fourth, we recently formed a new collaboration with Aspio, a leader in AAV gene therapy, to develop CRISPR medicines to treat neurological diseases. This marks the second therapeutic focus for our in vivo CRISPR medicine portfolio in an area with high unmet need. Finally, our ophthalmology portfolio is advancing, with the first patient dosing of EDIT-101 for LCA-10 anticipated by early 2020. With that, I'd like to turn the call over to Judith Abrams, our new Chief Medical Officer, to introduce herself. Thanks.

We recently formed a new collaboration with asked file a leader in HIV gene therapy to develop in vivo, Chris for medicines to treat neurological diseases. This marks our second therapeutic focus for Nvvault, Chris for medicine portfolio in an area with high unmet need.

Finally, our ophthalmology portfolio is advancing with the first patient dosing of at at 101 for LCH than anticipated by early 2020 with that I'd like to turn the call over to Judith Abrams, our new Chief Medical officer to introduce yourself.

Thanks, Andy for your warm introduction, thank you all for being with us on the call today.

Judith Abrams: Thank you for your warm introduction, and thank you all for being on the call today. Over the course of my career spanning more than 25 years, I've had the opportunity to lead the development of medicines through all stages of clinical development across a number of therapeutic areas, including immunology and neurology. I'm thrilled to join EdChess Medicine at a pivotal time and look forward to advancing EDIT101 as well as additional experimental medicines in our pipeline through clinical development, including EDIT301 for the treatment of sickle cell disease and future engineered cell medicines for the treatment of cancer. Now, I will turn the call over to our Chief Scientific Officer, Charlie Albright, to update you on our pipeline.

Over the course of my career spanning more than 25 years I've had the opportunity to lead the development of medicine through all stages of clinical development across a number of therapeutic areas, including immunology and neurology I'm thrilled to join interest medicine. During the pivotal time and look forward to advancing added one or one as well as additional experimental.

Medicines in our pipeline through clinical development, including editorial one for the treatment of sickle cell disease and future engineered cell medicines for the treatment of cancer.

Now, let me turn the call over to our Chief Scientific Officer, Charlie Albright to update you on our pipeline.

Charlie Albright: As Cindy mentioned, we have amended our collaboration with Celgene to focus on developing autologous and allogeneic engineered alpha-beta T cell medicines to treat cancer and autoimmune diseases. We've been working with our partners at Juno Therapeutics and now Celgene since 2015 to develop engineered T-cell medicines to treat cancer. As the original research term was set to expire in May of next year, we've extended and focused our collaboration to enable the advancement of medicines into the clinic. As a result of the amendment, we have regained rights to develop non-alpha-beta T-cells in all disease areas. These rights were previously exclusive to cell gene therapy for oncology. For example, we now have the right to pursue gamma-delta T-cells for oncology. Gamma-delta T-cells are part of the innate immune system, as are NK-cells, where we have a significant effort using both donor-derived and iPSC-derived NK-cells.

Thank you [laughter] Hemi mentioned, we amended our collaboration with Celgene to focus on developing autologous allogeneic engineered Alpha beta T cell medicine to treat cancer and auto immune diseases.

We've been working with our partners that Juno Therapeutics, and they'll celgene since 2015 to develop engineered T cell medicines to treat cancer.

The original research term was set to expire in May of next year, we've extended in focused our collaboration to enable the advancement of medicines into the clinic.

As a result of the amendment, we've regained rights to develop non alpha beta T cells and all disease areas. These rights for previously exclusive to Celgene for oncology. For example, we now have the right to pursue gamma Delta T cells for oncology, Jim a delta T cells are part of the innate immune system as our NK cells rehab.

However, you think both donor derived from I.P.S.C. derived NK cells, we believe that cells from the innate immune system, both complement alpha beta T cells and increase the potential to treat solid tumors and area of significant unmet need.

Charlie Albright: We believe that cells from the innate immune system both complement alpha-beta T cells and increase the potential to treat solid tumors, an area of significant unmet need. Moving on to our other area of focus in engineered cell medicines, we're developing EDIT301. It's a best-in-class medicine to treat sickle cell disease and beta thalassemia. EDIT 301 uses an engineered CPF1 enzyme to edit hematopoietic stem cells at the beta-globin locus. We are confident in this program as other editing approaches target the BC11a erythroid enhancer, which we believe may impact overall survival of the erythroid lineage. At last year's American Society of Hematology meeting, our work showing this effect was recognized as a Best of ASH award.

Moving onto.

Our other area of focus in engineered cell medicines, we're developing at a three or one is a best in class medicines to treat sickle cell disease and beta thalassemia.

At a three I want to uses an engineered CPF, one and bomb to edit amount of politics stem cells at the beta globin locus.

We're confident in this program as other editing approach is targets a b C 11, a reward enhancer, which we believe may impact overall survival or the reported lineage at last year's American Society of Hematology meeting our work showing this effect was recognized as the best to Bash Award.

Present additional data from our program at the upcoming ask meeting describing our product configuration in vivo efficacy data in off target analysis.

Charlie Albright: We will present additional data from our program at the upcoming ASH meeting describing our product configuration, in vivo efficacy data, and off-target analysis. The totality of the data captures why we are so encouraged by this program, and we think clinicians and patients will be excited as well. Switching gears to our In Vivo CRISPR medicines pipeline, in partnership with Allergan, we are developing a portfolio of gene-edited ophthalmology treatments for inherited retinal diseases. Our lead program, Edit 101, is a treatment for patients suffering from LCA-10, and the Brilliance Phase I-II interventional study is underway to evaluate its safety, tolerability, and efficacy. The first potential patient that we anticipate participating in the trial has been successfully screened, and confirmation of a surgery date by early 2020 is pending. With that being said, the drug product has been manufactured, and is available for dosing. Multiple sites are recruiting, and we are actively engaged with clinicians to identify, screen, and schedule patients for the initial cohort.

Totality of the data capture is while we are so encouraged by this program and we think clinicians and patients will be as excited as well.

Switching gears to our in vivo, Chris for medicines pipeline.

Partnership with Allergan, we're developing a portfolio of gene edited up ophthalmology treatments for inherited retinal diseases or lead program at one or one as a treatment for patients suffering from LCD 10, and the brilliance phase one two interventional studies underway to evaluate its safety tolerability and efficacy the first potential patients.

We anticipate participating in the trial has been successfully screen the confirmation of a surgery day by early 2020 is pending.

With that being said drug Park project has been manufactured in is available for dosing multiple sites a recruiting and we are actively engaged with clinicians to identify screen and schedule patients for the initial cohort.

From all the portfolio also includes an experimental medicine treatment for Usher syndrome type two way to restore fully functional osram protein and correct. The disease, we knockout exon 13, which can contains the most common disease, causing mutation at the European Society of gene and cell therapy meeting we demonstrated.

Charlie Albright: Our ophthalmology portfolio also includes an experimental medicine treatment for Usher syndrome type 2A. To restore fully functional Usherin protein and correct the disease, we knock out exon 13, which contains the most common disease-causing mutation. At the European Society of Gene and Cell Therapy meeting, we demonstrated therapeutically relevant editing of up to 60% in human retinal exons. This data gives us confidence in our ability to treat the disease and supports further preclinical development of our lead candidate. The program draws heavily on the work we've done to research and develop EDIT101, utilizing the same AAV vector, promoter, and Cas9 enzyme, leveraging many of the same functional assays and models, and following on the regulatory path paved by EDIT101. Beyond ophthalmology, we have recently formed a collaboration with Aspire to develop in vivo CRISPR medicines to treat neurological disease.

Therapeutically relevant editing of up to 60% and human retinal ex blast.

The state it gives us confidence on our ability to treat the disease and supports further preclinical development of our lead candidates for program draws heavily on the work we've done to research and develop at a 101 utilizing the same a big JV vector promoter and casnine enzyme leveraging many of the same functional essays models.

And following on the regulatory path hey by at a one on one.

Yeah on ophthalmology, we've recently formed a collaboration with as filed to develop in vivo, Chris for medicines to treat neurologic diseases.

Bio brings significant expertise Navy development and manufacturing.

Charlie Albright: SBIO brings significant expertise in AV development and manufacturing. With Askvi, we target cells in the peripheral and central nervous system, a well-known challenge for drug development. The combination of Aspire's expertise and knowledge in vector engineering and manufacturing, coupled with Editas' gene editing expertise, could address a host of neurologic diseases with high unmet need. For example, we are excited about the potential for gene editing to treat debilitating pain and Huntington's disease. We look forward to providing additional updates on our programs in the near future as Editas works to translate gene editing into transformative treatments for patients with serious diseases. With that, I'd like to turn the call over to Erick, who will provide a financial update.

With asked by we target cells in the peripheral and central nervous system, a well known challenge for drug development. The combination of asked by his expertise and knowledge and vector engineering and manufacturing coupled with edits houses gene editing expertise could address the host of neurologic diseases with high unmet need for example, we are excited about the potential for.

Gene editing to treat debilitating pain and Huntingtons disease.

We look forward to providing additional updates on our programs in the next in the near future as Editas works to translate gene editing of in France from formative treatments for patients with serious diseases with that I'd like to turn the call over to Eric who will provide a financial up.

Thanks, Charlie I'm pleased to update all of you on our business and presented latest financial results. These numbers are summarized in the press release that we issued an hour ago and full details will also be available in our Form 10-Q .

Eric Thomas Schmidt: Thanks Charlie. I'm pleased to update all of you on our business and present the latest financial results. These numbers are summarized in the press release that we issued an hour ago, and full details will also be available in our Form 10Q. Our cash, cash equivalents, and marketable securities increased by $15 million in the third quarter to $333 million as of September 30, 2019, from $318 million as of June 30, 2019. Our uses of cash totaled $29 million and included cash operating expenses of $27 million and capital expenditures of $2 million. Our sources of cash totaled $44 million and consisted of $41 million related to the at-the-market offering. $2 million of stock option exercises and $1 million of interest income. We believe our cash, cash equivalents, and marketable securities of $333 million as of September 30, 2019, provide at least 24 months of capital to fund our business. And with that, I will hand it back to Cindy.

Our cash cash equivalents and marketable securities increased by $15 million in the third quarter to $333 million as of September Thirtyth 2019.

From $318 million as of June Thirtyth.

2019, our uses of cash totaled $29 million and include cash operating expenses of $27 million and capital expenditures of $2 million.

Our sources of cash totaled $44 million and consisted of $41 million related to the aftermarket offerings $2 million or stock option exercises and a million dollars.

Interest income, we believe our cash cash equivalents and marketable securities of $333 million as of September Thirtyth 2019 provides at least 24 months of capital to fund or business.

And with that I will hand, it back to Cindy. Thanks, Eric It has been a busy past few months for attitude cost as we work to deliver the promise of Christopher into treatments for patients with serious diseases.

It is truly an exciting time for us with the work we have been doing to advance our programs and explore new possibilities for genome editing editas programs have the potential to revolutionize the treatment of genetic blindness cancer sickle cell disease, and neurological conditions, but our work is only getting started.

Cindy Collins: Thanks Eric. It has been a busy past few months for Editas as we work to deliver the promise of CRISPR into treatments for patients with serious diseases. It is truly an exciting time for us with the work we have been doing to advance our programs and explore new possibilities for genome editing. Editas programs have the potential to revolutionize the treatment of genetic blindness, cancer, sickle cell disease, and neurological conditions, but our work is only getting started. We are in, What the future holds with upcoming data readouts, scientific achievements, and program advancements. Thank you all for your interest and support during this journey we have been making alongside researchers, clinicians, investors, and most importantly, patients. With that, we are happy to take your questions. Operator?

We are Inc.

What the future halls with upcoming data read outs scientific achievements and program advancement.

Thank you all for your interest and support during this journey, we have been making alongside researchers clinicians investors and most importantly patients with that we're happy to take your questions operator.

As a reminder, Jeff a question you need to press Star one on your telephone to withdraw your question press the pound key please stand by what we compile the Q and a roster.

Our first question comes from Steve seed House with Raymond James Your line is now open.

Hi, This is Tim we're going to go on for Steve seed have and we have a couple of questions for added 101 based on recent a competitive readout. So they they had a couple of a super responders and LCH 10, and then they had to the worst vision at baseline and the low dose go forward and it turns out the best responder took the.

Operator: As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Steve Seedhouse with Raymond James. Your line is now open.

Timur Ivannikov: Hi, this is Timur Ivannikov on behalf of Steve Seedhouse, and we have a couple of questions for EDIT101 based on a recent competitive readout. So they had a couple of super responders in LCA10, and then they had the worst vision at baseline in the low-dose cohort, and it turns out the best responder took the longest time to lose his vision, and the company didn't specifically say what the genetic or epigenetic differences were. In addition, there was one patient whose contralateral eye improvement of 0.2 log-mar was, you know, relatively significant. So given the potential for super responders and potentially high placebo responses, we were wondering how you address those issues in your study. Thank you.

The longest time to lose his vision and the company didn't specifically say what the genetic or epigenetic differences were in addition, there was one patients who who is our contralateral eye improvement of point to lock more was relatively significant so given the potential for super responders and potentially high placebo.

Bonds. We were wondering how are you addressed those issues in York and your study. Thank you.

You're right. This Charlie those are.

Things, we will be monitoring and.

And they're not the.

Obvious explanations for some of the phenomena they've been seen today.

Okay, and I guess I'd also in terms of a safety follow up do you have.

An expectation for how many patients will develop counteracting Youre study.

Just to see what the baseline rate would be thank you.

Charlie Albright: You're right, Ms. Charlie; those are things we will be monitoring, and And there are not obvious explanations for some of the phenomena that have been seen to date.

We don't have any expectations will be any different than the other therapies in this space. The other avi based therapies, so, but it's something we're clearly be monitoring.

Charlie Albright: Okay, and I guess, do you also, in terms of safety follow-up, do you have an expectation for how many patients will develop cataracts in your study? See what the baseline rate would be. Thank you.

Okay, and then just a quick housekeeping question on your updated Celgene partnership so looks like you're getting additional 70 million.

Is that mostly just for the expanded timeline not clear is that how much. After 2020. It is because it seems like you're also getting back some of your rights. So if you could explain a little bit better. Thank you.

Charlie Albright: We don't have any expectations that it will be any different from the other therapies in this space, the other AAV-based therapies, but it's something we'll clearly be monitoring.

Timur Ivannikov: Okay, and then just a quick housekeeping question on your updated Celgene partnership. So it looks like you're getting an additional $17 million. Is that mostly just for the expanded timeline? Not clear how much after 2020 it is because it seems like you're also getting back some of your rights. So could you explain a little bit better? Thank you.

The 70 million as an upfront payment in recognition of the work we've done today than they are contributions going forward.

And yes, you're right we are getting some rights bag.

Okay. Thank you.

Our next question comes from Matthew Harrison with Morgan Stanley . Your line is now open.

Hi, Good morning does it cost us on for Mark you had it sounded like this question. These can you explain a little beat what caused the timeline for defense dozing off.

Charlie Albright: The $70 million is an upfront payment in recognition of the work we've done to date and the contributions going forward. And yes, you're right; we are getting some rights back.

111, no one can be pushed blocking 2020 from 2019.

Sure. This is a.

You can appreciate this is a rare inherited retinal disease and those with all of rare diseases.

Timur Ivannikov: Okay, thank you.

Operator: Our next question comes from Matthew Harrison with Morgan Stanley. Your line is now open.

Accruing patients is is challenging, particularly challenging since the entry criteria.

Kostas Son: Hi, good morning. This is Kostas Son from Matthew Harrison. My first question is, can you explain a little bit what caused the timeline for the first dosing of edit one one one oh one to be pushed back into 2020 from 2019?

For this first patient as restricted because that's the right thing to do this has to be an adult with a with light perception only and it's further complicated by challenges with the with the holidays or the patients typically need to bring a caregiver.

We need to ride before the surgery and need and they can't fly for 10 days. After the surgeries. The combination of those things is just made that complicated as we've approached the holiday season.

Charlie Albright: Sure, this is, as you can appreciate, this is a rare inherited retinal disease, and as with all rare diseases, accruing patients is challenging, particularly challenging since the entry criteria for this first patient are restricted because that's the right thing to do. This has to be an adult with light perception only, and it's further complicated by challenges with the holidays. The patients typically need to bring a caregiver, need to arrive before the surgery, and they can't fly for 10 days after the surgery. The combination of those things has just made it more complicated as we've approached the holiday season.

Thank you and how we just cleaning progressing Florida other patients beyond the first patient.

We are progressing well we've in addition to the patients Weve identified in the natural history study Weve opened two sites to more sites are pending and we continue to screen for patients outside the natural history study and so we have as part of our screening identified other patients which.

Our.

Potential patients in the subsequent cohorts.

Okay. Thank you and one more question please.

Charlie Albright: Thank you. And how is the screening progressing for other patients beyond the first patient?

Can you talk about cities on Florida, CPF, one enjoyed hemoglobin Albany, Jim opened will be Nobody's program.

Charlie Albright: We're progressing well. We've, in addition to

Charlie Albright: We're progressing.

Charlie Albright: We've opened two sites, two more sites are pending, and we continue to screen for patients outside the Natural History Study, and so we have, as part of our screening, identified other patients who are potential patients in the subsequent cohorts.

Sure and so our general strategy is to use the best enzyme for the for the application and then this hemoglobin program as a fascinating one because your knocking out hey transcription factor binding site and as we will show at the Ash meeting not all added to the transcription factors.

Charlie Albright: Okay, thank you, and one more question, please. Can you talk about the reason for CPF1 in your hemoglobinopathy program?

Site are actually productive at its where they knocked out the knock out the binding of the transcription factor. So it turns out in this case that when we ended with CTF, one we get a much higher fraction of a productive at its in the long term hematopoietic stem cells.

Charlie Albright: Sure, and so our general strategy is to use the best enzyme for the application. And in this, the hemoglobin program is a fascinating one because you're knocking out a transcription factor binding site. And as we'll show at the ASH meeting, not all edits at the transcription factor site are actually productive edits, where they knock out the binding of the transcription factor. So it turns out, in this case, that when we edit with CPF1, we get a much higher fraction of productive edits in the long-term hematopoietic stem cells. And so what we've done there is really to create a relatively unique product where we maximize the ability to induce fetal hemoglobin, which is, of course, the objective of this program. So it's really been an interesting journey there, and we look forward to the upcoming ASH meeting.

And so what we've done there is really to create a relatively unique product, where we where we maximized ability to induce fetal hemoglobin, which is of course the objective of this program. So it's it's really been a interesting.

The resting journey, there and we look forward to the upcoming Ash meeting.

Okay. Thank you and one one last question follow up on these.

Given that we expect data from and now that we spend maybe seen in chemical will be nobody's again before year end can you talk a little bit about how these data could inform your strategy.

Charlie Albright: Okay, thank you. And one last question to follow up on this. Given that we expect data from another CRISPR medicine in hemoglobinopathies again before year end, can you talk a little bit about how this data could inform your strategy in this area of diseases?

These 80 of disease.

Well, we carefully monitored the competitors in this space as we do in every program. We have we do have reason to believe that we have developed the best in class Medicine, and and we clearly monitor that with a with time and it will be interesting to see the upcoming data.

Charlie Albright: Well, we carefully monitor the competitors in this space, as we do in every program we have. We do have reason to believe that we have developed a best-in-class medicine, and we will clearly monitor that over time. And it will be interesting to see the upcoming data, particularly in light of the abstracts we've seen to date. Thank you very much.

Particularly in light of the abstracts, we've seen today.

Thank you very much.

Our next question comes from Whitney Ijem with Guggenheim Securities. Your line is helping.

Hi, Good morning, guys. This is on with the on phone with me this morning.

Could you please give us more color on the vectors that you may gain access to under your Oso bio collaboration and the initial indications that you maybe controlling interest on CNS space and then what attracted you to ask biologic Lewis's.

Operator: Our next question comes from Whitney Egyem with Guggenheim Securities. Your line is now open. Hi. Good morning, guys.

Anvita ONe: This is Anvita On One for Whitney. This morning, could you please give us more color on the vectors that you may gain access to under your AskBio collaboration and the initial indications that you may be considering in this CNS space? And then what attracted you to AskBio in particular versus other next-gen vectors in the space? And then I have an additional follow-up. Thanks.

Although net other other nexgen vectors in the space and then I have an additional funnel. Thanks.

Sure, we're very impressive that's fine and.

Not only are they a leader in a v. and have a track record the people involved in ASP, having significant track record of putting medicines into the clinic that are.

Charlie Albright: Sure, we're very impressed with Aspire and not only are they a leader in AAV and have a track record, but the people involved in Aspire have a significant track record of putting medicines into clinics that are efficacious. They've also developed a nice infrastructure, they have an excellent manufacturing facility, and they've acquired some significant businesses that go with their core business and complement the core expertise they've developed in AAV manufacturing. So it is a very impressive group, and we're super excited to be working with them on a neurological disease. Our initial efforts would be directed at severe pain, and so we don't want to say too much about it now, but it's an area of high unmet need where the targets are genetically validated, and we think we can do something very unique.

Or efficacious.

They've also developed a nice infrastructure they have an excellent manufacturing facility they've they've.

Acquired some significant businesses that go with their core business and complement the the core expertise they've developed and Avi manufacturing.

So it is a very impressive group and where we're super excited to be working that with them on a on a neurologic disease. Our initial efforts, we big point into a severe pain and so we don't want to say a tremendous amount to about it now but.

It's an area of high unmet need.

Where the targets are genetically validated and we think we can do something very unique.

Okay, and then and you'll be in APAC and seek us out of program. What is the SPF that doggett that youre aiming far and is it any difference between the two diseases. Thanks for taking my question.

Charlie Albright: Okay, and then in your Betafil and Sickle Cell program, what is the HPF target that you're aiming for, and is it any different between the two diseases? Thanks for taking my questions.

Well, we believe we need to get more than 30% fetal hemoglobin, the ducks in a increases and needs to be.

Significantly Pam so you're obviously.

Charlie Albright: We believe we need to get more than 30% fetal hemoglobin in the ducts, and it needs to be significantly pan cellular, obviously. So we'll show data at ASH that we've exceeded those targets and believe we have a very interesting experimental medicine.

So we'll show data at Ash that we've exceeded those targets and.

And believe we have a very interesting.

Experimental medicine.

[noise].

Our next question comes from Gena Wang with Barclays. Your line open.

Operator: Our next question comes from Gina Wang with Barclays. Your line is now open.

David: I think you've taken my questions. This is David speaking on behalf of Gina. My first question is regarding LCA-10 data read-through. How do you think that the LCA data reads through to Usher syndrome in terms of initial dosing?

I think if it taking my questions. The this is David on for Gina My first questions regarding LP tend to either through how do you think that LPDRAM you through to the Osher syndrome in terms of national dosing.

[noise] the.

Charlie Albright: The For each of these, we are doing pharmacology modeling to correlate the editing with the dose. We haven't shown that data, but we do anticipate that those responses between the medicines will be quite similar, and we've seen some of that pre-clinically. We'll show more of that next year. So, as with all molecular medicines, the pharmacokinetic relationship is typically reasonably well maintained across treatments in different spaces. We anticipate the same thing here.

In for each of these we will we are doing the the pharmacology modeling to correlate the editing with the with the dose we havent shown that data, but we do anticipate that those responses between the medicines will be quite similar.

And.

And we've seen some of that Preclinically will show more that next year.

So as with all molecular medicines.

The Pharmacodynamic and pharmacokinetic relationship is typically reasonably well maintained across across therapies and difference basis, we anticipate the same thing here.

Got it very helpful. Thank questions regarding.

Charlie Albright: Got it. It's very helpful. Seven questions regarding the preclinical data for beta thalassemia and sickle cell disease. Your preclinical data at ASH, how does it compare to the BCL11A approach, and what do we expect in terms of timing for phase one?

The preclinical data for but let's see me I think it's not disease.

You are putting the data at ash, how does compared to the Bcl 11 am approach and what do we expect in terms of timing to phase one.

Charlie Albright: Taking them in reverse order, we haven't disclosed the timing for Phase I. What we've said, though, is we're in a position to begin IND-enabling studies and are advancing them as rapidly as possible, and we, of course, stand by that the data compares favorably. I think you'll be able to judge that when you see the poster.

Taking them in reverse order, we haven't disclosed the timing to phase one always said those were in a position to begin I'd, enabling studies and are advancing it as rapidly as possible we of course.

Standby that the.

The data compares favorably I think you'll be able to judge that when you see the poster.

Charlie Albright: Okay, very helpful. And then last question on the recent prime editing news that came out. What do you think the impact of CRISPR will be?

Yes, we will hemoglobin is.

Okay very helpful.

And then last question on the the reason prime adding new stuff came out what do you think for the impact to the CRISPR.

We monitor the competition across the space both a direct.

Charlie Albright: We monitor the competition across the space, both the direct gene editing approaches and the modified gene editing approaches. The prime has many similarities to base editing and has many of the same; we anticipate many of the same issues quite frankly.

Gene editing approaches in the modified gene editing approaches the a prime is has many similarities to the base editing and.

And has many of the same we anticipate minute at the same issues quite frankly.

Okay, great. Thank you on the hop out how back on the Q.

David: Okay, great. Thank you. I'm going to hop back on the queue.

Our next question comes from Amanda Murphy with Beachy. Your line is open.

Operator: Our next question comes from Amanda Murphy with BTIG. Your line is now open. Hi, thanks. Good morning.

Hi, Thanks, good morning.

Amanda Murphy: So just a few questions, I guess, on the cell chain change or re-up the agreement and then also just kind of what you've been up to on that front. I know you've been presenting, for a while now, at various conferences, you know, preclinical data on GPF-1 and T-cells. So just curious, kind of, if you could update us on what, I guess, A, what happens to the work that's been done previously with TPF1 and T-cells that you've presented, and then... I'm assuming that also includes engineered TCRs in terms of taking that sort of back, if you will. So I'm curious if you can just update us on both of those programs, you know, where you are with those.

A few questions I guess on the cell gene.

Change or be a reality agreement and then also kind of what you've been up you on that front I know you've been presenting.

For a while now at various conferences.

Pre clinical update on CPF, one and so.

Just curious kind of if you could update us on what.

Just a what happens at the work that's been done previously received Atlantic I'll, let that he presented and then.

I'm assuming that also include engineered keeps yards in terms of Ticketmaster back. If you will so curious if you can just update us on both program.

Where yet where you're at windows immensely thank you might.

I have an update on timing and indications and things like that.

Yes, I wish I could be more clear about the about the timing and the and the.

Charlie Albright: Have a lovely day!

Charlie Albright: Yeah, I wish I could be more clear about the timing and the details of the cell gene programs, but unfortunately, that's not possible. I'd like to say that the work that we have shown will carry forward into the new collaboration, and we have shown a lot of data on multiplexing, targeted integration, and knockout of what one would say are the typical genes in the space. All of that work gets rolled into the new collaboration with cell genes. As you can imagine, as a leader in, we believe the leader in T-cell medicines for oncology, including arguably the best CD19 and the best PCMA CAR-T programs, they have a strong interest in maintaining their leadership position, and gene editing is certainly an important part of what is likely to be the next generation of T-cell medicines for oncology. So we're excited to continue to work with them in that space, and we'll be able to use the knowledge we've gained to date to do so, and unfortunately, we just can't be transparent about the nature of the products or the timing of the products.

And the details of the Celgene programs. Unfortunately, that's that's not possible licensed to say that the work that we have Sean will carry forward into the new collaboration.

We have shown a lot of data on multiplexing targeted integration knock out of the of what would one would say our that typical.

Genes in this space all of that work gets rolled into the into the new collaboration with Celgene.

As you can imagine as a leader in.

We believe the leader in.

T cell medicines for oncology, including arguably the best CD 19 of the best CCMA car T programs. They have a strong interest in maintaining their leadership position and gene editing is certainly an important part of what are likely to be the next generation of of T cell medicines for oncology. So we're we're on.

Excited to continue to work with them in that space and we'll be able to use the knowledge weve gained today to do that.

Unfortunately, just can't be.

Transparent about the the the nature of the products or the timing of the products.

Okay Fair enough a and then just on the Okay program I mean, I'm sorry, if I missed this.

Charlie Albright: Okay, fair enough. And I did some of the MK program. I mean, I'm sorry if I missed this. Have you kind of talked about it here? What your timing is? I know you had sort of an NK-Cell program that was sort of running individually, and then you obviously have the IPSC collaboration, and I think you've talked about IPSC-derived NK cells as well. So just looking for an update there if you can provide one.

Just kind of talked about their weight, what your timing as I know you had separate NK cell program that was sort of running individually and then you obviously have the I'd just be collaboration and I think you've talked about I PST derived NK cell well. So just looking for an update there you can provide.

Charlie Albright: We can provide a general update without the specifics that you probably really want. Suffice to say that the science is going really well, and you'll hear a lot more about that next year as we go into the oncology and stem cell meetings. We are able to... With our collaborators, Blue Rock, identify well-defined and characterized IPSC lines. We've been able to edit those IPSC lines, and we've been able to differentiate them into NK cells that have potent killing activity in vitro. We're starting to combine all those things now into what we believe will be interesting experimental medicines and accumulate data as rapidly as we can to advance those into the clinic. We have a similar effort in healthy donor-derived NK cells that we think complement the IPSC-derived NK cells. So we do anticipate providing a significant update next year that illustrates that progress in a scientific venue.

We provide a general update without the specifically you probably really want the.

Twice to say that the science, it's going really well and you'll hear a lot more about that next year as we go into the oncology and the stem cell meetings.

We are able to.

With our collaborators blue rock identify well defined.

Characterize IPO see lines for the near the editors IPO see lines, we've been able to differentiate them into NK cells that have a potent killing that killing activity in vitro.

We're starting to combine all those things now into what we believe will be interesting experimental medicine and accumulate today is rapidly Canada advance those into the clinic, we have a similar effort in the healthy donor derived NK cells that we think complement.

The IPO see derived NK cells. So we do anticipate providing significant update next year.

The illustrates that progress on them in a.

Charlie Albright: Got it. Okay, and then just if I can sneak in one more about... Edit 101. So it just reminds us again, from a protocol perspective, what's required for sort of a second patient dose. Is that going to be a little more? I forget, just a reminder on the timing there.

In a scientific venue.

Got it again, if I can sneak in one more about.

And it went online so just remind US again my protocol perspective, what's required for.

The second piece in testing.

Is that going to be a little more.

Forget reminder, on on the timing there.

Yes, so that the entry criteria for both patient one in patients who are quite similar light perception only adults. The there's a an interval between the dosing of those two patients, which I believe is six weeks.

Charlie Albright: Yeah, so the injury criteria for both Patient 1 and Patient 2 are quite similar. Light perception only, adults. There's an interval between the dosing of those two patients, which I believe is six weeks. And so we are obviously trying to recruit both the first and the second patient, because that's what's required in the first cohort.

And and so we are obviously trying to accrue both the first and the second patient because that's what's required in the first cohort.

Amanda Murphy: Yeah Okay, thank you very much. Our next question comes from Joe Tome with Cowan & Company. Your line is now open.

Yeah.

Okay. Thank you very much.

Our next question comes from Joe tone, with Cowen and company. Your line is open.

Operator: Hi there, thank you for taking my questions. The first one on the 101 program, in terms of patient screening, I know you mentioned that, you know, obviously, this first cohort we want patients with only light perception and kind of advanced disease. Have you screened patients that maybe just didn't have advanced disease enough that would be applicable for a later cohort, or kind of how is patient interest in the program sitting?

There. Thank you for taking my questions. The first one on the one to one program in terms of patient screening I know you mentioned that obviously the first cohort we want.

You know patients with only like perception and kind of advanced disease have you screen patients that maybe just didnt have.

Vance disease enough that would be applicable for a leader cohort or or kind of how how is patient interest in the program.

Joe Tome: Yes, the simple answer is yes. We have screened patients that did not fit the criteria for Cohort 1, but could fit the criteria for Cohort 2 and 3, and so obviously, we're interested in them. The interest from patients and physicians remains high, and we're optimistic that we're going to start to get this study dosed and further enrolled.

Sitting yes, yes. The simple answer is yes, we have screen patients that not the did not fit the criteria for cohort one could fit the criteria for cohort two and three.

And so obviously, we're we're interested in them the.

Is there some patients and physicians remains high.

And we're optimistic that we're going to start to get this study dosing and further enrolled.

Charlie Albright: Thank you. And then I'll do one more on that program.

Thank you and then and then when we're on that program I know, it's looking ahead, but in terms of data disclosure I know, you're calling for a year, but there is the potential for some interim how do you anticipate releasing data would you released data from the first cohort or would you wait for your until you had a few cohorts of patients dose for for a meaningful amount of time.

Charlie Albright: I know it's looking ahead, but in terms of data disclosure, I know you're filing for a year, but there is the potential for some interim. How do you anticipate releasing data? Would you release data from the first cohort, or would you wait until you had a few cohorts of patients dosed for a meaningful amount of time?

Charlie Albright: Right. It depends on the data, quite frankly. And so I remind you that we are partnering with Allergan on this study, and they're going to have an important say in the release of data. We have said we're not going to release data on a patient-by-patient basis because we don't believe that data will be representative. And as illustrated by one of the earlier questions, there are some super responders here, and you could be significantly misled by releasing patient-by-patient data. And so I think it will very much depend on what the data is and our discussions with our partners, Allergan.

Right.

It depends on the data quite frankly, and so remind you that we are partnering with Allergan in this study and they're going to have an important say in the release of data. We have said, we're not going release date on a patient by patient basis, because we don't believe that data will be representative and as.

As illustrated by one of the earlier questions. There are some super responders here and you can be significantly misled by releasing patient by patient data and so I think it'll vary much depends on what the data is.

And our discussions with our partners Alexander.

Joe Tome: And then just one last kind of housekeeping question on the Celgene deal. The $70 million milestone, do you expect to receive that in Q4, and maybe how are you going to account for that? And in terms of when Celgene can opt in on some of these programs, is there a specific time, you know, after Proof of Concept, before Privital, or how are they thinking about that?

Great and then just one last kind of housekeeping question on the Celgene deal the $70 million milestone.

Do you expect received in Q4, and maybe how are you going to account for that and in terms of when Celgene can opt in on some of these programs is there a specific time after proof of concept before pivotal or how are you thinking about that.

So yes, we are going to accrue in the fourth quarter.

Charlie Albright: So yes, we are going to accrue revenue in the fourth quarter; the deal is structured so they opt in; they can opt out at any point.

The deal with structure, so they often they cannot than at any point in time.

Okay, great. Thank you.

And again, if you have a question. Please press Star then one.

Charlie Albright: Okay, great. Thank you.

Our next question comes from goal a lift shifts with.

Operator: Again, if you have a question, please press star and then 1. Our next question comes from Gula Lifshitz with Chardon. Your line is now open. Thanks. Good morning, everyone, and thanks for taking my question.

Chardan Your line is now open.

Thanks, Good morning, everyone and thanks for taking my congrats on the progress. So quick one on LCR attendant than one on the oncology so with respect to the LC 10 program, let's make sure I understand was that for station that was identified rules in from the natural history study.

Yes.

Gula Lifshitz: Yes.

Great.

Charlie Albright: And then with respect to the Celgene collaboration and in terms of overall oncology strategy, a kind of broader question. So you have a number of tools at your disposal now. And I'm just wondering how you think about the decision process towards deploying a particular T or NK or gamma delta T cell therapy towards a given target or towards solid versus liquid tumors and internal versus Celgene collaboration. Yes, if there's any color they can provide on that.

And then on with respect to the Celgene collaboration and in terms of overall oncology strategy kind of a broader question. So you have a number of tools at your disposal now.

And I, just wondering how you're thinking about the decision process towards deploying a particular key or NK or gamut delta.

Therapy, I should say towards given target or toward selling prices liquid tumors and internal versus celgene collaboration.

Yes, if there's any clarity on that.

Yeah, the so the the.

Charlie Albright: Yeah, so the collaboration with Celgene is very much about working with somebody who's a leader in alpha-beta T-cells, and as you know, they're a leader in alpha-beta T-cells directed at hematologic indications. CD19 and BCMA are at the top of their portfolio, as we believe, and I said, they arguably have the best medicines in both of those spaces, and I think that maintaining that leadership will be at the top of their list of things to do. We are going to focus most of our effort on solid tumors, an area of significant unmet need where engineered cell medicines have been relatively unsuccessful to date, but we believe we can get there, and that's due to the need for significant genetic changes and editing.

The collaboration with Celgene is very much about working with somebody who is a leader in alpha beta T cells and as you as you know there a leader in elevated T cells director to hematologic indications.

Cdnineteena DCM, a or the at the top of their portfolio as we believe and I said, they arguably has the best medicines and both of those spaces and an item that I think that maintaining that leadership will be at the top of their list of things to do.

We are going to focus most of our effort on solid tumors, an area of significant unmet need where engineered cell medicines had been relatively successful to date, but we believe we can get there and that tier to need significant.

Genetic changes and editing to do that in the IPO see platform really provides that ability to make the genetic changes are gonna be required for instance, you your need targeting you're going to need.

The increase persistence ovation of the immune system evasion into tumor micro environment, and probably ability to stimulate the endogenous immune system and Theres no way, you're going to get there with any cell type from derived from healthy donors and so we're building a platform. We believe we believe is unique in this space.

Charlie Albright: to do that in the IPSC platform.

Charlie Albright: So we're building a platform we believe is unique in this space and affords the ability to make complex products, which will get us into a space that has a significant unmet need. Right now, our efforts internally are focused primarily on NK cells. They are one of the easiest cell types to make from the iPSC platform, and there's emerging clinical data that they are indeed efficacious in patients. I'll be at a hematologic indications debate, so we are very excited about that we've made a lot of progress in the area, and we look forward to disclosing all that at the meetings next year.

And affords the ability to make complex products, which will get us into a space that has a significant unmet need.

Right now our efforts internally are focused primarily on NK cells.

They are one of the easier cell types and make from the I.P.S.C. platform and there's emerging clinical data that they are.

Indeed efficacious in patients.

Albeit in hematologic indications today. So we're very excited about that we've made a lot of progress in that area and we look forward to disclosing all that at the meetings next year.

And so it's kind of theoretical but then with celgenes.

Charlie Albright: And so, this is kind of theoretical, but then with cell genes, potential opt-in rights include something like an iPSC-derived alpha-beta T cell, based on the structure of the agreement.

Potential often right include something like an eye PST derived alpha beta T cell.

Based on the structure of the agreement.

Charlie Albright: It could, but that's not the initial focus of the agreement.

It could that's not the initial focus so the agreement.

Gula Lifshitz: Great, and then just one last question on the AskBio collaboration. You mentioned what drew you to AskBio, and so just out of curiosity, under the collaboration, do you have access to the SymProMix informatics platform?

Great and then just one last one on the ask bio collaboration. So you mentioned, which are you task violence to just out of curiosity.

Under the collaboration do you have access to the same foamix informatics platform.

Charlie Albright: We do. We have access to whatever is under the ASPIRE umbrella, and that's a great example of the way they're expanding their technology footprint to really become what we believe is one of the leaders in the AAV field.

We do we have access to whatever is under the S. Bio umbrella and that's a great. A great example of the way, they're expanding their technology technology footprint to really become what we believe as one of the leaders in the Avi field.

Great. Thanks.

Gula Lifshitz: Great, thanks.

Our next question comes from Sylvan Churkin with Oppenheimer. Your line is open.

Operator: Our next question comes from Sylvan Turkin with Oppenheimer. Your line is now open.

Sylvan Turkin: Well, congratulations on the quarter and thank you so much for taking my question. First off, I wanted to ask you about Matthew Porter's approach, which is academic, that was presented at ESGCT for sickle cell disease. He will be starting up a phase two trial next year. Is there anything, could you maybe highlight the differences between your approach and his, and is there potential learning across from his trial that could apply to edit 101?

Well congrats on the court and thank you so much for taking my question.

First off I I do want to to ask you about Matt you Port Ices approach, which is academic or that was presented yes, GCT in sickle cell disease.

He will be starting up.

Phase two trial next year is there anything could you maybe highlight the differences between your approach and his and it's a potential read across from from it trials that couldn't applied.

To edit one of them.

Charlie Albright: Sure. But his approach, as I understand it, is to actually target correction of the sickle cell mutation. And that obviously has some theoretical appeal because you're going right after the mutation. As you can appreciate, though, not all of the genetic changes at the sickle cell allele are productive, i.e. Not all of them lead to correction of the mutation. And the problematic aspect of that strategy is that when you don't correct it, you actually make an indel, which is highly likely to be nonfunctional. So those alleles and potentially those cells will now not contribute hemoglobin to the patient, and so if you don't get enough correction, you actually have the potential to make beta thalassemia patients, take sickle cell patients and make them beta thalassemia patients, which we have found to be a significant risk.

Sure.

His approaches I understand it is to actually target correction of the Oh, the sickle cell mutation and that has some obviously has some theoretical appeal because you're going right. After the right at the mutation as you can appreciate though not all of the not all of the genetic changes at the same.

We will sell a wheel our productive.

Not all of them lead to correction of the mutation and the problematic S.S. aspect to that strategy is when you don't correct you actually make an Intel which is highly likely to be non functional so those will yield and potentially those cells. One now not contribute hemoglobin to them.

Asia.

And and so if you don't get enough correction, you actually had a potential than a beta thalassemia patients take sickle cell patients and make them beta thalassemia patients, which we we have found to be a significant risk.

Great. Thank you and could you please remind us of what's left to do.

Charlie Albright: Great, thank you. And could you please remind us of what's left to do to file an IAM?

File an island before a usher and and what could be a potential timeline.

We haven't disclosed the timeline will we have said is that the ended the year, we anticipate having a molecule that'd be ready for and I I Indy, enabling studies and so you recall that the Usher program as part of our collaboration with Allergan and it's an option agreement. So we provide packages at the end of the discovery phase to Allergan and then they have there.

Charlie Albright: Allergan is an option agreement, and we provide packages at the end of the discovery phase to Allergan, and then they have the right to opt in. So we anticipate delivering that package to them at the end of the year. We remain on track for that. And at that point, they'll have a decision to make, and once they've made the decision, we will potentially have a decision to make as well.

Right to opt in so we anticipate delivering that package to them at the end of the year, we remain on track for that and at that point they'll have a decision to make and once they made the decision. We will have this potentially have a decision to make as well.

Sylvan Turkin: Great! Thank you so much.

Great. Thank you so much.

Oh.

Mark Mulligan: And at this time, I'm sure there are no further questions. I'd like to turn the call back over to Mark Mulligan for any closing remarks.

And at this time Im showing no further questions I'd like to turn the call back over to Mark Martin for any closing remarks.

Mark Mulligan: Great. So, with that, we thank all of you for participating in today's call and for your support as we work to bring transformative new medicines to patients. Have a great day.

Great. So with that we thank all of you for participating in today's call and for your support as we work to bring transformative new medicines to patients have a great day.

Ladies and gentlemen. This concludes today's conference call. Thank you from participating you may now disconnect.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

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