Q1 2021 Editas Medicine Inc Earnings Call
Yeah.
Unknown Executive: Good day, and thank you for standing by. Welcome to the Q1 2021 Editas Medicine Earnings Conference.
Good day and thank you for standing by what time did a Q1 2021.
Medicine earnings Conference call.
Operator: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference over to your first speaker today, Ron Moldover, Investor Relations. Please go ahead.
This time, all participants are no listen only mode.
After the speaker's presentation, there will be a question and answer session.
During the session you won't get depressed star one on your thought is on a year credit any further assistance. Please press star zero.
The conference over anything with price the speaker today, Brian Moldova Investor Relations. Please go ahead.
Ron Moldover: Thank you, Julianne. Good morning everyone, and welcome to our first quarter 2021 conference. Earlier this morning, we issued a press release providing our financial results and corporate updates for the first quarter of 2021. A replay of today's call will be available on the investor section of our website approximately two hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various factors.
Thank you Julien good morning, everyone and welcome to our first quarter 2021 conference call earlier. This morning, we issued a press release, providing our financial results and corporate updates for the first quarter of 2021, a replay of today's call will be available on the investors section of our website approximately two hours after its completion.
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.
He only from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on form 10-K, which is on file with the SEC. In addition, any forward looking statements represent our views only as of today and should not be relied upon as representing.
Ron Moldover: On the last slide, we have various important factors, including those discussed in the RICS factors section of our most recent annual report on Form 10-K, which is on
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. Now, I will turn the call over to our Chief Executive Officer, Jim Mullen.
I think our views as of any subsequent date, except as required by law, we specifically disclaim any obligation to update or revise any forward looking statements. Even if our views change now I will turn the call over to our Chief Executive Officer, Kevin Mullen.
Good morning, everyone and thank you for joining us today.
Jim Mullen: Good morning, everyone. And thank you for joining us today. In addition to Ron, I'm joined by Lisa Michaels, our Chief Medical Officer, and Michelle Robertson, our Chief Financial Officer. I'll start by providing some highlights from the first quarter and reviewing our broader corporate strategy. Then I'll hand it over to Lisa to discuss our clinical and preclinical progress, and then Michelle will provide an update on our financial results and cash position. We have had a strong start to the year.
In addition to Ron I'm joined by at least the Michaels, our Chief Medical Officer, and Michelle Robertson, Our Chief Financial Officer.
I'll start from her providing some highlights from the first quarter reviewing our broader corporate strategy, then I'll hand, it over to Lisa to discuss our clinical and preclinical progress and then Michelle will provide an update on our financial results and cash position.
We've had a strong start to the year.
Jim Mullen: The brilliance trial for EDIT 101 is progressing very well, and we expect to share clinical data by year end. The first clinical site in the Ruby trial for EDIT 301 has been activated and has begun to screen and recruit patients. The pre-IND work for EDIT 301 in beta thalassemia is advancing, and we expect it to be filed before year-end.
Its trial for edit one on one is progressing very well with respect to share clinical data by year end.
The first clinical site in the Ruby trial for edit 301 has been activated has begun to screen and recruit patients.
He worked for edit 301 in beta thalassemia is advancing and we expect it to be filed before year end.
Jim Mullen: We've also made excellent headway in the manufacturing side as we compare to all patients in the RUDI trial. We continue to progress our oncology platform with our longstanding partner, Bristol Myers Squibb, opting into another program this past quarter. And finally, our capital raise from January gives us a comfortable financial position to advance our clinical trials and preclinical pipeline. From an organizational leadership perspective, I'm pleased to announce that Dr. Mark Shearman will be joining us next month as our new chief.
We've also made excellent headway in infection side as we prepare to all patients on a routine trial.
We continue to progress our oncology platform with our longstanding partner Bristol Myers Squibb upping into another program this past quarter.
Finally, our capital raise from January gives us a comfortable financial position to advance our clinical trials and preclinical pipeline.
From an organizational leadership perspective, I'm pleased to announce that Dr. Martin Chairman will be joining us net smoke as our new chief.
Scientific officer.
Jim Mullen: Mark is an experienced executive who has brought multiple programs from ideation into and through the clinic and led numerous successful projects. He brings an extensive track record of achievements in drug discovery and clinical development across multiple therapeutic modalities. There are two reasons why we believe Mark will be successful as Editas' new CSO.
Mark is an experienced executive who has brought multiple programs from ideation into and through the clinic.
As led numerous successful partnerships. He brings an extensive track record of achievements in drug discovery and clinical development across multiple therapeutic modalities.
There are two reasons why we believe mark will be successful and then post the CSO.
Jim Mullen: First, his areas of expertise in ophthalmology, immunology, and neurology have considerable overlap with Editas' current platform medication. Mark will advance our existing programs in these indications while utilizing our world-class gene editing technology to expand our preclinical pipeline into potentially other therapeutic areas. Second, and more importantly, Mark is a successful and respected leader of large global research teams. As Editas continues to grow, Mark's experience at companies like Merck and, most recently, Applied Genetic Technologies will help facilitate the right structure to support our progress and allow us to attract the right talent.
First as areas of expertise in ophthalmology, immunology, and neurology hubs considerable overlap with added cost per platform medications.
Mark will advance our existing programs on these indications while utilizing our world class gene editing technology to expand our preclinical pipeline and potentially other therapeutic areas.
And more importantly markets as successful and respected leader of large global research teams.
<unk> continues to grow marks experience of companies like Merck and most recently a pledge and other technologies will help facilitate the right structure to support our progress and allow us to attract the right talent.
Mark's addition, significantly strengthens our leadership team and I look forward to having him join us on our next earnings call.
Jim Mullen: Mark's addition significantly strengthens our leadership team, and I look forward to having him join us on our next earnings call. In addition to recruiting Mark, I spent time during my first month as CEO meeting with every Editas employee, albeit mostly through a virtual format.
In addition to recruiting Mark I have spent time during the first months as CEO by meeting with every other tough employee, albeit mostly through a virtual format. These conversations help me appreciate what people are drawn to advertise on what we can do as an organization to attract and retain world class talent.
Jim Mullen: These conversations helped me appreciate what people are drawn to Editas and what we can do as an organization to attract and retain world-class talent. Speaking with every editor has only strengthened my confidence in our people and the technology and platforms that we are developing. By having these conversations across all levels of the organization, I have a chance to better understand the intricacies of our gene editing technology and our platforms and how we can synergistically leverage these existing assets toward further development.
Speaking with editor has only strengthened my confidence in our people and the technology platforms that we're developing.
But having these conversations across all levels of the organization and the chance to better understand the intricacies of Virgin other technology platforms, and how we can synergistically leverage these existing assets towards further development.
Jim Mullen: Built on top of our gene editing technology, we have three principal platforms. First, we have in vivo gene editing, focused initially on ocular diseases. Next, we have the ex vivo platform focusing on sickle cell and beta thalassemia. And finally, we have our cellular therapeutic platform focusing on oncology. These three platforms have their own intrinsic values, and they also provide us with the building blocks for continued sustainable growth. Programs within each of these platforms serve as vehicles for proof of concept.
On top of our gene editing technology, we had three principle platforms first we have in vivo gene editing focused initially on ocular disease next we have the ex vivo block on focusing on simple fill in beta thalassemia.
Finally, we have our cellular therapeutic platform focusing on oncology.
These three platforms have their own intrinsic values and they also provide us with building blocks for continued sustained growth.
The programs within each of these vehicles are.
Within each of these platforms serve as vehicles for proof of concepts.
Once we demonstrate that we can reduce our gene editing technology to practical applications, then will have actual products that could impact patients lives in a way never seen before.
These are not just three different areas of therapeutic indications. These are three different ways to use gene editing to solve different problems.
Jim Mullen: Once we demonstrate that we can reduce our gene editing technology to practical applications, then we'll have actual products that could impact patients' lives in a way never seen before. These are not just three different areas of therapeutic indications. These are three different ways to use gene editing to solve different problems.
Finally, being leader in genomic medicine requires immense expertise and resources as we continued to advance our programs partnerships will be critical for development and commercialization, we will pursue opportunities to extend our leadership and accelerate enable and expand our pipeline.
Jim Mullen: And finally, being a leader in genomic medicine requires immense expertise and resources. As we continue to advance our programs, partnerships will be critical for development and commercialization. We will pursue opportunities to extend our leadership and accelerate, enable, and expand our pipeline. We believe we've been successful to date, as exemplified by our collaboration with Kirsten Meyers Squibb, a global leader in oncology. As mentioned, that partnership is progressing, along with BMS opting into an additional program this quarter.
We believe we've been successful day best exemplified by our collaboration with Bristol Myers Squibb, a global leader in oncology.
As mentioned that partnership is progressing along with BMS operating into an additional program this quarter and.
In addition to declare a development candidate day end of last year. This marks another important milestone in the span of six months under this collaboration further validating our technological expertise on the space.
Overall I'm extremely happy with the progress there is still challenged and we need to come and our confidence that we will have the right people in place to accomplish our short term milestones in our long term objectives with that let me turn the call over to Lisa.
Jim Mullen: In addition to a declared development candidate at the end of last year, this marks another important milestone in the span of six months of this collaboration, further validating our technological expertise in the space. Overall, I'm extremely happy with our progress so far. There are still challenges that we need to overcome, and I have confidence that we'll have the right people in place to accomplish our short-term milestones and our long-term objectives. With that, I'll turn the call over to Lisa.
Good morning, Jim Thank you.
Let me start with a brief update on the brilliance trial for edit one on one as you know we initiated dosing in the second cohort earlier this year with our regained momentum we continue to screen and enroll patients in the study it's part of our progress a protocol mandated meeting with the independent data monitoring Committee is actually planned for this summer.
And in this meeting we will review the existing data and decide the necessary steps require to begin dosing. The next two pediatric cohorts.
Lisa Michaels: Good morning, Jim. Thank you. Let me start with a brief update on the brilliance trial for EDIT101. As you know, we initiated dosing in the second cohort. With our regained momentum, we continue to screen and enroll patients in the study. As part of our progress, a protocol-mandated meeting with the Independent Data Monitoring Committee is actually planned for this summer.
An exciting milestone shins LCA, Ken is on early onset retinal degenerative disease, resulting in significant vision loss and blindness.
LCA 10 is on those common cause of inherited childhood blindness affecting three out of every 100000 children around the world. So I'm hopeful that we'll be able to report promising results from the future.
We continue to follow all of the treated patients for the primary endpoint of safety in every three months for the first year and concurrently we're collecting data to confirm the expected beneficial effects of editing.
Lisa Michaels: And at this meeting, we will review the existing data and decide the necessary steps required to begin dosing the next two Pediatrico. It's an exciting milestone since LCA10 is an early-onset retinal degenerative disease. Resulting in significant vision loss and blindness, LCA-10 is the most common cause of inherited childhood blindness affecting. I'm hopeful that we'll be able to report results soon. We continue to follow all the treated patients for the primary endpoint of safety. Every three months for the first year, and concurrently, we're collecting data.
Jim mentioned, we plan to share our initial clinical data from the brilliance trial before the end of this year.
Changes to include data net represents patients from the first two cohorts after trial.
The progress on the learnings from the edit one on one trial are also being applied to advance other in vivo ocular programs. This.
This year, we have presented preclinical data for Usher syndrome too in retinitis Pigmentosa force. The most recent annual meetings for the association for research.
Lisa Michaels: Beneficial Effects of Edi, As Jim mentioned, we plan to share our initial clinical data from the BRILLIANCE trial before, and our intent is to include data that represents patients from the first two cohorts of the study. The progress and the learnings from the EDIT 101 trial are also being applied to advance other in vivo ocular programs. This year, we presented preclinical data for Usher Syndrome 2A. Association, We've developed a human iPSC-derived retinal granuloid. Excuse me, I'm choking.
On an ophthalmology and we've developed a human Ips derived retinal organic granted excuse me on club.
Choking on for a moment retinal organoid platform, which provides a practical ex vivo model to study the effects of editing on the human retina.
Cash two way selected deletion of the exon 13 mutation restored Ashton protein complex expression and rescue deficit in photoreceptor mythology Nowadays.
These results provide evidence of the potential to restore functional <unk> protein function and rescue loss of visual function.
Lisa Michaels: Retinol Organoid Platinum, which provides a practical ex vivo model to study the effects of editing. Brush 2A is a selected deletion of the exon 13 mutation. Now, these results provide evidence of the potential to restore functional AGE2 protein function and rescue loss of visual function.
As for RP for we've demonstrated clinically relevant editing levels using a dual AAV editing system, which adds further validation to our therapeutic strategy.
We expect it to clear development candidate for RP for program by year end.
Now transitioning to our ex vivo programs, specifically edit 301 for sickle cell disease and also beta thalassemia.
Lisa Michaels: For RP4, we've demonstrated clinically relevant Dual AUAV Editing, which adds further validation to our therapeutic strategy. We expect it to clear development. RP4, Now transitioning to our ex-vivo, Specifically, Edit 301. We have actually completed our investor training meeting, which included investigators and their clinical trial staff on the protocol and the procedures needed through the complex steps that lead from patient enrollment to cell harvest and substitution. And I'm also very pleased to announce that our first clinical site for the RUBY trial for sickle cell disease has been activated, and that site has now started to approach patients for consent. We anticipate dosing the first patient before the end.
We have actually completed on our Investor training meeting, which included investigators and their clinical trial staff on the protocol and the procedures needed through the complex steps that lead from patient enrollment to sell harvest and subsequent dosing and I'm also very pleased to announce that our first clinical site for the rupee trough trial for sickle cell.
The disease has been activated.
And that site has now started to approach patients for consenting screening.
We anticipate dosing the first patient before the end of the year.
Additionally, we are completing preclinical work required to support our application for the IMD in beta thalassemia and we are currently still on track targeting filings the R&D by year end.
We continue to believe that edit 301 can differentiate from other approaches through use of our proprietary engineered cash 12 day enzyme, which specifically allows for editing the beta globin locus as opposed to other targets such as Bcl 11 day.
Lisa Michaels: Additionally, we are completing preclinical work required to support our application, and we are currently still on track to target filings, the IND. We continue to believe that EDIT 301 can differentiate from other approaches through use of our proprietary engineered capital, which specifically allows for editing as the beta-globin locus as opposed to other targets such as. Doing so, we mimic a natural by Demonstrating Robust and Sustained Fetal He
In doing so we mimic a naturally occurring mutation associated with hereditary persistence of fetal hemoglobin.
By demonstrating robust and sustained fetal hemoglobin expression and safety.
Moving to have a best in class medicine to treat sickle cell disease and beta thalassemia.
And finally, I want to mention our Ips derived NK cell program.
Lisa Michaels: We aim to have a best-in-class medicine to treat sickle cell disease and beta... And finally, I want to mention our IPSC-derived NK cells. We recently presented two separate posters at the American Association. The data showed that NK cells that have been edited to knock out CISH and TGF with our proprietary CRISPR-Cas9 system demonstrated superior tumor killing ability when compared to unedited NK cells. We've also shown that NK cells demonstrated, These findings support our belief that edited NK cells will play an important role in concurrently exploring additional edits to continue, and NAHLT to further enhance the activity of... So I will look forward to updating you more on that program. And with that, I'd like now to turn things over to Michelle. Thank you, Lisa, and good morning, everyone.
We recently presented two separate posters at the most recent American Association for cancer Research.
Data showed that NK cells that have been edited to knockout fish and TGF beta with our proprietary <unk> Christopher cash 12 Mg.
It demonstrates superior tumor, killing ability when compare to an edited NK cells. We've also showed that NK cells demonstrated improved cytotoxicity and enhanced metabolic function in certain tumor microenvironment.
These findings support our belief that edited NK cells will play an important role on the future treatment of solid tumor cancers.
Concurrently exploring additional edits containing knock ins and.
To further enhance the activity on K cells, and so I will look forward to updating you more on that program for the year.
And with that I'd like now to turn things over to Michelle to briefly run through the financial results.
Thank you Lisa.
On everyone.
Michelle Robertson: Editas continues to be in a strong financial position as our portfolio and operations advance forward. Our cash position as of March 31st, 2021 was $723 million compared to $512 million at the end of 2020. Proceeds we raised from our January equity offering have strengthened our balance sheet. We expect our current cash balance will fund our operating plan well into 2023. Our strong capital position leaves us poised to continue executing across our clinical and preclinical pipeline, funding our ongoing Brilliance and Ruby trials while also enabling the advancement of additional candidates into the clinic and enhancing our manufacturing capabilities.
On a test continues to be in a strong financial position as our portfolio and operations advance forward our.
Our cash position as of March 31, 2021 was $723 million compared to $512 million at the end of 2020.
The proceeds we raised from our January equity offering strengthened our balance sheet. We expect our current cash balance will fund our operating plan well into 2023 or.
Our strong capital position leaves us poised to continue executing across our clinical and preclinical pipeline funding our ongoing brilliance will really trial, while also enabling the advancement of additional candidates into the clinic.
Hansen, our manufacturing capabilities.
Now turning to revenue and expenses, which we have also summarize our financial results for the first quarter 2021 in the press release that we issued earlier today.
Revenue was $7 million compared to 6 million from the same period last year. The majority of the revenue recognized this quarter was attributable to our strategic alliance with Bristol Myers Squibb on.
Michelle Robertson: Now turning to revenue and expenses, which we have also summarized in our financial results for the first quarter of 2021 in the press release that we issued earlier today. Revenue was $7 million compared to $6 million for the same period last year. The majority of the revenue recognized this quarter was attributable to our strategic alliance with Bristol Myers-Swift. However, our operating expenses increased year over year by approximately $11 million. Research and development expenses increased by $7 million to $42 million compared to $35 million for the same period last year.
Our operating expenses increased year over year by approximately $11 million research and development expenses increased by 7 million to $42 million compared to 35 million from the same period last year.
This increase was driven by nonrecurring charges related to collaboration and success payments to our licenses as well as higher spending across clinical operations and manufacturing for our two clinical programs.
General and administrative expenses increased by 4 million to $21 million compared to approximately $18 million in the first quarter of last year.
This is mainly a result of increased employee related expenses.
Overall, <unk> remains very well capitalized as mentioned, we have sufficient capital to sustain our operations well into 2023, we continue to be confident on the fundamentals of our technology and expect our strong cash position will help advance our business through a series of potentially important value inflection point.
Michelle Robertson: This increase was driven by non-recurring charges related to collaborations and success payments to our licensors, as well as higher spending across clinical operations and manufacturing for our two clinical programs. General and administrative expenses increased by $4 million to $21 million, compared to approximately $18 million in the first quarter of last year. This is mainly a result of increased employee-related expenses.
With that I'll hand, it back to Jim.
Thank you Michele it's been a very busy past few months the company as I mentioned on our last call is truly an exciting time for us with the work we've been doing to advance our programs and explore new possibilities for gene editing this.
This incredible one some generation technology at the foundation of our science allows us to conceivably treat nearly every genetic mutation on the human genome.
Jim Mullen: Overall, Editas remains very well capitalized. As mentioned, we have sufficient capital to sustain our operations well into 2023. We continue to be confident in the fundamentals of our technology and expect our strong cash position will help advance our business through a series of potentially important value inflection points. With that, I'll hand it back to Jim.
Existing indications represent only a small fraction of diseases potentially addressable by our technological capabilities.
Continued progress solidifies our place among the pioneers and leaders in gene editing at a test was originally formed in order to discover and develop a novel class of genome medicine on a daily basis, we continue to overcome the numerous technical challenges of transforming gene editing technology into clinically practical therapeutics.
Jim Mullen: Thank you, Michelle. It's been a very busy past few months at the company.
Operator: As I mentioned on our last call, it's truly an exciting time for us with the work we've been doing to advance our programs and explore new possibilities for gene editing. This incredible once-in-a-generation technology at the foundation of our science allows us to conceivably treat nearly every genetic mutation in the human genome. Our existing indications represent only a small fraction of diseases potentially addressable by our technological capabilities. Continued progress solidifies their place among the pioneers and leaders of gene editing.
We will continue our efforts to expand the reach of gene editing across our platforms and look forward updating you on additional future developments.
And as always we thank all of you for your interest and support and with that we'll open it up to questions and answers operator.
Thank you so much.
We will now begin the question answer session. As a reminder, if you wish to ask a question. Please press star one with Amazon and the rest of ancillary request. Please press the hash again its star one to ask a question box for just a moment to come back.
The Q&A roster.
First question from the line of join me from cash Securities. Your line is open.
Operator: Editas was originally formed in order to discover and develop a novel class of genome medicines, and on a daily basis, we continue to overcome the numerous technical challenges of transforming gene editing technology into clinically practical therapeutics. We'll continue our efforts to expand the reach of gene editing across our platforms and look forward to updating you on additional future developments. As always, we thank all of you for your interest and support. And with that, we'll open it up to questions and answers. Operator. Thank you so much.
Hi, Thanks for taking our questions.
So looking at the ARVO poster for RP for you set the threshold for therapeutic gets gets you had 25% editing.
Which is higher than the 10% plus for LCA LCA 10, how do you get there and given.
This RFP for the daughter negative condition and require knock in knock out knockout knocking strategy.
Can you just walk us through day, the editing efficiency in vivo that you expect and I have a follow up.
Operator: We will now begin the question and answer session. As a reminder, if you wish to ask a question, please press star 1 on your telephone. If you wish to cancel your request, please press the hash key. Again, it's star 1 to ask a question. We'll pause for just a moment to compile the Q&A wassail. First question from the line of Joon Lee from Trust Securities. Your line is open
Alright, I'll jump in but I'm going to give you the clinicians rather than scientific answer more than anything else.
The <unk> program.
The main.
Our modeling data more or less suggested debt at least 10% of normal retinal function would be required in order to have to be able to restore or at least have some level of best visual acuity. It's only a threshold result, and in fact, 10% was identified at the limit the lowest dose debt with the lowest threshold at which we.
Joon So Lee: Hi, thanks for taking our questions. So, looking at the ARVA poster for RP4, you set the threshold for therapeutic efficacy at 25%, which is higher than the 10% set for
We would expect to be able to start to restore vision on <unk>.
Non clinical data more or less suggests that we're actually able to achieve editing deficiencies that are much higher than that.
Joon So Lee: LCA 10. How do you get there?
Joon So Lee: And given, you know, this RP4 is a dominant negative condition and requires knock-in, knock-out, knock-out.
Fact of the current dose that we're using in the clinical study in the middle cohort is actually predicted to provide 30% on a better muscles of editing so part of the dose finding of the study is to actually determine what the appropriate.
Joon So Lee: Knockout Knock-in Strategy Can you just walk us through the editing efficiency in vivo that you expect?
Joon So Lee: And I have a follow-up.
Level of editing is really required to get optimal response as for the RP for program, you're absolutely right and this is actually one of the real nice benefits of doing gene editing like LCA 10, CEP 290, James RP for Jean is actually way too large to be able to replace through a normal gene therapy type.
Lisa Michaels: All right, I'll jump in, but I'm going to give you the clinicians' answer rather than the scientific answer. For the LC-10 program, the main modeling data more or less suggested that at least 10% of normal retinal function would be required in order to be able to restore or at least have some level of visual function. It's only a threshold result. In fact, 10% was identified at the lowest threshold at which we would expect to be able to start to restore.
<unk>.
And as a consequence of being able to edit we're able to make the corrections in the particular case of RP for because it is an autosomal dominant effect the editing efficiency needs to take into account on both the ability to knock out the dominant gene, which is causing mutation as well as to actually knock in aging that's able to replace division. So what we have project.
Lisa Michaels: Our non-clinical data more or less suggest that we're actually able to achieve editing deficiencies that are much higher than that. And in fact, the current dose that we're using in the clinical study in the cohort is actually predicted to provide 30% or better levels of editing. So part of the dose finding of the study is to actually determine what the appropriate level of editing is really required to get optimal response. As for the RP4 program, you're absolutely right.
It here at the moment is 25% is the expected threshold to be able to get that response, but our ability to actually treat in the clinical setting may be higher.
Okay.
Okay looking forward to this clinical data and for the LCA 10 debt you are advancing.
So for.
For the second cohort and following our U heavy change in inclusion criteria to sort of accommodate the enrollment.
And how has.
The enrollment been since day, the vaccinations have rolled out.
Lisa Michaels: This is actually one of the real nice benefits of doing gene editing. Like LCA10, and CEP290, the RP4 gene is actually way too large to be able to replace through a normal gene therapy type approach. And as a consequence of being able to edit, we're able to make corrections. In the particular case of RP4, because it is an autosomal dominant effect, the editing efficiency needs to take, [inaudible] So what we have projected here at the moment is 25% is the expected threshold to be able to get that response, but our ability to actually treat in the clinical setting. Okay, I'm looking forward to this clinical data. And for the LCA-10 that you're advancing,
And.
How many.
Can you remind us how many patients you've done so far.
So far to date, we have dosed four patients the way the protocol as currently written is that the first two patients were selected largely on the basis of being only light perception and were dosed at the lowest dose is expected to provide some level of protective editing. The primary purchaser purpose of this study really is more dose finding.
Related to potential safety concerns.
Because we saw no safety concerns in those first two patients we actually made modifications to the protocol in order to allow enrollment of patients who actually have some measurable visual acuity and not be quite so strict and restricting the total patient population enrolled in that protocol change was actually may just before the beginning of the year.
Lisa Michaels: So, for the second cohort and following, have you changed any inclusion criteria to sort of accommodate the enrollment? And how has the enrollment been since the vaccinations were rolled out?
Probably the most important thing is that small change in the protocol by itself is actually allowed for a much more a much easier identification of patients.
And we actually are very well tracking moving forward to be able to continue enrolling and completing this mid dose cohort as well as being able to at least start if not complete the pet's cohort by the end of the year.
Lisa Michaels: Can you remind us how many patients you've dosed so far? So, so far, we have dosed four patients today. The way the protocol is currently written is that the first two patients were selected largely on the basis of only light perception and were dosed at the lowest dose expected to provide some level of predictive editing. The primary purpose of the study really is to find more doses related to potential safety concerns.
As for COVID-19 and vaccines I mean honestly, it's really it's a real benefit for US has been somewhat of a loosening of travel restrictions and also loosening of restrictions within the hospitals line itself that have allowed patients to travel to the treatment sites on to get their therapy and so at the moment I'm not sure that COVID-19 vaccination has changed anything but it has made things easier.
Lisa Michaels: Because we saw no safety concerns in those first two patients, we actually made modifications to the protocol in order to allow enrollment of patients who actually have some measurable visual acuity and not be quite so strict in restricting the total patient population enrolled. And that protocol change was actually made just recently. Probably the most important thing is that small change in the protocol by itself has actually allowed for much more, much easier identification of patients.
For being able to get the patients to the treatment centers.
Got it.
How many sites are capable of doing this.
Trained properly and at the end on a day is we really we have we're really going to sites and centers, where we have people that are comfortable with retinal injection.
And as of end really at the moment, we're continuing to expand our sites with looking at.
We have clinical sites that have been set up as part of our non interventional study on our natural history study and in fact, those patients are beginning now to roll into the treatment center in Saudi and so it's very nice that we have nice baseline observations on these patients as they begin to move into the study, but we are somewhat trying to limit it to a number of different sites and centers, where we know that the occupancy.
Lisa Michaels: And we are actually very well on track moving forward to be able to continue enrolling and completing this mid-dose cohort, as well as being able to at least start, if not complete, the third dose cohort by then. As for COVID and vaccines, I mean, honestly, the real benefit for us has been somewhat of the loosening of travel restrictions and also the loosening of restrictions within hospitals themselves that have allowed patients to travel to treatment sites and to get their therapy. And so at the moment, I'm not sure that the COVID vaccination has changed anything, but it has made things easier for being able to get the patients to treatment sites.
Retinal surgeons are very comfortable on and be able to give us reproducible and consistent injections in the back of the line.
Got it thank you.
<unk>.
Thank you so much.
Your next question from Cory <unk> from Jpmorgan. Your line is open Hey, good morning, guys. Thanks for taking my questions on two of them for you first one is what's the gating factor to dosing patients in the Ruby trials and sites are active and investigators are trained what more needs to happen there and then with regards to your <unk>.
LCA 10 program prior to the I D. M. C meeting. This summer do you have to dose any additional adult patients to have sufficient.
Lisa Michaels: Just remind us, how many sites are capable of doing this? Transcripts provided by Transcription Outsourcing, LLC, comfortable with right now injection, and as and really at the moment we're continuing to expand our sites with looking, We already have clinical sites that have been set up as part of our non-interventional study, our natural history study, and in fact, those patients are beginning now to roll into treatment, https://www.kenhub.com But we are somewhat trying to limit it to a number of different sites and centers where we know that the retinal surgeons are very comfortable.
That's sufficient safety package prior to dosing pediatric patients if so how many more do you think you'll need thank you.
Okay Cory.
Thanks for the question.
So the first question is what to what does it take I guess to dose a patient in the trial.
Actually in terms of site selection identified two sites from centers that had already told us they had patients asking for this for the transplant and had pre identified patients who would be willing to undergo the treatment.
So those centers at least one of those two centers is now up and running and we're expecting the second one relatively shortly so at that point. It gives the centered at the site. The opportunity is directly approach the patient to go through the details of the protocol and have consent side.
Kari Casimo: Your next question is from Kari Casimo from JP Morgan. Your line is open.
At this point, we actually started fairly laborious process, that's consistent across the entire space and that is the.
Kari Casimo: Hey, good morning guys. Thanks for taking my questions. Two of them for you.
<unk> ability to for <unk> patients with sickle cell disease is actually a relatively complicated and step wise process. So once the patient is identified and they've undergone all the screening procedures.
Kari Casimo: The first one is, what's the gating factor for dosing patients in the RUBY trial since sites are active, and investigators are trained? What more needs to happen there? And then, with regard to your LCA-10 program prior to the IDMC meeting this summer, do you have to dose any additional adult patients to have sufficient safety packaging prior to dosing pediatric patients? If so, how many more do you think you'll need? Thank you
Either need to start a transfusion regimen or already be on a chronic transfusion regimen, which allows these patients to basically from loose on the hemoglobin F. Because the process of mobilizing cells and putting them through the pheresis procedure actually can precipitate a precipitate sickle cell crises and they can be quite severe.
Lisa Michaels: Okay, Cory, thanks for the question. So the first question is, what does it take, I guess, to dose a patient in the Ruby trial? We actually, in terms of site selection, identified two sites and centers that had already told us they had patients asking for. Transcription by CastingWords. So those centers, at least one of those two centers is now up and running.
So it takes a bit of time to be able to get the patient to the screening then start the transfusion regimen, and then schedule them to come in to have the <unk> procedure and since multiple different.
Not a walk in the door, one time and walk back out the door at habits on patients actually do have to come back on consecutive days in order to collect enough sales that could be used for the editing process at that point the sales come back to at a task.
Editing procedures and then once we've been able to complete that we will have returned back to the sites and centers are scheduled to patient coming in for the for the.
Lisa Michaels: And we're expecting the second one to be relatively short. So at that point, it gives the center, the site, the opportunity to directly approach the patient to go through the details of the protocol and have consent signed. At this point, we actually start a fairly laborious process that's consistent across the entire space. And that is, the ability to freeze patients with sickle cell disease is actually a relatively complicated and step-wise process. So once the patient is identified, and they've undergone all the screening procedures,
For the process in order to get from treatment. Once we've calculated all up those those procedures and days on days and months Youre actually probably looking at about four to five months from the time that the consensus signed until the patient is treated and that's why we're communicating the plan to actually start to be able to dose. The first patient by the end of the year, but we're actually pretty confident that we have a number of patients who've already.
Demonstrated interest in advance.
To the second question.
Based upon the protocol. The DMC decision is made based upon the observations from the first cohort in the second two patients in the second adult cohort.
Lisa Michaels: They either need to start a transfusion regimen or already be on a chronic transfusion regimen, which allows these patients to basically dilute down the hemoglobin S because the process of mobilizing cells and putting them through the FRESIS procedure can actually precipitate sickle cell crises, and they can be quite severe. So it takes a bit of time to be able to get the patient to the screening, then start the transfusion regimen, and then schedule them to come in to have the phoresis procedure. And since multiple different, it's not like you walk in the door one time and walk back out the door and have it done.
The decision on whether or not safety has been adequate in those adults is really the decision tree in order to know whether or not we can open up the enrollment to pediatrics, it's primarily a safety decision, but as part of debt and also of our deep dive into the data we will be looking for signals of efficacy and signs of editing that we would at least.
So that there is a potential benefit for the patients moving forward and so that meeting is scheduled for June and we're hoping that that will determined for us whether or not we can go directly in children at that point in time or whether or not the DNC would like to have a few additional adults treated before we do that okay.
Lisa Michaels: Patients actually do have to come back on consecutive days in order to collect enough cells that can be used for the editing process. At that point, the cells come back to Editas where we will do the process in order to give them treatment. Once we've calculated all of those procedures in days and months, you're actually probably looking at about four to five months from the time that the consent is signed until the patient is treated.
Okay. Thank you Lisa I appreciate all the color.
Thank you. So much next question from Phil Nadeau from Cowen and company. Your line is open.
Good morning, and thanks for taking my questions.
First one is just a follow up to <unk>.
In terms of.
Efficacy measures that you can look at it the DMC meeting can you give us some sense, what you would consider promising and meaningful signals of efficacy and then more broadly.
What.
What do you hope to achieve in the adult patients and what you hope to achieve in the pediatric patients in terms of visual acuity is stabilization good enough or do you really hope to see improvements.
Lisa Michaels: And that's why we're communicating the plan to actually start to be able to dose the first patient by. We're actually pretty confident that we have a number of patients who've already demonstrated interest in it. To the second question, based upon the protocol, the IDMC decision is made based upon the observations from the first cohort and two patients in the second adult cohort. The decision on whether or not safety has been adequate in those adults is really the decision tree in order to know whether or not we can open up the enrollment to pediatrics.
Okay. So in this patient population in general what we've observed is there's not a lot of decline of vision.
In like follow up on these patients. So the majority of the vision loss actually takes place during childhood. So of course, one of the our real goal is to try to get into the kids sooner than later, when we hope that between neuroplasticity as well as some level of experience and vision.
Actually benefit to patients and potentially give them a better benefit but at the end of the day in LCA.
Unique about this particular diseases at the retina is more or less intact, there's not a significant amount of degeneration of the outer layer. So once we're able to restore normal ciliary function in the photo receptor actually hoping that we'll have normal function of the photoreceptor. It really comes down to the brain's ability to interpret those results.
Lisa Michaels: It's primarily a safety decision. But as part of this and also of our deep dive into the data, we will be looking for signals of efficacy and signs of editing that would at least show that there is a potential benefit for the patients moving forward. And so that meeting is scheduled for June, and we're hoping that that will determine, Okay, thank you.
So in terms of the clinical outcomes that we're looking I'm really looking at two fold. One of them is just functional evidence of having an effect of the editor itself and that can be measured solely in terms of following the anatomy of the back of the eye to see if theres been any changes related to the procedure itself.
Kari Casimo: Okay. Thank you, Liisa. I appreciate all the color.
Philip M. Nadeau: Thank you so much. Next question for Phil Nadeau from Cohen & Company. Your line is open.
Whether or not we're actually seeing changes in responses to light that could be measured in terms of pupil Larry responses from these patients tend to have very slow people every responses as well as.
Philip M. Nadeau: Good morning. Thanks for taking my questions. The first one is just to follow up on Corey's.
Responses to different types of colors on flight all of which will gives me a signal of whether or not the editing has actually resulted in a physiologic change that I can measure.
Philip M. Nadeau: In terms of efficacy measures that you're going to look at at the IDMC meeting, can you give us some sense of what you would consider promising and meaningful signals of efficacy? And then, more broadly, what do you hope to achieve in the adult patients and what do you hope to achieve in the pediatric patients in terms of visual acuity? Is stabilization good enough, or do you really hope to see improvements?
Manner, but of course, the ultimate goal is having something that's meaningful for patients and that will be part of the measurements that we're doing both for visual acuity as long as also our continued validation on the observations of the patients going through amaze.
A little bit differently, but similar to what was done by Luxe turn on.
That's very helpful. And then second question on the 301 program, because I'm sure where Theres a fair amount of controversy.
Lisa Michaels: So in this patient population, in general, what we've observed is there's not a lot of decline in vision and late follow-up of these patients. So the majority of the vision loss actually takes place during childhood. So, of course, one of our real goals is to try to get to the kids sooner than later when we hope to.
But pre conditioning and just generally on gene editing gene therapy treatments and sickle cell phone rang the cases of Mds and AML from a different program do you have any thoughts on.
The difficulty of treating sickle cell patients with genomic therapies in light of B cell phone conditioning core.
Lisa Michaels: Neuroplasticity as well as some level of experience and vision will actually benefit the patients and potentially give them some independence. But at the end of the day, and I'll see. What's unique about this particular disease is that the retina is more or less intact. There's not a significant amount of degeneration of the outer layer.
The type of vectors that are currently being used.
I'm kind of philosophical about it quite frankly, because I'm still not quite sure that we know what happened in the other study and I think it's interesting that one of the patients who was originally set to have Molly dysplasia now is being set to have a transfusion email, which still suggests something can be happened to the shelves. The good news is it's not malignancy on I think that's an important.
Lisa Michaels: So once we're able to restore normal ciliary function in the photoreceptor, we're actually hoping that we'll have normal function of the photoreceptor. But it really comes down to the brain's ability to interpret. So, in terms of the clinical outcomes that we're looking at, I'm really looking at two things. One of them is just functional evidence of having an effect of the edit itself. And that can be measured solely in terms of the following. [inaudible] as well as responses to different types of colors of light, all of which will give me a signal of whether or not the editing has actually resulted in a physiologic change that I can measure. That's very helpful. And a second question on the 301.
<unk>.
Whether or not we feel confident attributing this ship use olson.
I I'm almost an old timer in this space I was doing bone marrow transplant in patients with sickle cell disease as much as 30 years ago, and the potential and the toxicities associated with that as well as much more intensive chemotherapy plus the concerns related to graft versus host disease and rejection sort of risk benefit really does seem to be in favor at the moment in terms of the speed of.
Both.
Gene therapy gene editing methods.
At the end of the day I think one of the biggest limitations to acceptance of the therapy not just in this patient population, but and others who are also getting extra EBIT products is really the intensity of the chemotherapy and next big stop on the next big step in this space is to have lower toxicity. So it's one of the things that we are looking at.
At the end of the day, we're really looking right now for proof of concept of fare modality, showing the efficiency of our edits and the advantages of targeting the day to Lucas as opposed to Bcl 11 day.
Lisa Michaels: One program, as I'm sure you're aware, there's a fair amount of controversy.
Lisa Michaels: about preconditioning and just generally gene editing, gene therapy treatments in sickle cell following the cases of MDS and AML from a
But the next steps will of course be looking at other conditioning regimens that could lower the toxicity and maybe even the acceptance of the therapy.
Perfect. That's very helpful. Thanks for taking my questions.
Thank you. So much next question from Gena Wang from Barclays. Your line is open.
Lisa Michaels: Do you have any thoughts on... the difficulty of treating sickle cell?
Lisa Michaels: Medical Cell Patients with Genomic Therapies in Light of B-Cell-Fan Conditioning or the type of vectors that are currently being used. Well, I'm kind of philosophical about it quite a bit.
Thank you for taking my questions I have two one is regarding the Ruby trial in sickle cell disease, and just wondering if you can give us a little bit update regarding the partial clinical hold.
Lisa Michaels: Well, I'm kind of philosophical about it, quite frankly, because I'm still not quite sure that we know what happened. The other study, and I think it's interesting that one of the patients who was originally said to have myelodysplasia is now being said to have..., which still suggests something could be happening to those cells. The good news is it's not malignancy, and I think that's an important point, because whether or not we feel confident attributing this to the abused souls. I'm almost an old timer in this space.
And therefore, the product consistency that FDA is looking for do you need to clear that in order to also file on <unk> for beta thalassemia.
And second question is more like the.
Technology platform question.
Got in your eye disease indications putting on.
All of these indications are using AAV as a delivery vehicle.
Just wondering what is the longest animal data you showed a safety has given that the crisp mckesson on packing AAV could be long lasting.
Lisa Michaels: I was doing bone marrow transplants in patients with sickle cell disease as much as 30 years ago, and the toxicities associated with that, as well as much more. At the end of the day, I think one of the biggest limitations to acceptance of the therapy, not just in this patient population but in others who are also getting exudative products, is really the intensity of the chemotherapy. The next big step in this space is to have lower toxicity.
I'm going to skip the second question, because I'm not fully prepared to be able to answer you on the non clinical data that supported the program, but I will focus on the first one the channel that you asked which is.
So the first thing I want to say, it's the clinical sickle cell program is actually kind of a distinctly different creature than the beta thalassemia program, especially with the agency is looking for is clear evidence and a consistent manner, if our ability to reduce cycling in themselves.
Lisa Michaels: So it's one of the things that we are looking at. At the end of the day, we're really looking right now for proof of concept of our modality, showing the efficiency of our edits and the advantages of targeting the beta locus. But the next steps will, of course, be looking at other conditioning regimens that can lower the toxicity, maybe even prove the acceptance. Perfect. That's very helpful. Thanks for taking my questions.
And for beta thalassemia, that's not really the revenue outcome.
How come in fact in beta thalassemia hemoglobin F is probably our ability to demonstrate conversion to hemoglobin F is really really going to be the probably the more important thing.
So the good news is is that as of at least of today. We don't have any concerns regarding the potency for beta thalassemia or the assays that we have in place for sickle cell disease, it's not holding us back in any way or form are we.
Gina Wong: Thank you so much. Next question is from Gina Wong from Barclays. Your line is open.
Are at the moment on completing a number of non clinical studies to support our plans on how to move forward with the potency assay and we are going to engage with the agency. This summer.
Gina Wong: The second question is more like the technology platform question regarding your eye disease indications. I think all of these indications are using AAV as a delivery vehicle. I'm just wondering what the longest animal data you have shown for safety given that the CRISPR-Cas9 packing AAV could be long-lasting? I'm going to skip the second question because I'm not fully prepared to be able to answer you on the non-clinical day that it's supported. I will focus on the first one. I asked him, which is it?
This has always been something we were going to do in parallels it doesn't actually interfere with our plans moving forward, we hope to hazard festivals.
The clinical hold lifted in time for us to start the main part of after the run of the study.
Okay. Thank you.
Thank you. Your next question from Diego sought from Credit Suisse. Your line is open.
Hi, Thanks for taking our question. This is Roger on the Tiago.
Gina Wong: So the first thing I want to say is the clinical old sickle cell program is actually kind of a distinctly different creature than beta thalassemia. This is what the agency is looking for. Clear evidence in a consistent manner of our ability to reduce sickling in the cells. But for beta thalassemia, that's not really the relevant outcome. In fact, in beta thalassemia, http://www.kenhub.com. So the good news is that, as of at least today, we don't have any concerns regarding the potency of the treatment for beta thalassemia or the assays that we have in place.
So you heard from preclinical data on your in vivo ocular programs.
Just briefly highlight the key differences and construct among these programs and whether or not they're modular. Thanks.
Okay.
What do you mean by modular.
And the strength that it could be potentially applied to other indications within ocular diseases or any other areas that you are exploring in the future.
So I think on one of the things that's really interesting about the targets we are hitting on the ocular programs is that.
Between RP for Ash to a L. L. C. H <unk> visa programs have probably cannot be treated by traditional gene therapy type methods and the reason why is because two of them are genes.
Gina Wong: For sickle cell disease, it's not holding us back. We are at the moment completing a number of non-clinical studies to support our plans on how to move forward with the potency assay. Chief of S.H.A.R.M. This has always been something. Parallels. It doesn't actually inter- We hope to have the clinical hold lifted in time for us to start the main part after the run of the study.
Case actually fall to them at the genes are definitely way too large in order to be able to be treated through a traditional gene therapy approach. Therefore, there's a clear advantage to them to editing the gene in order to correct. The mutations that result in the disease and then also the same thing with RP for adoption.
Diago Sot: Thank you. The next question is from Diago Sot from Credit Suisse. Your line is open.
<unk> is also an extremely big gene, but the problem with those diseases is that theyre not obsessive inherited autosomal dominant inherited which means that the gene being produced actually partly what creates.
Roger: Hi, thanks for taking our question. This is Roger on behalf of Tiago.
The loss of vision and blindness. So again, we have a very clear ability here to be able to knock out the portion of the gene that's not functional and should knock in a corrected gene to allow for normal function in the eye. So they're very different debt. So the approach to these jeans really shows some of the advantages of why editing its problem editing.
Roger: So you shared some preclinical data, Arvo, on your in vivoocular programs. Could you just briefly highlight the key differences in construct among these programs and whether or not they're modular?
Roger: Thanks.
Roger: What do you mean by "modular?"
Roger: In the sense that it could potentially be applied to, you know, other indications within ocular diseases or
Is the right approach, whereas gene therapy, and then putting in a gene construct would not be able to correct. These diseases in terms of modular I guess youre talking sort of a cut and paste line cut and paste, whether or not we can just uncertainty. This is actually very high precision medicine and its very directed so each one of these is really targeted to the specifics on.
Roger: Any other areas that you're exploring in the future?
Lisa Michaels: you're exploring in the future. So I think one of the things that's really interesting about
Lisa Michaels: So I think one of the things that's really interesting about the targets we're hitting in the ocular programs is that between RPFAR, AASHTO-A, and LCA-10, these are programs that probably cannot be treated by traditional gene therapy types of treatments. The reason why is because two of them are genes, in the case actually for all of them, two of them the genes are definitely way too large in order to be able to be treated through a traditional gene therapy approach.
The disease. However, we are building upon similar platforms moving forward because.
A growing experience with sub retinal injection, our experience with being able to demonstrate the efficacy to translate the findings from one program in the eye to the other as well as to help us build additional models on it really is a stepwise progression from lately.
Leading to higher levels of on leases.
Lisa Michaels: Therefore there's a clear advantage to editing the gene in order to correct the mutations that result, and also the same thing with RP4, rhodopsin is also an extremely big gene, but the problem with those diseases is that they're not recessive inherited; they're autosomal dominant. So the approach to these genes really shows some of the advantages of why editing is the right approach, whereas gene therapy and putting in In terms of modularity, I guess you're talking sort of about cut and paste, whether or not we can just insert these.
With proof of concepts, but also higher levels of editing efficiency.
Alright, thank you.
Thank you. Your next question from Jay Olson from Oppenheimer. Your line is open.
Yes.
Your line.
Your line is open day now ask your question.
Yes.
Okay, that's pretty big E next.
Question is from Jan on you.
From Wells Fargo Securities. Your line is open.
Hi, Thanks for taking my questions.
So first on the Usher to eight syndrome program.
Have you started IND, enabling studies or are you are if you're not a what is the time line for starting our that our IND, enabling studies. Thank you.
Lisa Michaels: This is actually very high-precision medicine, and it's very directed. So each one of these is really targeted to the specifics of the disease. However, we are building upon similar platforms moving forward because of our growing experience with subretinal injection, our experience with being able to demonstrate the efficacy of translating the findings from one program in the eye to the other, as well as to help us build additional models. It really is a stepwise progression leading to higher levels of not only proof of concept, but also higher levels of editing efficiency. All right, thank you.
So we're still on the process of identifying the first clinical candidate and the timeline I'm, hoping we'll be able to communicate more later this year.
Okay and for the.
<unk>.
Our Q4 program you mentioned, you're pursuing a knock in knock on Nokia and strategy.
I was curious because there are many mutations that underlies this condition.
We're knocking in obviously the chain is very big.
Jay Olson: Thank you. Next question is from Jay Olson from Oppenheimer. Your line is open. Jay Olson, your line is open, you can now ask your question. Okay, let's proceed to the next question. This question is from Yanan Zhu from Wells Fargo Securities. Your line is open.
Walking on the whole gene.
Could you give me give us some idea of how many of the disease, causing mutations would you be able to address with your.
Okay and approach yes.
So you are right and the part that to a certain extent the knock out is going to be part of the value of debt from the perspective of.
Yanan Zhu: Hi, thanks for taking my questions. So first, on the Usher 2A syndrome program, have you started IND-enabling studies? Or are you, and if not, what is the timeline for starting that IND-enabling study? Thank you.
To reduce the autosomal dominant expression.
I'm not really quite prepared to give you a sense of the total range of what we're actually knocking again, so but I'd be happy to follow up with it.
Got it and.
Lisa Michaels: So we're still in the process of identifying the first clinical candidate and the timeline. I'm hoping we'll be able to communicate more later this year.
In terms of your NK cell.
Our strategy.
Could you.
You gave some updated thoughts on our income.
Yanan Zhu: Thanks, and for the RP4 program too.
In terms of the broad applications.
Yanan Zhu: You mentioned you're pursuing a knock-in, knock-out, knock-in strategy. I was curious because there are many mutations that underlie this condition. When you are knocking in, obviously, the gene is very big; you couldn't knock in the whole gene. Could you give us some idea how many of the disease-causing mutations would you be able to address with your knock-in approach?
Applications of that.
You might be pursuing with the IPO C on kcl strategy.
Such as our antibody mediated or a car car NK type strategy. Thanks.
So I am not no details yet quite at this point, but I think it's very helpful. Just simply say that day.
Lisa Michaels: Yes, so you're right in the part that to a certain extent, the knockout is going to be part of the value of this from the perspective of I'm not really quite prepared to give you a sense of the total range of what we're actually knocking in, but I'd be happy to follow up with you.
Data that we have at the moment supporting the Soc TGF beta knock out is actually quite impressive from the perspective of being able to show evidence of the ability to overcome the micro tumor environment and also TGF beta.
Suppression of immune responses. So I think the key thing that's really helpful. Here is that we really are committed to going into solid tumors and an easy entry price from that perspective would be targeting those tumors that have high production of TGF beta.
Yanan Zhu: Got it. And in terms of your NK-Cell strategy, could you give some updated thoughts on the broad applications that you might be pursuing with the ITSC NK-Cell strategy, such as antibody-mediated or a CAR-NK type strategy? Thanks.
As for the additional knock ins and double knockouts that we're talking about will be able to provide more information on that later.
Got it thank you for the color.
Thank you very much next question from Steve <unk> from Raymond James Your line is open.
Lisa Michaels: Yeah, so I'm not, no details yet quite at this point, but I think it's very helpful to just simply say that. The data that we have at the moment supporting the CISH TGF-beta knockout is actually quite impressive from the perspective of being able to show evidence of the ability to overcome the microtumor environment and also TGF-beta, Suppression of Immune Responses. So I think the key thing that's really helpful here is that we really are committed to going into solid tumors, and an easy entry point from that perspective would be targeting those tumors that have high production of TU. As for the additional knock-ins and double knockouts that we're talking about, we'll be able to provide more information on that later.
Hey, good morning, Thanks for taking the question I was hoping you could just comment on the safety of the mid dose patients I know you mentioned no safety signals in the first two patients.
So I was wondering if you could comment on that and Relatedly. It sounds like you are currently cleared or maybe even as we speak dosing the fifth.
And there were six patients in the study I just wanted to verify if that's the case.
So in terms of safety there have not been any safety signals that have required us to do any additional observations on we're actually feeling pretty optimistic at least for the ability to progress to the next doses in that study and the next patients are being lined up on scheduled as we speak.
Okay perfect. Thanks for that and then I might be misremembering. This so please correct me if I'm wrong, but I guess I thought the adult high dose cohort would be completed as well before advancing to pediatrics.
Or maybe contemporaneous with debt cohort it sounds like you're obviously looking to open the pediatric dose cohort after the middle dose I just wanted to clarify if you still intend to enroll and treat the higher third dose cohort in adults or if youre seeing anything in the data that suggests you don't.
Yanan Zhu: Got it. Thank you for the call.
Steven James Seedhouse: Thank you so much. Next question is from Steve Seedhouse from Raymond James. Your line is open.
Steven James Seedhouse: Hey, good morning. Thanks for taking the time to answer the question. I was hoping you could just comment on the safety of the mid-dose patient. I know you mentioned no safety signals in the first two patients. So I was wondering if you could comment on that and, relatedly, it sounds like you are currently cleared or maybe even as we speak, dosing the fifth and or sixth patients in the study. I just wanted to verify if that's the case.
Neither need to or want to test the dose the only thing that we keep me to go keep me from going up to the next higher dose would be any safety concerns because I really need to be explored the entire dose response and translation to efficacy. If you remember with flex journal, which didn't appear to have a dose response curve. They ultimately made the decision to go with the highest dose because it was.
Safe and there was no way to discern whether or not it's an advantage to a lower dose in this particular case, we do think that the non clinical data actually supports that we do have a dose response and that we can achieve even hires of levels of editing. So as long as there is no safety concerns I will be going ahead to the adult high dose cohort anyway.
Lisa Michaels: In terms of safety, there have not been any safety signals that have required us to do any additional observations. We're actually feeling pretty optimistic, at least for the ability to progress to the next doses in the study, and the next patients are being lined up and scheduled as we speak.
The protocol that I inherited and the one that's working quite well at the moment is basically allows for a DMC evaluation. After the dosing of the first adult patients to allows dosing of pediatric patients at the same dose level. So we wouldn't start the pediatric patients at a higher dose level until after we evaluated safety on adults.
Steven James Seedhouse: Okay, perfect. Thanks for that.
Steven James Seedhouse: And then I might be misremembering this, so please correct me if I'm wrong. But I guess I thought the adult high dose cohort would be completed as well before advancing to pediatrics, or maybe contemporaneous with that cohort. It sounds like you're obviously looking to open the pediatric dose cohort after the middle dose. I just wanted to clarify if you still intend to enroll and treat the higher third dose cohort in adults, or if you're seeing anything in the data that suggests you don't either need to or want to test that dose.
That's great. Okay I appreciate the clarification, thanks for the questions.
Thank you. Your next question from Madhu Kumar from Goldman Sachs. Your line is open.
Yeah. Thanks for taking our questions. So kind of following up on June's question at the beginning.
So the 10% threshold Billy's described before so that wasn't L. P. A specific and the 25% threshold described at ARVO was kind of specific to adopt them, but I mean, it seems like it can be generalizable. So.
I think we today what do you think is the fraction of corrected photo receptors that are going to be needed for clinical benefit in LCA 10 based on all the data you have right now.
Lisa Michaels: The only thing that would keep me from going up to the next higher dose would be any safety concerns because I really need to explore the entire dose response. If you remember with Luxternal, which didn't appear to have a dose-response curve, they ultimately made the decision to go with the highest dose because it was safe, and there was no way to discern whether or not it was an advantage to a... In this particular case, we do think that the non-clinical data actually support that we do have a dose response and that we can achieve even higher levels of editing.
Well for LCA 10 based upon the data we have what I'll certainly say is that the non clinical data certainly supports that at our mid dose level, we would protect to be able to achieve editing efficiencies of at least 30% or higher and moving on to the higher dose, we're actually looking at 50% or higher so with the ability to be able to translate actual.
Edits to vision are part of the study is going to help us define with the actual number of edits required or at least would be predicted to result in meaningful vision and that will be one of the secondary outcomes of the study.
Okay Cool, so then kind of <unk>.
Following from that from this 30% from the mid dose kind of average productive editing rates I'm hesitant, but on average guys within distribution. So.
Lisa Michaels: So, as long as there are no safety concerns, I will be going ahead with the adult high-dose cohort. The protocol that I inherited and the one that's working quite well at the moment basically allows for a DMC evaluation after the dosing of the first adult patients to allow dosing of the pediatric patients at the same dose level. So we wouldn't start the pediatric patients at a higher dose level until after we evaluated safety. That's right.
If say, 25% is the threshold like what fraction of patients and do you expect to be below that 25% threshold. If the average productive editing rate is 30% practically.
Well the average I think is actually a little bit higher I'm only talking 30% is the threshold that is what we're expecting to see at that dose.
Okay Cool and then.
Okay. So on and then thinking about the eye NK cell program. So you saw the data at ACR was pretty interesting and we looked at the kind of the tumor killing tumor cell, killing data as I recall the ratio of NK cells, the tumor cells and those experiments was five to one so if you use a lower ratio range maybe.
Steven James Seedhouse: That's right. Okay. I appreciate the clarification. Thanks for the questions.
Madhu Sudhan Kumar: Thank you. Your next question is from Madhu Kumar from Goldman Sachs. Your line is open.
Madhu Sudhan Kumar: Thanks for taking our questions. So, kind of following up on June's question at the beginning, So the 10% threshold that was described before, so that wasn't LCA specific, and the 25% threshold described at ARVO was kind of specific to rhodopsin, but I mean, seems like it could be generalizable. So practically today, what do you think is the fraction of corrected photoreceptors that are going to be needed for clinical
It's arguably more physiologically relevant to how you will therapeutically intervene what kind of killing right can you achieve with your effect on NK cells.
So on Friday for that level of detail I would probably refer you to the clinical scientists to the research scientists who ran those studies.
Okay cool, thank you very much everyone.
Yes.
Thank you. Your next question from Luca <unk> from RBC. Your line is open.
Madhu Sudhan Kumar: Clinical Benefit and LCA-10 are based on all the data you have right now.
Madhu Sudhan Kumar: Well, for LCA-10, based upon the data we have, what I'll certainly say is that the non-clinical data certainly supports that at our mid-dose level, on to the higher dose. So, with the ability to be able to translate actual edits to... Okay, cool. So kind of following from that, so just 30% for the mid dose kind of average productive editing rate. So I mean, as I said, that's an average value. So the distribution.
Fantastic. Thanks, so much for taking my questions and congrats on all the progress in bringing Mark on board, maybe circling back on sales questions earlier on the conversation. The recent setback from Bluebird Bio I guess, what's your appetite for exploring the collaboration with some of the novel companies that are developing <unk> sparing pre conditioning regimen. So any.
There would be great and then second question, maybe on pretty ocular pipeline. This my understanding that you are transferring the manufacturing from Abbvie to <unk> wondering if you have any update there and whether you think that the FDA may potentially ask you at some point to run a bridging study there. So again any color would be great. Thanks, so much.
Madhu Sudhan Kumar: So if say 25% is the threshold, like what fraction of patients would you expect to be below that 25% threshold if the average productive editing rate is practically 30%? Well, the average editing rate is actually a little bit higher. Okay, um, cool. And then
So at least on the drawing to try to take that one.
Madhu Sudhan Kumar: Okay, so on and then thinking about the INK cell program. So we
Yeah, I'm also thinking about the first one at the moment I just lost track of what my thought with them.
Madhu Sudhan Kumar: We saw the INK cell program, so we saw the data in AACR was pretty interesting, and we looked at the tumor cell killing data. As I recall, the ratio of INK cells to tumor cells in those experiments was 5 to 1. So if you use a lower ratio, a ratio that maybe is arguably more physiologically relevant to how you will therapeutically intervene, what kind of killing rate can you achieve with your effector INK cells?
Okay.
So the question is so.
The simple short question the short answer to the manufacturing question is.
At least for the.
The trial.
We have planned and the cohorts we have planned.
We don't need to make additional material you're correct in that there will ultimately be some.
Madhu Sudhan Kumar: Show up for I-Ming for that love. Okay, cool. Thank you very much.
Madhu Sudhan Kumar: Thank you. Your next question is from Luca Issi from RBC.
Comparability questions.
Luca Issi: Your line is open. Oh, fantastic. Thanks so much.
But we will have to answer.
Of course, we are going to try to do that mostly through analytical techniques and maybe some in vivo but.
Luca Issi: Well, fantastic. Thanks so much for taking my questions and congratulations on all the progress and bringing Mark on board. Maybe circling back on Phil's questions earlier in the conversation, the recent setback for Bloober Bio, I guess what your appetite is for exploring a collaboration with some of the novel companies that are developing busulfan, sparing preconditioning regimens, so any call there would be great. And the second question, maybe for the Ocular Pipeline, it is my understanding that you are transferring the manufacturing from AbbVie to a CDMO I was wondering if you have any update there and whether you think that the FDA may potentially ask you at some point to run a bridging study there. So again, any call would be great. Thanks so much.
In vivo non human studies.
That would be the attempt we have not had a conversation with the FDA about whether they would require anything in.
In addition to that.
A lot of this always turns on.
How well you can you can.
Characterize the product you have.
We had a pretty good characterization assays.
Cetera.
And then it also.
A little bit dependent on.
You know what the Fda's recent experience with similar things are and Thats always hard to predict.
Super helpful and maybe the first question was around novel pre conditioning regimen debt spare BSO fan any appetite, therefore, a collaboration or any big picture thoughts. Thanks.
Lisa Michaels: So Lisa, did you want me to try to take that one?
Lisa Michaels: Yeah, I'm also thinking about the first one at the moment, but I just lost track of what my thought was. Okay.
So I guess I'll fall back on a similar answer that I had earlier and that was basically that at the moment I'm really focused on getting proof of concept of the editing platform.
Lisa Michaels: So the question, so the short, simple answer to the manufacturing question is, at least for the trials that we have planned and the cohorts we have planned, we don't need to make additional material. You're correct in that there will ultimately be some product comparability questions that we will have to answer. Of course, we are going to try to do that mostly through analytical techniques and maybe some in vivo, but not necessarily non-, in vivo non-human studies. That would be the attempt.
So meaningful edits in the patients.
As we move forward in the clinical programs I do think that having new conditioning regimens is going to be important and I think that in order to have overall acceptance at the opportunity to test those will also become important because even if we're able to reduce the debt.
Toxicity, we don't know that the efficacy of the treatment will be changed from reduced as a consequence, but the appetite is there.
Lisa Michaels: We have not had a conversation with the FDA about whether they would require anything. In addition to that, you know, a lot of this always comes up. How well you can characterize the product you have. I think we have pretty good characterization assays, etc. And then it also is always a little bit dependent on just, you know, what the FDA's recent experience with similar things is. And that's always a bit hard to predict, super helpful, and maybe the first.
Thanks, so much.
Yes.
Thank you so much next question from Matthew.
Harrington from Morgan Stanley Your line is open.
Hi, Thanks for taking out question on beef cost us on for Matthew One quick question from US on day, one or two program.
From what we understand the safety somewhat dd's given that excusing day could you spare cash nine platform, but wondering how much work do you need to do on this front on the safety prior to <unk>. The program on these states. Thank you.
Luca Issi: Super helpful. And maybe the first question was around the novel pre-conditioning regimen that SPARE, Busulfan, any appetite there for collaboration or any big picture thoughts? Thanks. So I guess I'll fall back on that. That was good. At the moment, I'm really focused on getting proof of concept for our editing platforms and our ability to show meaningful edits. As we move forward, I do think that having, In order to have overall acceptance, the opportunity to test those will also be available. Even if we're able to reduce... [inaudible] But, yeah.
So what's the question about safety related too.
Yes, we do.
We do normal safety and toxicology testing as part of our eye on all of our IND, enabling program. So I'm not sure that I see something that's different.
In the article I'm, referring to the <unk> data because there was no safety data. They are that's why what you got to play on that.
That's the work that will follow so yeah.
Madhu Sudhan Kumar: Thank you so much. Next question from Madhu. Arichin from Morgan Stanley, your line is open.
So I don't think we're anticipating any unusual.
Different safety package and Tox package.
Madhu Sudhan Kumar: Hi, thanks for taking our question. This is Kostas Son for Matthew. One quick question from us on the 102 program, from what we understand the safety is somewhat at risk given that it's using the CRISPR-Cas9 platform, but we were wondering how much work do you need to do on this front on the safety prior to IND to risk the program at this stage? Thank you.
It was required for 101.
Okay. Thank you.
Thank you. So much next question from Jay Olson from Oppenheimer. Your line is open.
Oh, Hey, thanks for taking the question.
Can you walk us through the timeline to file an IND for the NK cell program and then for the manufacturing of your NK cell program is that something that you would do in house.
Lisa Michaels: So what's the question about safety? We do normal safety and toxicology testing as part of our eye and all of our eyes programs. So I'm not sure that I see anything.
So do you want me to take that one.
Lisa.
I can I'll.
Madhu Sudhan Kumar: In ARVO, I'm referring to the ARVO data because there was no safety data there. That's why what you are planning to do... No, no. So, I mean, that's the work that will follow, so... So I don't think we're into it.
I'll take both sides of it so.
Timeline for the IMD.
We have a number of contracts that we have developed with them.
Consulting with opinion leaders to make a decision about what first construct to move forward with.
Lisa Michaels: So I don't think we're anticipating any unusual or different safety package or tax package than was required for 101.
You have seen data on the.
Jay Olson: Thank you so much. Next question from Jay Olson from Oppenheimer. Your line is open.
On the TGF.
TGF beta.
But that by no means is the only sort of construct that we've been working on.
Jay Olson: Thanks for taking the question. Can you walk us through the timeline to file an IND for the NK-Cell program and then for the manufacturing of your NK-Cell?
Though we have just I don't believe we've disclosed the other countries.
With respect from the manufacturing.
We would anticipate doing.
Jay Olson: And for the manufacturing of your NKCEL program, is that something that you would do in-house?
The initial clinical manufacturing.
Either largely on house or partially in house.
Lisa Michaels: So do you want me to take that one, Liisa? I'll take both sides of it.
Along with.
Our strategic partner on that which would be turbulence on the manufacturing side.
Lisa Michaels: So the timeline for the IND, we have a number of constructs that we have developed. We've been consulting with opinion leaders to make a decision about what first construct to move forward with. You have seen data on the FISH TGF data, but with respect to manufacturing.
So I think debt.
Yet to be finalized on.
On whether we'll do the entire process in house.
Do part of the process in house on part of the process and Ketel one.
Lisa Michaels: We would anticipate doing the initial clinical manufacturing either largely in-house or partially in-house and along with our strategic partner on that, which would be Catalant on the manufacturing side. So I think that's, you know, yet to be finalized on whether we'll do the entire process in-house or do part of the process in-house and part of the process at Catalant. And there's actually a place in the process that we're developing where there's a natural sort of hand-off point, if you will, in the process, if you desire. Some of that just comes down to... You know, how many batches we think we're going to need to make.
Theres actually a place in this price and the process.
We're developing where there is.
On natural sort of handoff point.
If you will in the process if you desire.
That just comes down to.
How many batches, we take revenue need to make.
Great. Thanks for taking the questions.
Thank you so much we don't have any further questions at this time.
Jim.
You May proceed.
Okay. Thanks, Thanks, so much for all the questions. We've got a few quest.
Questions that we need to tidy up and get back to you with some answers on.
It'll be great to have Mark Sherman on the next call because I think some of those will probably more in his wheelhouse.
Jay Olson: Great, thanks for taking the questions.
Jim Mullen: Thank you so much. We don't have any further questions at this time. Jim, you may proceed.
And then maybe leases, but I want to thank everybody for participating on today's calls for the great questions.
Jim Mullen: Okay, thanks. Thanks so much for all the questions. We've got a few questions that we need to tidy up and get back to you with some answers. It'll be great to have Mark Sherman on the next call, because I think some of those were probably more in his wheelhouse than maybe in Lisa's, but I want to thank everybody for participating in today's calls, for the great questions, and for your support as we try to bring this transformational new technology and turn it into real medicines to help patients. Thanks so much, and we'll talk to you next quarter.
And for your support as we try to bring this transformational new technology turn it into real medicines to help patients. Thanks.
Thanks, So much on we'll talk to you next quarter.
That does conclude our conference for today. Thank you for participating you may all disconnect.
Moving now.
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