Q3 2021 Editas Medicine Inc Earnings Call
Operator: Good morning, and welcome to the Editas Medicine third quarter 2021 conference call. All participants are now in a listen-only mode.
Good morning, and welcome to the editors Medicine third quarter 2021 conference call.
All participants are now in a listen only mode there'll be a question and answer session at the end of this call. Please.
Operator: There will be a question and answer session at the end of this call. Please be advised, this call is being recorded at the company's request. I would now like to turn the call over to Ron Moldaver, Investor Relations at Editas Medicine. Thank you, Melissa. Good morning, everyone.
Please be advised this call is being recorded at the company's request I would now like to turn the call over to Ron mold <unk> Investor Relations at editors medicine.
Thank you Melissa good morning, everyone and welcome to our third quarter 2021 conference call earlier. This morning, we issued a press release, providing our financial results and corporate update 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 <unk>.
Unknown Attendee: And welcome to our third quarter 2021 conference call. Earlier this morning, we issued a press release providing our financial results and recent corporate updates. A replay of today's call will be available on the Investors section of our website approximately two hours after its completion.
Unknown Attendee: After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC and is updated by our subsequent filings.
As a reminder, various remarks that we make during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by these.
Forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC and as updated by our subsequent filings. In addition, any forward looking statements represent our views only as of today and should not.
Unknown Attendee: 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.
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.
Jim Mullen: Now, I will turn the call over to our Chief Executive Officer, Jim Mullen. Thanks, Ron, and good morning, everyone. I'm joined today by several members of the Editas executive team, including Mark Sherman, our chief scientific officer, Lisa Michaels, our chief medical officer, and Michelle Robertson, our chief financial officer. I want to start off by providing some highlights from the third quarter, including some important milestones for Editas. In our first ever clinical data readout, we announced positive initial data from our ongoing Phase 1-2 brilliance trial of EDIT-101 for the treatment of LCA-10, including clinical evidence of gene editing and potential early clinical benefits.
Ron and good morning, everyone I'm joined today by several members of the executive.
So it keeps a team, including our chairman our Chief Scientific Officer, Lisa Michaels, our Chief Medical Officer, and Michelle Robertson, our Chief Financial Officer.
I wanted to start off by providing some highlights from the third quarter, including some important milestones for editors.
And our first ever clinical data readout, we announced positive initial data from our ongoing phase one two brilliance trial of edit 101 for the treatment of LCA 10, including clinical evidence of gene editing and potential early clinical benefit.
Jim Mullen: We are dosing patients in the adult high-dose cohort and enrolling patients in the first of two pediatric cohorts of that trial. The Ruby study of Eta 301 for sickle cell diseases is enrolling patients, and we expect to begin dosing in the first half of 2022. The pre-IND work for EDIT 301 in transfusion-dependent beta thalassemia is progressing, and we remain on track to file the IND before year-end. And on our cell therapy platform, Bristol Mothers Squibb entered into a fourth alpha beta T cell program this quarter, further advancing our successful collaboration.
We are dosing patients in the adult dose cohort in enrolling patients in the first two first of two pediatric cohorts of that trial.
The Ruby study of edit 301 for sickle cell disease is enrolling patients and we expect to begin dosing in the first half of 2022.
<unk> work for edit 301 in transfusion dependent beta thalassemia is progressing and we remain on track to file the NDA the IMD before year end.
And then our cell therapy platform, Bristol Myers Squibb opted into a fourth alpha beta T cell program. This quarter further advancing our successful collaboration.
Jim Mullen: We presented data on our SLEEK technology platform demonstrating high-efficiency, multi-transgene knock-in in multiple cell types, which we believe can enable improved CAR-T and CAR-NK cell therapies for cell tumors. At the upcoming CITSE and ASH conferences, we will present data showing improved tumor killing ability through multiplex gene editing using SPLEEK in our INK program. And finally, we've appointed Emma Reeve and Bernadette Canutin to our board of directors.
We presented data on a sleek technology platform demonstrating high efficiency multi gene multi trans gene knock in multiple cell types, which we believe can enable improved car T and car NK cell therapies for solid tumors.
Okay.
Coming 650, and ash conferences, we will present data showing improved tumor killing ability through multiplex gene editing using sleek NRI NK program.
Finally, we've appointed Emma Reeve and Bernadette <unk> two.
Our board of directors, both Emma and Burns that are highly accomplished biopharma executives and we look forward to their contributions to editors.
Jim Mullen: Both Emma and Bernadette are highly accomplished biopharma executives, and we look forward to their contributions to Editas. This quarter showcased a critical advancement in clinical programs. The initial safety and efficacy data for the Brilliance trial was an important milestone for patients with LCA-10, and it marked a key step in Editas' mission of providing life-changing gene editing medicines to patients. These early data provide proof of concept for our in vivo gene editing platform and help strengthen our foundational technology with clinical evidence to progress our broader pipeline.
This quarter showcased a critical advancement for our clinical programs. The initial safety and efficacy data for the brilliance trial was an important milestone for patients with LCA 10, and marked a key step edit <unk> mission of providing life changing gene editing medicines to patients.
These early data provide proof of concept for in vivo gene editing platform and help strengthen our foundational technology with the clinical evidence to progress our broader pipeline.
Jim Mullen: We've made excellent progress this year with our programs and platform technologies, and we will continue at an aggressive pace to deliver against our long-term objectives. With that, I will turn the call over to Liisa to discuss our clinical programs. Thank you, Jim. I'll start with a recap of our recent data for the Brilliance Trial for EDIT 101 for the treatment of LTD. To give some quick background, CEP290-associated retinal degeneration, or LCA10, is a rare inherited disorder affecting about 3 out of every 100,000 children. Autosomal recessive, which means that to be impactful, the person has to inherit two copies of the defective gene, one from each parent. Now, if you can repair at least one of these.
Made excellent progress this year with their programs and platform technologies, and we will continue an aggressive pace to deliver against our long term objectives.
Let me turn the call over to Lisa to review our clinical programs. Thank you Jim.
I'll start with the recap of our recent data for the 1 billion strong and at one of its treatment of LCA 10.
To give some quick background Sep 290 associated retinal degeneration or LCA 10 is a rare inherited disorder affecting about three out of every 100000 children.
As autosomal recessive, which means that to be impactful the person has to inherit two copies of the defective gene one from each parent.
Now if you can repair at least one of these coffee you can potentially treat the disease.
Liisa Michaels: You can potentially treat the disease. Despite being rare, it is the most common cause of early-onset inherited retinal degeneration. The loss of vision is caused by early loss of photoreceptors in the eye.
Despite being where it is the most common cause of early onset inherited retinal degeneration and loss of vision is caused by early last a photo receptors in the eye.
Liisa Michaels: Patients are usually diagnosed during infancy and early childhood, with the majority of vision loss occurring in the first decade. However, even in adults, there remains a small area of preserved anatomy in the central part of the retina, and this provides the opportunity for gene correction. When Editas first started the Edit 101 program, this was the very first time that any company had attempted gene editing in the human body. As a result, the brilliance trial was designed primarily as a safety study with the purpose of identifying the highest tolerated dose for subsequent studies.
Patients are usually diagnosed in infancy and early childhood with the majority of vision loss occurring in the first decade.
However, even in adults.
Paul area preserved anatomy in the central part of the business and this provides the opportunity for gene correction.
When <unk> first started the edit 101 program. This was the very first time that any company that attempt to gene editing in the human body.
As a result of brilliance trial designed primarily as a safety study with the purpose of identifying the highest tolerated dose for subsequent study.
Liisa Michaels: At September's Retinal Degeneration Symposium, we shared safety data on two patients treated at the first and the lowest dose cohort and the four patients treated in the middle dose cohort as of the data cutoff date on August 4th. All observed adverse events were mild to moderate, and the majority of these reported events were directly attributable to the surgical procedure.
At September <unk> retinal degeneration symposium, we shared safety data on two patients treated at the first and the lowest dose cohorts and the four patients treated in the middle dose cohort as of the data cutoff date in August 4th.
Ill, let third for adverse events were mild to moderate and majority of that is reported events were directly attributable to the surgical procedure.
Liisa Michaels: Importantly, no detectable immune responses against the Cas9 enzyme were observed. This is great news, and the results are comparable for the two dose codes. Our pre-clinical data suggests that we would expect a greater number of photoreceptors to be effectively edited at each consecutive dose level. The safety observed has given us confidence to start treating the subjects at the highest planned dose and has allowed us to start enrolling the mid-dose pediatric cohort.
Importantly, no detectable immune responses against the enzymes were observed.
This is great news and results are comparable for the two dose cohorts.
Our non clinical data suggests that we would expect a greater number of photo receptors to be effectively edited at each consecutive days of travel.
Safety observed has allowed us confidence to start treatment of subjects in the highest planned dose cohort and has allowed us to start enrolling the pediatric dose coke into mid dose pediatric cohort.
Liisa Michaels: We expect that EDIT101 will have a differentiated safety profile as it is administered as a single, one-time injection directly to the part of the retina where the photoreceptors are preserved. The targeted approach treats not only those cells but only those cells, sorry, thereby limiting any potential effects on the structure. Although the primary endpoint of the study is safety, there are multiple exploratory endpoints that are focused on it. Preliminary findings were presented for five patients who had at least three months of follow-up after treatment.
We expect the edit 101 will have a differentiated safety profile as it is administered as a single onetime injection directly to the part of the rationale for the photo receptors are preserved.
Targeted approach treats not only those balance sheets only themselves sorry, thereby limiting any potential effects on the structures.
Although the primary endpoint of this study is safety there are multiple exploratory endpoints that are focused on efficacy.
Preliminary findings were presented for the five patients who had at least three months follow up after treatment.
Liisa Michaels: This included the two patients in the low-dose cohort and three in the mid-dose cohort. The three-month mark was selected as the earliest time point where we might expect to be able to pick up some signs of editing for several. Based on the injection procedure, there needs to be time for the retina to heal and for maximal editing to occur. It may also take additional time for the dysfunctional CEP290 protein to be replaced by the newly generated functional protein.
Included two patients in the low dose cohort and three in the mid dose cohort.
The three month Mark was selected as the earliest time point, when we might expect to be able to pick up some sign of editing for several weeks.
Based on the injection procedure, there needs to be time for the retina to heal and for maximal editing to occur and they also take additional time for the dysfunctional set to 90 protein to be replaced by the new lead generated functional protein.
Liisa Michaels: Three months is really when the clock starts, and it may take longer for the brain to respond to the news. One of the challenges of treating an is that we don't have a direct way of measuring how much of the normal CEP290 protein is being made or have a direct way to determine how many cells were edited. So we're dependent on surrogate measures, such as the Fulfield Light Sensitivity Threshold.
The months is really when the clock starts and it may take longer for the brain to respond to the new signals.
One of the challenges of treating in ocular disease.
That we don't have a direct way of measuring how much of a normal step to 90 protein is being made me high or have a direct way to determine how many cells were edited so we're dependent on surrogate measures of efficacy such as full field light sensitivity threshold testing best corrected visual acuity and improvements in individuals and.
Liisa Michaels: Best Corrected Visual. Improvement in an individual's ability to navigate standardized navigation courses with varying levels of difficulty; at least one positive change in any of these would suggest that a biological mechanism how the treated photoreceptors in the eye register. For this reason, we were very pleased to document meaningful changes from baseline in one or more measures in the two mid-dose subjects in whom we have the longest follow-up. Changes Prove Biological Activity, Most excitingly, and in at least one subject in the mid-dose cohort, there was a clinically meaningful change in best corrected visual acuity, and a real change in her ability to maneuver through obstacles at different levels of life. These are approvable clinical trials and, As for the other patients treated in the mid-dose co-op, may have been too easy to draw a conclusion. It may have been too early.
<unk> ability to navigate standardized navigation courses with varying levels of difficulty.
At least one positive change in any of these.
What does it suggest that a biologic effect has occurred on how the treated photo receptors in the eye registered light.
For this reason we were very pleased to document meaningful changes from baseline in one or more measures to mid dose subjects in whom we have the longest follow up.
Changes proved biological activity.
Most excitingly and in at least one subject in the mid dose cohort. There is a clinically meaningful change in best corrected visual acuity and a real change in her ability to maneuver through obstacles at different levels of light.
These are approvable clinical endpoints.
As for the other patients treated in the mid dose cohort. It may have been too easy to draw conclusion. It may have been too early I'm, sorry to draw conclusions, which is why we continue to follow them.
Liisa Michaels: I'm sorry to draw conclusions, which is why we continue to follow. In the meantime, we are eager to see whether the study can produce similar or stronger responses in the subjects who are now being treated in the high-dose group. We're very pleased with the safety we have observed so far and with the initial signals that effective editing has occurred. This is illustrated by clinically meaningful changes in the mid-dose cohort and in those subjects with the longest follow-up.
In the meantime, we are eager to see whether the study can produce similar or stronger responses in the subjects.
Who are now being treated in the high dose group.
We've been very pleased with the safety, we have observed so far and in the initial signals that effective editing has occurred.
As illustrated by clinically meaningful changes in the mid dose cohort and in those subjects with the longest follow up.
Liisa Michaels: Consequently, the Brilliant Study is moving forward. We continue to progress the adult high dose and the pediatric mid-dose cohorts and expect a complete dosing of these two cohorts in the first half of next year. Now, turning to our ex-VIVO, specifically edit 301 for sickle cell, transfusion-dependent beta Thalassemia. We believe that EDIT301 has the potential to be a leading gene editing medicine based on its highly efficient editing and specificity, which we expect to result in optimized safety and efficacy by demonstrating robust and sustained fetal hemoglobin or hemoglobin.
Consequently brilliant study is moving forward, we continue to progress the high dose and the adult hydro and the pediatric mid dose cohorts and expect to complete dosing of these two cohorts in the first half of next year.
Now turning to our ex vivo programs, specifically edit 301 for sickle cell disease, and transfusion dependent beta thalassemia.
We believe that edit 301 has the potential to be a leading gene edited editing medicine based on its highly efficient editing and specificity, which we expect to result, an optimized safety and efficacy.
Demonstrating robust and sustained fetal hemoglobin hemoglobin F expression with both short and long term safety. We aim to have a differentiated medicine to treat sickle cell disease, and beta thalassemia that will hopefully lead to longer lifespan and better quality of life for these patients.
Liisa Michaels: With both short- and long-term safety, we aim to have a differentiated medicine to treat sickle cell disease and beta thalassemia that will hopefully lead to longer lifespans and better quality of life for these patients. Currently, we are enrolling patients in the RUBY study for the treatment of sickle cell disease. And in this program, we are using our engineered CAS12A to target a region in the beta globe and lobe We believe this to be a potentially safer target for gene editing because several different mutations or polymorphisms that are not associated with human disease occur. More specifically, the Editas approach mimics naturally occurring mutations associated with a condition called hereditary persistence of fetal hemoglobin, which we know prevents.
Currently enrolling patients in the <unk> study for the treatment of sickle cell disease.
And this program we are using our engineered cast 12 eight enzyme <unk>.
We target a region in the beta globin locus.
We believe this to be a potentially safer target for gene editing because several different mutations or polymorphism that are not associated with human disease occur at this site.
Specifically, the <unk> approach mimics naturally occurring mutations associated with a condition called for <unk> persistence of fetal hemoglobin, which we know prevent siblings.
Liisa Michaels: We've demonstrated excellent preclinical data that support the benefits of editing the beta-globin locus and our Cas12a enzyme, and we're also very excited to be advancing the program to the. As mentioned, patient screening and enrollment are moving forward for EDIT 301 in SICL. We have patients who are currently undergoing cell harvesting cycles as a prerequisite to editing their own stem cells, and we look forward to dosing the first patient in the first.
We've demonstrated excellent preclinical data that support the benefits of editing the beta globin locus and our cast 12 of enzyme and we're also very excited to be advancing this program to the clinic.
As mentioned patient screening and enrollment is moving forward for edit 301 in sickle cell disease.
Have patients who are currently undergoing cell harvesting cycles as a requisite to editing their own stem cells and we look forward to dosing the first patient in the first half of next year.
Liisa Michaels: On edit 301 for transfusion-dependent beta thalassemia, we're going to be presenting data at the American Society of Hematology Conference next month. Preclinical data will demonstrate that edited CD34 cells showed significant improvement in erythroid maturation and health, along with increased total hemoglobin content.
On edit 301 for transfusion dependent beta thalassemia, we're going to be presenting data at the American Society of Hematology Conference next month.
Preclinical data will demonstrate that edited CD 34 cells showed significant improvement erythroid maturation and health along with increased total hemoglobin content.
Mark Sherman: This reinforces our belief that our therapeutic strategy has great potential for beta. Jason DeSicco, We remain on track to file our investigational new drug application for EDID 301, Theta Thalassemia, by year end. And with that, I'd like to turn things over to Mark to run through our pipeline and our gene editing. Thank you, Lisa.
This reinforces our belief that our therapeutic strategy has great potential for beta thalassemia.
In addition to sickle cell.
We remain on track to file our investigational new drug application for edit 301 data.
Alasania by year end.
And with that I'd like to turn things over to Mark to run through our pipeline and our gene editing technology.
Okay.
Thank you Lisa.
Mark Sherman: I'll start off with an important advance in our editing platform that we call Sleek, which we presented at the Cold Spring Harbor Conference in August. We are really excited about this proprietary technology. FLEEK is short for Selection by Essential Gene Exon Knock-In. It's a technology that was developed at Editas utilizing the AS-Cas12a nuclease to selectively and at high efficiency integrate transgenes into a specific locus. Essentially, this technique allows us to get high efficiency knock-in with a number of different cell types while also ensuring robust transgene expression.
I'll start off with an important advanced editing platform that we call sleek.
We presented that the Cold Spring Harbor conference in August.
I'm really excited about this proprietary technology.
The shortfall selection by essential gene Exxon knocking.
It's a technology that was developed at the test each of lies in the S class 12, a new <unk>.
High efficiency integrate trans genes into a specific Lucas.
Essentially the technique allows us to get high efficiency, knocking with a number of different cell types.
Also in showing robust transgene expression.
Mark Sherman: We've published data on iPSCs, T cells, and NK cells, and believe the knock-in rates are the highest in the gene editing field across these cell types. In addition to the high editing efficiency from ASCAS12A, we utilize a selection process where only those cells that have been successfully edited survive. The rates of transgene expression in the final cell population are extremely high.
We've published data on Ips P T.
T cells and NK cells.
Beliefs, knocking rates at the highest in the gene editing field across B cell type.
In addition to the high editing efficiency from <unk> 12.
We neutralize the selection process, where only those that have been successfully agitate survive.
So rates of transgene expression in the final stop population.
Our extremely high.
Mark Sherman: Furthermore, we can fine-tune the expression levels of transgene cargos by knocking in a different essential gene, which could be an important attribute of next-generation cell therapy medicine. We think this is a really powerful technology that is far superior to other modes of integration that we've seen published, and we've deployed this in our INK program as well as in our collaboration on the Alpha Beta T cell program with Bristol Myers Squibb. It's something that we've been working on for some time that can open up a lot of possibilities for more effective and safer cell therapy.
Furthermore, we can fine tune the expression levels of trenching cargos by locking in a different essential genes, which could be an important attribute of next generation cell therapy medicines.
We think this is a really powerful technology that is superior to other modes of integration that we've seen published and we have deployed this.
K program as well as in our collaboration on the Alpha Beta T cell program with Bristol Myers Squibb.
It's something that we've been working on for some time that can open up a lot of possibilities are more effective and safe.
South therapy.
Mark Sherman: Also related to our platform, we recently presented at the Tide's Oligonucleotide Therapeutics Conference about the advantages of our AF-Cas12A nucleate. Additionally, we described some of our process and analytical chemistry capabilities for guide RNA synthesis. With the completion of our Boulder, Colorado BMP manufacturing facility, we remain confident that our in-house guide RNA development will translate into high fidelity and quality manufacturing for our next generation enzyme. Our IPSC program utilizes both the AS Class 12 NUPAs and sleep technology.
Also related to our platform. We recently presented at the tides Oligonucleotide Therapeutics conference.
The advantages of our peso by nucleus.
Additionally, we described some of our process and analytical chemistry capabilities, our guide RNA synthesis.
With the completion of our Boulder, Colorado GMP manufacturing facility, we remain confident that our enhanced guide RNA development will translate into high fidelity and quality manufacturing for our next generation enzyme.
Oh, ICSC program, utilizing both Es and Uba technology.
Mark Sherman: One important goal is to customize an INK cell that addresses some of the current limitations of this type of therapy, specifically around persistence. We're using a combination of knockout and knock-in technologies to introduce a series of edits. For example, we've knocked out TGS beta receptor 2 to overcome resistance and CISH to improve persistence. At the upcoming CITSE and ASH conferences, we'll be presenting additional data indicating some of our knock-in and knock-out strategies.
One important goal is to customize an NK cell, which addresses some of the current limitations of best of class of therapy, specifically around persistence.
What are you using a combination of Nokia Nokia technologies to introduce the scheme.
For example, we've not that TGF beta receptor to overcome resistance and fish to improve persistence.
The upcoming <unk> conferences, we will be presenting additional data, indicating some of our marketing strategy.
Mark Sherman: We're building on a number of different strengths that we have to produce a customized INK cell that we believe will be superior across multiple tumor cell killing mechanisms, as well as persistence and potentially also targeting, which reinforces our view that it's an exciting allogeneic approach for a wide range of solid tumors.
We are building on a number of different spends that we have to produce the customized NK cell that we believe will be superior across multiple tumor cell, killing mechanisms as well as persistence and potentially also targeting which reinforces our view that it is an exciting allogeneic approach for a potential wide range of solid tumors.
Mark Sherman: On the knocking side of the equation, at the upcoming CITSE conference, we'll present data demonstrating that using sleek knocking genes for CD16 expression greatly improves sero-tumor killing, thereby enhancing antibody-dependent cell-mediated cytotoxicity of INK cells. This is important data as it provides evidence for the potential of our INK program as it advances towards the clinic. Adash will also demonstrate that a double knockout in INK cells of both the FISH and TGF beta receptor 2 genes, which I mentioned earlier, promotes high levels of cytotoxicity and enhanced in vivo tumor killing in preclinical models compared to unedited INK cells. Furthermore, we'll show that cryopreservation of these cells has no impact on their tumor-killing ability, which is an important property for an eventual off-
On the Nokia side of the equation at the upcoming Citi Conference will present data demonstrating that using sleep knocking genes for CD 16, especially and greatly improve female Cima kidding.
Thereby enhancing antibody dependent cell mediated cytotoxicity or by NK cells.
This is important data as it provides evidence for the potential of our <unk> program as it advances.
Towards the clinic.
At Ash, we will also demonstrate that the double knockout.
NK cells have both cash on TGF beta receptor two genes that I mentioned earlier.
High levels of cytotoxicity and enhanced in vivo Cima, killing in preclinical models compassion and agitate on NK cells.
Furthermore, we'll show that cryopreservation of these buyouts had no impact on the Cima cutting ability.
As an important property for an eventual off the shelf cell based medicine.
Mark Sherman: We also believe this to be a much safer approach to developing next-generation cell therapies because through our iPSC clone selection process, we specifically avoid potential cell abnormalities. After gene-editing iPSCs, we screen and select single clones that are fully characterized, including detailed sequencing and cytogenetic analysis. By doing this, we eliminate clones with chromosomal abnormalities. The selected edited clones only contain the desired allelic edit, ensuring a pure spinal population of iPSCs. These clones have highly characterized genomes and allow us to create a master cell bank that is stable and infinitely renewable, from which we differentiate the edited ICFDs into edited INK cells.
We also believe this to be a much safer approach developing next generation cell therapy, because to ICSC claims selection process, we specifically avoid potential sell abnormalities.
After gene editing Ips CS, we screen and select single closed fully characterized <unk>.
Including detailed sequencing and subject genetic analysis.
By doing this we eliminate close with chromosomal abnormality.
<unk> edge to cloud only contain the desired edit ensuring a pure final population of IPSA.
These clients have highly characterized genome and allow us to create a master cell bank that is stable and infinitely renewable from which we differentiate the IPF fees into edited by NK cells.
Mark Sherman: The INK cells will be fully characterized and analyzed with a well-developed analytical assay panel to confirm the genomic profile. This process and the preclinical data thus far may address some critical barriers to allogeneic NK cell therapy for solid tumors, and we're eager to move this program toward the clinic. And lastly, in our partner cell therapy program, we're excited that Bristol Myers Squibb has chosen a fourth alpha beta T cell program as part of our ongoing collaboration.
The NK cells will be fully characterized analyzed with a well developed analytical assay panel to confirm the genomic profile.
This process on the preclinical data thus far may address some critical barriers to allogeneic NK cell therapy for solid tumors and we are eager to move this program towards the clinic.
And lastly in our partner cell therapy program, we're excited that Bristol Myers Squibb has opted into our fourth Alpha Beta T cell program as part of our ongoing collaboration.
Mark Sherman: Over the last year, one of these programs has progressed to development candidate status. This has been a very productive collaboration, and we look forward to future programs. With that, I'd like to turn it over to Michelle to review our financial results. Thank you, Mark, and good morning, everyone.
Over the last year one of these programs has progressed to development candidate statement. This has been a very productive collaboration and we look forward to future program.
With that I'd like to turn it over to Michelle to review our financial results.
Thank you Mark and good morning, everyone I'd like to refer you to our press release issued earlier today for a summary of our financial results for the third quarter I will take this opportunity to briefly review a few items.
Michelle Robertson: I'd like to refer you to our press release issued earlier today for a summary of our financial results for the third quarter. However, I'll take this opportunity to briefly review a few items. Revenue for the first nine months of this year was $13.1 million compared to $79 million for the same period last year. During 2020, we recognized $71 million in revenue in connection with our agreement with Allegan, $63 million of which was earned during the third quarter of 2020 as a result of recognizing the remaining deferred revenue balance associated with this agreement when we regained control of our ACMA program last year. Comparing the first nine months of this year to last year, total operating expenses increased by approximately $15 million.
Revenue for the first nine months of this year at $13 1 million compared to 79 million for the same period last year. During 2020, we recognized $71 million in revenue in connection with our agreement with Allergan $63 million of which was earned during the third quarter of 2020 as a result of recognizing the remaining deferred revenue balance associated with.
This agreement when we regain control of our ocular program last summer.
Comparing the first nine months of this year to last year total operating expenses increased by approximately $15 million. This is related to an increase in stock based compensation of $18 million $9 million in success payments due under certain of our institutional licenses as well as an increase in expenses for our clinical program. These increases were offset by a $3 4 million.
Michelle Robertson: This is related to an increase in stock-based compensation of $18 million, $9 million in success payments due under certain of our institutional licenses, as well as an increase in expenses to support our clinical program. These increases were offset by a $3.4 million tax credit reported as a gain in operating expense during the period and a decrease of $9.5 million in in-process R&D that was reported in 2020 in connection with the allocation of transactions, as well as 2020 in-license expenses that did not recur in 2020. Comparing the third quarter of 2021 to the same period last year, total operating expenses decreased by approximately $8 million.
Tax credit reported as a gain in operating expense during the period and a decrease of $9 5 million in process R&D that was reported in 2020 in connection with the transaction as well as 2020 and license expenses that did not recur in 2021.
Comparing the third quarter of 2020 ones at the same period last year total operating expenses decreased by approximately $8 million.
Michelle Robertson: This was primarily related to expenses reported in 2020 in connection with the Allegand transaction that totaled approximately $9 million, as well as expenses that were incurred in 2020 in connection with an in-licensing agreement. During the third quarter of 2021, the company had an increase of $4 million in stock-based compensation, which we had for the same period last year, which was fully offset by decreases in legal patent fees and the tax credit that was reported as a gain in operating expenses during the pandemic. Editas continues to have a strong balance sheet and cash position, which as of September 30th was $657 million, compared to $698 million at the end of Q2.
This was primarily related to expenses recorded in 2020 in connection with the Allergan transaction that totaled approximately $9 million.
As well as expenses that were incurred incurred in 2020 and connections and in licensing agreement.
During the third quarter of 2021 company had an increase of $4 million in stock based compensation compared to the same period last year, which was fully offset by decreases in legal patent fees and the tax credit that was recorded as a gain operating during the quarter.
And it continues our strong balance sheet and cash position, which as of September $30 million to $657 million compared to $698 million at the end of the Q2.
Michelle Robertson: Capital will allow us to continue progress on our clinical program and further develop our pipeline as well as our internal manufacturing. We anticipate that this current cash position will fund our operations well into 2020. With that, I will hand it back to you, Michelle. This has been a strong quarter for Editas.
Capital will allow us to continue the progress on our clinical programs and further develop our pipeline as well as our internal manufacturing capability.
Dissipate that this cash current cash position will fund our operations well into 2023.
With that I will hand, it back to Jim.
Thank you Michelle this has been a strong quarter for editors, we presented the first clinical data for the company validating our in vivo gene editing platform, we made substantial progress on our other pipeline programs moving towards the clinic.
Jim Mullen: We presented the first clinical data for the company validating our in vivo gene editing platform. We also made substantial progress in our other pipeline programs moving towards the clinic. We've made fundamental advances in our platform technologies, including our best-in-class engineered AS-Cas12a enzyme and our innovative Sleek platform to deliver what we believe to be an unprecedented gene editing knock-in rate. We are building our manufacturing capabilities and supporting our multiple clinical programs. We have put together a world-class leadership team that is capable of executing on the tremendous opportunities we have for a technological platform, and we have the financial resources to deliver on these opportunities.
We've made fundamental advances in our platform technologies, including our best in class engineered cost 12, the enzyme and our innovative sleep platform to deliver what we believe to be an unprecedented gene editing Nokia and rates.
We build our manufacturing capability to support multiple clinical programs. We brought together world class leadership team that is capable of executing on the tremendous opportunities we have for technological platform and we have the financial resources to deliver on these opportunities.
I believe there has never been such an opportunity to deliver innovative new genomic medicines to patients.
Jim Mullen: I believe there's never been such an opportunity to deliver innovative new genomic medicines to patients. That is at the heart of everything we do and what motivates us to push forward with our programs and technological innovation. Thank you all for your interest and support. With that, we'll open it up to questions and answers. Thank you. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue.
Is it the hardware everything we do and what motivates us to push forward on our programs and technological innovation. We thank you all for your interest and support and with that we'll open it up to questions and answers.
Thank you at this time, we'll be conducting a question and answer session.
I'd like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue.
You May press star two if he'd like to remove your question from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star keys in the interest of time, we ask that you each keep to one question and one follow up thank you.
Operator: You may press star 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing star 2. In the interest of time, we ask that you each keep to one question and one follow-up. Thank you. Our first question comes from the line of Corey Kazimoff with JP Morgan. Please proceed with your question. Great. Hey, good morning. This is Thomas on for Corey.
Our first question comes from the line of Cory <unk> with Jpmorgan. Please proceed with your question.
Great Hey, good morning. This is Thomas on for Cory. Thanks for taking the question I guess, maybe just on 101 can you talk about how we should be thinking about the cadence of potential updates from here, including longer term follow up from the adult low and mid dose cohorts and then also data from the new cohorts.
Thomas: Thanks for taking the question. I guess maybe just on 101, can you talk about how we should be thinking about the cadence of potential updates from here, including longer-term follow-up from the adult, low, and mid dose cohorts, and then also data from the new cohorts? I'm curious, specifically, if you can comment on what kind of duration of follow-up you'll be looking forward to sharing these data updates. Thank you.
Curious specifically if you can comment on what kind of duration of follow up youll be looking forward to share. These data updates. Thank you.
So I'm going to keep it fairly shortened to the point I think one of the important things for us this year in terms of being able to share data.
It had been such a long period of time when the study has started and we thought it was important for us to be able to communicate and update on the trial. We were very happy with the safety that we observed as well as the clinical signs, suggesting that ethane had occurred.
Thomas: So I'm going to keep it fairly short and to the point. I think one of the important things for us this year in terms of being able to share data was the fact that it had been such a long period of time since the study started, and we thought it was important for us to be able to communicate and update on the trial. We were very happy with the safety that we observed, as well as the clinical time suggesting that editing had occurred.
I think in terms of our next planned update that's going to be primarily driven the trial is continuing to enroll both with pediatric and the high dose adult cohort and the timing of delivery will be totally upon our ability to give longer term safety data on the mid dose cohort as well as some preliminary efficacy data from the high dose cohort, which.
We'd like to have at least three months data on all the patients in that cohort before we move forward.
Okay. Thank you.
Thank you. Our next question comes from the line of Joon Lee with <unk> Securities. Please proceed with your question.
Liisa Michaels: I think in terms of our next planned update, that's going to be primarily data driven. The trial is continuing to enroll both the pediatric and the high dose adult cohort. And the timing of delivery will probably depend upon our ability to give longer-term safety data on the mid dose cohort, as well as some preliminary efficacy data on the high dose cohort, at which point we'd like to have at least three months of data on all the patients in that cohort before we move forward. Okay, thank you. Thank you. Our next question comes from the line of Joon Lee with Truth Securities. Hi, good morning.
Yeah.
Hi, Good morning. This is maybe for June My question is.
Related to edit 301.
And specific that we wanted to know what kind of a specific experiments you do to define the inversion or deletion rate.
Lucas if you have.
Compare that to the.
Same rates.
If you would have done with cash that's right. Thank.
Thank you.
Yes, I'll take that so.
We did a lot of experimental work pre clinically to define the on time on target at it.
Mehdi: This is Mehdi for June. My question is related to Edit 301. And specifically, we want to know what kind of specific experiments you did to define the inversion or deletion rate in the locus, and if you have compared that to, you know, the same rate if you had done that with the Cas9 enzyme. Thank you. Yeah, I'll take that.
To your point. This included extensive sequencing we had known ahead of time that the.
Activity was pretty much limited on target editing as opposed to any off target editing and so we found across both normal as well as cyclical as GDP.
Mark Sherman: So, we did a lot of experimental work frequently to find the on-target addicts. To your point, this included extensive sequencing. We had known ahead of time that the activity was pretty much limited to on-target editing as opposed to any off-target editing. So we found across both normal as well as sickle and TDP cells, the profile was fairly consistent, which appears to be a property of the combination of the guides and the S12A. We do not have comparable datasets with Class 9 and Class 12a.
Profiled with steady consistent.
Which appears to be a property of.
Combination of the guys in basketball.
Basketball.
We do not have comparable data sets with it.
Bandwidth focused on the use of past 12 language.
Given what we're trying to achieve with this approach which is to disrupt the binding of <unk> 11. This is the most appropriate you care to do that.
Thank you.
Thank you. Our next question comes from the line of Phil Nadeau with Cowen <unk> Company. Please proceed with your question.
Good morning, Thanks for taking my question I guess one of them.
Mark Sherman: We're focused on the use of Class 12a, which, given what we're trying to achieve with this approach, which is to disrupt the binding of BCL11A, this was the most appropriate time to do that. Thank you. Thank you. Our next question comes from the line of Phil Nadeau with Cowan & Company.
101 to start which patient population do you think is most appropriate.
For future development in pivotal studies, which you can move forward in both pediatric and adult patients or.
With pediatric patients would be more appropriate given their disease state.
Martin: Please proceed with your question. Martin, thanks for taking our question. I guess one on 101 to start: which patient population do you think is most appropriate for future development in pivotal studies? Would you move forward with both pediatric and adult patients, or would pediatric patients be more appropriate given their, So at this point in time, there's no reason to consider not going forward with both adults and pediatric patients. So far, we are seeing some clinically meaningful endpoints in adults.
So at this point in time, there's no reason.
We consider not going forward with both adult and pediatric patients. So far we are seeing some clinically meaningful endpoint.
The endpoints in the adults.
And in the pediatric patients it's expected that we should be able to get at least as good a benefit if not more so I don't see a reason to limit the patient population at this point.
Got it and one final question on chromosomal abnormalities, you mentioned, what you do to them.
Assay for them and the ICSC.
Our program itself what are you doing in say the 301 program do you feel like you have to change your release housekeeping what was seen.
Martin: And in pediatric patients, it's expected that we should be able to get at least as good a benefit, if not more, so I don't see a reason to limit the patient population at this point. Got it. And one follow-up question on chromosomal abnormalities, you mentioned what you do to assay for them in the IPSC program itself.
As seen by another gene editing company recently or do you feel that.
That you are asking would pick it up and all the programs.
Short answer is no we have no intention to really change the assays that we've applied to this program.
Mark Sherman: What are you doing in, say, the 301 program? Do you feel like you have to change your release houses given what we're seen by another gene editing company recently, or do you feel that that you're asked is would pick it up in all the I think a short answer is no; we have no intention to really change the assays that we've applied to this program. We've very thoroughly analyzed the changes at the editing site, and as we've expressed, we have no evidence of any chromosomal abnormalities created.
Very thoroughly analyzed.
The changes of the editing sites.
As we would expect we have no evidence of any chromosomal abnormalities created by this team.
Perfect. Thanks for taking our questions.
Okay.
Thank you. Our next question comes from the line of Yanan, Zhu with Wells Fargo. Please proceed with your question.
Hi, Thanks for taking my questions. So.
So first on <unk>.
I'm wondering if you could.
I know you just talked about timeline, what data is there a possibility.
Mark Sherman: Perfect. Thanks for taking our questions. Thank you. Our next question comes from Yanan Zhu with Wells Fargo. Hi, thanks. I'm wondering if you could, I know you just talked about a timeline for data. Is there a possibility to see data by the end of this year?
By the end of this year.
And also in terms of the.
Endpoints on OS.
Key changes.
And the evidence for it.
Gene editing.
Do you think you know.
At what time point do you think.
Okay.
May be possible to see.
Okay.
Yanan Zhu: So I guess the first question is, the patients are basically seen every three months after they pass safety at the very beginning of the trial. So that does limit the intervals and the periods of time we're able to give up. The second one is related to OCT. One of the challenges with these patients, especially very early on, is that they have significant nystagmus, so it's very difficult for their eyes to remain still enough for the OCD. To be able to measure those changes, you need to be able to have landmarks in the eye that you can compare them to.
So I guess the first question is the patients are basically seen every three months after they pass the safety at the very beginning of the 12 does that limit the integral to the periods of time, we're able to get update.
The second one is related to <unk>.
One of the challenges with patients, especially very early on is that they have significantly stagnant. So it's very difficult to treat their eyes to remain still enough with the OCC imaging and to be able to measure those changes you need to be able to have landmarks and you can compare it to we are firmly OTT.
Liisa Michaels: We are following OCT moving forward in these patients as best as we're technically able to. In the first iteration of the candidate, would you implement some kind of IL-15 receptor ligand? So I'll take that. So I think, based on the track that other people have taken, that would be a logical approach. I think you'll have to wait for the details, which we will present. Thank you. Our next question comes from the line of Dae Gun Ha with Stifel. Please proceed with your question. Hi, good morning.
Moving forward in these patient asbestos, we're typically able to do so.
Got it.
On that on the NK program.
Do you think in the first iteration of the.
Candidate.
Would we would you implement some kind of IL 15 receptor ligand engineering.
Persistence.
So I'll take that so I think based on.
The track that other people have taken that would be a logical approach I think.
We'll have to wait for the details.
Which we presented at the Ash conference on it.
Great. Thank you.
Okay.
Thank you. Our next question comes from the line of Dae Gon Ha with Stifel. Please proceed with your question.
Hi, good morning, Thanks for taking our questions first question is for Mark as we look into really in the pediatric going into the mid dose and eventually maybe higher.
Dae Gon Ha: Thanks for taking our questions. The first question is for Mark. As we look into brilliance, the pediatric doses are going into the mid dose and eventually maybe higher. I just wanted to get your take on one of the gene therapy companies that recently reported that basically tested the same dose as the adults. Adults were safe, but pediatrics started showing some inflammation after about a month mark. So can you talk about AAV safety as it pertains to pediatrics using the same dose? I know it's immune privilege, but any thoughts on that?
I just wanted to get your take on one of the gene therapy companies that recently reported that.
Basically test at the same dose as the adults adults were safe, but pediatric started showing some inflammation after about a one month Barack so can you talk to the AAV safety as it pertains to pediatrics using the same dose I know, it's Amy and privilege, but any thoughts on that and I've got a follow up thanks.
Mark Sherman: And I've got a follow-up thing. Yeah, thanks for the question. I think right now it's too soon to, so, go to, www.kenhub.com, I think that's all. Great, thanks for that. And then the other question is on Edit 301 with Ruby.
Yeah.
Yes, thanks for the question.
I think right now it's too soon to.
Determine if this finding that youre referencing will be recapitulated across other gene therapy programs I think right now we're focused on continuing enrollment, particularly in the agile iqos as well as initiating in the pediatric dose and we're doing that in a very careful stepwise manner and we will.
The tolerability of the effects of an MS patient population I think that's all I can say right now.
Great. Thanks for that and then.
The other question is on edit 301 with Ruby.
Unknown Executive: One of your colleagues here in Cambridge just this morning cleared the IND for Annex Vivo, also targeting the HBG 1 and 2 promoter regions. So maybe you can talk a little bit about what you can do strategically on the protocol side to perhaps accelerate patient enrollment as well as get that patient treatment going in that earlier part of the first half potentially versus say, the latter half. So I don't know that we can necessarily accelerate because the treatment of the first patient is safety driven and basically able to show that they have had meaningful improvement from the treatment.
One of your colleagues here in Cambridge, just announced this morning, they cleared the IND for an ex vivo also targeting H B G wanted to promote a region. So maybe can you talk a little bit about what you can do strategically on the protocol side to perhaps accelerate patient enrollment as well as get that patient.
Patient treatment going in that earlier part of first half potentially versus say latter half.
So I don't know that we can necessarily accelerate because the treatment of the first patient is safety, driven and basically being able to show that they have had meaningful and graph from.
From the treatment.
Unknown Executive: What I can tell you, however, is that we do have multiple patients in the pipeline with the intention that once we achieve that safety mark, we'd like to be able to start moving patients much more. Okay, great.
I can tell you however that we do have multiple patients in the pipeline to be essentially that once we achieve that safety mark we'd like to be able to start between patients much more rapidly.
Unknown Executive: Thanks for taking our questions. Thank you. Our next question comes from the line of Jay Olson with Oppenheimer.
Okay, great. Thanks for taking our questions.
Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Please proceed with your question.
Jay Olson: Please proceed. Oh, hey, thank you for the update. Can you talk about the timeline and gating factors for Edit 102 to enter the clinic and anything that you've learned from Edit 101. So we haven't given any specific guidance on EDIT102 other than that we are continuing to iterate and improve upon the editing efficiency for that program, and that it's our intention to present the results of those improvements at scientific conferences in the coming years.
Oh, Hey, Thank you for the update can you talk about the timeline and gating factors for.
Is it one or two to enter the clinic in anything that you've learned from edit 101 that can be applied to that program.
Yeah.
So we haven't given any specific guidance on it one or two other than we are.
Continuing to iterate and improve upon the editing efficiency for that program and that is our intention to present the results of those improvements at scientific conferences in the coming year.
Okay. Thank you and then.
Jay Olson: Okay, thank you. And then maybe as a follow-up for 301 in fickle cell disease. Like you said, the target enrollment is 40 patients. How long do you think it will take to enroll 40 patients, and do you know how long you will need to follow those patients before filing? So basically, this is the same. It's a well-trod path.
Maybe as a follow up for 301 in sickle cell disease. I think you said the target enrollment is 40, how long do you think it will take to enroll 40 patients and do you know how long you will need to follow those patients before filing.
So basically this is let's say is a well trodden path of what we're doing is not necessarily any different from what our competitors.
Unknown Executive: So what we're doing is not necessarily any different from what our competitors have been doing in the same way. But, in general, the primary goal for getting to these patients is first to be able to demonstrate graspment. As I've already mentioned, the plan is basically to be able to start moving more patients in tandem and in parallel moving forward. And at the moment, we're not having any issues related to enrollment. It's actually quite strong.
Exactly.
But in general the primary growth getting to these patients is first to be able to demonstrate craftsman as I've already mentioned the plan to basically be able to start moving more patients in tandem and in parallel moving forward and at the moment, we're not immune issues related to the enrollment it's actually quite strong.
Unknown Executive: Great, thanks for taking the question. Thank you. Our next question comes from the line of Luca Issi with RBC Capital Markets. Please proceed with your, Oh, great.
Great. Thanks for taking the questions.
Thank you. Our next question comes from the line of Luca <unk> with RBC capital markets. Please proceed with your question.
Luca Issi: Thanks so much for taking the question. Congratulations on all the progress. I have two, one on brilliance and one on strategy.
Oh, great. Thanks, so much for taking the question congrats on the progress I have two one umbrella and one on strategy.
Unknown Executive: A little bit bigger picture. So maybe on a whim, I think the data at RD show the serum neutralizing antibody against AAV5 at the 10 to the fourth, 10 to the fifth level. So wondering if you can expand a bit more on what gives you confidence that such levels are low enough that they do not prevent you from either re-dosing or dosing the fellow eye. And then maybe a bigger picture on strategy. We're about to see one of your competitors break up the company, spinning off the oncology pipeline into a new company and focusing on rare genetic diseases. I was wondering what your take on that decision was.
Bigger picture. So maybe it really is I think the data at <unk> showed a CRM neutralizing antibody against <unk> 85 in the.
Turning to the fourth fifth level. So I'm wondering if you can expand a bit more on what gives you confidence such levels are low enough that do not prevent you from either re dosing or dosing. The fellow eye and then maybe a bigger picture and strategy.
Good to see one of your competitors breaking up the company spinning off the oncology pipeline and a new company and focusing on rare genetic diseases are wondering what was your take on that decision and if that is something that you are contemplating. Thanks. So much.
Jim Mullen: And if that is something that you're contemplating, thanks. Thanks for the question. I'll address the first part on neutralizing antibodies. Certainly, the levels we see in do not give us any concern about one correlation with any other immune response and two, no issue with potential re-dosing in the same eye or even dosing of the second eye. That's based on a fairly extensive non-human primate series of studies that we've done. We're not concerned with that. It's a pretty typical program. Yeah, and this is Jim. I'll take the second one.
Thanks for the question I'll address the first part on neutralizing antibodies suddenly the levels we've seen.
Do not give us any concern about one correlation with any other immune responses to.
Issue with potential we can see in the same aisle, even dosing of the second dive thats based on an ex fairly extensive nonhuman primate series of studies have been published so yes.
We are not concerned with that as a pretty typical profile.
Yes.
Jimmy I'll take the second one so as you know we already have.
Jim Mullen: So, as you know, we already have a nice collaboration going that's, I would say, gaining momentum with BMS on the T cell side of oncology. And as I have said previously, and I think we've been fairly public about it, on the INK front, we are certainly going to entertain another collaboration or an expansion of the collaboration we do have. So, you know, I do think it's an area where collaboration with an established oncology player is important for success.
Nice collaborations going this I would say gaining momentum with BMS on the T cell oncology.
And as I have said previously I think we've been fairly public about it.
Okay.
We're certainly going to entertain.
Another collaboration or an expansion of the collaboration we do have.
So.
I do think it's an area where collaboration with an established oncology player is important for success.
Jim Mullen: And so we'll continue to pursue that. Got it. Thanks so much. Actually, this is Mark. I want to correct something I said earlier. The IL-15 data is actually going to be at SITC, not ASH. So you don't have to wait.
And so we will continue to pursue that.
Yeah.
Got it thanks, so much.
Actually this is mark I wanted to correct something I said earlier, the IL 15 data is actually going to be at 50, not ash. So you don't have to wait until December.
Okay.
Mark Sherman: Thank you. Our next question comes from the line of Joel Beattie with Baird. Please proceed. Hi, thanks for taking the question. For the Alpha Beta T cell program partnered with BMS, could you discuss what they based their decision on to opt into a fourth program? And then could you also discuss the timelines for those programs in general for advancing in development?
Thank you. Our next question comes from the line of Joel Beatty with Baird. Please proceed with your question.
Alright, Thanks for taking the question for the Alpha.
Alpha Beta T cell program with BMS could you discuss what they basically decision and to opt into a fourth program and then did you ask.
Discuss the timelines for those programs in general for advancing.
Joel Beattie: Could you just repeat the first part? I didn't catch the question. Yeah, the first part is just what did DMS base their decision on to opt into a fourth program? You know, what kind of data did they look at? Yeah, so they looked at good data. We're not at liberty to disclose the details of the programs with them all.
And development.
Could you just repeat the first partnering catch.
Question.
Yes.
First part is just what did BMS base their decision on to opt into a fourth program what kind of data that they look at.
Yeah.
Yes, so they looked at good data.
We're not at Liberty to disclose the details of the programs with them or obviously, we don't have complete visibility into that timelines of interest if you're making tremendous progress.
Unknown Executive: Obviously, we don't have complete visibility into their timelines or their decision making processes. Okay, thank you. Thank you. Our next question comes from the line of Dana Wong with Barclays. Please proceed with your question. So I have two parts to my question regarding translocation.
Okay. Thank you.
Thank you. Our next question comes from the line of Gena Wang with Barclays. Please proceed with your question.
Thank you for taking my question two maybe.
Two parts of the question regarding insurance location.
Dana Wong: First, I was wondering if you could remind us the translocation or chromosomal abnormality rate for the edit 101. And then second, you do have a few approaches with multiplexing, and we know that that will lead to some translocation. So just wondering, and then you did mention that you do have very deep sequencing to identify these. So just wondering, what is the process in place to monitor translocation, and what will be the cutoff for the drug product in terms of product release?
Just wondering if you can remind us the translocation or chromosomal abnormalities rage for the added 101 and the second you do have a few approaches with multiplexing and we know that they will.
Linked <unk> translocation. So just wondering I know you did mentioned that you do have deep sequencing to identify because its so just wondering what is the process in place should monetary translocation and what will be the cutoff.
Food and drug product.
In terms of the product.
Dana Wong: So the processes that we have in place are actually pretty extensive in addition to multiple different approaches to sequencing at the expected, intended, edited site. To determine the profile of the edits, which includes indels, deletions, reversions, transactions, and resections, I should say, and so on, the rate of those that we've determined quickly is very, very low, a fraction of a percent.
So the processes that we have in place actually pretty extensive in addition to multiple different approaches to sequencing.
At the expected intended edited side.
To determine the profile of the edits, which includes endow deletions and revisions.
Transactions and reductions I should say and so the rate of those that we've determined pre clinically is very very low a fraction of a percent.
Mark Sherman: We have not seen anything in any of the in vitro genotoxicity assays or an in vivo mouse study that would indicate any potential for malignancy or cell abnormality. And then, as I mentioned in the script for the INK program with the induced pluripotent stem cell editing, we select a single cell clone that has the exact edits that we want across multiple different constructs on both alleles and will only progress forward with a clone that has those. Thank you. Our next question comes from line Erick Bienkowski with SVB Leering.
We have not seen anything in any of the in vitro toxicity Juno toxicity assays or an in vivo mice study that would indicate any.
Potential for malignancy wholesale abnormality to date and then as I mentioned in the script for the NK program with the increased throughput and stem cell editing, we select a single cell <unk>, which has the exact edits that we want.
Months across multiple different constructs on both the <unk> and Malone and progressed forward to claim that has those and nothing else.
Okay.
Thank you. Our next question comes from the line of Rick.
<unk> with SBB Leerink. Please proceed with your question.
Rick Stephen Bienkowski: Please proceed with your. Good morning and congrats on all the progress. Looking forward to the poster at 50 later this week. I have a follow-up question from Dagon's question on the pace of dosing for Editorial 1. Could you please say exactly how long the observational period for safety and engraftment is after the first patient is dosed in the trial? And are there any other mechanisms built into the trial protocol that could limit the pace of dosing after that first observational period is complete?
Hey, good morning, and congrats on all the progress looking forward to the poster execute later this week.
As a follow up from Jay Johns question on the pace of dosing for edit 301.
Could you say exactly how long the observational period for safety and congrats thing is after the first patient is dosed in the trial.
And are there any other mechanism you spoken to the trial protocol that could limit the pace of dosing after that first observational period is complete.
Rick Stephen Bienkowski: So, basically, in alignment with regulatory guidance, the first patient needs to ingest the product. That can take place anywhere from six weeks to three months, depending upon the course, as well as the second patient basically showing reproducibility of the product.
So basically in alignment with regulatory guidance first patient needs to engraft that can take place anywhere between six weeks to three months dependent upon.
Of course of events.
As well as the second patient basically reproducibility of the Permian asset that we have the ability to start enrolling more patients in parallel.
Unknown Executive: After that, we have the ability to start enrolling more patients. Great. And is there anything else built into the trial protocol after that initial period that could limit dosing?
Okay, Great and is there anything else looking to the trial protocol after that initial period that could limit the dosing.
Unknown Executive: As soon as we're able to establish reproducibility of the process, as well as the patient's ability to recover and show that they have a meaningful endpoint, we go. All right, great. Thanks for taking our questions. Thank you. Our next question comes from Madhu Kumar with Goldman Sachs.
And as we've been able to establish reproducibility of the process as well as the patient's ability to recover and showed that they have the meaningful endpoint we go.
Yeah.
Okay, great. Thanks for taking our questions.
Yeah.
Thank you. Our next question comes from the line of Madhu Kumar with Goldman Sachs. Please proceed with your question.
Madhu Sudhan Kumar: Please proceed with your, Well, hey, great. Thanks for taking our question. So thinking about the high dose edit one on one data and really, what do you think you need to see in terms of the kind of visual function endpoints that you compare to what you've seen so far in the low and mid dose that would kind of get you really excited about pursuing the high dose into a registrational study? I'm already excited because we actually had really great outcomes in one of our patients, the first patient in the mid-dose cohort.
Great. Thanks for taking our question so thinking about the high dose and it went on one data and brilliance.
What do you think you need to see in terms of the kind of visual function endpoints that you. Congrats on what you've seen so far in the low and mid dose that would kind of gets you really excited for pursuing the high dose into our Registrational trial.
I'm already excited because we actually had really great outcomes in the third patient. The first patient is a mid dose cohort. She is the one that we actually have the longest followed up on at the moment and it's very clear that her improvements did seem to get better with each subsequent follow up so I think it's too early to be able to make any.
Madhu Sudhan Kumar: She's the one that we actually have the longest follow-up on, and it's very clear that her improvements did seem to get better with each subsequent follow-up. So I think it's too early to be able to make any real conclusions regarding efficacy of the mid-dose cohort, and that will depend upon the continued follow-up of the patients in that group. However, we do expect there to be enhanced with each additional concentration applied over the area of the fovea. We're fully expecting to have more photoreceptors effectively edited.
No conclusions regarding efficacy at the mid dose cohort and that will depend upon the continued follow up with the patients in that group, we do expect there to be enhanced.
Each additional concentration applied over the area of the fovea, we're fully expecting to have.
Our photo receptors effectively ended it so as a consequence, we are just.
Liisa Michaels: So as a consequence, we are just, as long as everything remains safe as it has so far to date, and we continue to see the types of changes that we saw in the mid-dose cohort, we're actually excited to expect that we will have a product. Okay, so then, just to make sure I understand. Unknown Attendee, Huidong Wang, Dae Ha, Mani Foroohar, Yanan Zhu, Jin Law, Gilmore ONeill, Certainly, that's the goal.
As long as if everything remains stable as it has so far to date and we continue to see the type of changes that we saw in the mid dose cohort. We're actually excited to expect that we would have a problem.
Okay. So then just to make sure I understand.
From that if the high dose profile shows the efficacy profile seen to date with a mid dose cohort that would be sufficient for you to pursue that into Registrational development.
Certainly that's the goal.
Operator: Okay, great. Thank you. Thank you. This concludes our Q&A session and thus concludes our call today. We thank you for your interest and participation. You may now disconnect your line.
Okay, great. Thank you.
Thank you. This concludes our Q&A session and thus concludes our call today. We thank you for your interest and participation you may now disconnect your lines.
Goodbye.