Q3 2021 Intellia Therapeutics Inc Earnings Call

Good morning, and welcome to the <unk> Therapeutics third quarter 2021 financial results Conference call. My name is drew and I will be your conference operator today.

Drew: Good morning, and welcome to the Intelliatherapetrapeutics third quarter 2021 Financial Results Conference Call. My name is Drew, and I will be your conference operator today.

Ian Karp: 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 rather than 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 Intelia.

Owing 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 then 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 Antonio. Please proceed.

Ian Karp: Please proceed. Thank you, and good morning, welcome to Intelia Therapeutics' third quarter 2021 earnings call. Earlier this morning, Intelia issued a press release outlining the company's progress this quarter, as well as topics for discussion today. This release can be found on the investor and media section of Intellia's website at InteliaTX. This call is being broadcast live, and a replay will be archived on the company

Thank you and good morning, everyone welcome to <unk> Therapeutics third quarter 2021 earnings call earlier. This morning, and tells you issued a press release outlining the Companys progress this quarter as well as topics for discussion on today's call. This release can be found on the investor and media section of <unk> website at <unk> Dot com.

This call is being broadcast live and a replay will be archived on the Companys website.

Ian Karp: At this time, I would like to take a minute to remind listeners that during the call, Intelli Management may make certain forward-looking statements and ask that you refer to our SEC filings available at sCC.gov for discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intelia undertakes no duty to update this information unless required by law. Joining me on the call today are Dr. John Leonard, Chief Executive Officer; Dr. David Levall, Chief Medical Officer; Dr. Laura Sep Lorenzino, Chief Scientific Officer; and Glenn Goddard, Chief Financial Officer.

At this time I would like to take a minute to remind listeners that during the call <unk> 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. All information presented on this call is current as of today and <unk> undertakes no duty to update this information unless required by law.

Sure.

Joining me on the call today are Dr. John Leonard Chief Executive Officer, Dr. David Lebel, Chief Medical Officer, Dr. Laura Sepp learn Zeno, Chief Scientific Officer, and Glenn Goddard Chief Financial Officer.

Ian Karp: On today's call, John will lead with the company's third quarter and recent business highlights, followed by David, who will provide an update on clinical efforts surrounding NTLA 2001, NTLA 2002, and NTLA 501. Laura will then recap the company's R&D progress, and Glenn will review Intellia's financial results for the quarter. John will close with final remarks, and then we will open the call for Q&A.

On today's call John will lead with the company's third quarter and recent business highlights followed by David who will provide an update on clinical efforts surrounding MTL, a 20th one N T. L. A 20 O two in MTL, a 50 or one Laura will then recap the company's R&D progress and Glenn will review <unk> financial results for the quarter.

John will close with final remarks, and then we will open the call for Q&A.

John M. Leonard: With that, let me turn the call over to our CEO, John. Thank you, Ian, and good morning, Following our landmark clinical data earlier this year, demonstrating the first systemically delivered CRISPR-based therapy and patient, Our team at Intelia has remained intently focused on advancing our full-spectrum pipe, and building upon our industry leading scientific capabilities to realize the full potential of CRISPR-based medicine. A modular platform deploys differentiated solutions for both in vivo and exvvvvipothera Therapeutic App, genetic diseases, our in vivo approach leverages our proprietary own P-based platform for systemic Our XVEval approach is designed to produce homogeneous robust cell products that epitomize the patient's natural immune, treatment of cancer and autoimmune disease, who generated a robust pipeline that continues to grow, and now includes multiple clinical candidates and an expansive research stage portfolio to fuel future opportunities.

With that let me turn the call over to our CEO John.

Thank you Ian and good morning, everyone.

Following our landmark clinical data earlier this year, demonstrating the first systemically delivered CRISPR based therapy and patients our team at <unk> has remained intently focused on advancing our full spectrum Python and building upon our industry, leading scientific capabilities to realize the full potential of CRISPR based medicines.

Our modulus platform deploys differentiate solutions for both in vivo and ex vivo therapeutic applications.

Diseases R&D will approach Leverages, our proprietary LNP based platform for systemic gene edit our ex vivo approach is designed to produce how much genius robust sell products that he <unk> patients natural immune system for the treatment of cancer and autoimmune diseases.

We generated a robust pipeline that continues to grow and now includes multiple clinical candidates and an expansive research stage portfolio to fuel future opportunities.

John M. Leonard: And today, we're pleased to share an update on recent progress against our core strategic priorities for the, and to look forward to upcoming cattle, for a lead program until A2001 for the treatment of transthyredin amyosis or ATPRM. We've made important progress in establishing the dose response relationship in our first in human study. Notably, we began dosing patients in cohort four earlier in the quarter at a 0.7 megs per kig dose level and believe we are closing in on identifying the recommended dose to move forward into Part 2.

We're pleased to share an update on recent progress against our core strategic priorities for this year and look forward to upcoming catalysts.

For our lead program until late 'twenty, one for the treatment trans by reading Amyloidosis R. A T. T. R. M doses, we've made important progress in establishing the dose response relationship and our first in human study, notably we began dosing patients in cohort four earlier in the quarter at a 0.7 megs per kg dose level.

And believe we are closing in on identifying the recommended dose to move forward into part two.

John M. Leonard: We remain highly encouraged by the safety profile, consistency of TTR reduction, and the ongoing effect of IntelA21 thus far in the phase one study. Additionally, it has long been our plan to develop IntelA201 for all forms of ATPR and loidosis to accelerate the evaluation of IntelA201 in patients whose primary clinical manifestation is cardiomyopin. Based on the strength of our interim data presented in June, we're happy to share that we intend to include patients with cardiomyopics in our current phase one study.

We remain highly encouraged by the safety profile consistency of GTR reduction and the ongoing effect of until late 'twenty, one thus far in the phase one study.

Additionally, while it's long been our plan to develop until late 'twenty. One one for all forms of <unk> amyloidosis, we're accelerating the evaluation of it until a 21 in patients whose primary clinical manifestation is cardiomyopathy based on the strength of our interim data presented in June we're happy to share that we intend to.

Include patients with cardiomyopathy in our current phase one study this could leapfrog what would've been a separate study and as a result, we believe will produce the necessary information we seek in this patient population earlier as compared to patients with Polyneuropathy cardiomyopathy represents the larger opportunity in terms of.

John M. Leonard: This could leapfrog what would have been a separate study and, as a result, we believe will produce the necessary information we seek in this patient population earlier. As compared to patients with polyneropathy, cardiomyopathy represents the larger opportunity in terms of patient numbers, level of unmitting, and commercial potential.

Patient numbers level of unmet need and commercial potential.

John M. Leonard: We're excited to begin evaluating patients with charyomyopathy as quickly as possible once we receive regulatory approval, and continue to believe NTLA 20- has the potential to dramatically transform future treatment lands. In terms of next steps, we plan to present interim data from all four cohorts from part one in Q1 of 2022 at a company-hosted event. By taking this approach, it allows us to provide a comprehensive data set from part one, which will include safety and serum TTR knockdown for cohorts 3 and 4, as well as meaningful extended observation across all four. This lays the foundation for next steps, which include selecting a recommended dose for part two of the trial and beginning dosing in patients with curry myopopin.

Excited to begin evaluating them. So a 21 patients with cardiomyopathy as quickly as possible. Once we receive regulatory approval. We continue to believe NPL a millennial one has the potential to dramatically transform the future treatment landscape.

In terms of next steps, we plan to present interim data from all four cohorts from part one in Q1 of 2022 at a company hosted events like taking this approach. It allows us to provide a comprehensive dataset from part one which will include safety and serum <unk>.

ER knockdown for cohorts, three and four as well as meaningful extended observation across all four cohorts.

Lays the foundation for next steps, which include selecting a recommended dose for part two of the trial and beginning dosing in patients with cardiomyopathy, our decision to slightly adjust the timing to present the interim data reflects our commitment to the principles. We've established from the beginning which is to present data when we've accumulated a robust body.

John M. Leonard: Our decision to slightly adjust the timing to present the interim data reflects our commitment to the principles we've established from the beginning, which is to present data when we've accumulated a robust body of data. We also plan to initiate part two, a single dose expansion cohort, in the first quarter of next year. Beyond NTLA 2001, we've made tremendous progress across our full spectrum pipeline. First, we received regulatory clearance to advance our second and vivo knockout, NTI202 for hereditary angioma or H. First in human studies.

You can convention.

We also plan to initiate part two a single dose expansion cohort in the first quarter of next year.

Beyond until late 'twenty, one we've made tremendous progress across our full spectrum pipeline.

First we received regulatory clearance to advance our second in vivo knockout candidates until late 'twenty two for hereditary angioedema E into first in human studies. This is a significant step forward improving our platform modularity for treating a variety of genetic diseases that originate in the liver with her nonfederal deal.

John M. Leonard: This is a significant step forward, improving our platform modularity for treating a variety of genetic diseases that originate in the liver with our non-thiral delivery technology. Second, now that we've clinically validated our ability to safely inactivate a gene in the liver, we're committed to moving ahead with her targeted insertion. If successful, this will unlock treatment for a whole new category of diseases that require restoring a missing or defective protein. During the past quarter, we nominated two in people as seen insertion candidates.

Technology.

Second now that we have clinically validated our ability to safely inactivated gene in the liver we're committed to moving ahead with a targeted insertion approach.

Successful this will unlock treatment for a whole new category of diseases that require restoring a missing or defective protein.

During the past quarter, we nominated two and people gene insertion development candidate.

John M. Leonard: This includes our first and wholly-gen insertion candidate for a 3001 per alpha-an antitripsin deficiency or AAPD. Plus, as a result of our co-development efforts with Regenoron, where they are, we have nominated a Factor 9 gene insertion development candidate for hemotility B. In both programs, we demonstrated our ability to durably restore a functional protein to normal human levels in nonhuman cells. These results, if reproducible in humans, highlight the promise of CRISPR mediated gene insertion in solving key limitations of traditional gene therapy.

This includes our first wholly owned gene insertion candidate until a 31 for Alpha one antitrypsin deficiency or a T D plus as a result of our co development efforts with Regeneron, where they are the lead party. We've nominated a factor nine gene insertion development candidates for hemophilia B.

Both programs, we've demonstrated our ability to durably restore a functional protein to normal human levels in non human primates ease resolves if reproducible high.

Highlights the promise of CRISPR mediated gene insertion and solving key limitations of traditional gene therapy.

Third we made equally substantial progress on our ex vivo pipeline with the Fda's approval of our I N D. <unk> 51 for the treatment of acute myeloid leukemia or AML. This pipeline development was further enhanced with the presentation of new preclinical data highlighting our proprietary LNP.

John M. Leonard: Third, we made equally substantial progress on our Exceval pipeline with the FDA's approval of RI&D for NTLA 5001 for the treatment of acute myeloid leukemia (AML). This pipeline development was further enhanced with the presentation of new preclinical data highlighting our proprietary LMP-based cell engineering process and novel aligenic solution at last month's ESGCP Annual Congress. These technology enhancements provide us the opportunity to shape the landscape of next generation cell-based earth. In summary, the third quarter has been incredibly productive for Intelia as we continue to advance our leading genome editing pipeline. In the coming weeks, we will have three programs in clinical, and look forward to sharing interim clinical data from our lead program until 8201 in Q1 of 2020. With that introduction, I'll hand over the call to our chief medical officer, David Lev David?

Based cell engineering process and novel Allogeneic solution at last month's <unk> annual Congress.

These technology enhancements provide us the opportunity to shape the landscape of next generation cell based therapies.

In summary, the third quarter has been incredibly productive for Impella.

We continue to advance our leading genome editing pipeline in the coming weeks, we will have three programs in clinical development and look forward to sharing interim clinical data from our lead program until late 'twenty one in Q1 2022.

With that introduction I'll now hand over the call toward Chief Medical Officer, David Loeb Wall, who will provide an update on our progress for until late 'twenty, one and other programs entering the clinic David.

Thanks, John and welcome everyone.

David Neil Lebowitz: Thanks, John. Our lead candidate, 201, is the first systemically delivered CRISPR-based therapy to be dosed in patients and a potentially curative treatment for ATTR amyloidosis. 2001 applies our in vivo LNP delivery technology to knock out the TTR gene in the liver, which is a source of circulating TTR protein, thereby permanently reducing amyloid deposition after a single dose. We shared landmark interim data from the first two dose cohorts of part one of the ongoing phase one trial of 201 earlier this year.

Our lead candidate <unk> hundred one as a first systemically delivered CRISPR based therapy to be dosed in patients.

And the potentially curative treatment for <unk> amyloidosis.

101 applies our in vivo LNP delivery technology to knock out the TCR gene in the liver, which is the source of circulating <unk> protein, thereby permanently reducing amyloid deposition after a single dose.

We shared landmark interim data from the first two dose cohorts of part one of the ongoing phase one trial of 20 year one earlier this year.

David Neil Lebowitz: These positive results not only support 21's therapeutic potential as a one-time treatment for ATP Amloid dose but also offer proof of concept for our non-viral delivery platform. These data demonstrated an encouraging safety profile and dose-dependent reduction in serum TTR. At the 0.3 milligram per kilogram dose level, we achieved an average TTR reduction of 87% among the three patients at day 28, exceeding the current standard of care for patients with polyneuropics. During the third quarter, we began dosing patients in cohort 4 at the 0.7 milligrams per kilogram dose level, as we continue to evaluate the dose response relationship of 2001.

These positive results not only support 21 therapeutic potential as a one time treatment for <unk> amyloidosis.

So offered proof of concept for our non viral delivery platform.

These data demonstrated an encouraging safety profile.

And dose dependent reductions in serum GTR.

At the 43 milligram per kilogram dose level, we achieved an average GTR reduction of 87% among the three patients at day 28.

Exceeding current standard of care for patients with Polyneuropathy.

During the third quarter, we began dosing patients in cohort four at <unk> seven milligrams per kilogram dose level as we continue to evaluate the dose response relationship of 20 or more.

As John noted.

David Neil Lebowitz: As John noted, he remains very encouraged by the safety and activity profile of 20-th-1 thus far. To date, we've not observed any concerning safety signals from any cohort. Once we select the recommended dose, we expect to initiate part two, a single dose expansion cohort to further characterize the activity of 2001. This includes an assessment of clinical measures of neuropathy and neurologic content.

I'm very encouraged by the safety and activity profile of 'twenty or one thus far.

To date, we've not observed concerning safety signals from any cohort.

Once we select a recommended dose we expect to initiate part two.

Dose expansion cohort to further characterize the activity of 'twenty one.

This includes an assessment of clinical measures.

And neurologic function.

Furthermore, based on the interim clinical data and continued confidence in this program. We are accelerating the evaluation of 'twenty one for the treatment of patients with <unk> amyloidosis with cardiomyopathy.

David Neil Lebowitz: Furthermore, based on the interim clinical data and continued confidence in this program, we are accelerating the evaluation of 201 for the treatment of patients with ATPR amlydos who have cardiomyopathy. Currently, the only approved drug for patients with cardiomyopathy is a TTR stabilizer, which slows disease progression but does not address its underlying cause. We believe 20-20 has the potential to treat all forms of the disease since it targets both wild type and mutant PTR genes.

Currently the only approved drug for patients with cardiomyopathy.

GTR stabilizer with slows disease progression, but does not address underlying cogs.

We believe 21 has the potential to treat all forms of the disease since it targets both for wild type and mutant <unk>.

The company is intending to expand the population to include patients with cardiomyopathy.

David Neil Lebowitz: The company intends to expand the population to include patients with chroniciopopoeia. If approved, this expansion accelerates gaining clinical data in patients with cardiomyopathy and expedites our path to registrational trials. We plan to present interim data from all four cohorts of part one, including safety and serum KTR knockdown for cohorts 3 and 4, as well as an early look at durability across all cohorts, in the first quarter of 2022. Additionally, we also expect to initiate part two of the study in the first quarter of 2020.

If approved this expansion accelerates gaming clinical data in patients with cardiomyopathy, and expedite our path to Registrational trial.

We plan to present interim data from all four cohorts of part one including safety and serum <unk> knockdown for cohorts three and four as well as an early look at durability across all cohorts in the first quarter of 2022.

Additionally, we also expect to initiate part two of the study in the first quarter of 2022.

Finally, we were pleased to share that in October 21 was granted orphan drug designation by the FDA for <unk> amyloidosis.

David Neil Lebowitz: Finally, we were pleased to share that in October, 2001, the FDA granted orphaned drug designation by the FDA for ATTR Amolid. Given the modularity of our platform, we have accelerated the development of additional Indevo programs targeting the liver, such as in 2002, and we believe with an increased probability of technical success. 2002, our wholly owned candidate in the development for HAE leverages the same L&T delivery system as 201 but targets the KLKB1 gene to permanently reduce Plasma Calaccharase protein protein protein.

He has been the modularity of our platform, we have accelerated the development of additional in vivo programs targeting the liver such as 20 O two.

And we believe with increased probability of technical success.

When you go to our wholly owned candidate in development for <unk> Leverages. The same LNP delivery system as 'twenty, one targets with <unk> to deliver to permanently reduce.

Plasma <unk> protein.

This approach is intended to provide continuous impression of Calvert current activity as we've demonstrated in our preclinical work, which we anticipate will eliminate HCA attacks.

David Neil Lebowitz: This approach is intended to provide continuous suppression of calicine activity, as we've demonstrated in our preclinical work, which we anticipate will eliminate H.A.E. In October, we received authorization of our clinical trial application from both the UK and New Zealand regulatory authorities to initiate our Phase 1-2 study in 2002. The study will evaluate safety, polarability, and activity, including levels of Calicine lockdown in adults with type 1 or type 2 HAE.

In October we received authorization of our clinical trial application for both the U K and New Zealand regulatory authorities to initiate our phase one two study of 'twenty two.

The study will evaluate safety tolerability and activity.

Including levels of <unk> knockdown in adults with type one or type two petrie.

As previously guided we expect to enroll the first patients by year end.

David Neil Lebowitz: As previously guided, we expect to enroll the first patients by year end. Our lead XVvo program, 5001, a potential best-in-class engineered T cell therapy for AML, leverages our TCR-Based approach. With this approach, we target an intracellular antigen not accessible by CAR-T. 501 in autologous T-cell therapy targets the Wilms tumor 1 intercellular antigen, which is over-expressed in more than 90% of AML patients regardless of mutation sometimes.

Our lead ex vivo program <unk> hundred one a potential best in class engineered T cell therapy for AML Leverages, our TCR based approach.

With this approach we target intracellular antigens not accessible by car Ts.

This tier one an autologous T cell therapy targets, the wilms tumor one intracellular antigen, which is over expressed in more than 90% of AML patients regardless of mutation some time.

Despite recent therapeutic advances delivering improved response rates and subsets of AML long term outcomes continue to be poor with overall five year survival below 30%.

Laura Sepp: Despite recent therapeutic advances delivering improved response rates in subsets of AML, long-term outcomes continue to be poor with overall five-year survival below 30%. Between our proprietary cell engineering process, which Laura will speak to in a moment, and the frequent expression of WT1 on AML cells, we believe 5001 will be a highly active and well-tolerated agent to improve outcomes for patients with AML. In September, we announced that the FDA accepted our I&D application for 50-1.

Between our proprietary cell engineering process, which Laura will speak to in a moment.

And the frequent expression of WT, one on AML cells, we believe fifth tier one will be a highly active and well tolerated agents to improve outcomes for patients with AML.

In September we announced that the FDA accepted our IND application for 50, Oman we.

Laura Sepp: We remain on track to begin screening patients by year end for a phase one, two-way study evaluating 5001 for safety, colorability, cell kinetics, and antitumor activity in doses who have detectable AML after having received standard first-line therapy. I'll now turn over the call to our chief scientific officer, Laroseplerenv, to provide updates on our platform and R&D. Thanks, David.

We remain on track to begin screening patients by year end for our phase one <unk> study evaluating <unk> hundred one for safety Tolerability cell kinetics, and anti tumor activity in adults, who have detectable AML. After having received standard first line therapy.

I'll now turn over the call to our Chief Scientific Officer, Laura Sepp Lorenzi now provide updates on our platform and R&D efforts.

Thanks, David I'll start with some of our recent advances with our in vivo pipeline.

Laura Sepp: I'll start with some of our recent advances with our in-eval pipelines. As John noted, we're excited today to introduce our newest wholly-owned development candidate, NTLA 3001, being developed as a potentially curative treatment for AATD associated lung. NTLA 3001 is designed to insert a functional copy of the Serpene A1 gene, which encodes the alpha 1 protein, with the potential to permanently restore functional protein We believe this could dramatically advance the treatment of alpha-1 deficiency and eliminate the need for suboptimal weekly IV infusions of augmentation therapy or transplant in severe cases. At ESGCT, Intellia presented data showing that the insertion of Serp1 led to normal levels of human alpha-1 protein in non-human primates, which were durable through one year in an ongoing status.

I don't know that we're excited today to introduce our newest wholly owned economy can do they MPLA. Thank you one being developed as a potentially curative treatment for HPV associated language.

NPL a tricky one.

Signs inside a functional copy of the therapy.

A one gene which encodes the protein.

The potential to permanently restore functional protein after a single dose.

We believe this will dramatically advance the treatment of Alpha one deficiency.

The need for us to have optimal weekly IV infusions augmentation therapy or transplant incipient cases.

Is TCP intelligent presented data showing that the assertion.

A one led to normal levels of human Alpha one protein nonhuman primates, which were durable and on volumes.

The company is advancing towards.

Laura Sepp: The company is advancing towards INDNAV activities for NTLA 3001. In addition, in collaboration with Regenoron, we have also just submitted a Sector9 gene insertion development candidate for hemophilia B. With these two new insertion DC nominations, we're continuing to deliver against the ambitious goals we set out at the beginning of the year. Furthermore, we believe our CRISPR-based gene insertion platform represents a potential best in glass modality for permanently restoring high levels of therapeutic protein.

Activities for N DNA, Turkey at one <unk>.

Issue in collaboration with Virginia. We had also just nominated it factor nine gene insertion development candidate push hemophilia B.

With these two new essentially reducing emissions, while continuing to deliver against the ambitious goals, we set out at the beginning of it yet.

We believe our CRISPR based.

That's one represents a potential best in class modality.

We started with high levels of therapeutic protein.

If successful we could revolutionize kidney replacement therapy and open the opportunity to intervene early in the patient's life and cause a host of genetics.

Laura Sepp: If successful, we could revolutionize gene replacement therapy and open the opportunity to intervene early in the patient's life across a host of genetic diseases. Moving on to additional developments at ESGCT, we share important preclinical data featuring the benefits of our N&P-based sequential CRISPR cell engineering platform that avoids the use of elective operations. Commonly used elective operations have several limitations that impair our product development. Beyond the well-recognized cytotoxicity of the procedure, elite cooperation also introduces random DNA breaks contributing to genotoxicity.

Moving on to additional development at GGP, we shared important preclinical data teach them the benefits of our LNP based sequential CRISPR <unk> excellent.

The use of any corporation.

How long do you use any corporation persimmon have mutations that Dan spoke around like development.

There was like a nice tight that the pace of different procedure.

The operation also introduces friendly DNA base contributed to tune up the TCP.

Multiple edits are required.

Laura Sepp: If multiple edits are required, these edits are introduced simultaneously, further contributing to on and off-target transportation and structural bear. In contrast, our proprietary process utilizes LMP-based delivery for highly-ecession sequential editing of cells for ex-bub application. As presented for T-cells, our platform allows session sequential editing, knockouts, and insertions, leading to high yield of its sole product with desired characteristics and functional performance while minimizing the risk of We believe our platform solution will translate to meaningful advantages in terms of safety, cell genetics, persistence, and ultimately efficacy for ex-bivotherapy.

Got it.

Produce simultaneously, Florida completed on an off target towards location.

Sure.

In contrast, our proprietary process utilize it and been based in delivering highly efficient sequentially everything ourselves.

Ex vivo applications.

Presented for T cells, our platform allows efficient sequentially.

No.

Eating into a yield co brand that we desired characteristics and financial performance when we licensed the rights for Ciena toxicity.

We believe our platform solution will translate to meaningful advantages in terms of safety genetics persistence and ultimately efficacy for ex vivo therapies.

Additionally for the first time, we presented data on our allogeneic cell engineering platform that can be deployed for TCR T. I D.

Laura Sepp: Additionally, for the first time, we presented data on our Allogenic cell engineering platform that can be deployed for TCRD and Card D CERX. By utilizing our approach, we're able to address these three immunological requirements for allogenic therapy, not currently addressed by alternative approaches in clinical development. Our allogeneic approach is designed to not only avoid graft versus host disease and graft elimination by host CD8 and CD4 T cells but also to avoid rejection that holds natural killer or NK cells without the need for host immune suppression. Data presented at ESGCT clearly demonstrated diesel performance, including efficient editing rates, robust expansion, persistence against NK Medivated killing in vivo, and no impairment in their tumor killing ability in vitro and in vivo mouse models.

By utilizing our approach we're able to address the study immunological requirements for allogeneic therapy, not currently addressed by I'm sorry, with your approach is in clinical development.

Our allogeneic approach.

Not only avoid graft versus housekeeping and grasp elimination my hope TV 810, CD four T cells.

Also to avoid rejection the coast natural killer or NK cells without the need for host Isabel.

<unk>.

They end up with something that is.

Clearly demonstrated this outperformance, including efficient editing rates robust expansion persistence against.

It can be.

No impairment.

Kidney liability.

Hum.

Models.

Laura Sepp: We look forward to nominating our first allogenic development candidate by the first half of next year. Outside our holding on efforts, our partnering strategy includes enabling pipeline options outside our core areas of focus and accessing novel technology. These strategies have been reflected in our previous announcements to form a new company, along with Blackstone Life Sciences and Felix, focused on developing allogenicic universal cardiac therapies. And more recently, we also announced our collaboration with Sparing Vision, a Genomic Medicine company, to develop novel CRISPR-based treatments for ocular diseases using viral and non-viral delivery strategies. With that, I will hand the call to Glenn, our CFO, who will provide an overview of our third quarter financial results. Thank you, Laura, and good morning.

When we look forward to eliminating our first under generic listen let me do they buy the first half of next year.

I would say our wholly owned efforts our partnering strategy includes 11 tightly option outside our core areas of focus and interesting novel technology.

The strategy is reflected in our previous announcements to form a new company along with Blackstone life Sciences in Phoenix focus on developing allogeneic so got it.

Yeah.

And more recently, we also announced our collaboration with stereo vision.

The 86 company to develop another CRISPR based treatments for ocular diseases using viral bioavailability package.

With that I will hand, the call to Glenn our CFO, who will provide an overview of our third quarter financial results.

Thank you Laura and good morning, and <unk> is in a strong financial position as we aggressively advance and expand our pipeline.

Glenn G. Goddard: Entelia is in a strong financial position as we aggressively advance and expand our pipeline. Our cash, cash equivalence, and marketable securities were approximately $1. $1 billion as of September 30, 2021, compared to $597.97.4 million as of December 31, 2020. The increase was mainly driven by net proceeds of $648.3 million from our July follow-on offering, $45.3 million of net proceeds from the company's ATM agreement, $40.8 million in proceeds from an employee-based stock plan, and $4.2 million from regenerant cost sharing.

Our cash cash equivalents in marketable securities were approximately $1 $1 billion as of September 32021, compared to $597 4 million as of December 31, 2020.

The increase was mainly driven by net proceeds of $648 3 million from our July follow on offering.

$45 $3 million of net proceeds from the Companys ATM agreement.

$48 million in proceeds from an employee based stock plan.

And $4 $2 million from Regeneron cost sharing.

These increases were offset in part by cash used to fund operations of approximately $187 3 million.

Glenn G. Goddard: These increases were offset in part by cash-fund operations of approximately $187. However, our collaboration revenue decreased by $15 million to $7. during the third quarter of 2021, compared to $22.2 million during the third quarter of 2020. The decrease was driven by $15.3 million of revenue recognized for a one-time catch-up adjustment related to the amendment and expansion of our Regenron collaboration in Q2 of last year.

Our collaboration revenue decreased by $15 million to $7 $2 million during the third quarter of 2021 compared to $22 $2 million during the third quarter of 2020.

The decrease was driven by $15 $3 million of revenue recognized for a one time catch up adjustment related to the amendment and expansion of our Regeneron collaboration collaboration in Q2 of last year.

Our R&D expenses increased by $27 million to $60 $5 million during the third quarter of 2021.

Glenn G. Goddard: R&D expenses increased by $20.7 million to $60.5 million during the third quarter of 2021, compared to $39.8 million during the third quarter of 2020. This increase was mainly driven by the advancement of our lead programs and the expansion of the R&D organization to support these programs. Our GNA expenses increased by $8.1 million to $18.3 million in the third quarter of 2021 compared to $10.6 million during the third quarter of 2020. This increase was mainly due to employee-related expenses, including stock-based compensation of $3.

<unk> to $39 $8 million during the third quarter of 2020.

This increase was mainly driven by the advancement of our lead programs.

In the expansion of the R&D organization to support these programs.

Our G&A expenses increased by $8 1 million to $18 $7 million during the third quarter of 2021 compared to $10 6 million during the third quarter of 2020.

This increase was mainly due to employee related expenses, including stock based compensation of $3 8 million.

John M. Leonard: Finally, we expect our current cash balance to fund our operating plans beyond the next 24 months. With that, I will turn the call back over to John for closing remarks. Thank you. In summary, our team and Intelli continues to execute across her pipeline and platform as we move into the fourth quarter and the. I look forward to sharing an interim update from a phase one study at a company-hosted event in Q1 of 2022 with additional details to power.

Finally, we expect our current cash balance to fund our operating plans beyond the next 24 months.

With that I will turn the call back over to John for closing remarks.

Thank you Glenn and summary, our Cayman until it continues to execute across our pipeline and platform as we move into the fourth quarter and beyond.

We look forward to sharing an interim update from our phase one study at a company hosted event in Q1 of 2022 with additional details to follow.

John M. Leonard: In the coming weeks, we plan to initiate our first human studies for NTLA 2002 and NTLA 5001, as well as advance the first insertion candidate in TLA 3001 towards I&D enabling activities. As we approach 2022, we look forward to updating you on new programs as we continue to leverage our industry-leading genome editing platform.

The coming weeks, we plan to initiate our first in human studies French late 'twenty, two and until a 50 on one as well as advance our first insertion candidates until a 31 towards IND, enabling activities.

As we approach 2022, we look forward to updating you on new program since we continue to leverage our industry, leading genome editing platform.

Operator: With that, we'll conclude our prepared remarks. Operator, you may now open the call for questions. We will now begin the question and answer session. To ask a question, you may press any star than one on your touchtone phone. If you are using a speaker phone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Maury Raycroft with Jeffreys.

With that we'll conclude our prepared remarks, operator, you may now open the call for questions.

We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone. If you were using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.

At this time, we will pause momentarily to assemble our roster.

The first question comes from Maury Raycroft with Jefferies. Please go ahead.

Maurice Thomas Raycroft: Hi, good morning everyone. Congratulations on the Quarter, and thanks for taking my questions.

Hi, good morning, everyone. Congrats on the quarter and thanks for taking my questions.

For the plans to accelerate clinical development in their cardiomyopathy patients can you say if you collected cardiac exploratory biomarkers from for many patients that have been done so far and is this change supported by those biomarkers.

Maurice Thomas Raycroft: For the plans to accelerate clinical development in cardiomyopathy patients, can you say if you collected cardiac exploratory biomarkers from many patients that have been

Maurice Thomas Raycroft: for many patients that have been dosed so far, and is this change supported by those biomarkers?

David first of all good morning, Maury Nice to hear your voice, David do you want to touch on that.

David Neil Lebowitz: David, well, first of all, good morning, Maury. Nice to hear your voice. David, do you want to touch on that?

Yes, hi, yes in the current study as you know this is patients who are predominantly the predominant symptoms of polyneuropathy.

David Neil Lebowitz: Yeah, in the current study, as you know, these are patients who have predominantly symptoms of polyneuroptomia, so they don't have, in general, significant signs of cardiomyopathy. Even though that's true, we do know they have some kind of infiltration of their hearts with the amyloid, and we are collecting MRIs, but the time points to look at that are longer than the time points of getting this amendment started for cardiomy So this is really based on our knowledge that reduction of TTR is strongly associated with improvement of symptoms, and that's what we want to see, obviously going forward. I'm also wondering if you can provide more specifics on what protocol changes will be made to include cardiol, and how many patients will you enroll? Can you talk more about

They don't have.

General significant signs of cardiomyopathy, even though that's true we do know they do kind of infiltration.

Their heart with.

With the amyloid and we are collecting mris, but the time points to look at that are longer than the time points with getting.

This amendment started for cardiomyopathy. So this is really based on our knowledge that reduction of GTR is strongly associated with improvement of symptoms and that that's what we want to see.

Obviously going forward.

Okay. It makes sense.

I'm also wondering if you can provide more specifics on what protocol changes will be made to include the cardiomyopathy patients. How many patients will you enrolling can you talk more about the cardiomyopathy profile you aim to enroll I guess, we used to like for a certain anti probably E&P range.

David Neil Lebowitz: the cardiomyopathy profile you aim to enroll. I guess you will select for a certain NP Pro B&P range.

David Neil Lebowitz: Mori will lay that out. Go ahead, David. Let's keep going. Sorry. Yeah, no, you're right, yeah. Now, we're not going to talk about the details right now, but we have said we do expect, based on biology, that the dosing will be the same in these patients. As you know, we've had a very good safety profile so far, so we also expect that to go well in the patient's cardiomyopathy, but the details of that will be coming out later. And thanks, John.

Laura give any of that out.

Go ahead David.

Yeah, you're right Yeah, no we're not going to talk about the details right now, but we have said we do expect.

Based on the biology that the dosing will be the same in these patients as you know we've had a very good safety profile. So far. So we also expect that to go well and the patients with cardiomyopathy, but the details of that will be coming out later thanks John.

Okay. Okay. Thanks for taking my questions I'll hop back in the queue.

Maurice Thomas Raycroft: Okay, thanks for taking my questions off.

Joon So Lee: Thanks for taking my question. The next question comes from June Lee with Truist Securities. Please go ahead. Hi, thanks for taking that question and congrats on all the progress. Regarding your dosing for the ATP program, does the fact that you're dosing down for cohort 1 imply that you have already achieved 90 to 95%?

The next question comes from Joon Lee with Truest Securities.

Please go ahead.

Hi, Thanks for taking the question and congrats on all the progress.

Regarding your dosing for the <unk> program does the fact that Youre dosing down for cohort four imply that you have already achieved 90% to 95% ETR knockdown as you had hoped.

Joon So Lee: and TPR Knockdown, as you had hoped in Core 3. Can you share anything about durability?

In cohort three.

Joon So Lee: from cohort 2 so far, and any plans to re-do those cohort 1 patients.

Joon So Lee: cohort One page.

John M. Leonard: I would wait until we share the full complement of information in Q1, as we said. I think then you'll get a chance to see exactly what we're looking at, and you'll see why we're excited. And, you know, I just want to remind you that the purpose of the study has been to explore the dose response curve, which we think just addresses good quality drug development, knowing, you know, the safety and efficacy profile with each respective dose, so that as we move forward, we can feel confident about how the drug is likely to perform in the set of patients, et cetera. With respect to redoing, I think we'll talk more about that as we go forward.

John M. Leonard: But as we said from the outset, once we establish what we consider to be the optimal biological dose, we'll make that available for patients who did not receive it. Just a quick question on 2301 for AAP: you know, where are you targeting for the insertion of the wall type gene? Is that the endogenous Trapunae 1 locus to achieve the dual purpose of knocking out a knockout, or are you targeting a different region? I'm just curious because you mentioned it as sequential editing, but it seems like you can't.

At 230 O 148 P. You know where are you where are you targeting for the insertion of the wall Tech Jean is that the endogenous or play one locus to cheap the dual purpose of not getting knocked out or are you targeting a different major and I'm. Just curious because you mentioned it as a sequential editing, but it seems like you can achieve that with the sink was shot.

John M. Leonard: It seems like you can achieve that with a single shot with the approach, just if you can provide an additional call.

Approach just if you can.

Laura Sepp: providing this beneficial color. Thank you. When we turn to Laura, Laura, you want to give us a little more detail in terms of what the gene you're targeting, and what the gene insertion is. Sure, so for 31, we are inserting it into the album in the local following the same, you know, platform approach that we're taking for Factor 9, the other development candidate that has recently been nominated.

Providing expenditure Nicole.

When we turned to Laura Laura you Wanna, just a little more detail in terms of what the gene you're targeting with the gene in surfing.

Sure Yeah. It's at 431, we R E N D. I've been following the same platform approach that we're taking perfecto nine you know the other developing gundy laid that has recently when I'm needed. So you know we we have for both programs trying to demonstrate and then you know with this approach we can achieve Nora.

Laura Sepp: So, you know, we have, for both programs, right, demonstrated that, you know, with this approach, we can achieve, you know, normal levels of both proteins and the ability to, you know, carefully select doses that will allow us to achieve that in the patient. Thank you. The next question comes from Mani Suruhar with SVB Lyrink. Please go ahead. Hey, good morning. This is Rick on the line for Moni.

<unk>, so both produce and the ability to carefully select those decide whether or not what sides with that information.

Alright, thank you.

The next question come from money <unk> with Us V. B link. Please go ahead.

Rick Stephen Bienkowski: Congratulations on all the progress. Just two quick questions from us. So first, could you maybe expand on the follow-up data we'll see for the earlier cohorts of the 20-01 patients in the interim readout, and I do understand that durability implies you'll be looking at certain TTR levels. But if you could just expand on what other metrics will be evaluated here to get a read on longer-term safety and durability, that would be helpful.

Hi, good morning, or this is Rick on the line for money Oh, Congrats on all the progress just two quick questions from us.

So first could you maybe expand on the follow up data will see for the earlier cohorts of the 20th one patients in the interim right out.

And I I do understand that better ability implies you'll be looking at certain PTR levels.

But if you could just expand on what other metrics will be evaluated here to get a read on longer term safety and durability that would be helpful.

And second how should we think about the pace of the dose escalation for their cardiomyopathy cohort do you anticipate that you could potentially start on one of the mid doses evaluated in polyneuropathy for well before full dose escalation needs to be repeated here.

Rick Stephen Bienkowski: And second, how should we think about the pace of the dose escalation for the cardiomyopathy cohort? Do you anticipate that you could potentially start at one of the mid doses evaluated in polyneuropathy, or will the full dose escalation need to be repeated here? David, do you want to address each question individually? Yeah, so the main readout, and the longer term readout are two things. Of course, we want to look carefully at safety, and that's part of what's built into the trial.

David do you Wanna interest for each question.

Yeah, Hi, so that the the main read out the longer term read out or two cents of course, we want to look carefully at the safety.

And and that that's part of built into the trial, but the the main read out in terms of activity will be the T. T. R levels and that's what we'll learn and if you'd seen that is correlated with the benefit where you expect to see patients.

David Neil Lebowitz: But the main readout in terms of activity will be the TTR.R, and that's what we'll learn. And if you see that it is correlated with the benefit we expect to see in patients. For the patients with the second question was about, dose escalation? No, we do think we can use the information we've learned in the patients with polyneuropathy to modify the doses that we study in patients with cardiomyopathy. All right, great. That's it for months.

For the patients with the second question was about.

Oh, how 'bout dose escalation, though we do think we can use the information we've learned from the patient polyneuropathy.

To modify the the the.

Doses that we study impatience with cardiomyopathy.

Alright, great that's it from us thanks for taking our questions.

Rick Stephen Bienkowski: Thanks for taking our questions. Thank you. The next question comes from Salveen Richter with Goldman Sachs. Please go ahead. Hey, good morning. This is Matt On for Salveen.

Thank you.

The next question comes from solving Richter with Goldman Sachs. Please go ahead.

A good morning. This is Matt on for solving congrats on the quarter.

Matt On: Congratulations on the quarter. Just a couple questions. Could you remind us what the expectations are for the additional ATTR data? And then separately, could you also share your thoughts on the translocation risk observed recently for a gene editing company and the differentiation of Intelliase. Thank you.

Just a couple of questions could you remind us what the expectations are for the additional a T. T. R data and then separately could you also share your thoughts on translocation risk observe recently for a <unk> company.

And the differentiation I've been telling you it's approach thank you.

Matt On: So why don't we start with Laura? Do you want to speak about how we think about translocations and how we avoid them with our approach? And then we can turn to the other question. David, that'll go to you.

So why don't we start with Laura do you want to speak about how we think about transportation and how we avoid them with our approached and then we can turn to the other question David.

Go to Ya.

Laura Sepp: Yeah, and thank you very much for the question. So, you know, I tell you whether the programs are in vivo or ex-bibo, the approach for safety starts at the beginning, selecting a guide of anise that will not have any detectable, validated off targets at multiples of the intended pharmacological doctors. So that's a given, and that's what we apply throughout all of our programs. I think that the recent data you're referring to for Ex-Bivo, right?

Yeah, and and thank you much for the question. So I can tell you whether the programs are illegal or <unk>. The you know the approach for safety starts at the beginning it's like the guy that Rene that will not have any detectable validated off targets at multiples of being done the pharmacological doubts.

So that's in David and that's what they apply throw out all of our apartments I think that the recent date that you're referring to four X Belvoir Friday, so that he said and number of differences that differentiates with one of the line from that program.

Laura Sepp: So there are a number of differences that differentiate what we're doing from that program, starting with, you know, careful selection of the guide molecule for Nays, the mode of introducing the CRISPR machinery in our case. We have a proprietary method that we describe at ESGCT, looking at sequential editing, using an LMP-based method, and that minimizes any potential for translocations or other structural variants. This is different from what others are using, where they're using multiplex, all at once, using electroporation, you know, just by having multiple editing events at once, that leads to translocations.

Starting with you know careful connection with a diet of amazed D mode of introducing the customer machinery in our case, we had it proprietary method that we describe E. S. T D. Looking at sequential anything using my LNP base method and that.

<unk>.

Any potential for translocation to added a structural there Ya D.

D. C is different from what others are you seeing whether they're using multiplex ordered ones using electroporation you know just.

Just by having multiple anything events at once you know that leads to translocations and an additional side before we can see electra operation that by itself even in the absence of Jean anything machinery with your style in the crisper lead to significant that was from breaks that they run them I don't.

Laura Sepp: And in addition to that, if you're using electroporation, that by itself, even in the absence of gene editing machinery, whether it's Stalin or CRISPR, leads to significant, that was tram breaks that are random. And all that can contribute to, you know, structural variance and translocations that we are avoiding. David, do you want to take the first question?

<unk> can contribute to you know to stretch on the variance I'm translocations that we are appointing.

David you wanted to take the first question.

David Neil Lebowitz: Yeah, thank you. So, what we've said is that we now have patients treated at both 1 milligram per kilogram and 0.7 milligrams per kilogram. So with this next release, we'll be able to talk to you about the whole range of dose escalation, as well as follow-up on the patients. And certainly, just to get early follow-up on the higher doses, we'll be able to do that in a couple of months.

Yeah I too. So we we're we've said is that we've now have patients treated at both one milligram per kilogram add 0.7 milligrams per kilogram. So with this next release will be able to talk to you about uhm.

The the the whole range of a dose escalation as well as the follow up on the patients certainly.

Just to get early follow up on the on the higher doses.

Do that a couple of months.

Uhm that will also allow us to talk about the dose of part two which will be starting in the first quarter. So you'll get a really pretty complete picture of where we are with this study.

David Neil Lebowitz: That will also allow us to talk about the dose of part two, which will start in the first quarter. So you'll get a really pretty complete picture of where we are with the study. Great. Thank you very much. The next question comes from Gina Wong with Barclays. Hi, this is Sheldon, on behalf of Gina.

Yeah.

Great. Thank you very much.

The next question comes from <unk>, what Barclays. Please go ahead.

Hi, This is Sheldon all 14, thanks for taking my question, maybe two one of 2001 and one on 2002 for the P. P. T. R program your toes down from one milligram per kilogram 2.7 could you elaborate more whether that was driven primer.

Sheldon: Thanks for taking our question. Maybe to one on 2001 and one on 2002. For the ATDR program, you dose down from one milligram per kilogram to.7. Could they elaborate more on whether that was driven primarily by efficacy or by safety? And the HAA question is on, For the patient characteristics at baseline, do you have any criteria on their background attack rates? Do you need to maybe implement a running phase to collect those data or use patients' reports? So let's ask the question. So let me start with 2001.

Already by efficacy or by safety reasons.

<unk>.

M. A J U a question is.

For the patient characteristics at baseline do you have any criteria aren't there background attack right and do you need to maybe implements of onion phase to collect those data or.

Hi, all patients Ah reporting.

Thanks. So thanks for the question. So let me show it she doesn't Wanna, David just Gonna address 2002.

John M. Leonard: David's going to address 2002. The way we think about the study is, from the outset, it's been about establishing the relationship of dose and response. And response, obviously, is characterized by efficacy, which for the purposes of where we are in the program, is primarily measured by TTR reductions. And, as I think was clear from the data that we presented back in June, we were already at the second dose achieving pretty substantial reductions in TTR.

The way, we think about the study is from the outside it's been about establishing the relationship of dose and response in response, obviously is characterized by.

I forget she which for the purposes of where we are in the program is primarily measured by T. T R reductions.

And as I think was clear from the data that we presented back in June we were already at the second those cheating pretty substantial reductions in P. T R.

John M. Leonard: So we sought to further characterize higher doses just to make sure we had a good understanding of how the drug would perform and get some notion of what additional TTR knockdown there is to get. So we've done that work.

So we sought to further characterize higher doses just to make sure. We had a good understanding of how the drug would perform and get some notion of what additional T. T. R. Knockdown, there's to get so we've done that work, we continue to now and purple late.

John M. Leonard: We continue to now interpolate with cohort four, and we think we've, you know, as we said, we think we're closing in on what we're going to want to do going forward. So the drug is being performed in ways that we've been really very, very, very gratified by in terms of not only the efficacy, again, as determined by TTR, but also the safety process. And so this is the time to get that relationship right because it lays the foundation for all subsequent studies going on from where we are.

With cohort for and we think we've you know as as we said we think we're closing in on what we're Gonna Wanna do going forward. So the drug is performed in ways that we've been really very very very gratified by in terms of not only the efficacy again is determined by T. T R. But also by the safety profile.

So this is the time to get that relationship right because it lays the foundation for all subsequent studies going on now from where we are so you'll see in February exactly what we're looking at then you'll understand what <unk> what were shooting for as we continue to admit.

John M. Leonard: So you'll see in February exactly what we're looking at, and you'll understand what we're shooting for as we continue to advance the program. I'd hasten to add that a goal would be to do this in February, but we can't guide at this point to say, David, do you want to speak to H. Yeah, thanks. So we'll start to see the details of the H.A.E. study on WhenTrials.gov. I think it may not quite be out very soon. But the most important baseline characteristics are, as you mentioned, the attack rate. This will be, you know, obviously collected as we patients enter into the trial. And the other piece is the calicrine level.

The program.

Hates mad that a goal would be to do this is February but we can't guide at this point any specific point in time.

David do you want to speak to a H a.

Yeah. Thanks, So let's start you'll you'll start to see the details of the H a study on when trials Dot Gov I cause it may not quite be out very soon but the most important baseline characteristics are as as you mentioned the the attack rate. This will be this will be fault you know obviously collected as we.

Patients enter into the trial and the other pieces Keller crime level. So you both have a biomarker in this case and Ah clinical effect that you can follow giving us now you've been a bit more than what we have with a T. T. R. In a way so that that's the plan.

David Neil Lebowitz: So you both have a biomarker in this case and a clinical effect that you can follow, giving up even a bit more than what we have with TTR in a way. So that's the plan. Maybe just a quick follow-up. So for the 5,002 trial, would you also report any reduction in attack rates when you present the data? Yeah, you know, obviously we will be following the attack rate after treatment as well.

Maybe just a quick follow up so for the <unk> to the trial or what are you also a report any reduction in a tech rates when you present the data.

Yeah, you know obviously, we will be following the attack right after treatment as well. So you know whether that will be you know, it's not it's not really a prime and what are the primary endpoints, but yeah. We'll.

David Neil Lebowitz: So, you know, whether that will be, you know, it's not really a prime, you know, one of the primary end points, but, yeah, we'll be collecting it would be, yeah, I characterize it as descriptive more than anything else. You know, at these early stages, Sheldon, it's hard to get, you know, the precision of the measurements that we'd be looking for that you get across a larger population

Will be collecting it would be yeah, I I characterized as descriptive more than anything else you know at these early stages Sheldon it's hard to get you know the precision of the measurements that we'd be looking for that you'll get across the larger population, but of course will will be looking at that but it's not a major determinant of.

Sheldon: But, of course, we'll be looking at that, but it's not a major determinant of the study. That's very helpful. Thank you so much.

Of the study.

That's very helpful. Thank you so much.

The next question comes from <unk>, you see with our B C. Please go ahead.

Buka EC: The next question comes from Buka EC with RBC. Please go ahead. So great, thanks so much for taking my question.

Oh, great. Thanks, so much for taking my question and congrats on on the progress I have two one or T. T argue I wanted hemophilia b. So in D. T. R. Wondering if <unk>. If you have shared the data with the F. D. A yet again wondering if you can comment on what is gaining to file a 90 day U S. And then maybe for hemophilia be honestly a few companies are right in the space security care is going.

Buka EC: Congratulations on the progress. I have two, one on TTR and the other one on Hemophilia B. So in TTR, wondering if you have shared the data with the FDA yet, again, wondering if you can comment on what is gating to file a NID in the U.S. And then maybe for Humophilia B, obviously, a few companies are right in the space. I think Unicure is going to file next year, Pfizer's in Phase 3, Freeline also as a clinic. Can you just remind us of the key differentiating factors of your approach versus others?

File next to your Pfizer's a phase three free line also has a clinic can you just remind us what are the key differentiating factors of your approach versus others. Thanks, So much.

John M. Leonard: Thanks. So with respect to regulatory interactions, that's something that we don't want to characterize at this point in time. And as we have a more complete picture, we'll share that when we think it's pertinent. With respect to hemophilia, and more broadly, I would say with respect to gene insertion, which we relate to gene therapy.

So with respect to regulatory interactions that's something that we don't want to characterize at this point in time and as we have a more complete picture will sure that when we think it's a curtain pregnant uhm with respect to hemophilia beep and more broadly I would say with respect to cheat insertion.

Which we relate to gene therapy, we think that there's some very significant advantages to the approach that we're advancing here. So [noise] step back and remember which in therapy is typically what you're trying to do is deliver a transgene often in the form of a virus.

John M. Leonard: We think that there are some very significant advantages to the approach that we're advancing here. So step back and remember what gene therapy is. Typically, what you're trying to do is deliver a trans gene, often in the form of a virus, which persists in a cell for some period of time as an epiome. In dividing cells, that can be lost, and it can be lost even in non-dividing cells.

Which persists Michelle for some period of time as an episode.

In dividing cells that can be lost and it can be lost even non-biting. So so the durability of that effect it seems and seems to be corroborated by some clinical data that's been emerging.

John M. Leonard: So the durability of that effect, it seems, and seems to be corroborated by some clinical data that's been emerging, is incomplete. It doesn't appear to be lifelong. So when we think about the advantage that we can bring, particularly for diseases like hemophilia, which manifests in childhood, a permanent insertion that one hopes normalizes or very, very significantly improves on existing therapy that a child can grow up with represents a very significant advantage, we think, over, you know, the epistemal approach that just is not ideally suited for that patient population. And as we know, in hemophilia, a lot of the damage occurs in youngsters, and that is lifelong.

Is incomplete I mean, it doesn't appear to be lifelong so when we think about the advantage that we can bring particularly this disease like hemophilia, which manifests in childhood.

A permanent insertion that one hopes normalizes or very very significantly improves on existing therapy that a child can grow up with represents a very significant advantage. We think over you know.

Some will approach that just does not ideally suited for that patient population and as we know and hemophilia a lot of the damage occurs and youngsters and noticed lifelong so we're excited about having that kind of an outcome and that's the in game for a program like this.

John M. Leonard: So, we're excited about having that kind of outcome, and that's the end game for a program like this. And, again, we're starting in the early stages here, but that's the, the best. Got it. Super helpful. Thanks, John. The next question comes from Lisa Beko with Evercore ISI. Please go ahead.

And again, we're starting in the in the early stages here, but that's the destination.

Got it Super helpful. Thanks, John.

Sure.

The next question comes from Lissa Peco with Evercore ISI.

Please go ahead.

[noise] hi, there. Thanks for taking my question. It just based on some follow up work, we've done with K O L. As in such I wanted to get a sense of how you're thinking about the level of T. T. R. Knockdown that you're trying to achieve I know you're exploring different doses, though.

Lisa A. Walter: Hi there, thanks for taking the question. Just based on some follow-up work we've done with KOLs and such, I wanted to get a sense of how you think about the level of TTR knockdown that you're trying to achieve. I know you're exploring different doses, so it's kind of a relevant question here. You know, some of the feedback has been that obviously, you know, there's a function for wild-type TTR that may be important over the longer term and sort of the balance between knocking it down and keeping some, you know, potential wild-type TTR available.

Kind of a relevant question here you know some of the feedback has been that obviously you know there's a function for awhile type T. T. R that may be important over the longer term and sort of the balance between knocking it down and and and keeping some you know potential awhile type of T. T are available uhm. So maybe you could comment on that how you were thinking about it. Thank you.

Lisa A. Walter: So maybe you could comment on that how you're thinking about it. Thank you. Sure. This is something we've thought about from the outset. And, as you might imagine, we look carefully across other programs to see if there are any insights that we can gain from, you know, data that they collect over time.

Sure. This is something we thought about from the outset and as you might imagine we look carefully across other programs to see if there's any insights. So we can gain from data.

Data that they collect over time and to our knowledge us far there's been no reports anywhere of any kind that relate to knocked down a T. T. R. I.

John M. Leonard: And to our knowledge, thus far, there's been no reports anywhere of any kind that relate to the knockdown of TTR. I remind you that no one, including us, has knocked TTR to zero. We don't think that's even possible because some TTRs are produced outside the liver. And, you know, as we watch space and as we understand more and more about how DTR functions, it's our belief that that risk, if it even is real, is remote at best.

I remind you that no one including us as knockdown T. T. R. Two zero, we don't think that's even possible because some T T r's produced outside the liver.

And you know as as we watched the space and as we understand more and more about how P. T. R functions, it's our belief that that risk if it even Israel is this remote at best.

John M. Leonard: By the way, you know, the primary function of the protein is to carry vitamin A, and as we know, these patients are all supplemented with vitamin A, proceed, and I think at this point, with each passing month across the field broadly, we are getting more and more confident that that risk is really remittable.

By the way, we you know the primary function of the proteins to carry vitamin a and as we know these patients are all supplemented with vitamin E. As we proceed in.

I think at this point with each passing month across the field broadly, we get more and more confident that that risk is really remote.

Okay. Thank you.

Lisa A. Walter: Okay, okay, thank you.

Sure.

Yanan Zhu: The next question comes from Yan'u at Wells Fargo. Please go ahead.

The next question comes from you on on you with Wells Fargo. Please go ahead.

John M. Leonard: Hi, thanks for taking my questions and congrats on the progress. So first question, it sounds like you have further accelerated the cardiomyopsy program. I know you have always planned to move quickly on that program, but it seems like the schedule has been further moved up. I'm wondering if any information that you saw in the, uh, Polyneuropsy study has informed this acceleration, and also related to the question of whether TTR reduction will cause any difference in cardiomyopsy patients compared with polyneuropsy patients. Thanks.

Hi, Thanks for taking my questions and congrats on the progress. So far first question. It sounds it sounds like you have a further accelerated cardio.

Myopathy program I know that you have always planned to move quickly on that program, but it seems like the the schedule has been further moved up wondering if you have and whether any information that you saw in the.

Pardon your option neurotic study has informed this acceleration at.

And also related to the the the question is that is whether T. T. R reduction could you expect any difference Ah in Ah cardiomyopathy patients comparatively party neuropathy patient. Thanks.

Well the second question bears on the first try because we believe that there's no reason why for at a purely biological point of view White cardiomyopathy patient should have a different T. T. R response, given the data that we presented back in June that made us very enthusiastic about.

John M. Leonard: Well, the second question bears on the first, right? Because we believe that there's no reason why, at a purely biological point of view, why cardiomyopathy patients should have a different TTR response. Given the data that we presented back in June, that made us very enthusiastic about moving forward more quickly with the cardiomyopathy program. So David and his team has looked at, alternative ways to do that and you know the range of choices there go from starting a new study and all of the you know administrative efforts that go with that or looking to bring patients directly into the study that's ongoing and we chose the latter for the reasons that you stated we believe that that's a way of getting to the data faster and building on the information that we already have and we one hopes sets us up for that next really important phase of studies, which will be, you know, larger studies that hopefully will move us in the direction, getting the drug approved.

Moving forward more quickly with the cardiomyopathy program, so David and his team's looked at.

Alternative ways to do that and you know the the range of choices there you know.

Go from starting a new study and all of the.

You know administrative efforts that go with that four looking to bring patients directly into the study that's ongoing and we chose the latter for the reasons that you stated we believe that that's the way of getting to the data faster and building on that the information that we already have and one hopes such a sub for.

For the next really important phase of studies, which will be you know larger studies that hopefully will moves in the direction getting the drug approved.

Oh, great Ah, maybe Ah two additional questions.

John M. Leonard: Great. I have two additional questions, if I may. One on the translocation for ex-vivo therapy side, how much reduction do you think the sequential editing approach can bring, and how much reduction do you think the LMP approach brings to reducing translocation? And the other question is about hemophilia programs. Wondering if you have evaluated hemophilia. A, the uran regenerant, have evaluated hemophilia A, and what's the reason to move with hemophilia B at the first, you know, currently? Thanks.

<unk>, if I may one on the translocation for acts of evil therapy side, how much reduction do you think the sequential editing approach can bring and how much reduction do you think the L. M. T approach Ah brings to reducing translocation and.

Other questions on the hemophilia programs I'm wondering if you have evaluated hemophilia, a urinary regeneron have evaluated hemophilia a and it.

What's the reason to move with haemophilia it'd be Ah Ah Ah Ah Ah Ah Ah Ah currently X.

Laura Sepp: Yeah, so let me do the second one first. With Regeneron, we're working on both hemophilia A and B. You will have seen data that we present for hemophilia B for some time now, and that program, you know, got the jump, I would say, on some of the other work that we're doing, although they're highly related. So we're not giving data and timelines yet for hemophilia A, but rest assured, That's something of great interest to us.

Yeah. So let me do the second one first with Regeneron, we're working on both hemophilia a N D. You will have seen data that we present for hemophilia b for some time now in that program.

Yeah got the jump I would say on some of the other work that we're doing below their highly related so we're not giving date and time lines yet for hemophilia, a but rest assured that something of great interest to us and obviously hemophilia b sets us up to for some foundational work that I should.

Laura Sepp: And obviously, hemophilia-B sets us up for some foundational work that should apply to that program. With respect to the proprietary approach to transducing cells, I'm going to let Laura speak to any quantitative aspects that one or the other elements of the approach can take. But I would just start by saying that what we did and what we tried to do with all the work we did is just go back to basic principles and ask what's doing what instead of making assumptions on, you know, what represents the standard approach at any given point in time.

Applied to that program with respect to the proprietary approach to.

Branch Duesing cells, I'm Gonna, let Laura speak to any quantitative aspects that one or the other elements of the approach can take but I would just start by saying that what we did and what we tried to do with all the work that you do is just go back to basic principles and ask what's doing what instead of.

Making assumptions on you know what represents the standard approach in any given point in time.

And Laura and her team I think it's just on a really nice job of going back to those basics and dissect thing what what many people accept [laughter] from the outset with respect to translocations irrespective of whatever editing technique, they're they're trying to break and like being <unk>.

John M. Leonard: And Laura and her team, I think they've just done a really nice job of going back to those basics and dissecting what many people accept from the outset with respect to translocations, irrespective of whatever editing technique they're trying to and, by being open-minded and, I think, pretty creative, they made what we believe are very, very substantial improvements on what is the standard approach in the field that pretty much is used across all of the approaches that Now, Laura, maybe you can add a little more color on how much of it is just L&P and kind or gentler, you know, then electroporation versus sequential. Why don't you take a shot?

Open minded and I think pretty creative that made but we believe are very very substantial improvements on you know what is the standard approach in the field that pretty much just used across all of the approaches that we're familiar with now Laura maybe you can add a little more color. If you think it with respect translocations how much of it.

Just yelling P and kind of Chandler you know then electroporation versus sequential.

Once you take a shot at that.

Laura Sepp: Yeah, you know, we have shared actual data most recently at ESGCT that we will be happy to, you know, share with you if you don't have access to it, really comparing electric operation versus our sequential methods and, you know, versus untreated cells, and we minimize any translocations on target, on target translocations, you know, significantly. You know, the data we share, it's. you know, one log lower as compared to electrooperation, and it's basically distinguishable from and editable by itself. Happy to discuss that more offline.

Yeah, No and you know, we have chair and let's face with a yes, Jessica until date that would you be happy to share. It with you. If you don't have access to and you know really comparing electric creation versus Taiwan sequential methods and you know versus and trade. It has and we need the ninth at.

[noise] transplantation on tied to get tired of it sounds like.

You know significantly even today that was sure <unk> you know one log nowhere as compared to elect operation and basically indistinguishable from and it it sounds happy to to discuss add more Oh fine.

Yanan Zhu: Great, great, very helpful. Thank you.

Great very helpful. Thank you.

Degon Ha: The next question comes from Degon Ha of people. Please go ahead. Great, good morning. Thanks for taking our questions and congratulations from me as well on all the progress. I guess just delving into 2001 for the first part of the question and then circling back on the hemophilia plans. So with regard to 2001, the two words I've heard repeatedly from your team have been between depth and consistency. So to what degree?

The next question comes from Dagon Hall.

People. Please go ahead.

Great. Good morning, Thanks for taking our questions and congrats from me as well and all the progress I guess just delving into 2001 for the first part of the question and then circling back on hemophilia plans. So with regards to 2001. The two words I've heard repeatedly from your team has been between depth.

And consistency so to what degree is your decision to pursue cohort for the 0.7, Meg reflective of depth or consistency and I guess, if we think about the timeline and one Q with both part one update as well as initiation of part two I guess, what additional information are you hoping to derive from cohort for but.

Degon Ha: your decision to pursue cohort for the.7MIG is reflective of depth or consistency. And I guess if we think about the timeline in one queue with both Part 1 update as well as initiation.

Degon Ha: of part two, I guess, what additional information are you hoping to derive from the cohort?

Degon Ha: for before making that decision into part two. And then, with regard to hemophilia, recognizing that Regeneron and you guys are both juggling hemibalal.

For making that decision into part two and then with regards to hemophilia recognizing regeneron and you guys are both juggling him B and he may but just wanted to get your thought around is this reflective of maybe the underlying biology of the endothelial expression versus hepatocytes expression and how that might be.

Degon Ha: He may, but just wanted to get your thoughts around, is this reflective of maybe the underlying biology of the endothelial expression versus hepatocyte expression and how that might be perhaps interfering with long-term durability? Thanks so much.

Perhaps interfering with long term durability. Thanks, so much.

[noise] with respect to 2001 those words, obviously apply as we look at the data to the extent that determines what we do is something that will share more when we present a more complete data set here in the first quarter and you can see exactly what we're looking at and why we make the decision sweet.

John M. Leonard: With respect to 2001, those words obviously apply as we look at the data, but to the extent that it determines what we do is something that we'll share more when we present a more complete data set here in the first quarter. You can see exactly what we're looking at and why we make the decisions we make. I don't, Laura, if you want to speak to the hemophilia question in terms of where the gene is expressed and why he may be versus why he may go for it. Yeah, and that's what you're bringing it up for, right?

We make.

Laura if you want to speak to the hemophilia question in terms of you know.

Where the cheese expressed an why him.

Lightning be verses he may go for it.

Yeah, no no and and what they're bringing up 40 name a tele <unk> Hunter 80, <unk> six fancy any of the towns.

Laura Sepp: So it's, you know, the factor rate is, you know, it's a larger dream, it's expressing endophilia cells, it's, you know, and it has been associated with, you know, stress, right? When, you know, when you force expression into the liver, I think that, you know, one of the differences, and I should, you know, make sure that, you know, regenerates the program lead So I would, you know, point out that, you know, you should be asking for... additional color on this.

I need has been agitated with me and it's transferred <unk> you know what.

<unk> expression in the living room, I think that you know wonder if they they've been Tuesday night should you know make sure that you know regenerate B program need here. So I would you know you know plain that you know you shouldn't be asking and then additional color in this.

Laura Sepp: But one of the benefits of our approach is that we're aiming to introduce a copy of the gene into the chromosome, right, in the genome stably, and we don't need to have overexpression or over-delivery of multiple epistemal copies that would lead to inappropriate, abrogated expression that could lead to toxicity. So I think that's a difference from traditional AAB gene therapy that we're trying to exploit here.

But for one of the benefits of our approach you said, we're aiming to interviews you know a copy of the G.

<unk> chromosome I'm, writing E. G M. A stately and we don't need to have over expression or over the library multiple it'd be someone come from eight a copy afraid that would lead to inappropriate aggravated expression that could lead to <unk>.

I think that's a difference from traditional a E. G. B that'd work dreamed explained here and then your other question was why hemophilia be first I think again, you know I I would put that question to Virginia and both programs you know they are leaving Burger Bergen says you know with us.

Laura Sepp: And then your other question was why hemophilia should be first. I think, again, you know, I would point that question out to regenerate both programs; they are leading both programs as, you know, with us, and there is progress being made for both.

<unk> and <unk> provinces make for about.

Degon Ha: Great. Appreciate the caller. Thanks for taking the question.

Great I appreciate the color. Thanks for taking my question.

Seathouse: The next question comes from Seathouse with Raymond James. Please go ahead. Yes, hi, this is Timor Ivanov on behalf of Steve Seedhaus.

The next question comes from Steve Street House with Raymond James. Please go ahead.

Yes, Hi, this is tomorrow vodicka on for Steve Seedhouse.

Yeah. So this question was sort of ask but just to clarify further in terms of the data and Q1 22 I'm not sure I saw a description of functional end points. It should be disclosed and they are listed a day 168, and day 365, which seemed to be achievable for patience and cohorts wanted to so can you just talk about.

Timor Revance: And so this question was sort of asked, but just to clarify further, in terms of the data in Q122, I'm not sure I saw a description of functional endpoints to be disclosed, and they are listed at Day 168 and Day 365, which seem to be achievable for patients in cohorts 1 and 2. So can you just talk about why the functional endpoints would or would not be available, especially with respect to the MNIS plus 7 endpoint? Thank you. David, do you want to speak to him about that? Yeah, no, thank you.

Why the functional end points would or would not be available, especially with respect to M. S plus seven important.

Yep.

David do you want to speak to that.

Yeah.

Thank you.

So I just couldn't imagine right there may be data for cohort, one and maybe even cohort too but of course cohort one got it adequate those.

David Neil Lebowitz: So, as you can imagine, you're right, it may be data for cohort one and maybe even cohort two, but of course, cohort one got an inadequate dose. They just haven't had enough of a reduction in TTR to be interesting for those endpoints. And really, where we, you know, the most important range, you think, would be from 0.3 to 1.0, where we do think that TTI is very important. It's been talked about a couple of times about the depth of TTIP.

No. They don't have enough a reduction in C. P R to be interesting for those that point.

And really where we are the most important range I think would be uhm from three to two 1.0, where we do think the P. T is very important it's been talked about a couple of times about the depth with two T. R reduction what we saw at three with 87% reduction. So this is already.

David Neil Lebowitz: reduction. What we saw at 0.3 was an 87% reduction, so this is already greater than the 80% average when being with a standard of care. And if you think about that, what it also said is every patient at 80 or greater percent, while half the patients getting the standard of care have a lesser degree of TTR. So we think that's what's going to make the big difference for this drug; by getting to consistent speed reduction, we think we can be able to benefit patients. Okay, thank you very much. The next question comes from Jay Olsen of Oppenheimer.

Greater than the 80 per cent average of thing with the standard of care and if you think about that but it also said as every patient at 80 or greater percent, while half the patients getting standard of care have a lesser degree of P. T. R. So I think that's what's gonna make a big difference for this drug my savings are consistent reproduction.

Okay sure.

Okay. Thank you very much.

The next question comes from K Olson of Oppenheimer. Please go ahead.

Jay Olson: Please go ahead. Oh, congrats on the progress and thank you for taking the question. Can you talk about how the excitement surrounding the initial clinical data for 201 may have influenced the pace of enrollment at existing clinical sites? And then if you plan any geographic expansion into additional study sites, David, I'll invite you to respond to that. Go for it. Yeah, you've got the positive.

[noise], Oh, hey, congrats on the progress and thank you for taking the questions could you talk about how the excitement surrounding the initial clinical data for 20 O. One man's influence the pace of enrollment at existing clinical sites and then if you plan any geographic expansion into additional study sites.

David [laughter], Oh, and thank you to respond to that that got four guys that deposit there. Thank you for that question. We have noticed an extraordinary interest coming from the investigators as well as patients calling into those investigators. So it's been very very helpful. This study and in fact, we don't.

David Neil Lebowitz: Thank you for that question. Yeah, no, there's been extraordinary interest coming from the investigators as well as patients, you know, pulling into those investigators. So it's been very helpful to study. And in fact, we don't need additional sites based on what's been happening at the sites already.

Needed additional sides based on what what's been happening at the sites already so we're really in good shape in terms of enrollment to the trial.

David Neil Lebowitz: So we're really in good shape in terms of enrollment in the trial. Great, thank you for that. And then for 30-1, can you comment on the doses you're considering in the phase one study? And should we expect that clinical trial to be conducted initially at XUS study sites? I think that's premature at this time. I would expect that we'll treat that exactly from a communication point of view as we have done the other programs as, you know, they come into more focus and we get further down the regulatory path. Lay out a protocol will share the information as it solidifies, but it's, Okay, great. Thanks for taking the questions. Sure. And the last question today will be from Sylvan Turkan with JMP Securities. Please go ahead.

Great. Thank you for that and then for 30 O. One can you comment on the doses you're considering in the phase one study and should we expect that clinical trial to be conducted initially it X U S study sites.

I think that's premature at this time I would expect that will treat that exactly from a communication point of view as we've done the other programs as you know they come into more focus and we get further down the regulatory path and lay out a protocol will share the information is.

[noise] solidifies, but at this point that's pretty mature.

Okay, great. Thanks for taking the questions.

Sure.

And the last question today will be from Sylvan too can with JMP Securities. Please go ahead.

Silvan Can Tuerkcan: Good morning.

Hi, good morning, and thanks for taking my questions.

Silvan Can Tuerkcan: Thanks for picking my questions. Could you please tell us where you are at with the process for your team?

Could you please tell us where you're at what the process for your TCR program as you're moving at the end of the clinic by year end and also will there be any modifications in the near term to this process based on that data that you've presented that yes G. C. T with the lipid nanoparticle transfection or is that already incorporated perhaps thank you.

Silvan Can Tuerkcan: program as you're moving it into the clinic by year end, and also, will there be any modifications in the near term to this process based on the data that you've presented at ESGCT with the lipid nanoparticle transfection, or is that already incorporated, perhaps?

David Neil Lebowitz: David, is that something you want to address? Yeah, so the process is set, you know; we've had an I&D approved by the FDA, so they've obviously looked at what we plan to do in the study in terms of both manufacturing and the clinical study. So that is going forward as planned. It does incorporate the L&P process, so we want to have the advantages of the LNP process in this manufacturer.

David is that something you want to address.

Yeah. So the the process is set you know, we'd we'd had an I N D approved by the F. D. A so they obviously looked at what we plan to do in the study in terms of both manufacturing and in a clinical study. So that that is going forward as planned it. It it does incorporate the LNP process. So we want to help the advantages of.

Yeah, I want to be processes and this manufacturing.

David Neil Lebowitz: Thank you. Can you tell us at this point? I think you mentioned that the first patient will be screened by the end of the year. Can you characterize the trial design and the patient population at this point? Keep going, David.

Okay. Thank you and Kenny at this point have US I think you mentioned that the first picture will be screened by the end of the year can you characterize a kind of a trial design a at the patient population at this point.

Keep going David.

David Neil Lebowitz: David? Yeah, so this is, it's in Clintrials.gov at this point, right? So there are two populations that we have, patients with minimal residual disease, so less than 5% blasts, and then patients who have full relapse, which is considered greater than 5% blasts. Otherwise, the trial design is fairly standard for an oncology trial, a 3 plus 3 design at various doses.

Yeah. So this is it isn't Quinn trials dot Gov. At this point right. So there are two populations that we have patience with uhm minimal residual disease, so less than five per cent Blass, and then patients who have full relapse, which is considered is greater than 5% plus it otherwise the trial was.

That is fairly standard for oncology trial, a three plus redesign at at various doses, but there are some more details now available for you.

David Neil Lebowitz: But there are some more details now available. Great. Thank you very much. This concludes our question and answer session. I would like to turn the conference back over to Ann Karp for closing remarks. Great, thanks so much, Drew, and thank you all for joining us today and for your continued interest and support in Intelia. And we look forward to updating you on our progress in the future. Have a great day, everyone! The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Great. Thank you very much.

This concludes our question and answer session I would like to turn the conference back over to an <unk> for closing remarks.

Great. Thanks, so much through and thank you all for joining us today and for your continued interest and support and tell Ya and we look forward to updating you on our progress in the future have a great day everyone.

The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

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