Q1 2024 Intellia Therapeutics Inc Earnings Call
Drew: Good morning, and welcome to Intellia Therapeutics' first quarter 2024 financial results conference call. My name is Drew, and I will be your conference operator today. Following formal remarks, we will open the call up for a question-and-answer session. This conference is being recorded at the company's request and will be available on the company's website following the end of the call. As a reminder, all participants are currently in listen-only mode. If anyone requires operator assistance during the conference, please press star zero on your telephone keypad. I will now turn the conference over to Ian Karp, Senior Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed.
Good morning, and welcome to <unk> Therapeutics first quarter 2024 financial results Conference call. My name is drew and I will be your conference operator today.
Following formal remarks, we will open the call up for a question and answer session. This conference is being recorded at the company's request and will be available on the company's web site. Following the end of the call.
As a reminder, all participants are currently in listen only mode. If anyone requires operator assistance during the conference. Please press star zero on your telephone keypad.
I will now turn the conference over to Ian Karp, Senior Vice President of Investor Relations and corporate communications at <unk>. Please proceed.
Ian Karp: Thank you, operator, and good morning, everyone. Welcome to Intellia Therapeutics' first quarter 2024 earnings call. Earlier this morning, Intellia issued a press release outlining the company's progress this quarter, as well as topics for discussion on today's call. This release can be found on the Investors & Media section of Intellia's website at www.intelatx.com. This call is being broadcast live, and a replay will be archived on the company's website. At this time, I'd like to take a minute to remind listeners that during this call, Intellia Management may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties.
Ian Karp: Thank you operator, and good morning, everyone. Welcome to Intel you Therapeutics first quarter 2024 earnings call earlier. This morning until you issued a press release outlining the company's progress this quarter as well as topics for discussion on today's call. This release can be found on the investors and media section of <unk> website at Intel It TX Dot com.
Ian Karp: This call is being broadcast live and a replay will be archived on the company's website.
Ian Karp: At this time I'd like to take a minute to remind listeners that during this call and Telia management may make certain forward looking statements and ask that you refer to our SEC filings available and actually see that Gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today and then tell you undertakes no duty to update this information unless required.
Ian Karp: By law joining.
Ian Karp: All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me from Intellia are John Leonard, Chief Executive Officer, David Lebwohl, Chief Medical Officer, Laura Sepp Lorenzino, Chief Scientific Officer, and Glenn Goddard, Chief Financial Officer. John will begin with an overview of recent business highlights, David will provide an update on our clinical pipeline progress, Laura will review our R&D updates, and Glenn will review our financials before we open up the call for your questions. With that, I'll now turn the call over to John, our CEO.
Speaker Change: Joining me from Intel you are John Leonard Chief Executive Officer, David Lebel, Chief Medical Officer, Laura Laura Zeno, Chief Scientific Officer, and Glenn Goddard, Our Chief Financial Officer, John will begin with an overview of recent business highlights David will provide an update on our clinical pipeline progress.
Laura will review, our R&D updates and Glenn will review our financials before we open up the call for your questions with that I'll now turn the call over to John <unk>, Our Chief Executive Officer.
John M. Leonard: Thank you, Ian. Good morning, everyone, and thank you all for joining us today.
John M. Leonard: Thank you Ann good morning, everyone and thank you all for joining us today.
John M. Leonard: We've made outstanding progress in the first quarter of 2004, with one ongoing in two soon-to-be initiated pivotal phase three trials. Entelia is undoubtedly leading the gene editing revolution, and with well over 100 patients already dosed across our two lead programs, we have already amassed the largest set of safety and clinical activity data for any inviolibre-based therapy. Notably, we believe our one-time treatments for ATTR and HAE, offering potentially unmatched clinical profiles, could overcome key hurdles faced by patients in two large and rapidly growing commercial markets.
John M. Leonard: We've made outstanding progress in the first quarter of 2024 with one ongoing into soon to be initiated pivotal phase III trials and Kelly I, it's undoubtedly leading the gene editing Revolution.
John M. Leonard: And with well over 100 patients already dosed across our two lead programs. We have already amassed the largest set of safety and clinical activity data for any in vivo CRISPR based therapies.
John M. Leonard: Notably we believe are one time treatment Strachey T. R E offering potentially unmatched clinical profiles could overcome key hurdles faced by patients in two large and rapidly growing commercial markets.
John M. Leonard: Moreover, our first two investigational gene editing therapies are designed to be especially patient-friendly and convenient for physicians and caregivers. There is no extensive preconditioning regimen, no long-term steroid requirement, and no hospital stay, all of which can be very challenging for patients and limit commercial uptake associated with other gene therapies. And, of course, with a one-time treatment, there's no annual insurance re-verification needed, which is typically required for chronic specialty therapies and can be a tremendous burden.
John M. Leonard: Moreover, our first two investigational gene editing therapies are designed to be especially patient friendly and convenient for physicians and caregivers.
John M. Leonard: There is no extensive pre conditioning regimen, no long term steroid requirement and no hospital stay.
John M. Leonard: All of which can be very challenging for patients and limit commercial uptake associated with other gene therapies.
John M. Leonard: Of course with a onetime treatment, there's no annual insurance for verification needed, which is typically required for chronic specialty therapies. It can be a tremendous burden.
John M. Leonard: But this is just the beginning for our industry-leading CRISPR-based technology. We're now entering the next stage of growth, pushing the boundaries of what we can do and expanding where we can go with CRISPR, from gene knockdown to gene insertion, from liver targets to a broader set of tissues. Our first wholly-owned CRISPR-based gene insertion program, NTLA-30.01, is expected to enter human clinical development this year. NTLA-30.01 holds the potential to provide normal alpha-1 levels after single-dose treatment for people with alpha-1 antitrypsin deficiency.
But this is just the beginning for industry, leading CRISPR based technology. We're now entering the next stage of growth pushing the boundaries of what we can do and expanding where we can go with CRISPR from gene knockdown to gene insertion from liver targets to a broader set of tissues.
John M. Leonard: Our first wholly on CRISPR based gene insertion program in Chile, 31 is expected to enter human clinical development. This year until a 31 one holds the potential to provide normal alpha one levels. After a single dose treatment for people with Alpha one Antitrypsin deficiency. We will also have a second clinical program utilizing our modular gene insertion.
John M. Leonard: We will also have a second clinical program utilizing our modular gene insertion platform run by Regeneron for hemophilia B expected to start patient dosing later this year. Building on our clinical success, we are now pursuing gene editing in five new tissue types outside the liver. As part of this expansion strategy, we have established collaborations with external innovators. These R&D efforts have already yielded at least a dozen potential drug candidates utilizing our technology. In addition, we are advancing our modular platform by developing a diverse set of editing and delivery tools for InVivo and ExVIvo applications.
John M. Leonard: [noise] platform run by Regeneron for Hemophilia B expected to start patient dosing later this year.
John M. Leonard: Building on our clinical success, we are now pursuing gene editing and five new tissue types outside the liver.
John M. Leonard: As part of this expansion strategy, we have and will continue to establish collaborations with external innovators. These R&D efforts have already yielded at least a dozen potential drug candidates utilizing our technology.
John M. Leonard: Further we are advancing our modular platform by developing a diverse set of editing and delivery tools for in vivo and ex vivo applications, whether it's our proprietary LNP formulations novel gene editing tools or differentiate the allogeneic cell therapy approach, we emphasize safety and therapeutic activity at each step with develop.
John M. Leonard: Whether it's our proprietary LMP formulations, novel gene editing tools, or differentiated allogeneic cell therapy approach, we emphasize safety and therapeutic activity at each step of development. Through our commitment to these principles, we are well on the path toward transforming cutting-edge scientific tools into real-world medical treatments. With this as a backdrop, we expect to end this year with five enrolling clinical studies, three of which are in phase three. This includes a newly planned phase three study for NTLA-2001 in patients with ATTR polyneuropathy.
John M. Leonard: Through our commitment to these principles, we are well on the path towards transforming cutting edge scientific tools into real world medical treatments.
John M. Leonard: With this as a backdrop, we expect to end this year with five enrolling clinical studies three of which are in phase III. This includes a newly planned phase III torrential late 'twenty one one in patients with a T T R. Polyneuropathy.
John M. Leonard: Additionally, we plan to submit a BLA submission in 2026 Perenchio late 'twenty O two which we anticipate will lead to the first ever approval for an in vivo CRISPR based therapy by that time, our expectation is we'll have accumulated safety efficacy and durability data for over seven years and have tree.
As many as a thousand patients in our clinical studies.
John M. Leonard: Additionally, we plan to submit a BLA submission in 2026 for NTLA-2002, which we anticipate will lead to the first-ever approval for an in vivo CRISPR-based therapy. By that time, our expectation is that we'll have accumulated safety, efficacy, and durability data for over seven years and have treated as many as 1,000 patients in our clinical study. In summary, we will continue transforming medicine with gene editing therapies, with at least three important clinical data readouts expected this year. I'll now hand the call over to our Chief Medical Officer, David Lebwohl, who will provide an update on our clinical programs. David?
John M. Leonard: In summary, we will continue transforming medicine with gene editing therapies with at least three important clinical data readouts expected this year.
Speaker Change: I'll now hand, the call over to our Chief Medical Officer, David Loeb Wall, who will provide an update on our clinical programs David.
David Lebwohl: Thanks, John, and welcome, everyone. I'll begin with 2001, our in vivo CRISPR candidate for the treatment of ATTR amyloidosis. This multisystem disease primarily manifests as either cardiomyopathy, due to amyloid deposits in the heart, or polyneuropathy, due to progressive accumulation of protein deposits in the nervous system. As demonstrated in our Phase 1 study, a one-time treatment of 201 led to greater than 90% TTR reduction. Importantly, we demonstrated best-in-class reduction of absolute TTR levels among TTR silencing, which we believe will be a key differentiator for treating patients with CM and or PS. In ATTR-CM, despite the introduction of TTR stabilizers, patients continue to experience worsening heart failure, hospitalizations, strokes, and heart attacks. Ultimately, it remains a fatal disease.
Speaker Change: Thanks, John and welcome everyone.
Speaker Change: I'll begin with 20th one our in vivo CRISPR candidate for the treatment of H T. T. R amyloidosis.
Speaker Change: The multi system disease, primarily manifest either cardiomyopathy due to amyloid deposits in the heart or Polyneuropathy is a progressive accumulation of protein deposits and the nervous system.
As demonstrated in our phase one study a one time treatment of 20th one to greater than 90% T T. Our reduction.
Speaker Change: Importantly, we demonstrated best in class reduction of absolute P. T. R levels among T. T. R. Silencing agent, which we believe will be a key differentiator for treating patients with C M and R. P M.
Speaker Change: And a T T. R. C M. Despite the introduction of GTR stabilizers patients continue to experience worsening heart failure hospitalization strokes and heart attacks.
Speaker Change: <unk> it remains a fatal disease.
David Lebwohl: Today I am pleased to report that patient enrollment in the Phase 3 magnitude trial for patients with cardiomyopathy is off to a great start. In March, we announced that the first patients in both the U.S. and globally had been dosed. With over 30 patients already dosed and another 40 plus in screening, we are tracking well ahead of our initial projections. Furthermore, we expect many additional sites to open in the weeks and months ahead, which will further accelerate enrollment in the trial.
Speaker Change: Today I am pleased to report that patient enrollment in the phase III magnitude trial for patients with cardiomyopathy is off to a great start.
Speaker Change: In March we announced the first patients in both the U S and globally had been dosed.
Speaker Change: With over 30 patients already dosed and another 40 plus in screening we are tracking well ahead of our initial projections.
Speaker Change: Further we expect many additional sites to open in the weeks and months ahead, which will further accelerate enrollment in the trial.
David Lebwohl: While we will not be providing patient-by-patient enrollment updates moving forward, we will look for opportunities to keep you abreast of our progress. The rapid rate of enrollment reflects the enthusiasm we hear from physicians and patients who believe 2001 holds the potential to revolutionize the ATTR treatment landscape. In parallel, we are also excited to announce today that we now expect to initiate a new phase 3 trial for patients with ATTR polyneuropathy by year end.
Speaker Change: While we will not be providing patient by patient enrollment updates moving forward, we will look for opportunities to keep you abreast of our progress.
Speaker Change: The rapid rate of enrollment reflects their enthusiasm we hear from physicians and patients who believe 20th one holds the potential to revolutionize the a T T our treatment landscape.
Speaker Change: In parallel we are also excited to announce today that we now expect to initiate a new phase III trial for patients with H T. T. R. Polyneuropathy by year end.
David Lebwohl: Importantly, ATTR-PN patients are typically diagnosed earlier in adulthood, and their disease often progresses more rapidly than ATTR-CM. Published data from chronically dosed TTR silencing therapies demonstrate that deeper reductions of TTR are highly correlated with improvements on standard measures of neuropathy.
Speaker Change: Importantly, a T T. R. P. M patients are typically diagnosed earlier in adulthood and their disease, often progresses more rapidly than a T. T R. Yep.
Speaker Change: Published data from chronically dosed GTR spirochaete therapies demonstrate that deeper reductions in Q T. R are highly correlated with improvements on standard measures of neuropathy.
David Lebwohl: To date, no other agent, approved or in clinical development, has demonstrated the depth and consistency of TTR reduction, regardless of baseline levels like 2001, which gives us tremendous confidence in our ability to positively impact patients. Based on productive discussions with the FDA, we have aligned on a trial design to support a BLA filing for 2001, subject to review of the IMD application. We plan to initiate phase three by year end. The study is expected to be a small placebo-controlled trial of approximately 50 patients conducted in ex-U.S. regions with limited or no access to silencers.
Speaker Change: To date, no other agent approved or in clinical development as demonstrated the depth and consistency of ctr reduction regardless of baseline levels like 'twenty, one, which gives us tremendous confidence in our ability to positively impact patient.
Speaker Change: Based on productive discussions with the FDA, we have aligned on a trial designed to support our BLA filing for 'twenty one.
Speaker Change: Object to review of the IMD application.
Speaker Change: We plan to initiate the phase III by year end.
Speaker Change: Study is expected to be a small placebo controlled trial of approximately 50 patients conducted an ex U S region with limited or no access to silencers.
David Lebwohl: We are making significant strides in advancing 2001 and look forward to presenting data from the ongoing Phase I trial in the second half of the year. Additionally, we plan to present for the first time data beyond TTR levels, such as NT ProBMP, 6-minute walk test, and MNIS Plus 7. In summary, we continue to believe 2001 may halt and potentially reverse the disease, as well as dramatically reset the ATTR treatment plan for. I'll now turn to 2002, our in vivo CRISPR program for the treatment of hereditary angioedema, or HAE.
Speaker Change: We are making significant strides in advancing 20 O one.
Speaker Change: Look forward to presenting data from the ongoing phase one trial in the second half of the year.
Speaker Change: We expect to be presenting safety and T. T. Our reduction data on all 72 patients from both the C M and P M arms.
Speaker Change: Additionally, we plan to include for the first time data beyond GTR levels, such as N. P. Probie M. P. Six minute walk test and M. This plus seven.
Speaker Change: In summary, we continue to believe 20th one may halt and potentially reverse the disease as well as dramatically reset the H T T. Our treatment landscape.
Speaker Change: I'll now turn to 20 O to our in vivo CRISPR program for the treatment of hereditary angioedema or H E E.
David Lebwohl: In January, landmark findings from Phase I were published in the New England Journal of Medicine, highlighting that a single dose of 2002 led to a 95% attack rate reduction. On June 2nd, we will be presenting updated data from the study at the European Academy of Allergy and Clinical Immunology Annual Congress. These long-term data will speak to the safety and durability of the effect on both calocrine and attack rate reduction. Importantly, we will also present the number of patients who remain completely attack-free, with extended follow-up now reaching beyond 18 months for all patients and longer than two years in some.
Speaker Change: In January landmark findings from the Phase one were published in the New England Journal of Medicine, highlighting a single dose of 20 O. Two led to a 95% attack rate reduction.
Speaker Change: On June 2nd we will be presenting updated data from this study at the European Academy of allergy and clinical Immunology annual Congress.
Speaker Change: These long term data will speak to the safety and durability of effect on both kalla crime and attack rate reduction.
Speaker Change: Importantly, we will also present on the number of patients who remain completely attack free with extended follow up now reaching beyond 18 months for all patients and longer than two years and from.
David Lebwohl: Additionally, we plan to report top-line results from the randomized placebo-controlled Phase 2 study shortly thereafter. Full results evaluating the 25mg and 50mg doses are expected to be presented at an upcoming medical meeting. These data updates will provide clarity on which dose to move forward into the Phase 3 trial. Assuming 2002 continues to show a strong safety and efficacy profile, we believe that 2002 will become the preferred prophylaxis treatment in a growing commercial market. In the U.S. market, for example, currently, about 70% of HAE patients use chronic prophylaxis treatments, and that number is increasing. Many patients continue to seek better efficacy and more convenience.
Speaker Change: Additionally, we plan to report top line results from the randomized placebo controlled phase two study shortly thereafter.
Speaker Change: Full results for evaluating the 25 milligram and 50 milligram doses are expected to be presented at an upcoming medical meeting.
Speaker Change: These data updates will provide clarity on which dose to move forward into the phase III trial.
Speaker Change: Assuming 20 O. Two continues to show a strong safety and efficacy profile. We believe the 20th two will become the preferred prophylaxis treatment and a growing commercial market.
Speaker Change: In the U S market for example, currently about 70% of HD patients use chronic prophylaxis treatment.
Speaker Change: And that number is increasing.
Speaker Change: Many patients continue to seek better efficacy.
Speaker Change: And more convenience expressing a strong willingness to switch to new treatments that can deliver on both fronts.
David Lebwohl: Expressing a strong willingness to switch to new treatments that can deliver on both fronts. As previously discussed, we plan to initiate the Pivotal Phase III trial in the second half of 2024. At this point, we are mainly waiting for the Phase 2 data before submitting regulatory amendments to begin our global Phase 3.
Speaker Change: As previously discussed we plan to initiate the pivotal phase III trial in the second half of 'twenty 'twenty four.
Speaker Change: At this point, we are mainly waiting for the phase two data before submitting regulatory amendments to begin our global phase III.
David Lebwohl: Notably, we have now also completed the additional pre-clinical mouse study requested by the FDA to support inclusion of women of childbearing age in the U.S. As expected, these data did not show an impact on female reproductive health in the animals treated with 2002. This is consistent with the extensive preclinical work completed and reviewed by regulators prior to our initial IND clearance, and we plan on submitting these data to the FDA prior to Phase 3.
Speaker Change: Notably we have now also completed the additional preclinical mouse study requested by the F. D. A to support inclusion of women of childbearing age in the U S.
Speaker Change: As expected these data did not show an impact to female reproductive health and the animals treated with 20 O two.
Speaker Change: This is consistent with the extensive preclinical work completed and reviewed by regulators prior to our initial I N D clearance.
Speaker Change: And we plan on submitting these data to the F D. A prior to phase III.
David Lebwohl: Let me now turn to exciting developments with our modular gene insertion platform. Here, we are leveraging the same LNP platform used in our gene knockout programs to deliver the CRISPR machinery along with an AAV to deliver a functional gene. Unlike traditional gene therapy, we expect our approach will permanently restore a missing or defective protein without a waning of effect over time. We expect to begin a first in human study of 30.01, our wholly owned gene insertion program for alpha 1 antitrypsin deficient. As a reminder, the main hurdle with treating this disease is getting patients to consistently normal levels of alpha-1.
Speaker Change: Let me now turn to exciting developments with our modular gene insertion platform.
Speaker Change: Here, we are leveraging the same LNP platform news that our gene knockout programs.
Speaker Change: Liver, the CRISPR machinery, along with an AAV to deliver a functional gene.
Speaker Change: Unlike traditional gene therapy, we expect our approach will permanently restore a missing or defective protein without a waning of effect overtime.
Speaker Change: We expect to begin this year a first in human study.
Speaker Change: Of 30 of one our wholly owned gene insertion program for Alpha one Antitrypsin deficiency.
Speaker Change: As a reminder, the main hurdle with treating this disease is getting patients to consistently normal levels of alpha one.
David Lebwohl: Current standards of care, which involve weekly infusions of augmentation therapy, do not achieve normal levels of alpha-1 and, in some cases, have only been able to produce a modified version of the protein with unknown consequences. 30.01 is the only drug candidate to show AAT levels restored to normal levels after a single dose in non-human primates. It is designed to precisely insert the wild-type SerpinA1 gene and permanently restore production and secretion of fully functional alpha-1 proteins, assuming success.
Speaker Change: Current standards of care, which involve weekly infusion of augmentation therapy.
Speaker Change: Does not Jesus.
Speaker Change: Other approaches in development have also been unable to yield normal levels of Alpha one and in some cases have only been able to produce a modified version of the protein with unknown consequences.
Speaker Change: 30 of one is the only drug candidate to show a T levels restored to normal levels. After a single dose in nonhuman primates.
Speaker Change: It is designed to precisely insert the wild type, surpassing a one gene and permanently restore production and secretion of fully functional alpha one protein.
Speaker Change: Assuming success.
Laura Sepp: 3001 could be life-changing for Alpha 1 patients and unlock a whole new category of diseases we can pursue with in vivo gene insertion. Meanwhile, separately, our collaborative Regeneron has achieved clearance from both U.S. and EU authorities for the Factor IX program using our modular gene insertion platform and plans to enroll the first patient later this year. Our clinical development of the in vivo pipeline is rapidly accelerating, and Intellia is well positioned as the leader in this new era of medicine. I'll now hand over the call to Lara, our Chief Scientific Officer, who will provide updates on our R&D efforts and what's coming next.
Speaker Change: 31 could be life changing for alpha one patients and unlock a whole new category of diseases, we can pursue with in vivo gene insertion.
Speaker Change: Separately, our collaborator Regeneron has achieved clear them from both U S and EU authority for the factor nine program using our modular gene insertion platform and plan to enroll the first patient later this year.
Speaker Change: Our clinical development of the in vivo pipeline is rapidly accelerating.
Speaker Change: I'm, telling you is well positioned as the leader in this new era of medicine.
Speaker Change: I'll now hand over the call to Laura our Chief Scientific Officer, who will provide updates on our R&D efforts and what's coming next.
Laura Sepp: Thank you, David. Good morning, everyone.
Laura Zeno: Thank you David good morning, everyone.
Laura Sepp: At Intellia, we're advancing novel gene editing and delivery technologies for in vivo and ex vivo therapeutic applications. As John mentioned, core to our strategy is the emphasis on safety and performance at each step of development. Our success to date is not by chance, and it's a common misconception that gene editing and delivery tools have become commoditized. By leveraging the experience of a world-class team and making dramatic improvements and adaptations to our platform technology, we have been able to lead the entire industry forward. But don't just take my word for it. Let me give you some real-world examples.
Laura Zeno: Danielle we're advancing novel gene editing and didn't have any technology for in vivo and ex vivo therapeutic applications.
Laura Zeno: As John mentioned close to our strategy is the emphasis on safety and performance at each step of development.
Laura Zeno: Our success today is not by chance and it's a common misconception.
Laura Zeno: I think he meant anyway tools have become a commodity.
Laura Zeno: By leveraging the experience of a world class team and making dramatic improvements in other patients to our platform technology, we have been able to really didn't pay it forward.
Laura Zeno: But don't just take my word for it let me give you some real World example.
Laura Sepp: Intellia is now 5-for-5 in INDs approved by the FDA for our investigational therapy. Groundbreaking clinical data sets for both MDLA-2001 and MDLA-2002 have been published in the New England Journal of Medicine. We have already gained regulatory clearance for multiple clinical trials in eight different countries. Together with Regeneron, we're conducting the largest global phase 3 study of genetic medicine. Intellia has become the reference gene editing company, which has helped us foster important relationships with the world's leading scientific and medical experts as well as advocacy organizations. And now, building on the success of our work in diseases that originate in the liver, we're expanding tissue types that can be targeted with our CRISPR-based technology. We now have active research programs in five different tissues outside the liver, either independently or in collaboration with partners. This includes the bone marrow, brain, eye, lung, and muscle.
Laura Zeno: He will tell you he's now apply for five I am these approved by the FDA for our investigational candy.
Laura Zeno: Groundbreaking clinical dataset for both MDA late 'twenty, one and MD&A 22 have been published in journal of Medicine.
Laura Zeno: We have already gained regulatory clearance for multiple clinical trials.
Laura Zeno: Different countries.
Laura Zeno: Together with Regeneron, we're conducting the largest global.
Laura Zeno: Betty genetic medicine.
Laura Zeno: And Tony has been from the restaurants.
Laura Zeno: A company, which has to help I suppose the important relationships with the worlds leading medical experts.
Laura Zeno: Well I look I see already.
Laura Zeno: Great.
Speaker Change: And now moving on.
Speaker Change: Different sites with our work.
Speaker Change: That brings me, making the liver we're expanding that.
Speaker Change: That can be targeted with our CRISPR based technology.
Speaker Change: We now have active research programs implies tissues outside the liver either independently or in collaboration with partners.
Speaker Change: This includes the bone marrow.
Speaker Change: I am.
Speaker Change: I myself.
Laura Sepp: We're particularly excited about pursuing diseases such as sickle cell disease, muscular dystrophy, cystic fibrosis, ALS, and many other debilitating genetic conditions. We're also advancing a pipeline of ex-bio programs, both wholly owned and in collaboration with partners for the treatment of immune oncology and autoimmune disease. In fact, two of our partners are leveraging our allogeneic platform, one of which is already in the clinic. Our differentiated allogeneic solution, including HLA-matching, is uniquely positioned to avoid both T-cell and NK-cell mediator rejection and result in cell persistence and disease control.
Speaker Change: We're particularly excited about pursuing diseases, such as sickle cell disease muscular dystrophy, cystic fibrosis E&S among others.
Speaker Change: Yes.
Speaker Change: We're also advancing our pipeline of New York.
Speaker Change: All of them, both wholly own and in collaboration with partners or the Cleveland.
Speaker Change: Allergy and autoimmune disease.
Speaker Change: In fact, who our partners are leveraging our allogeneic platform, one of which is already in the clinic.
Speaker Change: Our differentiated.
Speaker Change: Solution, including HLA matching.
Speaker Change: Hey, good completions my boy ball.
Speaker Change: So I always tell you that the rejection.
Speaker Change: Result.
Speaker Change: Understood.
Laura Sepp: Further, therapies engineered with our allogeneic platform, combined with edits to enhance cell function, offer a new approach to target solid tumors. We look forward to updating you on our progress across our R&D platforms more broadly this year. I now hand over the call to Glenn, our Chief Financial Officer, who will provide an update on our financial results for the first quarter of 2024.
Speaker Change: Further we're happy.
Speaker Change: With our allogeneic platform combined with adults 20 times consumption offering your approach to target solid tumors.
Speaker Change: We look forward to updating you on our progress.
Speaker Change: Across our R&D platform more broadly this year.
Speaker Change: I'll now hand over the call to Glenn our Chief Financial Officer, who will provide an update on our financial results I suppose first quarter 'twenty 'twenty four.
Glenn G. Goddard: Thank you, Laura. Good morning, everyone.
Glenn G. Goddard: Thank you Laura good morning, everyone and tell you. It continues to maintain a strong balance sheet that allows us to execute on our pipeline and platform.
Glenn G. Goddard: Intellia continues to maintain a strong balance sheet that allows us to execute on our pipeline and platform. Our cash, cash equivalents, and marketable securities were approximately $953.4 million as of March 31, 2024, compared to $1 billion as of December 31, 2023. The decrease was driven by cash used to fund operations of approximately $137.2 million. However, the decrease was offset in part by $58 million of net equity proceeds from the companies under the market program.
Glenn G. Goddard: Our cash cash equivalents and marketable securities or approximately $953 4 million as of March 31, 2024, compared to $1 billion as of December 31, 2023.
Glenn G. Goddard: The decrease was driven by cash used to fund operations of approximately $137 $2 million.
Glenn G. Goddard: The decrease was offset in part by $58 million of net equity proceeds from the company's at the market program.
Glenn G. Goddard: $12.6 million of interest income, $5.9 million of collaborator reimbursement, and $2 million in proceeds from employee-based stock. Our collaboration revenue was $28.9 million during the first quarter of 2024, compared to $12.6 million during the first quarter of 2023. The $16.3 million increase was mainly driven by a $21 million non-cash revenue recognition adjustment related to the Avancel collaboration. R&D expenses were $111.8 million during the first quarter of 2024, compared to $97.1 million during the first quarter of 2023.
Glenn G. Goddard: $12.6 million of interest income.
Glenn G. Goddard: $5 $9 million of a collaborator reimbursements.
Glenn G. Goddard: And $2 million and proceeds from employee based stock plans.
Glenn G. Goddard: The $14.7 million increase was mainly driven by the advancement of our LEAD program. Stock-based compensation included in R&D expenses was $20.2 million for the first quarter of 2024. G&A expenses were $31.1 million during the first quarter of 2024 compared to $27.4 million during the first quarter of 2023. The $3.7 million increase was primarily related to stock-based compensation.
Glenn G. Goddard: Our collaboration revenue was $28 $9 million during the fourth quarter of 2024.
Glenn G. Goddard: <unk> to $12 6 million during the first quarter of 2023.
Glenn G. Goddard: The $16 3 million dollar increase was mainly driven by a $21 million noncash revenue recognition adjustment.
Glenn G. Goddard: To the App itself collaboration.
Glenn G. Goddard: R&D expenses were $111 $8 million during the first quarter of 'twenty 'twenty, four compared to $97 $1 million during the first quarter of 2023.
Glenn G. Goddard: The $14 7 million dollar increase was mainly driven by the advancement of our lead programs.
Glenn G. Goddard: Stock based compensation included in R&D expenses was $22 million for the first quarter of 'twenty 'twenty four.
Glenn G. Goddard: G&A expenses were $31 $1 million during the first quarter of 'twenty 'twenty four.
Glenn G. Goddard: Compared to $27.4 million during the first quarter of 2023.
Glenn G. Goddard: The $3 $7 million increase was primarily related to stock based compensation.
Glenn G. Goddard: Stock based compensation included in G&A expenses was $14 million for the first quarter of 2024.
Glenn G. Goddard: Finally, we expect our cash balance to fund our operating plans until late 2026. Notably, our strong balance sheet gives us the financial power to execute on the three-year strategic priorities laid out at the beginning of this year, first to execute pivotal trials for our first two in vivo CRISPR-based therapies, second, to launch the next wave of in vivo and ex vivo clinical programs, and third, to deploy new editing delivery modalities. We're well on our way to realizing the promise of gene editing.
Glenn G. Goddard: Finally, we expect our cash balance to fund our operating plans until late 2026.
Glenn G. Goddard: Notably our strong balance sheet gives us the financial power to execute.
Glenn G. Goddard: On the three year strategic priorities laid out at the beginning of this year.
Glenn G. Goddard: First execute pivotal trials for our first two we'd be about CRISPR based therapies second to launch the next wave of in vivo and ex vivo clinical programs and third to deploy new editing and delivery modalities.
Glenn G. Goddard: We're well on our way to realizing the promise of gene editing.
Glenn G. Goddard: This will be a catalyst rich year for Intel yet and we look forward to updating you on our continued progress.
Glenn G. Goddard: This will be a catalyst-rich year for Intellia, and we look forward to updating you on our continuing progress. With that, we will now open the call for questions. Operator, you may now open the call for Q&A. We will now begin the question and answer session.
Speaker Change: With that we will now open the call for your questions. Operator, you May now open the call for Q&A.
Operator: We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then 2. Please limit yourself to one question. At this time, we will pause momentarily to assemble our rosters.
Speaker Change: We will now begin the question and answer session.
Speaker Change: To ask a question you May press Star then one on your Touchtone phone, if you're using a speaker phone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two please.
Speaker Change: Please limit yourself to one question.
Speaker Change: At this time, we will pause momentarily to assemble our roster.
Operator: The first question comes from Maury Raycroft with Jeff... Please go ahead, go to the next questioner, Yanan Zhu with Wells Fargo Securities.
Speaker Change: The first question comes from Maury Raycroft with Jefferies. Please go ahead.
Speaker Change: Okay.
Speaker Change: We'll go to the next questioner.
Non Jew: Non Jew with Wells Fargo Securities. Please go ahead.
Yanan Zhu: Great, thanks for taking our questions and a lot of progress this quarter, so congrats on that progress. So I have a question about your comment about the speed of enrollment in ATTR phase 3 trial tracking ahead of internal expectations. I was wondering how many sites you have opened? What is the number of U.S. versus ex-U.S. sites, and what is the number of patients per site per month that you are currently tracking? and any updated thinking on the enrollment completion timeline, definitions used in terms of the currently enrolled patients.
Non Jew: Great. Thanks for taking our questions and a lot of progress this quarter. So congrats.
Speaker Change: On the progress.
Speaker Change: I have a question about your comment about the speed.
Speaker Change: Speed up enrollment.
Speaker Change: In our Atg, our phase III trial tracking ahead of them expect like internal expectation. One are wondering how many sites have you opened what are what's the number of U S versus ex U S. U S sites and what is the per site per month.
Speaker Change: Patient number that you are currently tracking.
Speaker Change: And any updated thinking on the enrollment completion timeline.
Speaker Change: The family that's use pets.
Speaker Change: In terms of the currently enrolling patients.
David Lebwohl: I think, yeah. Yeah, thank you. A lot of questions. Sorry about that.
Speaker Change: I think yeah.
Speaker Change: Yeah. Thank you.
Speaker Change: Question, sorry about that.
David Lebwohl: Yanan, thank you for the many questions you just asked, and that one question. We're not going to be giving updates on patients per site, numbers of sites, etc. As we said before, this is a balanced study around the world. We're still actively initiating study sites. We've said that we expect about a third of all of the final sites will be in the United States, and the remainder will be spread around the world.
Speaker Change: Thank you Jan and thank you for the many questions you just asked in that one question.
Speaker Change: We're not going to be giving updates on patients per site numbers of sites et cetera. As we said before this is a balanced study around the world, where it's still actively initiating.
Speaker Change: Waiting study sites, we've said that we expect about a third of all of the ultimate sites will be in the United States and the remainder will be spread around the world I think the takeaways that I would encourage you to see here is that we're early in this process and things are going very well I mean, we're very excited about that.
David Lebwohl: I think the takeaway that I would encourage you to take away is that we're early in this process, and things are going very well. I mean, we're very excited about the enthusiasm that we see in investigators. We've been clearing the regulatory submissions expeditiously, and we've been able to initiate sites, and patients have been waiting to come into the study. We think it's testimony to what patients and physicians see with the current state of therapy, which, as you know, with current approved drugs, patients continue to suffer from the morbidity and mortality of the disease with ongoing progression.
Speaker Change: Enthusiasm that we see with our investigators.
Speaker Change: Investigators we've been clearing the regulatory submissions expeditiously, we've been able to initiate sites and patients have been waiting to come into the study.
Speaker Change: We think it's a testimony to <unk>.
Speaker Change: What patients and physicians see with the current state of therapy, which as you know what's current approved drugs patients continue to suffer from the morbidity and mortality of disease with ongoing progression. So we will not be giving updates.
David Lebwohl: So we will not be giving updates, you know, patient by patient as we go, but I would encourage you to see that we're off to a very, very strong start. We're enthusiastic about the progress we're making.
Speaker Change: On a patient by patient as we go.
Speaker Change: But I would encourage you to see that we're off to a very very strong start we're enthusiastic about the progress we're making.
David Lebwohl: Thanks for those colors. If I may make a quick follow-up on that, from what you, your, from your interaction with the, in particular the U.S. sites, what do you hear from PIs and patients in terms of how they think about the potential upcoming approval of silent gene therapy? How did that impact their thinking of going on the gene therapy treatment? Thank you.
Speaker Change: Thanks for those color if I may a makeup.
Speaker Change: A quick follow up.
Speaker Change: On that on that you know from what you from your interaction with the you put in particular in the U S sites.
Speaker Change: What do you hear from Ti and patience in terms of how long do you think about the potential upcoming approval of <unk> how did that.
Speaker Change: The impact they're thinking of going on be a gene therapy treatment. Thank you.
David Lebwohl: In our interactions thus far, it hasn't influenced how they're thinking about the trial or putting patients on it. Again, I think people have been very impressed with the data that we presented and are encouraged to put their patients on the study. I'll remind you that we created a study that's very favorable to patients. We put into the study the ability for patients with stage three heart failure, a higher pro-BMP level, et cetera, a two-to-one randomization that favors the drug over placebo. There are lots of reasons for patients and physicians to want to participate in the trial, and we're seeing that in these early results. Thanks. I look forward to the next question.
Speaker Change: And our interactions thus far it hasnt influenced how they're thinking about the trial are putting patients on it.
Speaker Change: Again, I think people have been very impressed with the data that we presented and are encouraged to put their patients under study I'll remind you that we created a study that's a very favorable to patients.
Speaker Change: We've put in the study.
Speaker Change: The ability for patients with stage III heart failure, a higher pro BNP level et cetera.
Speaker Change: Two to one randomization that favorite struggle for placebo, there's lots of reasons to patients for patients and physicians to want to participate in the trial and we're seeing that in these early results and I look forward to the next question.
Operator: The next question comes from Maury Raycroft with Jeffre. Please go ahead.
Speaker Change: The next question comes from Maury Raycroft with Jefferies. Please go ahead.
Maurice Thomas Raycroft: Hi, sorry about the technical issue and thanks for taking my question and congrats on the progress. For the ATRPN study, I'm just looking at precedent studies in the space. So Ionis, their study was 168 patients, Apollo A was 225, and then Helios A was 164. And so just wondering if you can talk about how the conversation went with FDA to align your phase three with 50 patients, maybe talk about what expectations are for clinical endpoints and results on those endpoints. And what does this imply about the size of your H-A-E phase three study?
Hi, sorry about the technical issue in and thanks for taking my question and congrats on the progress.
Maurice Thomas Raycroft: For the ADT R. P M.
Maurice Thomas Raycroft: Ah study.
Maurice Thomas Raycroft: Just looking at precedent studies in this space. So I own is their study was 168 patients at Pollo a was 225 and then Helios a it was 164 and so just wondering if you can talk about how the conversation went with F D a to <unk>.
Maurice Thomas Raycroft: Your line on your phase III with 50 patients.
Maurice Thomas Raycroft: Maybe talk about what expectations are for clinical endpoints and results on those endpoints and what does this imply about the size of what your H E E Phase III study could be.
John M. Leonard: Well, let me take the last point first and then I'm going to hand it over to David to address the specifics of polyneuropathy. H-A-A-E-Npoints and polyneuropathy endpoints are two totally different animals.
Speaker Change: Well, let me take the last 0.1st and then I'm going to hand, it over to David to address the specifics upon neuropathy.
David Neil Lebowitz: Hey, endpoints and Polyneuropathy endpoints are two totally different animals and I wouldn't read how one study is designed into how do we think about the other.
John M. Leonard: And I wouldn't read how one study is designed into how we think about the other. As we get more specific with respect to both of these trials, we'll certainly speak to that, so you can see. But I would just emphasize, before David speaks, some of the specifics. We've developed a very close working relationship with the Food and Drug Administration and other regulatory agencies around the world. I think they have a very good understanding of the expected effects of these drugs and have a very good understanding of how to show them in a meaningful way for their own purposes, as well as for physicians and ultimately for other regulatory agencies around the world. David, maybe you can say a few things about how we're approaching that study and why we think it will be successful.
David Neil Lebowitz: And as we get more specificity with respect to both of these trials will certainly speak to that so you can see but I would just emphasize before David speaks to some of the specifics.
David Neil Lebowitz: We've developed a very close working relationship with the food and drug administration and other regulatory agencies around the world I think they have a very good understanding of the expected effects of these drugs and have a very good understanding of how to show them in a meaningful way for their own purposes, as well as for physicians and ultimately for other <unk>.
David Neil Lebowitz: <unk> agencies around the world.
Speaker Change: But maybe you can say a few things about how we're approaching that study and why we think it'll be successful.
David Lebwohl: First, the big picture is that we and the FDA recognize that patients are still progressing despite the existing drugs, and we talked about this design, what they have seen in our clinical data. An important part of that is that we're getting very deep and consistent reductions in TTR, and we do think that's had a positive effect on our discussions with them. In terms of the number of patients, the FDA also has seen a number of studies that show TTR reduction leads to a benefit in patients.
Speaker Change: First the.
Speaker Change: Big picture is that we.
Speaker Change: We and the FDA recognize that patients are still progressing despite existing drugs and we talked to them about this design what they they have seen our clinical data and important part of that is that we're getting very deep and consistent reductions in T. T. R. And we do think thats been a positive effect on our discussions with them.
Speaker Change: In terms of the number of patients. The FDA also has been number of studies that show GTR reduction leads to a better presentation. So that's becoming a well established fact.
David Lebwohl: So that's becoming a well-established fact. Of course, the FDA is more interested in how biomarkers may be a way to not only reflect what happens with disease but actually go forward with approvals in the future. So I do think that the size of the trial has to do with their confidence in how we're working. And, of course, we also have not only the 50 patients that have been trialed but a much larger database from phase one, as well as the ongoing cardiomyopathy phase three.
Speaker Change: Of course, the FDA is more interested in how biomarkers may be a way to to.
Speaker Change: I would only reflect what happens with disease, but actually go forward to approvals in the future.
Speaker Change: So I do think that the size of the trial has to do with their confidence in how we're working and.
Speaker Change: Of course, we also have not only the 50 patient trial.
Speaker Change: Larger database from the phase one as well as the ongoing cardiomyopathy phase III.
Speaker Change: Got it thanks for taking my question I'll hop back in the queue.
David Lebwohl: Got it. Thanks so much, and I'll hop back in. The next question comes from Troy Lankford with TD Cowan. Please go ahead. Hi, congratulations on all the progress this quarter and thanks for taking our question.
Operator: The next question comes from Troy Lankford with TD Cowan. Please go ahead.
Speaker Change: The next question comes from Troy Lankford with TD Cowen. Please go ahead.
Troy Lankford: Hi, Congrats on the progress this quarter and thanks for taking my question. So for <unk> 301, how quickly do you think you can move to development with this asset. So do you think you would try to take this asset into a pivotal study shortly after the phase one dose work like with <unk> to 'twenty, one where do you think we'll have more traditional placebo controlled phase two to further refine the dose of <unk>.
Troy Lankford: Steady like with until late 'twenty two.
Operator: Thanks for the question, Troy. I just start by saying, as was emphasized in our comments earlier today, we emphasize understanding these drugs, especially from a safety as well as from an efficacy point of view, and that those will be our guiding principles as we carry out the study of 30.01. The shortest, most efficient way to regulatory approval. So that lies ahead, and we'll give you updates as we proceed.
Speaker Change: Thanks for the question Troy.
Speaker Change: I'd just start by saying as was emphasized in our comments earlier today, we emphasize understanding these drugs, especially from a safety as well as from an efficacy point of view and so that those will be our guiding principles as we carry out the study of 31.
Speaker Change: We're excited with what we think the drug can do I'll remind you that in the <unk>.
Speaker Change: The clinical data, we've established that we're able to nonhuman primates to reach normal levels as seen in human beings. We think that's fundamental to the regulatory strategy.
Speaker Change: Our hope is that we'll show that in phase one studies and assuming that we see that we will progress as quickly as we can working with the food and drug administration and other.
Speaker Change: Related agencies to establish what is the shortest most efficient way to get regulatory approval. So that lies ahead and we will give you updates as we proceed.
Speaker Change: Okay. Thanks for the color.
Luca Issi: The next question comes from Luca Issi with RBC Capital. Please go ahead.
Speaker Change: The next question comes from Luca <unk> with RBC capital. Please go ahead.
John M. Leonard: Oh great, thanks so much for taking my question. Congratulations on all the progress. Maybe David, on TTR cardiomyopathy, given the recent changes from your competitor, are you rethinking any aspects of your trial design? In a scenario where Helios B hits only monotherapy and shows no benefit as add-ons to FAMDAS, do you have any optionality to split the primary endpoint between the overall population and the monotherapy arm, similar to what they did? And then maybe quickly on TTR poloneuropathy, can you just expand on why not enrolling patients in the U.S. for the pivotal trial?
Luca: Oh, great. Thanks, so much for taking my question Congrats on all the progress maybe David does Ctr cardiomyopathy, given the recent changes from your competitors or are you rethinking any aspect of your trial design is scenario, where Helios b hits, all the monotherapy and show no benefit as add on to sandwiches do you have.
Luca: Any optionality to split the primary end point between the overall population and the monotherapy arm similar to what they did.
Luca: And then maybe quickly on Ctr, Poland neuropathy can you just expand on why not enrolling patients in the U S for dependable.
David Lebwohl: So, I'm, well, David, speak to some of the specifics of the trial, but I'll just start by pointing out that, you know, there are some fundamental differences in how we've approached the PISO trial. In the case of TPR, we've certainly been mindful of understanding the rates of progression. We've been able to learn from other drugs as they present data as we go, that have gone before us. And we've been really thoughtful about an endpoints-driven study, which is driven by the rate at which things happen, not by some pre-specified moment in time when we surmise that all the events may be in.
Speaker Change: So well David speak to some of the specifics of the trial, but I'd just start by pointing out that.
Speaker Change: There are some fundamental differences in how we've approached the pivotal trial.
Speaker Change: In the case of PPR, we've certainly.
Speaker Change: Been mindful of understanding the rates of progression, we've been able to learn from other drugs as they presented data as we've gone.
Speaker Change: It's kind of gone before us and we've been really thoughtful about the endpoints driven study, which is driven by the rate at which things happen not by some pre specified a moment in time, when we surmise that all the events may be and I think the standard approach. These trials is in fact endpoints driven approach.
David Lebwohl: I think the standard approach to these trials is, in fact, an endpoints-driven approach, and that's what we've embraced from the beginning. I think, David, maybe you could just say a few words about how Helios does or does not affect our thinking at this current time.
Speaker Change: And that's what we've embraced from the beginning.
Speaker Change: I think David maybe you can just say a few words about.
David Neil Lebowitz: How helios does where it does not affect our thinking at this current time.
David Lebwohl: The first point is that we are confident, as John is saying, in the design of the magnitude study because, in all those points we made, we've been conservative in the assumptions we made as we designed it. Of course, it is a larger study than Helios, so I think that's very important. And we also took on some more advanced disease in these patients. Pro BMP is higher, and we don't have an upper limit at that.
David Neil Lebowitz: The first one is that we are confident as John is saying in the design and the magnitude study because all those points you've maybe been conservative in the assumptions. We've made as we designed it of course it is a larger study than Helios. We think that's very important and we also took on some more advanced disease in these patients.
David Neil Lebowitz: Pro BNP as fire and we don't have an upper limit that we don't limit the amount of time that we follow these patients and this event driven trial.
David Lebwohl: We don't limit the amount of time that we follow these patients in this event-driven trial. Of course, as we've stated before, because we get consistently deep and durable TTR reductions, we do think we can be the best in class and can be better than drugs in other studies. So we will be paying very, obviously, very close attention to the data that comes out from Helios B. We do expect it to be a positive trial.
David Neil Lebowitz: Of course, we.
David Neil Lebowitz: As we've stated before because we could consistently deep and durable ctr reduction we do think we can be the best in class and it can be better to.
David Neil Lebowitz: Drugs in other studies.
David Neil Lebowitz: So we will be paying very obviously very close attention to the data that comes out from Helios B. We do expect it to be a positive trial did you point out how much it will add to the families. We don't know at this point, but whatever comes out from those results we have the potential to modify our trial in order to address.
David Lebwohl: Would you point out how much it will add to defamidus? We don't know at this point, but whatever comes out from those results, we have the potential to modify our trial in order to address whatever is found with the other drugs.
David Neil Lebowitz: Whatever is found the other drugs.
David Lebwohl: I think Luca is also looking for some insight into the polyneuropathy study for phase 3 and where we're conducting it and why.
Speaker Change: Thank you Lucas also looking for some insight into the Polyneuropathy study for phase III, where we're conducting it in N Y so our discussions with the FDA.
David Lebwohl: So in our discussions with the FDA, it's clear that it's important to have a control arm, a placebo control arm. So these are patients in the world who do not have access to silencers. In the U.S., there is very good access to silencers.
Speaker Change: It was clear that was important to have a.
Speaker Change: Control arm of placebo control arm. So these are patients in the world, who do not have access to our silences.
Speaker Change: In the U S. There is very good access to silences. So the main reason, we would not be paying having patients in the U S is because it satisfies the need for that for.
David Lebwohl: So the main reason we would not be having patients in the U.S. is because of a satisfied need for that by those patients. And it's important to note that we're aligned with that approach. They understand how we would be doing a study and where we'll do it. And because the treatment practices are so similar, we think that this information should be readily applicable to the United States.
Speaker Change: For those patients and it's important to note that we're aligned with that approach. They understand how we would be doing the study and where we will do it and because the treatment practices are so similar we think that these this information should be readily applicable to the United States.
Speaker Change: Got it thanks, so much.
Operator: The next question comes from Gena Wang with Barclays. Please go ahead.
Speaker Change: The next question comes from Gena Wang with Barclays. Please go ahead.
Harshita Polishetty: Hi, good morning. This is Harshita on behalf of Gena.
Speaker Change: Hi, Hi, good morning. This is Michelle on for Gena. Thanks for taking our question just a quick one on us.
Speaker Change: From us on until it too.
Speaker Change: Now that you've completed the preclinical and biological development study are you able to provide more granular color on when you plan to submit these data if the submission eminent and any color you can provide on how long it'll take the agency to review these data and I understand that you can't speak for the agency and each situation is unique.
Speaker Change: But if you are able to provide at least a range on timelines that would be helpful. Thank you.
John M. Leonard: Thanks for the question, Hershita. We don't go through report by report and submission processes and procedures for each of those things.
Harshita Polishetty: Thanks for taking our question. Just a quick one on us from us at NTLA-2002. Now that you've completed the preclinical embryological development study, are you able to provide more granular details on when you plan to submit these data? Thanks for the question, Harshita.
Speaker Change: Thanks for the question Hershey.
Speaker Change: We don't go through report by report and submission processes and procedures for each of those things.
John M. Leonard: And I remind you that this is not even gating from the Phase 3 program. You know, the first point I think to make is that we've seen the data. It's as expected.
Speaker Change: And I remind you that this is not even gating for the phase III program.
Speaker Change: The first point I think to make is that we've seen the data it's as expected.
John M. Leonard: There are no issues, and you know, we're in a really good position to proceed. What's really going to drive the start of phase 3 is getting the... data in with respect to our phase two program. And as David mentioned during the comments earlier, when we have those, we'll be sharing those later this year, and that's something we're very enthusiastic about. And because we have some regulatory designations that allow us to interact more readily with the FDA, we think we're going to be in a really strong position, actually poised to take that data and very, very quickly submit it to the FDA. to begin Phase 3, which, as a reminder, we said, well, we expect to start this year, and hopefully, we'll be in a position to enroll patients before the end of the year.
Speaker Change: There is no issues and you know we're a really good position to proceed what's really going to drive the phase III start is getting the data in with respect to our phase II program and as was referred to by David draining the comments earlier when we have those will be sharing those later this year.
Speaker Change: And that's something we're very enthusiastic about.
Speaker Change: And because we have some regulatory designations that allow us to interact more readily with the FDA. We think we're going to be in a really strong position actually poised to take that data and very very quickly submitted to the FDA to begin phase III, which has a reminder, we said well we expect to see.
Speaker Change: Art this year and hopefully we'll be in a position to enroll patients before the end of the year.
Operator: The next question comes from Konstantinos Biliouris of BMO. Please go ahead.
Speaker Change: The next question comes from cost US Lewis with BMO. Please go ahead.
Konstantinos Biliouris: Good morning, everyone. Thanks for taking our questions and congratulations on the great progress. One question, 2001 from us. You have previously shown data from other types of amyloidosis that suggest that the lower the residual TTR levels post-treatment, the higher the survival may be. Given that you are presenting more data from NTLA2001 this year, I'm wondering whether the data you have collected so far across different doses can be sufficient to ultimately show trends that allow you to test the relationship between TTR levels and survival. Thank you.
Speaker Change: Good morning, everyone and thanks for taking a question sent a congrats on the great progress one question or 200 lines from US you had previously so data from other types of amyloidosis.
US Lewis: That's not the lower that a G P.
Lewis: P P at levels post treatment the higher the survival may be up given that you are presenting more data from L. P. A L 82001 piece, yet I'm wondering whether the data you have collected so far across different doses can be soft PCM to ultimately showed trends that allowed.
Lewis: To test the relationship between P P outlet and survival.
Lewis: David.
David Lebwohl: You want to speak to what we can extract so far from TTR decreases in endpoints. I know it's early, but any additional comments you might want to provide. Yeah, so you're right.
Speaker Change: You want to speak to what we can extract so far fun PTR decreases endpoints I know, it's early but any additional comments you might want to promote.
David Lebwohl: So you're right when you say that what's been found with other diseases is lowering the protein is extremely important. In fact, when you achieve a complete response, for example, with light chain disease, the patients essentially have normal survival. So we do see this as an important goal and why we're very excited about the deep level of reductions we're getting. To do that, because our results are so consistent, in our own data, we won't be able to see a relationship between TTR reduction and survival because all the patients are getting very deep reductions.
David Neil Lebowitz: Yeah. So the you are right when you say that the what's been found with other diseases is lowering the protein is extremely important fact, when you achieve a complete response for example, with light chain disease patients essentially have a normal survival, but we do see this as an important goal and why we're very excited about the the deep level.
Speaker Change: Reductions we're getting.
Lewis: To do that because our actually our results are so consistent in our own data, we won't be able to see a relationship between T. TR reduction survival because all the patients are getting very deep reductions.
David Lebwohl: But you can look back, for example, to the data from polyneuropathy with silencers and see, for example, a greater improvement in neuropathy. This is one really important finding already. It goes along with the findings in other types of cardiomyopathy and just gives us the confidence that this trial will be successful in what it's trying to do. Thank you very much. The next question comes from Degondha with Steve. Please go ahead. Hi, this is Benaziron for Dagon. We just noticed that recently there was a problem.
Lewis: But you can look back for example to the data from Polyneuropathy or with silence or is that.
Lewis: Did you do go to deeper reduction you see for example, a greater improvement in the neuropathy.
Lewis: It's a really really important finding already that goes along with the findings.
Lewis: Other types of cardiomyopathy, and just gives us the confidence that this trial will.
Lewis: It will be successful and what it's trying to do.
Lewis: Yeah.
Speaker Change: Thank you very helpful.
Operator: The next question comes from Daegon Ha with Stiefel. Please go ahead.
Speaker Change: The next question comes from Dae Gon Ha with Stifel. Please go ahead.
Speaker Change: Hi, This is Ben on for David on we noticed that recently there was a Stanford group that published on Uncategorized insertion and cast an avian mediator repair templates are introduced can you comment on what methods, you're employing to detect such incidents with and he only has 1001.
Speaker Change: And in your interaction with the FDA have they kind of discussed the phenomenon at all.
Operator: Maybe Laura, the question was, an academic group has found concatamers for insertion, and are there techniques that one can employ to understand the extent to which that might occur in a cell? Oh, yeah, of course. You know, that's part of the proclinical development, right?
Speaker Change: Maybe Laura if you take the question was.
Laura Zeno: An academic group has found CAD emerge for insertion.
Laura Zeno: And are there techniques that one can employ to understand the extent to which that might occur in a sell oh. Yeah of course, you know that's kind of yeah in preclinical development. By then you could use different types of next generation sequencing.
Laura Sepp: Oh, yeah, of course. That's part of the proclinical development, right, and you could use different types of next-generation sequencing, including long-range sequencing to understand whether you have a single insertion or concatenose. Okay.
Laura Zeno: In long range sequencing to understand whether you have a single intention are contacting us.
Speaker Change: Okay excellent. Thank you.
Speaker Change: <unk> brought us anything about why that kind of information.
Laura Sepp: The FDA hasn't asked about that at all. Thank you very much. The next question comes from Brian Cheng with J.P. Morgan. Please go ahead. Hey guys, thanks for taking our question this morning.
Speaker Change: The FDA hasn't asked about that.
Speaker Change: Thank you very much.
Brian Cheng: The next question comes from Brian Cheng with J.P. Morgan. Please go ahead.
Speaker Change: The next question comes from Brian Cheng with J P. Morgan. Please go ahead.
Brian Cheng: Hey, guys. Thanks for taking our question this morning.
Brian Cheng: Have a call from a prior conversation the goal is to always have about two years cash on debt on the balance sheet can.
Brian Cheng: Can you give us a sense of how you're thinking about your cash burn and runway overall insurance that to tee off to pivotal study later in this year, how are you prioritizing and allocating resources when you.
Speaker Change: Moving far less focus that's like T. G. I F E N a H N D. Thank you.
Glenn G. Goddard: Yeah, Brian, this is Glenn. Thanks for the question. So basically, what we talked about this morning is that we have runway now to late 2026. That's about two and a half years worth of cash that contemplates the three-year strategic priorities all being funded that we've been laying out for investors. So we feel like we're in pretty good shape there. The other thing I would say is just the operating expenses are going to stay pretty consistent as we go forward here from what you've seen in the last couple of quarters. The next question comes from Debjit Chattopadhyay with Guggenheim Security. Please go ahead. Hey, good morning, team.
Speaker Change: Yeah, Hey, this is Glenn thanks for the question.
Glenn G. Goddard: So basically with what we talked about this morning, as we were having runway now to late 2026.
Glenn G. Goddard: That's about two and a half year's worth of cash and that contemplates the three year strategic priorities all being funded that we've been laying out for investors. So we feel like we're in pretty good shape. There. The other thing I would say is just the operating expenses are going to stay pretty consistent as we go forward here from what you've seen last couple of quarters.
Operator: The next question comes from Debjit Chattopadhyay with Guggenheim Security. Please go ahead.
Glenn G. Goddard: The next question comes from Doug <unk>.
Doug: <unk> <unk> with Guggenheim Securities. Please go ahead.
Doug: Hey, good morning team. This is Robert Thanks.
Robert: Thanks for taking my questions two from US this morning.
Robert: What does it tell you that view on potential synergistic effects of 2001 knocked down into family of stabilization.
Robert: And then gene insertion, how does until you're in Regeneron plan to maintain expression.
Speaker Change: Is it a therapeutic window, particularly in a disease like can be thank you.
Debjit D. Chattopadhyay: David, do you want to say a word or two about how we're thinking about the interaction between 2001 and tephamidus? And then maybe Laura, you can follow up as you know, how we aim for the therapeutic levels that we're pursuing. With a reminder that hemophilia B is being pursued primarily by Regeneron at this point.
Robert: David do you want to say a word or two about how we're thinking about the interaction between 'twenty, one and <unk>.
David Neil Lebowitz: Then maybe Lora you can follow up is how we aim for the therapeutic levels that we're.
Speaker Change: We're pursuing.
Speaker Change: Yeah.
Speaker Change: With a reminder, that hemophilia b is being pursued primarily paper turnaround at this point.
Robert: David.
David Lebwohl: The way we think about it is that the lower the amount of this precursor protein, of the abnormal protein, the better the effect on the disease. And in fact, if the protein gets low enough, then what we expect, not only that you don't start accumulating amyloid, but you actually might see a reduction in amyloid, that the body will remove the amyloid from organs.
Lora: But as discussed already the way, we think about it is that the lower the amount of the precursor protein would be abnormal protein.
Lora: The better the effect on the disease.
Lora: And in fact, if the protein gets low enough then what we expect not only that you don't start cumulative don't keep accumulating amyloid, but you actually might see the reduction of amyloid, but the body will.
Lora: Remove the Animaloid from Oregon.
David Lebwohl: So our goal is to get the lowest absolute TTR levels. We've talked about that in some of our recent work. In fact, at some point, people may ask, "What is your TTR number?"
Lora: So our goal is to get the lowest absolute GTR levels, we've talked about that in some of our recent work in fact that some people at some point people may asking what is what is your TTM number that's to me the important thing.
Lora: Moving forward, so what happens with the family.
David Lebwohl: That's going to be the important thing moving forward. So what happens to tefamidin? If you do get the levels low enough, then tefamidin could still be valuable because the bit of remaining abnormal protein could be stabilized. So you go from what is a very low amount already with our drug to make it even somewhat better, perhaps with tefamidin. So it may be a valuable interaction. It might be a synergistic interaction as you get to these very low levels.
Lora: If you do get the levels low enough then for family this could be valuable still because the bit of remaining abnormal protein could be stabilized. So you go from what was a very low amount already with our drug.
Lora: To make it even somewhat better perhaps with it's a family. So it may be a valuable interaction it might be a synergistic interaction as you go through these very low levels.
Laura Sepp: With regard to the question about gene insertion and how you maintain therapeutic levels, you know, part of the preclinical development package involves doing a matrix of doses of how much LNP and how much insertion template, right? And you clearly and deeply characterize what's the range of insertion that results in therapeutic protein production. And that data is then taken, taken into account, you know, allometric scaling for humans, right?
Lora: So with regards to the question on the gene insertion and Hadley and maintain therapeutic levels and that's part of the preclinical development packaging bulks and doing matrix off.
Lora: So how much and then being how much insertion template faith in you.
Lora: Clearly and deeply characterize what's the range of inflation that we saw two therapeutic protein production.
Lora: And then they base then taken taken into account and then you know allometric scaling for I shouldn't say that's part of 13, you can see the unemployment.
Laura Sepp: That's part of your clinical development plan. In the clinic, there will be a very purposeful and, you know, safe way of escalating those levels to understand, you know, what's the level of expression and how does that translate across multiple patients in the cohort. So, you know, reminding you that, you know, Factor IX is being driven by Regeneron. So, you know, they're already approved to move into the clinic, and we're expecting to be seeing, you know, data, clinical data in due time, which is not only important for that program, but it's a validation of the insertion platform that will translate to 31 and a number of other diseases for which insertion is the most appropriate gene editing modality.
Speaker Change: Hey, Glenn it's amazing to me very purposeful and safe way dose escalating to understand you know, what's the level of expression and told us that translate across multiple patients in the cohort.
Glenn G. Goddard: And I reminded them that sometimes means me then I will turn it on.
Glenn G. Goddard: So you know that or maybe a post them to move into the clinic and we're expecting we're going to be seen.
Glenn G. Goddard: Data clinical data.
Glenn G. Goddard: And in due time, which not only is important so that program, but it's a validation and also the insertion platform.
Glenn G. Goddard: That will translate to 31, I mean remember it's either because he says for wechat search.
Glenn G. Goddard: And you said most of appropriate gene editing.
Laura Sepp: Part of the question was how to maintain levels. Maybe you could say a word about the stability that we expect. Oh, yeah, and for maintenance, right?
Glenn G. Goddard: Part of the question was how to maintain levels. Maybe you can say a word about the stability that we expect for for maintaining the slide we have shown now for Panther 941, and other in search that you know when such savings 13, two N. G. Now you see very very stable insertion.
Laura Sepp: We have shown now for Placto 9, for Alpha 1 and other inserts that, you know, once it's stayed inserted into the genome, you see very, very stable insertion. This is a key difference from, you know, traditional gene therapy where you have an epistem, or over time, that episode could be silenced or can be lost just by the proliferation of the liver cells over time. So we expect that once you achieve those stable levels, those are going to be persistent and well-controlled. The next question comes from Mary Kate Davis with Bank of America. Please go ahead.
Glenn G. Goddard: D C say TD friends from traditional gene therapy, where you had an episodic where over time, you know that episodic could be silence or it can be lost Josh snively proliferation, often be Oh, Steve you know leave ourselves over time. So we expect that once they get to use those stable levels those are going to be persistent and wake them.
Glenn G. Goddard: Yes.
Speaker Change: The next question comes from Mary Kate Davis with Bank of America. Please go ahead.
Speaker Change: Good morning. Thank you for taking my question I guess looking at your earlier stage pipeline with your recent collaboration with three could could you talk about the opportunity and potential market, but gene editing medicine in cystic fibrosis, and maybe also the opportunity of utilizing your DNA, writing technology chip address this indication. Thank you.
John M. Leonard: I'll start by explaining why we're excited about cystic fibromyalgia, and maybe Laura can talk about some of the technical things that we believe we can address successfully with our approach. As I think is well known, there are many people who suffer from cystic fibrosis in the United States and around the world, and therapies that are currently addressed are chronically administered. There's no doubt that that's an advance for patients relative to where they were some years ago.
Speaker Change: Oh, Oh starch why we're excited about cystic fibrosis.
Speaker Change: And maybe Laura can talk about.
Laura Zeno: So the technical things that we believe we can address successfully with our approach.
Laura Zeno: As I think is well known there.
John M. Leonard: As many people who suffer from cystic fibrosis in the United States and around the world.
John M. Leonard: Therapies that currently addressed are chronically administer theres no doubt thats represented in advance for patients relative to where they were some years ago, but the fact remains this is chronic therapy and many as patients continue to progress. There's a set of patients for whom no therapy is available and as excited.
John M. Leonard: But the fact remains, this is chronic therapy, and many of these patients continue to progress. There's a set of patients for whom no therapy is available, and as exciting as some of them are, they're just irrelevant to a large subset of these patients. This is a very large market, as we've seen with other companies, and it's something that we think we can make some very, very significant contributions to. Maybe, Laura, you could say a word about how we can address that and our work with RICO.
John M. Leonard: As some of the advances are irrelevant to a large subset of these patients. This is a very large market.
Laura Sepp: As we've seen with other companies and it's something that we think we can make some very very significant contributions to maybe lora you can say a word about how we can address that.
Laura Sepp: Our work with Ricoh, Yeah. So you know as in.
Laura Sepp: Yeah, so, as John was saying, we believe that cystic fibrosis is, you know, there is still a significant medical need, not only for the people who don't respond to current therapies, but there are patients who don't tolerate them. And important among those patients is what's called class one, that they don't make CFTR protein. So, we believe that that's, you know, a perfect place for us to start by combining our DNA writing efforts with RECODE's LNP.
Laura Sepp: John was saying right, we believe that cystic fibrosis.
Laura Sepp: Is there still a significant unmet medical need not only the people who don't respond to kind of in therapy, but there are patients who don't tolerate them.
Laura Sepp: Important among those patients. He is what's called a class one that they don't make CFT. Our proteins. So we believe that that's a perfect place for us to start by combining our DNA writing efforts when we coach M. P. We were encouraged to see you know C. M. P. These elements by but we could and.
Laura Sepp: We were encouraged to see, you know, the LNP development by RECODE, and particularly, they're in the clinic, right, we inhale LNP for two indications, one being CFTR. They have really robust preclinical data demonstrating that they can get to the cells that we need to edit to have, you know, persistent, long-term CFTR correction. So, we're very enthusiastic about the collaboration and really pushing experiments to move as fast as we can, and a great team on both sides working together. I think the RECODE work is...
Laura Sepp: Particularly they are in the clinic right. We can tell A&P or are two indications one be in CFT on they had really robust preclinical data demonstrating that they can get to the south and we need to and then to have a system long term CFT iron correction. So we're very enthusiastic about it.
Laura Sepp: Collaboration and.
Laura Sepp: Really pushing our experiments to move us from essentially gone a.
Laura Sepp: Great team on both sides working together I think the re code work is a good example of our approach to partnerships in general we look for leaders in the space people that share our values and approaches to patients.
John M. Leonard: I think the RECODE work is a good example of our approach to partnerships in general. We look for leaders in the space, people that share our values and approaches to patients, and those are the partnerships that we think are going to yield important new drugs. And we look forward to the five areas that we've talked about in our comments as we progress outside the liver.
John M. Leonard: And.
John M. Leonard: Yeah. Those are the partnerships that we think are going to yield important new drugs and we look forward to.
John M. Leonard: The five areas that we've talked about in our comments as we progress outside the liver.
Operator: The next question comes from Rick Bienkowski, who has cancer. Please go ahead.
John M. Leonard: The next question comes from brick when Koski with Cantor. Please go ahead.
Rick Stephen Bienkowski: Hey, good morning everyone. Congratulations on all the progress and thanks for taking the questions. So for 201 in TTR, I had a follow-up question from Luca's earlier question on magnitude, and I was hoping to hear your thoughts on how important it is for 201 to show a strong treatment benefit on top of defamitis and what the potential commercial implications would be for showing different treatment effects in patients on baseline defamitis versus those not on treatment.
Rick Stephen Bienkowski: Hey, good morning, everyone. Congrats on all the progress and thanks for taking the questions.
Rick Stephen Bienkowski: So for 'twenty or wandering GTR I had a follow up from earlier question on magnitude I was hoping to hear your thoughts on how important it is for 'twenty I want to show a strong fit on topics of Fabless and what's the potential commercial implications would be for showing different treatment effects in the patients on baseline parameters first there was not on treatment.
David Lebwohl: David, do you want to address the benefit and importance thereof?
Rick Stephen Bienkowski: David do you want to address the benefit and its importance thereof.
David Lebwohl: And so the thing that we believe is that the drug can be, 201, can be better than tefaminase as a single agent. We also believe that there will be a benefit on top of tefaminase. Of course, that's still to be proven. What we are hearing from investigators and physicians is that they're looking for better drugs for this disease. Patients continue to progress on tefamidis, virtually all the patients, as best we can understand from investigators and from the literature.
Speaker Change: And so the.
David Lebwohl: We believe is that the drug can be 'twenty, one could be better LINTA family. This as a single agent.
David Lebwohl: We also believe that there will be a benefit on top of the family of course, that's still to be proven.
David Lebwohl: The.
David Lebwohl: What we are hearing from investigators and physicians is that they are looking for better drugs for this disease patients continue to progress on to families.
David Lebwohl: Hmm.
David Lebwohl: Virtually all the patients as best we can understand from investigators and from from the literature. So we do think there is a role for a single agent that is better than what the family is doing this can be seen in the patients who are obviously are not receiving for families. In the study, but this will be an important analysis as part of our work I think it's.
David Lebwohl: So we do think there is a role for a single agent that is better than what the famines are doing. This could be seen in the patients who are obviously not receiving the famines in the study, so this will be an important analysis as part of our work.
Speaker Change: Important to state that.
John M. Leonard: It's important to state that nobody is satisfied with Tifambidus. I mean, patients all progress on that drug. The disease remains a mortal illness, and investigators and patients know that. And what we think will prevail in the marketplace are drugs that offer the very best outcomes to patients. And that's the approach we've taken from the beginning of the development program. We're excited with the data we've seen thus far, which we've been sharing
David Lebwohl: Nobody is satisfied with the sandwich, I mean patients or progress on that drug.
John M. Leonard: Disease remains a mortal illness.
John M. Leonard: Investigators and patients know that.
John M. Leonard: And what we think will prevail in the marketplace as drugs that offer the very best outcomes to patients and that's the approach we've taken from the beginning of the development program. We're excited with the data we've seen thus far which we've been sharing and we expect to show that at the end of our phase III trial that we represent a significant advance.
John M. Leonard: And we expect to show that at the end of our phase three trial that we represent a significant advance over what is currently the state of treatment, whether used in combination or alone. And that will be a real advance for the field.
John M. Leonard: Or what is currently the state of treatment, whether used in combination or alone and thats going to be a real advance for the field.
David Lebwohl: Great. Thank you. And a quick follow-up on Alpha 1. Since there are two moving parts here, the LNP and the AAV, I was hoping you could just comment on how you're thinking about the dose escalation. Would you be able to escalate both components in tandem, or would you have to maybe do an extended dose escalation to control for those two different delivery vehicles?
Speaker Change: Alright, great. Thank you and a quick follow up.
Speaker Change: I just had a quick follow up on Alpha one.
David Lebwohl: Since theres two moving parts here the LNP AAV I was hoping you could just comment on how youre thinking about the dose escalation.
David Lebwohl: Are you be able to escalate both components in tandem or would you have to maybe do an extended dose escalation to control for those two.
David Lebwohl: Delivery vehicles.
John M. Leonard: I'll turn to David, but just to set the table, we do a lot of preclinical work to try to address as many of the variables as possible before ever entering the clinic. So I don't want anybody to think that we go in with a complete unknown.
Speaker Change: I'll turn to David but just to set the table, we do a lot of preclinical work to try to address as many of the variables as possible before ever entering into the clinic. So I don't want anybody to think that we go in with a complete unknown just as our work with 'twenty, one and 'twenty two.
David Lebwohl: Just as with our work with 2001 and 2002, which we shared earlier, our modeling was essentially dead on in terms of what we saw in the clinic. We expect that many of the insights we've learned from the preclinical work will apply very, very directly to 3001 as well. So David, maybe you could just say a word or two about some of the contraction of what would be a standard sort of checkerboard study to 3001.
David Lebwohl: Where we shared earlier our modeling.
David Lebwohl: It was essentially dead on in terms of what we saw in the clinic, we expect that many of the insights we have learned from the preclinical work will apply very very directly at the 301 as well so David maybe you could just say a word or two about some of the contraction of what would be a standard sort of a checkerboard.
David Lebwohl: Studied.
David Lebwohl: 31 right.
David Lebwohl: Right, so with these two parts, the LNP and the AAV, we've learned a lot already about LNP, the ability to go to a particular site and target that site. And what we've learned from both the 2002 and 201 programs is that we can achieve essentially every allele being targeted with this so that we can open that up for the contribution that the AAV will make. So we think it's more as we have a good idea of the LNP.
David Lebwohl: So with these two park the LNG and the a b we've learned a lot already about LNP the ability to.
David Lebwohl: Go to a particular site and target that side and what we've learned from both the 20th two in 'twenty. One program is that we can achieve essentially.
David Lebwohl: Every every allele beam.
David Lebwohl: dose, and the variation will be more in terms of how much AAB is needed to optimally get the expression of alpha 1 antitripsin. Again, our goal is to get normal levels. That's what we've achieved pre-clinically, and that's what we want clinically as well.
Operator: Are you ready for your next question? The next question comes from Joon Lee with Truist Securities. Please go ahead.
Joon So Lee: So once a year dosing could change the treatment landscaping.
Joon So Lee: Thank you.
John M. Leonard: Well, I would point out that things that follow us will be by definition after a while. And we expect to be in a position where we will demonstrate the effect of our drug, which we think is going to be defining for the space. And our belief is that people will be comparing themselves to us as opposed to the agents that are out there. And regardless, it's I have not seen data that surpasses anything that we've presented thus far.
Joon So Lee: Well I would point out that things that follow us will be.
John M. Leonard: By definition after us and we expect to be in a position, where we will demonstrate the effects of our drug which we think is going to be the finding for the space and our belief is that people will be comparing themselves to us as opposed to the agents that are out there and regard.
John M. Leonard: <unk>, it's I would not seen data that surpasses anything that we presented thus far patients will still be receiving the drug chronically, which brings with it all of the issues that apply to that and we think that the one and done approach.
John M. Leonard: Patients will still be receiving the drug chronically, which brings with it all of the issues that apply to that, and we think that the one and done approach is ideal for this patient set. And we are unique in that space. So, you know, it's important for patients to have different options. But nonetheless, we think that we will be setting the standard.
John M. Leonard: Is ideal for this patient set and we are unique in that space. So.
John M. Leonard: Nope, it's important for patients to have different options, but nonetheless, we think that we will be setting the standard.
Speaker Change: Thank you.
Operator: The next question comes from Silvan Tuerkcan with JMP Securities. Please go ahead.
John M. Leonard: The next question comes from Sylvan <unk> with JMP Securities. Please go ahead.
Silvan Can Tuerkcan: Thank you for taking my question. Mine is more strategic.
Silvan Can Tuerkcan: Thank you for taking my questions Uhm.
Silvan Can Tuerkcan: Strategically maybe you can give us like a 10000 foot view on your strategy in the new tissue <unk> I know you touched before on bone marrow and and to deal with it on on first pet process, but with an all of the tissues that you've mentioned, which ones are closer to I N D, enabling studies, which ones.
John M. Leonard: Maybe you can give us like a 10,000-foot view of your strategy and the new tissues. I know you touched on bone marrow before, and today, a little bit on cystic fibrosis. But within all of these tissues that you've mentioned, which ones are closer to IND-enabling studies? Which ones are further along? And how should we think about those programs coming to fruition over the next couple of years as we move towards IND? Thank you. Thanks for the question.
John M. Leonard: Further along in and how should we think about those programs coming to proportions over the next couple of years towards you know moving towards minded. Thank you.
John M. Leonard: Thanks for the question. It's an important one, but I don't want you to think it's a horse race, and we give updates on the individual laps that these relay races run. All of these tissues are very, very important. It really goes back to the philosophy and the strategic intent that, you know, have been the basis of the company since we first set out.
Speaker Change: Alright. Thanks for the question, it's an important one but I don't want you to think it's a horse race and we give updates on the individual lamps [laughter] he's relay races run.
John M. Leonard: All of these tissues are very very important and really goes back to the philosophy and the strategic intent that you know it has been the basis of the company since we first set out.
John M. Leonard: It's a very deliberate approach that thinks about delivery and editing technologies. So, as it is apparent, we started out with knockouts in the liver, which you see with the 3001 program as a gene insertion into the liver. We have technology to add to that in the form of gene writing in the liver. And the goal has been to take these various editing technologies and apply them to diseases that reside outside the liver.
John M. Leonard: It's a very deliberate approach that thinks about delivery and editing technology. So as as a parent we started out with knockouts and the liver, which you see with the 31 program is a Jean insertion into delivered we have technology to add to that in a form of gene writing in the liver.
John M. Leonard: <unk> and the goal has been to take these various editing technologies imply then to diseases that reside outside the liver and as Laura as mentioned earlier, we do that with collaborators where people have <unk> technique.
John M. Leonard: And as Laura mentioned earlier, we do that with collaborators where people have technologies that can supplement our own and take us to places that we may not be able to get to by ourselves. We're excited about the work with Recode. We're doing work with Sparing Vision. We have a collaboration, as you know, with Regeneron. Each of these tissues, five of them that were delineated earlier, has very important diseases with large populations with unmet medical need.
John M. Leonard: <unk> technologies that can supplement around and take us to places that we may not be you'll get there by ourselves. We're excited to work with three code [noise].
John M. Leonard: Doing work with sparing vision, we have collaboration as you know with Regeneron.
John M. Leonard: Each of these tissues five of them that were delineated earlier have very important diseases with large populations with unmet medical need some of those opportunities surpassed what we see in the liver at the current time and so all of them benefit from the common approach.
John M. Leonard: Some of those opportunities surpass what we see in the liver at the current time. And so, all of them benefit from the common approach from an editing point of view, and all of them are being resourced very, very aggressively to get to those preclinical development candidates. The next question comes from Steve Seedhouse with Raymond James Financial. Please go ahead. Hi, good morning. This is Timor Vanuatu from Timor Vanuatu speaking for Steve Seedhouse.
Timor Vanuatu: From an editing point of view and all of them are being for source very very aggressively to get to those preclinical development candidates.
Timor Vanuatu: Okay. The next the next question comes from Steve Seedhouse with Raymond James Financial. Please go ahead.
Operator: The next question comes from Steve Seedhouse with Raymond James Financial. Please go ahead.
Timor Vanuatu: Hi, Good morning. This is <unk>. So congrats on rapid enrollment basically magnet to study one thing we would like to clarify is what type of patients are expressive and more interested in this study is that patients who have no access to it'll treatment of.
Timor Vanuatu: Patients who couldn't enroll under the trials are patient <unk> or some other category and one other thing I would like to clarify is what is the screen failure rate. So out of the 40 patients that are screened what proportion do you think will be dosed. Thank you.
Operator: Thanks for the question. We're not going to go into the details of screening failures.
Timor Vanuatu: Thanks for the question, where we're not going to go into the details screening failures and as I said earlier number of sites and patient precise and all that that's that's our work to do and will share is appropriate as we go forward, but David is there any general and insight you can provide in terms to the type of patient that's coming.
Timor Vanuatu: Or not coming into the study at this point Yeah. We were actually just meeting with investigators earlier this week.
Speaker Change: There is excitement somebody's investigated for all all of their patients, but this can affect the disease at all stages that you can imagine patients with early disease. They wanted to prevent.
Timor Vanuatu: Some of the reviews, if they're doing well for the sicker patients they want to at least.
Speaker Change: Stabilize or even reverse the disease.
Timor Vanuatu: They are really coming forward from what we're hearing from the investigators with all their patients.
Timor Vanuatu: What we expect is about half of them have access with families without half don't around the world. So that's what the proportions, we expect them to trial the screen failure rate.
Timor Vanuatu: As low, but we will continue that's obviously.
Timor Vanuatu: Any trial.
Timor Vanuatu: Some patients who might be too sick or.
Speaker Change: Or two healthy in some cases, it's going very well as you've heard with more than 30 patients already randomize in more than 40 right behind them.
David Lebwohl: And as I said earlier, number of sites and patients per site and all that, that's our work to do. And we'll, you know, share as appropriate as we go forward. But David, is there any general insight you can provide in terms of the type of patient that's coming or not coming into the study at this point? Yeah, we were actually just meeting with investigators earlier this week.
David Lebwohl: What we expect is that about half of them have access to families, about half don't around the world. That's the proportions we expect in the trial. The screen failure rate is low, but we will continue. You know, that's obviously the case with any trial with some patients who might be too sick or too healthy in some cases.
Speaker Change: Thank you very much.
Operator: And our last question comes from William Pickering with Bernstein. Please go ahead.
David Lebwohl: But it's going very well, as you've heard, with more than 30 patients already randomized and more than 40 right behind them. Thank you very much. And our last question comes from William Pickering with Bernstein. Please go ahead. Hi, good morning. Congratulations.
David Lebwohl: And our last question comes from William Pickering with Bernstein. Please go ahead.
William Pickering: Hi, good morning, Congrats on all the progress this quarter and thank you for taking my question.
William Pickering: I believe you said that you filed the a T. D. C. C application in December could you share if you've received any response or feedback to that application.
William Pickering: And once the trial is under way what duration of follow up would you want to include in any initial data presentation. Thank you.
William Pickering: David, do you want to speak to the CTA status of the Alpha-Pro 1 program? Yeah, so with the CTA, we've got
William Pickering: David do you want to speak to Cta status for Alpha one program.
David Lebwohl: So with the TCTA, we've gotten some straightforward questions that we've addressed, and we're expecting to hear back from the status of that any day now. In terms of follow-up, we will follow the principle we always have, that when we have a significant body of data to report on, we will bring the data forward. As a reminder, Regeneron has gained approvals in both Europe and the IND cleared, so that, you know, in terms of the application itself, the platform, we have high confidence in its ability to go forward around the world.
William Pickering: Yeah, so with the teeth Cta, we've gotten some straightforward questions that we've addressed where we're expecting to hear any day back about the status of that.
David Lebwohl: In terms of follow up will follow the principle you always have that when we have a significant body of data to report on alright.
David Lebwohl: We will be bringing the data forward.
David Lebwohl: As a reminder.
David Lebwohl: Regeneron has gained approval to both Europe.
David Lebwohl: Europe and the I M D cleared so that.
David Lebwohl: In terms of the application itself the platform, we have high confidence in its ability to do go forward around the world.
Speaker Change: Thank you very much.
Ian Karp: At this time, I would like to turn the conference back over to Ian Karp as this concludes our question and answer session. For any closing remarks,
David Lebwohl: At this time I would like to turn the conference back over to Ann Carp. As this concludes our question and answer session for any closing remarks.
Ian Karp: Great. Thanks so much, Drew. And thanks, everyone, for joining us today, for your great questions and for your continued interest in Intellia. And we look forward to updating you as we continue to progress. Have a great day, everyone.
Ian Karp: Alright, thanks, so much through and and thanks, everyone for joining us today for your great questions and for your continued interest in Italia and we look forward to updating you as we continue to progress have a great day everyone.
Operator: The conference has now concluded. Thank you for your participation. You may now disconnect.
Speaker Change: The conference has now concluded. Thank you for your participation you may now disconnect.
Operator:
Operator: [music].