Q4 2021 Passage Bio Inc Earnings Call

[music].

Operator: Good morning, and welcome to the Passage Bio fourth quarter and full year 2021 financial and operating results conference call. At this time, all participants are on a listen-only mode.

Good morning, and welcome to the passage bio fourth quarter and full year 2021 financial and operating results conference call. At this time all participants are in a listen only mode. Following the formal remarks, we will open up the call for your questions. Please be advised that this call is being recorded at the company's <unk>.

Operator: Following the formal remarks, we will open up the call for your questions. Please be advised that this call is being recorded at the company's request. At this time, I'd like to turn the conference over to Stuart Henderson, Vice President of Investor Relations and Strategic Finance. Stuart, please.

Request.

At this time I'd like to turn the conference over to Stuart interesting Vice President of Investor Relations and strategic Finance Stuart. Please proceed.

Stuart Henderson: Thank you, Operator. This morning we issued a press release that outlines the topics we plan to discuss today. This release is available on the Passage Bio website under the Press Releases and Statements section of Investors & You. On today's call, Bruce Goldsmith, President and Chief Executive Officer, will review our recent and 2021 business highlights. Eliseo Salinas, our Chief Research and Development Officer, will review our pipeline programs, including the GM1 data recently presented at the World Symposium.

Thank you operator. This morning, we issued a press release that outlines the topics we plan to discuss today. This release is available in the passage bio Webster.

Under the press releases and statements section of the investors and views.

On today's call Bruce Goldsmith, President and Chief Executive Officer will review, our recent 2021 business highlights let sales Salinas, our Chief Research and development Officer, who will review our pipeline programs, including the GM. One data recently presented at the World Symposium and Simona King Our Chief Financial Officer will review, our fourth quarter and full year.

Stuart Henderson: And Simona King, our Chief Financial Officer, will review our fourth quarter and full year 2021 financial results. Before we begin, please note that today's call may include a number of forward-looking statements, including, but not limited to, comments on our expectations about timing and execution of anticipated milestones, including the initiation of clinical trials and the availability of data from such trials, our expectations about our collaborators' and partners' ability to execute key initiatives, the ability of our lead product candidates to treat their respective target CNS disorder, manufacturing plans and strategies, trends with respect to financial performance and cash flows, the company's ability to fund research and development programs, impacts of the COVID-19 pandemic on the company's operations, and its ability to manage costs, along with uses of cash and other matters.

2021 financial results.

Stuart Henderson: These forward-looking statements are based on assumptions that are subject to risks and uncertainties that could cause the company's actual results to differ significantly from those suggested by these, Given these risks and uncertainties, you should not place undue reliance on these forward-looking, Please refer to the company's filings with the SEC for information concerning risk factors that could cause its actual results to differ materially from expectations, including any forward-looking statements made on this call, accept as required by law, the company disclaims any obligation to publicly update or revise any forward-looking statements to account for or reflect events or circumstances that occur after this call. It is now my pleasure to pass the call over to CEO, Bruce Goldsmith. Bruce.

Before we begin please note that today's call may include a number of forward looking statements, including but not limited to comments on our expectations about timing and execution of anticipated milestones, including the initiation of clinical trials and the availability of data from such trials, our expectations about our collaborators and partners ability.

To execute key initiatives the ability of our lead product candidates to treat their respective target CNS disorder Manny.

Manufacturing plans and strategies trends with respect to financial performance and cash flows the company's ability to fund research and development programs impacts of the COVID-19 pandemic on the company's operations and its ability to manage costs along with the uses of cash and other matters.

These forward looking statements are based on assumptions that are subject to risks and uncertainties that could cause the company's actual results to differ significantly from those suggested by these statements. Given these risks and uncertainties you should not place undue reliance on these forward looking statements.

Please refer to the company's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from expectations, including any forward looking statements made on this call except as required by law. The company disclaims any obligation to publicly update or revise any forward looking statements to account for or.

To reflect events or circumstances that occur after this call.

It is not in my pleasure to pass the call over to CEO Bruce Goldsmith Bruce.

Bruce Goldsmith: Thanks, Stuart, and thank you all for joining us this morning. I would like to first reflect on the significant evolution of our company over the last year. During 2021, we advanced three programs into the clinic, reported our first in human data, and substantially grew our pipeline, enhanced our executive leadership team and board, and scaled our organization to support clinical and commercial success. We continue to be guided by our three strategic pillars, which are our strong partnership with the University of Pennsylvania's renowned gene therapy program, our broad and robust pipeline and our dedicated manufacturing and analysts.

Thanks, Stuart and thank you all for joining us this morning.

I'd like to first reflect on the significant evolution of our company over the last year.

During 2021, we advanced three programs into the clinic reported our first in human data.

Dan Chile grew our pipeline enhanced our executive leadership team and board and scaled our organization to support clinical and commercial success, we continue to be guided by our three strategic pillars, which are our strong partnership with the University of Pennsylvania's renowned gene therapy program.

Our broad and robust pipeline and our dedicated manufacturing and analytics through our partnership with GTP, we are creating sustained value for our company as well as the patients we serve by employing a diversified pipeline strategy. As a result, we now have a robust and differentiated CNS pipeline that stands pediatric and adult <unk>.

Bruce Goldsmith: Through our partnership with GTP, we are creating sustained value for our company, as well as the patients we serve, by employing a diversified pipeline strategy. As a result, we now have a robust and differentiated CNS pipeline that spans pediatric and adult, as well as rare and large disorders. Today we have a total of nine pipeline programs and two additional exploratory research programs. That leaves us with the option to license eight additional CNS programs from GTP, as our pipeline advances, our primary focus continues to be on the execution of our three lead, For our lead program, Imagine 1, for GM1 gangliosidosis, we were excited to recently share positive safety, biomarker, and clinical efficacy data from Cohort 1.

As well as rare and large disorders.

Today, we have a total of nine pipeline programs and two additional exploratory research programs.

That leaves us with the option to license eight additional CNS programs from GTP.

As our pipeline advances our primary focus continues to be on the execution of our three lead programs.

For our lead program imagine one for GMO and Gangliosidosis, we were excited to recently share positive safety biomarker and clinical efficacy data from cohort one.

Bruce Goldsmith: Aliseo will review this interim data in more detail shortly, but in summary, for the low dose late infantile cohort, we have observed a positive safety profile with no serious adverse events and no complications related to intercisterna magna, or ICM, delivery. There was also no evidence of dorsal root ganglia or DRG toxicity.

Dale will review this interim data in more detail shortly but in summary for the low dose late infantile cohort, we observed a positive safety profile with no serious adverse events and no complications related to into cisterna magna or ICM delivery.

There was also no evidence of the dorsal root ganglia or DRG toxicity. The data showed functional transgene expression and meaningful gains in developmental milestones for both patients, including regaining lost milestones.

Bruce Goldsmith: The data showed functional transgene expression and meaningful gains in developmental milestones for both patients, including regaining lost mileage. With these early results, we are experiencing strong interest and momentum in our GM1 program. So much so, we recently reported that we have already achieved one of our key 2022 goals, which is the dosing of the first patients in cohorts 2 and 3 for the Imagine 1 trial. We expect to report interim safety and biomarker data for each cohort in the second half of 2022.

With these early results, we are experiencing strong interest and momentum in our GM on program. So much. So we recently reported that we have already achieved one of our key 2022 goals, which is the dosing of the first patient in cohort two cohort two and three for the <unk> one trial.

We expect to report interim safety and biomarker data for each cohort in the second half of 2022.

Bruce Goldsmith: Our focus for each of our clinical programs is selecting, in partnership with GTP, an optimal AAV-CAF-SID expression cassette and delivery meshes, which is ICM for our first three clinical trials. Positive interim data reinforces our confidence as we advance our additional global trials for Crab A disease and frontal temporal dementia with granuloma. We are also pleased with our progress in activating multiple clinical trial sites in multiple. Thus far, we have activated sites for our three clinical programs in the United States, Brazil, Canada, UK, and the Netherlands.

Our focus for each of our clinical programs as selecting in partnership with GTP and optimal AAV capsid expression cassette and delivery method method, which is ICM for our first three clinical trials the positive interim data reinforces our confidence as we advance our additional global trials for krabbe disease and frontal temporal.

Dementia with granular mutations.

We're also pleased with our progress in activating multiple clinical trial sites in multiple countries.

Thus far we have activated sites for our three clinical programs in the United States, Brazil, Canada, U K and the Netherlands, we accomplished this despite the challenges we have faced related to COVID-19, and we continue to bring remaining sites for those programs online.

Bruce Goldsmith: We accomplished this despite the challenges we have faced related to COVID-19 and we continue to bring remaining sites for those programs online. In addition to advancing our clinical programs, we are also excited about progressing a robust and differentiated pipeline. As I mentioned, we have exercised options for nine programs from GTP, most recently adding programs for Canavan and Huntington.

In addition to advancing our clinical programs. We are also excited about progressing our robust and differentiated pipeline.

As I mentioned, we have exercised options for nine progress from GTP. Most recently, adding programs for cat event in Huntington's disease. We also have two ongoing exploratory research programs in all timers disease and temporal lobe epilepsy that we continued to advance.

Bruce Goldsmith: We also have two ongoing exploratory research programs in Alzheimer's disease and temporal lobe epilepsy that we continue to advance. We also plan to submit an IND application for our MLD program in mid-2020, and we look forward to sharing additional data on our pipeline throughout the year, including at scientific meetings. In addition to our robust pipeline and strategic partnership with GGP, our third key strategic focus is manufacturing and analytics.

We also plan to submit an IND application for our MLD program in mid 2022.

And we look forward to sharing additional data on our pipeline throughout the year, including at scientific meetings. In addition to our robust pipeline and the strategic partnership with GGP. Our third key strategic focus is manufacturing in analytics, we continue to invest in our manufacturing in CMC capabilities to ensure product supply from.

Bruce Goldsmith: We continue to invest in our manufacturing and CM&C capabilities to ensure product supply from clinical development through commercialization in a capital efficient manner. We currently have a dedicated GMP suite at Keteland for clinical product manufacturing. In mid-2021, we opened a Passage Bio CM&C research and development lab focused on analytics, process development, and clinical product testing. Since then, our team has made significant progress in developing and advancing differentiated analytics using the latest technologies and methodologies. At this time, we are now investing in a pilot manufacturing suite to add scale-up capabilities to support our R&D pipeline as well as future development. We expect that our pilot suite will be operational by year.

Clinical development through commercialization in a capital efficient manner. We currently have a dedicated GMP suite of Catlin for clinical product manufacturing.

In mid 2021, we opened at passage Bio CMC research and development lab focused on analytics process development and clinical product testing. Since then our team has made significant progress in developing advanced a differentiated analytics using the latest technologies and methodologies.

At this time, we are now investing in our pilot manufacturing suite to add scale up capability to support our R&D pipeline as well as future development plans.

We expect that our pilot suite will be operational by year end.

Bruce Goldsmith: Lastly, we ended the year in a strong cash position, which allows us to deliver on multiple value drivers throughout 2022 and 2023. We are pleased with our progress over the last year, and we look forward to an execution-focused and data-rich 2022 on our path to developing transformative therapies for patients with devastating CNS disorders with significant, With that, I will now turn it over to Eliseo, who will discuss our clinical programs, including our recently presented data for GM.

Lastly, we ended the year in a strong cash position, which allows us to deliver on multiple value drivers through throughout 2022 and 2023. We are pleased with our progress over the last year and we look forward to it an execution focused and data rich 2022 on our path to developing transformative therapies for patients with devastating.

CNS disorders with significant unmet need with that I will now turn it over to <unk>, who will discuss our clinical programs, including our recently presented data for GM one.

Bruce Goldsmith: Thank you, Bruce. I will start by discussing our GM1 probe. Gene 1 is a fatal neurological lysosomal steroid disease caused by a GLB1 gene mutation that results in low activity of the beta-galactosidase enzyme. This leads to rapid neurological decline, and in the most severe forms, unfortunately, a relative rapid death.

Thank you Bruce I will start by discussing our GM one program.

Jim wanted to fatal neurological lysosomal storage disease caused by <unk>, one gene mutation that we sold in low activity of the <unk> enzyme.

This leads to rapid neurological decline.

The most severe forms unfortunately, a relatively rapid def.

Eliseo Salinas: Life expectancy for children with infantile gene 1 ranges from 2 to 10 years. After initially gaining miles, Children with late infantile onset typically plateau at 12 to 13 months of age, meaning that they stop gaining normal milestones, before they regress. Patients with GM1 are a rare and underserved population. Currently, there are no disease-modifying treatments for the disease.

Life expectancy for children with infantile gene one ranges from two to 10 years.

Also.

After initially gain milestones children with late infantile onset typically plus two at 12% to 13 months of age meaning that the stope, gaining normal milestones before data requests.

Patients with Jim one are a rare and underserved population.

Currently there are no disease modifying treatment for the disorder.

Eliseo Salinas: Imagine one trial focuses on the early and late infantile forms of GM1, which are the most severe forms of the disease. The GLOBAL PHASE I-II trial is an open-label, dose-escalation study with PBGMO-1, enrolling four distinct cohorts, divided by age and dose level. As a reminder, our approach uses a next-generation proprietary AVHU68 capsid administered via the cisterna magna to deliver a carbon-optimized GLB1 transgene to increase beta-galactosidase enzyme activity in the brain and peripheral tissue.

Although I imagine one trial focuses on the early and late infantile form till June one which are the most severe forms of the disease.

The global Phase two trial is an open label dose escalation study with BB GMO, one enrolling four distinct cohorts divided by age and dose level.

As a reminder, our approach uses our next generation proprietary <unk> 68 capsid.

Easter via this is during a magnet to deliver a cobham optimized <unk> transgene to increase be Doug I'd like to say this enzyme activity in the brain and peripheral tissues.

Eliseo Salinas: We recently shared positive interim safety, biomarker, and clinical efficacy data from Cohort 1, consisting of two late infantile patients treated with a low dose of PBGM-01. This interim data showed that PBGM01 was, well-correlated and had a safety profile, a positive safety profile, with no serious adverse events and no complications related to ICM delivery. Demonstrated also no evidence of DRG toxicity based on nerve conduction status, and substantially increased beta-gal enzyme activity in both the CSF and serum after ICM delivery. In terms of clinical efficacy, We presented developmental milestone data using two standardized norm-referenced scales, the Bayley-3, formal assessment tool used by trained healthcare providers, and DivineLine 2. Care for Caregiver Assistants.

We recently shared positive interim safety biomarker and clinical efficacy data from cohort one consisting of two late infantile patients treated with low dose of <unk> one.

This interim data showed that <unk> was well tolerated and had a safety profile a positive safety profile with no serious adverse events and no complications related to ICM delivery.

Demonstrated also no evidence EOG toxicity based on nerve conduction studies.

And substantially increase beta gal enzyme activity in both the CSF and serum after ICM delivery.

In terms of clinical efficacy, we presented development on milestone data using to standardize non referenced scales. The bailey three.

A formal assessment tool used by trained health care providers and the Vineland two are scaled for caregiver assessment.

Eliseo Salinas: Today, I will review assessment, which solves for each phase, patient one, at a chronological age of 14 months and a developmental age of 12 months at Baynes. It's important to know that for the Vineline, we were able to share up to nine month assessment for this patient after dosing, conducted by the healthcare provided. But that was not the case for the Bayley-3 assessment as the patient was not able to be scored due to a potential COVID-19 exposure.

Today I will review assessment, we sold for each patient.

Patient one.

Had a chronological age of 14 months and the Devil of mental age of 12 months at baseline.

It is important to know that for the Vine line, we were able to share up to nine month assessment for these patients after dosing.

Inducted by the healthcare provided but that was not the case for the Bally three assessments at the patient was not able to be scored due to a potential COVID-19 exposure.

Eliseo Salinas: Let's review the Bayley assessment for patient one first. There was improvement in all developmental areas through the six months observed following administration of PBGMO1G9, overall development age, progress consistently, and track closely to chronological, The Vineland scale assessments at nine months documented that following PGM-01 administration, there was also improvements in all developmental areas for this patient, with notable progress in the domains of fine motor skills. Receptive Language, and Interpersonal Relations.

Let's review the Bayley assessment for patient one first.

There was improvement in all developmental areas through the six months observed following administration of <unk> gene therapy.

Overall development age progressed consistently and track closely to current logical speeds.

The vineland scale assessments at nine months documented that following <unk> administration was also improvements in all development areas for these patient with notable progress in the domains of fine motor skills.

And receptive language and interpersonal relationships.

Eliseo Salinas: Overall, the development age for patient one progressed from 12 months at study start to 23 months at the nine-month interim assessment, approaching the current patient's chronological age of 24 months, joining the patient too. He got a severe developmental delay at baseline with a chronological age of 31 months and a developmental age of 13 months on the Vineland scale, and seven months on the base. For this patient, there was a single follow-up available at three months.

Overall, the development H, a four patient one progress from 12 months at study start to 23 months up to nine months interim assessment approaching the current patients current logic age of 24 months.

Turning to page two.

He's got a severe developmental delay on baseline baseline with a chronological age of 31 months and a development that age of 13 months on the Vineland scale.

Seven months on the Bailey.

For these patients there was a single follow up available at three months.

Eliseo Salinas: Improvements in the Bayley assessment were documented in patient two in motor, receptive language, and cognitive domain. The overall development age progressed during the three months following administration of the product from seven months at baseline to nine months. For the Vineline assessment, significant improvements were also observed, notably in expressive language and interpersonal relationships, despite a severe developmental disability. The overall development age progressed from 13 months at baseline to 16 months at the three-month assessment following administration of PBG M01, important, patient two not only acquired new miles, but also regained previously lost milestones, in particular, the ability to walk, and to use specific words in summary. We believe the increase in beta-galenosine activity observed in both CSF and serum after ICM delivery are positive indicators that PBGMO1 is exerting a biological effect.

Improvements in the Bayley assessment were documented in patient two and mater.

Captive language and cognitive domains.

Overall development H progressed during the three months following administration of the product from seven months at baseline to nine months.

Well defined line assessment significant improvements were also observed notably in expressive language and interpersonal relationships. Despite a severe developmental delay.

The overall development age progressed from 13 months at baseline to 16 months at the three month assessment following administration of <unk> one.

Importantly.

Patient to not only acquire new milestones.

But also regained previously lost milestones in particular, yes.

To walk and to use.

Specific words.

In summary.

We believe the increase in beta Gal enzyme activity observed in both CSF and serum after ICM delivery are positive indicators.

<unk> one is exerting a biological effect.

Eliseo Salinas: We were also pleased to see meaningful improvements in development milestones for these children, including the regaining of low-stress. While we remain cautious in the context of an open-label study and a small number of patients, we are very encouraged by these initial reports of clinical improvement and about the potential of PBGM1 for patients. We look forward to further follow-up and continue with additional cohorts in the Imagine One step, as Bruce said. Following this positive interim safety and biomarker data for Cohort 1, the Imagine 1 study has progressed to enroll additional costs. We are enrolling Cohort 2 with two late infantile GM1 patients receiving the high dose of PBGM1, and Cohort 3 with two early infantile GM1 patients receiving the low dose of PBGM-O1.

We were also pleased to see meaningful improvements in Devil of milestones for these children, including the regaining of lost milestones.

While we remain cautious in the context of Enel open label study in a small number of patients. We are very encouraged by these initial reports of clinical improvement and about the potential of <unk> for patients.

We look forward to for the follow up and continue with additional cohorts in the imagine one study.

As Bruce said <unk>.

Following these positive interim safety and biomarker data for cohort one the imagine one study has progressed to enroll additional cohorts.

We are enrolling cohort two with two late infantile <unk> patients receiving the high dose of PV GM on one end.

In cohort three with two early infantile <unk> patients receiving the low dose of <unk> one.

Eliseo Salinas: Thus far, the first patient in each of these cohorts has been those. We look forward to being able to share initial safety and biomarker data for these two cohorts in the second half of 2022. Moving on now to our global PBKRO3 program in carotid disease called GALAX-C. Krebs disease is a condition that progresses rapidly, damaging both the brain and the peripheral nervous system, and resulting in a life expectancy of only two years in the severe case. Krebs disease results from decreased enzyme activity of galactosilceramidase, or GalC.

Thus far the first patient in each of these cohorts has been dosed.

We look forward to being able to share initial safety and biomarker data for these two cohorts in the second half of 2022.

Moving on now to our global <unk> three program in <unk> disease Galaxy.

<unk> disease is a condition that progresses rapidly damaging both the brain and the peripheral nervous system and resulting in a life expectancy of only two years into severe cases.

Kobe disease with sold from decreasing decreased enzyme activity of galaxy ceramic days or galaxy.

Eliseo Salinas: Like GM1, this is also a pediatric leukodystrophy and lysosomal storage disease with an underserved population with a very devastating disease progression. GALAXY is an open-label, dose-escalation study of PBKR3 in patients with early infantile Crabi disease. TBK03 uses the same proprietary AAVHU68 viral vector to deliver a functional GALC gene that codes for GALC. PBK03 will be delivered directly to the CSF by ICM delivery with the goal of increasing activity of the GALC enzyme in both the CNS and the peripheral nervous system.

Like GM. One. This is also a pediatric look of these trophy and lysosomal storage disease with at underserved population with a very devastating disease progression.

Galaxy is an open label dose escalation study of <unk>, our three in patients with early infantile krabbe disease.

<unk> three uses the same proprietary AAV <unk> viral vector to deliver a functional galaxy gene that codes for galaxy.

<unk> will be delivered directly to the CSF by ICM delivery with the goal of increasing activity of the galaxy enzyme in both the CNS and the peripheral nervous system.

Eliseo Salinas: The study will run similarly to our Imagine One trial, with the first cohort evaluating an initial dose of PD-KRO3 in late-onset patients, and then progressing to early-onset and high-dose cohorts after an assessment of cohort. Additionally, there will be a confirmatory expansion cohort for both age groups once the dose escalation phase of the study is completed. The main goal of the initial part of the study is to assess the safety and tolerability of ascending doses of PD-KIO3 in patients with early infantile cardiac disease, as well to assess the impact of Ongal-C in CSF and sera.

The study will run similarly to our imagine one trial with the first cohort evaluating an initial dose of <unk> three in late onset patients.

And then progressing to early on.

And high dose cohorts after an assessment of cohort one.

Additionally, it will be a confirmatory expansion cohort for both age groups once the dose escalation phase of this study is completed.

The main goal of the initial part of the studies to assess the safety and Tolerability of ascending doses of <unk> or <unk> in patients with early infantile krabbe disease.

Well do as said the impact of on Galaxy in CSF and serum.

Eliseo Salinas: We had the privilege of having the clinical trial design for GALAXY as well as IMAGINE.1 presented at the World's Impulsion last month. We are grateful for the interest and support we are seeing from both the research and the patient advocacy community for our programs. And we look forward to seeing those in the first patient in our gallery, turning to our third clinical group. PBFTO-2 for Frontotemporal Dementia with Granulin Repair.

We have the privilege of having the clinical trial design for Galaxy as well as imagine one presented at the awards Impulsion will last month.

We are grateful for the interest and support we are seeing from both the research and the patient advocacy community for our programs and we look forward to assume dosing the first patient in our Galaxy trial.

Turning to our third clinical program.

<unk> for Frontotemporal dementia with gradually mutation.

Eliseo Salinas: FTD is a devastating form of early-onset dementia affecting patients between the ages of 40 to 60. The form of the disease we are seeking to treat with our therapy is caused by a granulin, or GRN, gene mutation, which results in a deficiency of progranulin. It is estimated that 5-10% of all FTD is caused by a GRN mutation. In the most typical forms of FTD with GRN mutation, patients experience significant speech alterations and severe behavioral changes culminating in dementia.

Ftes a devastating form of early onset dementia affecting patients between the ages of 40% to 65.

Before the disease, we are seeking to treat with our therapy is caused by a granule or GRN gene mutation, which we sold in the deficiency of pro Granularly.

It is estimated at 5% to 10% of all FTB is caused by a GRM mutation.

And the most typical forms of FTB with GRN mutation patients experiencing significant speech alterations and severe behavioral changes, culminating in dementia.

Eliseo Salinas: This is an underserved population with no disease-modifying therapies approved and an average survival of eight years after the onset of neurocognitive deterioration. Our Global Phase I-II Clinical Trial, UPLIFT-D, is an open-label, dose-escalation study of PVFTO2 in FTD-GRN patients. PBFTO2 uses an AAV1 viral vector to deliver a modified DNA encoding the granulin gene to a patient's cell. Based on proclinical data, PVFTO2 has the potential to increase programming levels to more than 50 times normal human levels.

This is an underserved population with no disease modifying therapies approved.

And in average survival of <unk> after the onset of neurocognitive deterioration.

Our global Phase one two clinical trial I believe is an open label dose escalation study of PBF deal.

In <unk> patients.

<unk> users.

The one viral vector to deliver a modified DNA encoding the granular and gene to a patient cell.

Based on preclinical data <unk> two has the potential to increase pro granular levels to more than five.

Ft tonne normal human levels.

Eliseo Salinas: In the clinical study, the construct will be administered into the CSF by ICM delivery. The goal of this treatment and delivery approach is to potentially provide higher than normal levels of the progranulin protein to the CNS to overcome the progranulin deficiency in GRN gene mutation cancer.

And the clinical study to comfortably be administered into the CSF by ICM deliver.

The goal of this treatment and delivery approach is to potentially provide higher than normal levels of the pro granule improved into the CNS to overcome the pre grounding deficiency in GRE GRN gene mutation carriers.

Eliseo Salinas: We plan to enroll two cohorts of three patients each, receiving two different ascending doses of PVFTO2, with an optional third cohort treated with a higher dose, depending on safety and biomarker results observed in the first two. Like our other LEAD programs, our two key goals are to assess the safety and durability of ascending doses of PBFTO2, as well as its impact on progranulin levels. We anticipate that we will be dosing our first patient soon.

We plan to enroll two cohorts of three patients each receiving two different ascending doses of PVH.

With an option of third cohort treated with a higher dose dependent on safety and biomarker results observed in the first two cohorts.

Like our other lead programs our two key goals are to assess the safety and tolerability of ascending doses of <unk> as well as its impact on pro granular levels.

We anticipate that we'll be dosing our first patient soon.

Eliseo Salinas: Turning now to our proclinical program for MLD or metachromatic leukodysis. Infantile MLD is a fatal inherited disease characterized by muscle weakness, rigidity, gait disorder, and developmental delay. It is caused by a mutation in the ARSA, or the aryl sulfatase A gene, which reduces the enzyme activity. Children typically die by the age of five, and the worldwide prevalence is one in about 100,000 live birds.

Turning now to our preclinical program for MLD or Metachromatic <unk> dystrophy.

Infantile MLD for fatal inherited disease characterized by muscle weakness rigidity gait disorder and developmental delays.

It is caused by a mutation in the <unk>, a real sulfatase, a gene which reduces the enzyme activity.

Children typically die by the age of five and the worldwide prevalence is one in about 100000 lifeboats.

Eliseo Salinas: As Bruce noted earlier, we plan to submit an IND for our MLD program by mid-year. Our approach here is very similar to our GM1 and Krabi programs, where we are using a next-generation proprietary AAVHU68 capset to deliver a functional arsa gene via, Advancing programs for CNS diseases requires tremendous support from a variety of stakeholders. I would like to conclude by recognizing and thanking the caregivers, healthcare providers, advocacy organizations, and patients in this community.

As Bruce noted earlier, we plan to submit an IND for our MLD program by mid year.

Our approach here is very similar to our GM one in credit programs. We are using our next generation proprietary AAV HEU 68, capsid to deliver a functional <unk> gene.

Cisterna Magna injection.

Advancing program for CNS diseases, and requires tremendous support from a variety of stakeholders.

I would like to conclude by recognizing and thanking the caregivers healthcare provider advocacy organizations and patients in these communities.

Eliseo Salinas: With that, I will now turn the call over to Simona to review of our final. Thank you, Eliseo. As we reported in our press release this morning, we ended the year with approximately $315.8 million in cash, cash equivalents, and marketable securities, compared to $304.8 million as of December 31, 2020.

With that I will now turn the call over to Simona to review of our financials.

Thank you.

So we reported in our press release. This morning, we ended the year with approximately $315 $8 million in cash cash equivalents and marketable securities compared to $304 $8 million as of December 31st 2020.

Simona King: R&D expenses were $33 million and $117.7 million for the quarter and year end of December 31, 2021 compared to $27.9 million and $81.8 million for the same quarter and year in 2020. The increase for the year was primarily due to a $19.7 million increase in personnel-related expenses, including share-based compensation, due to a higher employee headcount, an $18.7 million increase in clinical manufacturing expenses, a $10.9 million increase in clinical operations expenses to support the clinical trials for our clinical product candidates, and a $3.7 million increase in facility and other expenses.

R&D expenses were $33 million and $117 $7 million for the quarter and year ended December 31, 2021, compared to $27 9 million and $81 $8 million for the same quarter and year end 2020.

The increase for the year was primarily due to a $19 $7 million increase in personnel related expenses, including share based compensation due to higher employee head count and an $18 $7 million increase in clinical and manufacturing expenses, a $10 9 million dollar increase in <unk>.

Nickel operations expenses to support the clinical trials for our clinical product candidates and a $3 $7 million increase in facility and other expenses.

These increases were partially offset by a $2 $5 million decrease in professional services and consulting expenses and a $14 $6 million decrease in research and development expenses with Penn, which relates to expenses incurred for preclinical work performed in preparation for IND filings.

For our clinical program.

Simona King: These increases were partially offset by a $2.5 million decrease in professional services and consulting expenses and a $14.6 million decrease in research and development expenses with Penn, which relates to expenses incurred for preclinical work performed in preparation for IND filings for our clinical program. Acquired and processed R&D expenses were $1 million and $8 million for the quarter and year ended December 31, 2021, compared to $1 million for the quarter and year ended in 2020.

Acquired in process, R&D expenses were $1 million and $8 million for the quarter and year ended December 31, 2021, compared to $1 million for the quarter and year ended in 2020.

Simona King: The increase for the year was primarily due to an extension of the research, collaboration, and license agreement with Penn, additional option exercises, and the achievement of certain clinical milestones occurring in 2021. GMA expenses were $17.2 million and $60.1 million for the quarter and year ended December 31st, 2021, compared to $10.1 million and $30.1 million for the quarter and year ended in 2020. The increase for the year was primarily due to a $21.8 million increase in personnel-related expenses, including share-based compensation, resulting from an increase in employee headcount.

The increase for the year was primarily due to an extension of the research collaboration and license agreement with Penn.

Additional option exercises and the achievement of certain clinical milestones occurring in 2021.

G&A expenses were $17 $2 million and $60 $1 million for the quarter and year ended December 31, 2021, compared to $10 $1 million and $30 1 million for the quarter and year ended in 2020.

The increase for the year was primarily due to a 21 $8 million increase in personnel related expenses, including share based compensation, resulting from an increase in employee and employee head count Professor.

Simona King: Professional fees and other expenses also increased $8.2 million as we expanded our operations to support our research and development efforts and incurred expenses operating as a public company. Net loss was $51.2 million and $185.4 million for the quarter and year ended December 31, 2021 compared to $38.9 million and $112.2 million for the quarter and year ended in 2020. As we continue to advance our pipeline and invest in our capabilities, we are supported by the strength of our balance sheet.

Professional fees and other expenses also increased $8 $2 million as we expanded our operations to support our research and development efforts and incurred expenses operating as a public company.

Net loss was $51 $2 million and $185 4 million for the quarter and year ended December 31, 2021, compared to $38 $9 million and $112 2 million for the quarter and year end debt in 2020.

As we continue to advance our pipeline and invest in our capabilities. We are supported by the strength of our balance sheet, we expect our cash cash equivalence and marketable securities to fund our operations to year end 2023.

Simona King: We expect our cash, cash equivalents, and marketable securities to fund our operations to year-end 2023. Let me now turn it back to Bruce for a closing remark. Thank you, Simona. We look forward to continuing to deliver on multiple clinical and corporate milestones, including enrolling additional patients across our clinical studies and providing more data throughout 2022. Now with the first patient's dose in cohorts 2 and 3 for the GM1 trial, we expect to report interim data in the second half of 2022. Our patient engagement team also has built productive partnerships with the advocacy community, which has helped tremendously in raising awareness of our clinical trial program.

Let me now turn it back to Bruce for closing remarks.

Thank you Simona, we look forward to continuing to deliver on multiple clinical and corporate milestones, including enrolling additional patients across our clinical studies and providing more data throughout 2022.

Now with the first patient dosed in cohort two and three for the <unk> trial, we expect to report interim data in the second half of 'twenty two.

Our patient engagement team had also has built productive partnerships with the advocacy community, which has helped tremendously in raising awareness of our clinical trial programs.

Bruce Goldsmith: Our clinical operations team is executing well as we continue to open clinical trial sites around the globe. Our clinical pipeline is also expanding as we plan to file an IND in mid-2022 for MLD. We continue to invest in our in-house CMC capabilities, and we expect our pilot plant suite to be operational by year.

Our clinical operations team is executing well as we continue to open clinical trial sites around the globe.

Our clinical pipeline is also expanding as we plan to file an IND in mid 2022 for MLD we.

We continue to invest in our in house CMC capabilities, and we expect our pilot plant suite to be operational by year end.

Bruce Goldsmith: Before taking your questions, I'd like to thank the incredible Passage Bio team and Jim Wilson and his team at GTP for our many accomplishments over the last year. I'd also like to echo Eliseo by personally thanking the patients as well as the caregivers, healthcare professionals, scientists, and advocacy groups who share and support our mission of developing transformative therapies for devastating CNS disorders. With that, I would like to open the call-up for questions. Operator.

Before taking your questions I'd like to thank the incredible passage bio team and Jim Wilson and his team at GTP for our many accomplishments over the last year I'd also like to Echo LSA out by personally thanking the patients as well as the caregivers givers healthcare professionals scientists and advocacy groups, who share and support our mission of developing.

Transformative therapies for devastating CNS disorders.

With that I would like to open the call up for questions operator.

Operator: Thank you. We will now take any questions you may have. If you have a question, please press star 1 and you'll be placed into the queue. If you would like to cancel your question, please press the pound key. Our first question comes from Tessa Romero with JP Morgan. Your line is now open. Hey, guys.

Thank you we will now take any questions. You may have if you have a question. Please press star one and youll be placed into the queue. If you would like to cancel your question. Please press the pound key.

Our first question comes from Tessa Romero with Jpmorgan. Your line is now open.

Tessa Romero: I hope everyone's doing well. Thanks for taking the question. I wanted to ask about the CRAB-A and FDD-GRN studies. You've reiterated the guide now to dose the first patients in early 2022. Just curious, what underscores the conviction here of achieving this milestone for both trials?

Hey, guys hope everyone's doing well thanks for taking the question.

Goodbye.

FCB Geron study you've reiterated the guidance you gave us the first patient in early 2022.

Just curious what underscores that conviction here at Keybanc with milestones for both trials.

Bruce Goldsmith: Have these patients been identified, screened, and or enrolled yet? And is there any queue of patients in either of the indications that's building? Thanks so much.

Thank you.

Identified screen.

<unk> enrolled yet.

Is there any can you ask patients in either of the indications that building. Thanks, So much hi, Tessa. Thanks, so much for the question. This morning.

Bruce Goldsmith: Hi Tessa, thanks so much for the question this morning. So, we continue to do several things that are leading indicators of our progress. One is to continue to work through the site openings.

Yeah.

So we continue to do several things that are leading indicators of our progress. One is to continue to work through the site openings. We've obviously had challenges in the past doing that and we are we are pleased that the <unk> study sites are continuing to open.

Bruce Goldsmith: We've obviously had challenges in the past doing that, and we are pleased that the Crab Egg Study sites are continuing to open, and we believe that additional FTD sites will open in the coming weeks to months. So that's certainly areas of progress that we're very happy with, but we definitely recognize the challenge that we've had in moving the patients from identification into the studies. So we have not announced, and we don't typically announce enrollment status, because for all of these programs there is a significant amount of work for each patient, not only pre-identification, but once patients are enrolled they have to go through a several-week screening process, which is typical for gene therapy programs, as well as for neurology programs, CNS programs.

We believe that additional FTE sites will open in the coming week.

So thats certainly areas of progress that we're very happy with but we definitely recognize the challenge that we've had in moving to patients from identification into the studies. So we have not.

We've not announced and we don't typically announce enrollment status because for all of these programs. There is a significant amount of work for each patient not only pre identification, but once patients are enrolled they have to go through a several week screening process, which is typical for gene therapy programs as well as.

For neurology programs CNS programs.

Bruce Goldsmith: So what we will do is once a patient is dosed, make that first patient dose announcement, and we certainly hope to do that in the early part of this year. We do have an ongoing effort to identify patients across all of our studies. One of the things that we pointed out in the frontal temporal dementia space is that while there are patients that are identified with FTD, because there have been no traditional treatments, the genetic genotyping to identify patients with GRN mutations hasn't traditionally been done.

So what we will do is once a patient is dosed make that first patient dose announcement and.

And we certainly hope to do that.

In the early part of this year.

We do have an ongoing effort to identify patients across all of our studies one of the things that we pointed out in the frontal temporal dementia space is that while there are patients.

That are identified with FTE, because there have been no traditional treatments the genetics geno typing to identify patients with GRN mutations hasn't traditionally been done with the <unk>.

Bruce Goldsmith: With the start of multiple studies, including our own, that is increasing. And we've also gone to sites where there are patient populations identified through various programs such as the GENFI program and the AFTD database. So those are some of the areas that we're focused on. And then for CRAB-A, we're also replicating what we've done in the initial stages of the GM1 study for reaching out for both patient advocacy as well as patients that may be on those, at those sites. The difference there is that obviously similar to GM1, the patients with CRAB-A disease do progress very, very quickly.

Start of multiple studies, including our own that is increasing and we've also gone to sites, where there are patient populations identified through various programs such as the Gen fee program and the FTB database. So those are the those are the some of the areas that we're focused on.

And then for Krabbe.

Also we're replicating what we've done in the initial stages of the GM one study for reaching out for both patient advocacy as well as patients that may be on those.

Those sites.

The difference there is that obviously similar to Jan one the patients with <unk> disease do progressive very very quickly. So we have to move fast once we identify those patients and get them into the centers. So those are all the initiatives that we're working on and we continue to make progress and we certainly look forward to not only enrolling.

Bruce Goldsmith: So we have to move fast once we identify those patients and get them into the centers. So those are all the initiatives that we're working on. And we continue to make progress and we certainly look forward to not only enrolling but dosing our first patients in both of those. Okay, thanks Bruce so much, and yeah, thanks for the call, I appreciate it.

But dosing our first patients in both of those studies.

Yes.

Thanks, so much.

Yeah. Thanks for the color I appreciate it thank you.

Operator: Thank you. Thank you. Our next question comes from Madhu Kumar with Goldman Sachs. Your line is open. Good morning. This is Omar Aoun for Madhu.

Thank you.

Next question comes from Madhu Kumar with Goldman Sachs. Your line is open.

Good morning, this is omar or for module.

Omar Aoun: So, for our first question, we're wondering how do you think about quantifying the clinical improvements observed in month for the last patient described at world? And also, like, do you think these improvements could translate over into the early infantile cohort? Thanks.

So for our first question wondering how do you think about quantifying the clinical profile observed a month for the last patient describing it world.

And also like do you think these improvements could translate over into the early <unk> cohort.

Thanks, I'm going to make an introductory comment and then turn it over to <unk>. So to your point, we're extremely happy to for these two patients for the initial data one with three months follow up and one with one with longer follow up up to nine months that we've actually not only seen.

Bruce Goldsmith: I'm going to make an introductory comment and then turn it over to Elseo. So to your point, we're extremely happy for these two patients, for the initial data, one with a three-month follow-up and one with longer follow-up, up to nine months, that we've actually not only seen improvements in the milestones, but for patient two, for example, we saw restoration of previously gained milestones that had been lost. So really exciting.

Eliseo Salinas: This is obviously early data and two patients. So maybe Elseo can add some comments about what we interpret that to be and also how that may translate into the early infantile population. Right. Regarding the first part of your question, the quantification, fortunately the Bayley in particular gives you a very precise... Quantification of the patient status. The Bailey has more than 300 items, and on the motor is more than 140.

If proven some of the milestones but for a patient to for example, we saw restoration of previously gained milestones that had been lost so really exciting. This is obviously early data in two patients.

So maybe I will say it can add some comments about what we can what we interpret that to be and also how that may translate into the early infantile population.

Regarding the first part of your question the quantification Fortinet. The Bally in particular gives you a very precise kwan.

Quantification.

Patient status.

Bailey has more than 300 items and on the model is more to add around 40. So very specific items that are assessed during the interview.

Eliseo Salinas: So very specific items that are assessed during the interview. Patient number one, a baby, had a developmental age of 12 months and a chronological age of 14. It was at the beginning of his platoin, and that patient grew from 12 to 17 pounds on the six months of observation period. So significant and quantifiable benefits. Patient two also on the Bayley, the clinician rated scale, was much more severely delayed with an overall developmental age of seven months, for a baby with a chronological age of 31 months.

Number one a debate.

Developmental age of 12 months.

We're not logical age of 14 it was at the beginning of a plateauing in that basin grew from <unk>.

12 to 17.

On the on the six months of observation period, so significant unquantifiable.

<unk>.

Patient two also on the Bailey.

Clinician rated scales was much more severely delayed we've done although they will.

Developmental age of seven months.

We're a baby with a chronological age of 31 months.

Eliseo Salinas: And that patient also gained two months of developmental age in the three months of the treatment. And as I said, these are very specific. This is not an overall assessment, gestalt type of assessment. These are specific things that the child does or doesn't do during the interview. So yeah, we're confident that those developmental milestones have been documented very clearly. Regarding extrapolation of the early infantile, well, it's the same enzyme, it's the same disease, and it's a more aggressive disease on the earlier children, the early infantile.

<unk> also gained two months of development on age.

In the three months after treatment and as I've said. These are very specific that this is not an overall assessment guest adult type of assessment. These are specific things that the child does or doesn't do doing the interview.

So yes, we are confident.

Dose development milestones have been documented very clearly regarding extrapolation.

Early infantile well, it's the same enzyme is the same disease and it's a more aggressive disease early.

Earlier.

Sure.

Eliseo Salinas: So we can make promises, but we think that what we observe in these first two patients is a very reasonable basis to be cautiously optimistic about the rest of the study. Great. Thanks. And for the second question, what are the gating events for starting the FTD CRAB-A trial? So we have, yeah, thanks for the question. So we have the sites that can enroll in-dose patients open. It's really getting those patients into the centers that have both the appropriate mutations as well as entry criteria, and then enrolling them in screening.

So we can make promises, but we think that what we observed in these first two patients is a very reasonable basis to be cautiously optimistic about the rest of the study.

Alright, Thanks and for the second question what are the gating event for starting the FTB credibly trial.

So we have yes. Thanks. Thanks for the question. So we have the sites that can enroll and dose patients open.

It's really getting those patients into the centers that have both the.

Appropriate mutations as well as entry criteria, and and then enrolling them in screening and screening as I said.

Eliseo Salinas: And the screening, as I said, does take quite some time to both establish the, there's a pre-screening when patients are initially identified at various centers. When they get actually to the site, then there is an onsite screening as well to confirm final eligibility.

Does take.

Quite some time to both establish the.

There is a pre screening when when patients are initially identified at various centers when they get actually to the site and there is an onsite screening as well to confirm final eligibility.

Bruce Goldsmith: And then once they're there, all of the baseline assessments occur. So the real gating item is identifying those patients and getting them enrolled in the study. They're slightly different considerations for both. For the patients with Crab A disease, similar to patients with GM1, it is a rapidly progressing disease. We're actually focusing on an earlier population than initial for GM1.

Then once they are there all of the baseline assessments occur so the real gating item is.

Getting identifying those patients and getting them enrolled in the study.

They are slightly different.

Considerations for both for the patients with krabbe disease similar to patients with GM. One it is a rapidly progressing disease, we're actually focusing on an earlier population that initial for gen. One in these patient crab eight children or for the nine months old.

Bruce Goldsmith: And these patients, the Crab A children are four to nine months old. In the second part of the study, that will even go down to one month to four months because this is a very rapidly progressing disease. And some patients with Crab A disease and their families do opt for the potential for going for a stem cell transplant that's appropriate for patients that are not symptomatic and have a donor and are qualified for stem cell.

And the second part of the study that will even go down to one month to four months. Because this is a very rapidly progressing disease and some patients with krabbe disease and their families do opt for the potential for going for stem cell transplant, that's appropriate for patients that are not simple.

<unk> and and have a donor.

Alright qualified for stem cell. So that is all of the considerations that go into the krabbe disease patient population and moving those patients into the study for frontal temporal dementia really it is it is having the patients identified and moving to the sites.

Bruce Goldsmith: So that is all of the considerations that go into the Crab A disease patient population and moving those patients into the study. For frontal dementia, really it is having the patients identified and moving to the sites.

Bruce Goldsmith: We have identified patients previously and there unfortunately have been considerations that have precluded them for moving on to the study, such as comorbidities or, unfortunately, side effects that have occurred for their current interventions prior to actually enrolling in the study. So that's just a really challenging time for us to identify the patients and move them onto the study. So to back to your earlier point, the real gating item is simply moving those patients to identification and enrollment. All right, thanks for answering our questions and the update. Thank you. Thank you. Our next question comes from Nina Petrito, GARB with City. Your line is open.

We have identified patients previously and unfortunately have been considerations that are precluded them for moving on to the study.

Such as Comorbidities or.

Unfortunately side effects that have occurred for their current interventions prior.

Prior to actually enrolling in the study. So that's just a really challenging time for us to identify the patients and move them onto the study.

Back to your earlier point, the real gating item is simply moving those patients to identification and enrollment.

Alright, Thanks for answering my question is isn't the update thank.

Thank you.

Thank you. Our next question comes from Neena <unk> Garg with Citi. Your line is now open.

Nina Petrito: Hey guys, thanks for taking the question. Just kind of a follow-up to some of the questions that were already asked around the FTD study. I know some of the sites that you're using, like you said, are associated with some of the major registries for FTD, and so I'm just curious, are some of the challenges that you're seeing with getting the patients actually into the study, do you think that those are kind of similar challenges that are being seen by other studies in FTD that are being run, or is there something unique here, I guess in terms of the screening process, that's maybe making it more difficult for patients to get enrolled in the study? Thank you for the question. Thanks for joining us this morning. It's a great question.

Hey, guys. Thanks for taking my question just kind of a follow up just one of the questions already asked around the FTB study.

I know some of those sites that youre using like you said are associated with some of the major registries for TD and so I'm. Just curious are some of the challenges that youre seeing with getting the patients actually into the study.

Do you think that those are kind of similar challenges that are being seen by other studies in FTE that are being run or is there something unique here I guess in terms of the screening process, that's maybe making it more difficult for patients to.

Get enrolled in the study thanks.

Bruce Goldsmith: What we've done over the last six to 12 months is really look at our protocol, other protocols, as well as feedback from our investigators. And we have adjusted the protocol, to your point, to make sure that we're as appropriately broad as possible, while ensuring that, you know, that we, both the patients that we're treating as well as the therapeutic, PBFTO2, has an opportunity to provide therapeutic benefit. And that's always the challenge, I think, for all studies, nothing unique to what we're trying to do.

Thank you for the question thanks for joining us this morning.

It's a great question.

We've done over the last six to 12 months is really look at our protocol other protocols as well as feedback from our investigators and we have adjusted the protocol to your point to make sure that we're as.

Appropriately broad as possible.

While ensuring that their debt.

Debt.

The patients that we're treating as well as the therapeutic PBF tier two has an opportunity to provide therapeutic benefit and thats always the challenge I think for all studies nothing unique to what we're trying to do.

Bruce Goldsmith: And so that is certainly one consideration. I think the other consideration that we've certainly seen is that, as we've entered the program, we obviously have come on to the clinical development with two other companies enrolling. One, one gene therapy, and obviously one of a much larger patient population looking at a phase three study for the sirtillin antibody. And what, you know, the challenge that presented is that the immediately available patients, maybe 12 months ago, were obviously, if possible, that is a viable alternative because there are no treatment opportunities.

And so that is that is certainly one consideration I think the other consideration that we've certainly seen as that.

Yes.

As we've entered the program, we obviously have come onto the <unk>.

Clinical development with two other companies enrolling one gene therapy, and obviously, one a much larger patient population looking at a phase III study for <unk> for.

For the start till it antibody.

And what the challenge that presented is that the immediately available patients maybe 12 months ago, where obviously.

If possible.

<unk> is a viable alternative because there are no treatment opportunities. So what we're focusing on is.

Bruce Goldsmith: So what we're focusing on is really the patient population that was not addressed by those opportunities, or identifying new patients. So, I don't think there's anything idiosyncratic about our enrollment criteria or our process that we've seen or, in fact, gotten feedback from our various sites.

Is really the patient population that was not addressed by those.

Those opportunities or identifying new patients.

So I don't think theres anything idiosyncratic about our enrollment criteria or our process that we have seen or in fact gotten feedback from our various sites, but it is it is just the challenge I think of enrolling patients in this patient population, where there is not typically a screening from a genetics perspective, so that's why.

Bruce Goldsmith: But it is just the challenge, I think, of enrolling patients in this patient population where there is not typically a screening from a genetics perspective. So that's why we, and just to go back one further step, that's why we and others are investing quite a bit of time and funding for genetic testing and for FTD awareness. Got it.

And just to go back one further step that's why we and others are investing quite a bit of time and funding for genetic testing and for STD awareness.

Nina Petrito: So just to clarify, when you say that you're looking kind of for a population that's not addressed by some of the other programs, that's not something necessarily built into the actual inclusion criteria, right? It's just patients that haven't been identified yet. So you have to do a little bit more like work to kind of identify them.

Got it so just to clarify when you say that youre looking kind of for a population that is not addressed by some of the other programs that's not something necessarily built into the actual inclusion criteria. It's just patients that haven't been identified haven't been identified yet. So you have to give a little bit more like mark to kind of identify them first.

Bruce Goldsmith: Correct. And just to clarify, it's not that we have entry criteria that's different or a different patient population. We wanted to make sure that we had as broad a population as feasible and appropriate for studying the therapeutics. So we looked at the other protocols and we looked at and we discussed with investigators to make sure that we were as aligned as possible, taking into consideration our own goals as well.

Correct and just to clarify it's not that we are have entry criteria, that's different or a different patient population. We wanted to make sure that we have as broad a population as feasible and appropriate for studying the therapeutic so we looked at the other protocols and we looked at and we discussed with investigators to make sure that.

We were as aligned as possible taking into consideration our own goals as well.

Bruce Goldsmith: But also the timing, I think, has just made it so that the population has changed because the available previously identified patients may have gone to other studies. So that's why we and others are focusing on the genotyping and identifying additional patients and moving those patients into therapy. Okay, got it.

But also the timing I think is just.

Made it so that the population has changed because the available previously identified patients may have gone to other studies. So we are that's why we and others are focusing on.

Geno typing in identifying additional patients and moving those patients into therapy.

Okay got it. Thank you. Thank you.

Operator: Thank you. Thank you. Our next question comes from Yaron Werber with Cowan. Your line is open. Great, thanks for taking my question. Bruce, I actually wanted to shift to MLB.

Thank you. Our next question comes from Iran. Werber with Cowen Your line is open.

Great. Thanks for taking my question.

Bruce I actually wanted to shift to MLP youre going to be filing the IND.

Yaron Werber: You're going to be following the IND mid-year. I assume you're targeting the aryl sulfatase A enzyme. Can you comment a little bit, what kind of an AV vector are you planning on using?

Year.

I assume you are targeting.

Sulfur.

Enzyme.

Can you comment a little bit what kind of an AAV vector are you planning on using.

Bruce Goldsmith: I assume it's obviously going to be ICM. Are you going to be doing late infantile or early juvenile? What kind of end point and how is the approval of MLB in Europe, admittedly sales and so forth, fairly small impact enrollment?

I assume it's obviously going to be ICM or youre going to be doing late infantile early juvenile.

What kind of endpoints and how does the.

Approval of <unk> in Europe .

Admittedly sales and so far fairly fairly small impact enrollment. Thank you.

Bruce Goldsmith: Thank you. Thank you, Ron. Yeah, great question and I appreciate it. And we're really excited about the potential of moving forward with MLB because of the synergy we have across the GM1 CRAB-A experience as well as the alignment with MLB. So to your point, we're using the exact same capsid, which is HU68. Obviously, the synergy is with GM1 that it is a lysosomal storage disease. In addition, it is ICM as well.

Yes, great question and I appreciate it and we're really excited about.

The potential of moving forward with MLD because of the synergy we have across the GM one crab.

Experience as well as.

The alignment with MLD so to your point, we're using the exact same capsid, which is <unk> hundred 68, obviously the synergy is with GM. One that is a lysosomal storage disease. In addition, it is ICM as well so.

One of the one of the things that we are certainly interested in is the GM. One program continues to develop as well as the krabbe disease is that these there's a lot of synergy both between the research and development ideas and also the potential the potential market to your second question.

Bruce Goldsmith: So one of the things that we're certainly interested in is the GM1 program continues to develop as well as the CRAB-A disease is that there's a lot of synergy both between the research and development ideas and also the potential market to your second question. The way we're thinking about this is actually quite similar to the approach for CRAB-A disease. Lameldi has had absolutely remarkable effects on patients with MLD.

The way we're thinking about this is actually quite similar to the approach for krabbe disease.

It has had absolutely remarkable effects on patients with with MLD, obviously, that's a patient population there that takes a stem cells ex vivo.

Bruce Goldsmith: Obviously, that's a patient population there that takes stem cells ex vivo, has gene therapy, and then re-infused, and with myeloblation as well. So it has similarities to a stem cell approach for CRAB-A disease in that there is a focus on patient population, which are largely asymptomatic in MLD as well as CRAB-A disease. So the way we're thinking about this is potentially moving earlier in the disease treatment for pre-symptomatic or asymptomatic, as well as potentially initial signs of the disease for MLD.

Has gene therapy, and then re infused so and with my oil ablation as well. So it has similarities to a stem cell approach for krabbe disease and that there is a focused on patient population, which are largely asymptomatic and in MLD as well as krabbe disease. So the way we're thinking about this as potential.

Moving earlier in the disease treatment for <unk>.

Pre symptomatic or asymptomatic as well as potentially initial signs of those diseases the disease for MLD.

Bruce Goldsmith: And most likely, we haven't gone into a lot of detail about MLD, but what we're thinking about is also going after an infantile population first, similar to GM1 and CRAB-A, for initial clinical proof of concept. So it's been some time since we brought forward the initial programs, but what we prefer to do is have the discussions with FDA as we file the IND and then go into more details about the actual clinical protocol because, as you know, based on feedback from FDA, that can change over time.

And most likely we will also we haven't gone into a lot of detail around the MLP, but what we're thinking about is also going after in infantile population first.

Similar to GM on crab eight for initial clinical proof of concept so.

It's been sometime since we brought forward the initial programs, but what we prefer to do is have the discussions with FDA as we file the IND and then go into more details about the actual clinical protocol because as you know based on feedback from FDA that can change over time.

Bruce Goldsmith: So that's the way we're thinking about it is really just a alignment with where a limaldi may have benefit or may have benefit obviously in Europe and then the US and then treating patients that that doesn't quite meet or earlier in the patient population. So really excited about the IND and again the synergy between the various programs.

So that's the way we're thinking about it is really just a alignment with where <unk> may have benefit or may have benefit obviously in Europe and in the U S. And then treating patients that that doesn't quite meet or earlier in the patient population. So really excited about the IMD and again the synergy between the various programs.

Thank you.

Operator: Thank you. Thank you. Our next question comes from Deb Chattopadhyay with Guggenheim. Your line is open.

Thank you.

Next question comes from Doug <unk> with Guggenheim Your line is open.

Deb Chattopadhyay: Hey, good morning and thank you for taking my question. So just to follow up on the MLD program. How should we think about reconstitution of glial cells and its implication for disease reversal versus the bucellophane conditioning that's used for antiviral gene therapy?

Hey, good morning, and thank you for taking my question. So just to follow up on MLD program.

How should we think about reconstitution of clear cells and its implication for disease reversal versus the b cell phone conditioning thats used for antiviral gene therapy.

Eliseo Salinas: Yeah, no, that's a great question. I'm going to ask Aliseo to jump in. Okay, so, yeah, so, we have a decent knowledge of the mechanism of action of lipomyelid and how it achieves the clinical result that we have seen. As you know, the approach with the transgene in our construct is completely different, it's orthogonal to that, and we believe it's more fundamental. So it's early, soon we're going to have the publications, the pro-clinical publications showing a little bit more details about your specific question in terms of clear intervention and participation on the mechanism of action. At this stage, what we can say is that it's a completely different approach that we believe is closer to the core of the side of the action and the disease. Got it, that's helpful.

Yes, no. That's a great question I'm going to ask <unk> to jump in.

Okay. So yes.

We have a decent knowledge of the mechanism of action of Lytham, LD and and how how is achieved.

Yes.

The clinical.

All of that that we have seen.

As you know the approach with the transgene.

And in our comp stroke.

Different orthogonal to that and we believe it's more fundamental so it's early suite, we're going to have their applications.

The preclinical publications showing a little bit more detail about your specific question in terms of glial intervention and participation on the mechanism of action, but.

At this stage, what we can say is that is a completely different.

Approach that we believe is closer to the cohort of the.

<unk>.

Side of the action and disease.

Got it that's helpful and just to.

Eliseo Salinas: And just a follow-up question on the FTD-GRN program. Could you help us think through where the starting dose could line up versus the GM-1 program, given that you'll be treating adults versus infantile patients? Yeah, absolutely. So in all of the programs, we dose based on anticipated or expected or projected brain weight in terms of genocopies per gram. So the starting dose for FGD is 3.3 E10 per estimated gram weight. And for adults, the estimated gram weight of an adult brain is approximately 1.6 kilograms.

Follow up question on the <unk> program.

Could you help us think through where the starting dose could line up versus the GM one program given that you'll be treating adults versus.

Infantile patients.

Yes, absolutely so in all of the programs we dose based on.

Anticipate our expected or projected.

Brain weight in terms of genome copies per Gram.

So the starting dose for FTE is three three <unk> for estimated graduate and for adults the estimated grandma or an adult brain is approximately one six kilograms.

Eliseo Salinas: Approximately, sorry. Yeah, okay. And the pediatric patients is, it depends on the age, but it's approximately between 800 grams and one kilogram depending on the age.

Proximately sorry.

Yes, Okay and.

Ed.

Pediatric patients is it depends on the age but its approximately between 800 grams and one kilogram depending on the age so in absolute Gino copies. It may be double but in the genome copy program. It's basically the same as the GM on starting dose.

Eliseo Salinas: So in absolute genocopies, it may be double, but in the genocopy per gram, it's basically the same as the GM1 starting. Appreciate it. Thank you so much and good luck. Thank you. Thank you. Our next question comes from Laura Chico with Redbush. Your line is open.

I appreciate it. Thank you so much and good luck.

Thank you.

Thank you. Our next question comes from Laura Chico with Wedbush. Your line is open.

Laura Chico: Good morning. Thank you for taking the question. I actually have two.

Hi, Good morning, Thank you for taking the question.

Actually have two so first obviously early days here for a TV anchor Bay, but I'm wondering how much should we read into whether it's screening complexities and formula future addressable market and then Ah.

Question on capital allocation R&D prioritization.

What levers do you have available to extend cash runway beyond 'twenty, three and I guess kind of related to that any comments you might be able to private directionally.

Now it's been could change over that period.

Operator: So first, obviously early days here for FTD and CREB-A, but wondering how much should we read into whether screening complexities inform on a future addressable market. And then a question on capital allocation, R&D prioritization, what levers do you have available to extend cash runway beyond 23? And I guess kind of related to that, any comments you might be able to provide directly on how spend could change over that period? Thanks. Thank you. Yeah, Laura, thanks very much. I'm going to make a comment and then turn over to Eliseo.

Yes, Laura Thank you very much I'm going to make a comment and then turn it over to LSA.

Bruce Goldsmith: So that I think the entire field for frontotemporal dementia is actually increasing the amount of screening that's going on with the recognition that genotype is actually important in interventions. But up until recently, there really haven't been a lot of studies involved in doing that. So there's certainly a lot of interest. And, for example, we attended the all FTV study group meeting last fall. And there is an increase in the need for genotyping for C9R, for GRN, etc.

So I think the entire field for frontal temporal dementia is actually increasing the amount of screening that's going on with the recognition that genotype genotype is actually important in interventions.

But up until recently, there really haven't been a lot of studies involved in doing that so there's certainly a lot of interest in for example, we attended the all FTB study group meeting last fall and there is an increase in the need for genotype for C&I, nor for F <unk> and et cetera.

Bruce Goldsmith: It's really getting that message out there. And I think there are a number of companies trying to do that. So it's really just the, I think the, it's like a pediatric disease where there's not newborn screening. There's just a lot of efforts then in terms of getting those patients screened and the subtype identified. So it's really a, it's not a, I think, read through on the, on the field.

It's really getting that message out there and and I think theres a lot. There are a number of companies trying to do that so it's really just I think the it's like a pediatric disease, where theres not newborn screening.

Just a lot of efforts then in terms of getting those patients screened and the subtype identified so it's really it's not a I think read through on the field I think its just that its early days.

So with that as introductory comments I will say Oh do you want to jump in as well, yes, Laura so.

Bruce Goldsmith: I think it's just that it's early days. So with that as introductory comments, Eliseo, do you want to jump in as well? Yes, Laura. So, so the, First, a statement of fact. We are very happy with the momentum of GM1 and we are disappointed, with Crabbe on it.

So.

First our statement of facts.

We are very happy with the momentum on June one and we are disappointed with.

<unk>.

But that should it clouds the analysis of the facts.

Indeed, we are a proven January and February last year, that's 14 months ago.

Eliseo Salinas: But that shouldn't cloud the analysis of the fact. The INDs were approved in January and February last year, that's 14 months ago. In a trial like this one, you need two things, identify patients and open insights, but those are sequential. Before you open insights, identifying patients cannot result in enrollment.

In a trial like this one you need two things identified patients and opening sites, but those are sequential before you opened besides I think defined patients cannot result in enrollment.

Eliseo Salinas: In the first seven months of those 14th, we opened one site. In the second seven months, we opened 10 sites. Now we have six sites open in GM1, and the momentum is great. As you know, there are fewer GM1 patients than granulin-FPB patients, and yet we're finding it very easily because those sites are open. In the FTD we have one side and soon, as Bruce said, there will be more open sides that will open up the gate to that funnel that we already see.

In the first seven months of those 14th we opened one site.

And the second seven months, we opened 10 sites.

Now we have six sites opened on June one and the momentum is great.

As you know there are fewer GM, one patients that granularly FTB patient and yet were founded very easily because those sites are open.

And in the in the FTP, we have one site and soon as Bruce said, there will be more open sites that will open up the gates to <unk> that we already initiated so thats. What we are now 100% focused on executing the opening of the sites and continuing the patient identification.

Eliseo Salinas: So that's what we are now 100% focused on executing the opening of the site and continuing the patient identification that Bruce summarized. So that's why we are confident that both for PREP-A and FPD, for PREP-A, we have four sites open now. That's enough to open the gates to the patients available. So that's why we are confident that soon we'll have patients in both two states. And Laura, on your second question, you have Simone, go ahead, please.

That Bruce summarized so thats why we are confident that both for <unk> and if you leave for Columbia, We have four sites open now.

Enough to open the gate to the patients available. So that is why we are confident that soon we will have patients in both two studies.

And Laura on your second question, yes.

Simona King: Yeah, great. Thanks, Laura, for the question. Yeah, so let me start off addressing, I think, the first part of your question on capital allocation.

Great. Thanks, Laura for the question, Yes, So let me start off addressing I think the first part of your question on capital allocation. So I think what's important to note and you can see that in our historical financials as we broke down the program specific expenses.

Simona King: So I think what's important to note, and you can see that in our historical financials, is we broke down the program-specific expenses by our three clinical programs, PEN, as well as MLD, and the rest being other programs in Discovery, so the other PEN expenses. So when you look across those investments, it's very clear that a lot of our investment, about 85% of that, is really targeted towards the three clinical programs plus MLD.

Our three clinical program spend.

As well as the MLP and the rest of the other programs in discovery.

<unk> expenses and when you look across those investments, it's very clear that a lot of our investment about 85% of that is really targeted sorry, three clinical programs plus MLP.

Simona King: And within that, we don't break it down specifically around manufacturing and clinical operations, but that's inclusive of PEN behind these two areas. And we expect that, you know, essentially to continue in terms of the focus from an overall investment on those three programs. And then in terms of the other question on the cash runway, you know, as we stated, we feel very confident that we can fund our operations until the end of 2023, but of course, we can continue to focus on cash management and refine how we're investing behind not only our key programs, but there are other expenses that support the company's infrastructure and so forth. Generally, we do expect our cash firm to be relatively consistent with prior orders and continue to be within the range, as you've seen there, about $35 to $45 million.

Within that we don't break it out specifically around.

Manufacturing and clinical operations, but that's inclusive.

And behind two areas and we expect that.

To continue in terms of the focus from an overall investment.

Program.

And then in terms of the.

The other question on the cash runway.

We stated we feel very confident that we can fund our operations until the end of 2023, but of course, we can continue to focus on cash management and refine how we are investing behind our not only our key program, but there are other expenses.

So part of the company's infrastructure and so forth.

In Italy, we do expect our cash burn to be relatively consistent.

With prior quarters and continue to be within the range that we've seen there are about $35 million to $45 million per quarter.

Thanks very much.

Operator: Thanks very much. Thank you. Our next question comes from Daniel Brillo with Raymond James. Your line is open. Hey guys, this is Alex on for Danielle.

Thank you. Our next question comes from Daniel <unk> with Raymond James Your line is open.

Hey, guys. This is Alex on for Danielle Thanks for taking my question.

Alex: Thanks for taking our question. Forgive me if you've already stated, I've got a granular question and then a zoomed out one. Has UPenn, with respect to the FTD program, has UPenn permitting, are they permitting elective procedures now, as well as in-person screenings? And if so, could you comment on the cadence of the screening process if COVID is permitting an increased cadence in in-person screenings? And then to zoom out, have you seen any, you know, translating the GM1 world results, the increased patient enthusiasm for those results? Do you see, have you seen those translate to recruitment enthusiasm for your other FTD and CREB-A programs? Thanks so much.

Forgive me if you've already stated I've got a granular question and then assumed outlined has U Penn with respect to the <unk> program is U Penn permitting are they permitting elective procedures now.

As well as in person screenings, and if so could you comment on the cadence of the screening process.

Covid is <unk>.

Permitting.

<unk> cadence in person screenings, and then to zoom out.

Have you seen any.

Were translating the GM one world results the increased patient enthusiasm for those results do you see have you seen those translate to recruitment enthusiasm for your other XD and crab programs. Thanks, so much.

Bruce Goldsmith: Thanks very much for the question. So in general, what we have seen is that the interrupt, and I'll go to your Penn question in particular, but in general, what we've seen is that most of the sites that we have been interacting with, the COVID restrictions are starting to lift, the elective surgery, you know, interruptions that we saw really intensely last summer and somewhat over the fall have also started to lift. So Penn, for example, was not, was going for a, was going through a hybrid on-site visit throughout the winter that is starting to lift as well.

Thanks very much for the question so in.

In general what we have seen is that the.

So to your pen question in particular, but in general what we've seen is that most of the sites that we have been interacting with the COVID-19 restrictions are starting to lift the elective surgery.

Interruptions that we saw really intensely last summer and somewhat over the fall have also started to lift so.

<unk> for example was not was going for was going through a.

Hybrid onsite visit throughout the winter that is starting to lift as well so to your point, we have had difficulty, especially patients with frontal temporal dementia.

Bruce Goldsmith: So to your point, we have had difficulty, especially patients with frontal temporal dementia, you know, that have both severe speech aphasia and emotional disturbances, just on-site visits have been challenging, not particularly for us, but just we've heard from sites. So we do hope that that's going to help alleviate things. And Penn has allowed, to our knowledge, elective procedures as well as freed up now on-site visits, those two things being very important for final assessments and moving forward with the ICM procedures. So great question and certainly been interrupted throughout the year.

That hassle severe speech of Asia, and emotional disturbances just onsite visits have been challenging.

Particularly for us, but just we've heard from sites. So we do hope that thats going to help alleviate things intend.

Has allowed to our knowledge elective procedures as well as freed up now onsite visits those two things being very important for final assessments and moving forward with the ICM procedures. So great question and certainly been interrupted throughout the year.

Bruce Goldsmith: For GM, for the other question on GM1 and CREB-A, yes. So it's a great and important question. There hasn't been, I think, so much read-through on necessarily on the frontal temporal dementia, although we've certainly talked to our physicians about this. And one of the pieces of feedback we've heard is certainly very positive that ICM is safe in the pediatric patients. We've also seen at World, I think, up to around 20 or just over 20 procedures using ICM across various studies have been reported with no safety effects.

For for the other question on <unk>, Yes, so it's a great and important question. There hasnt been I think so much read through on necessarily on the frontal temporal dementia, although we certainly talk to our physicians about this and one of the pieces of feedback. We've heard is certainly very positive that ICM.

Is safe in the pediatric patients. We have also seen at world I think up to around 20% or just over 20.

Procedures using ICM across various studies have been reported with no safety effects, we've been communicating that message as well and that helps I think from the frontal temporal dementia perspective, just knowing that ICM is gaining traction not only in the adult populations, but also pediatric.

Bruce Goldsmith: We've been communicating that message as well. And that helps, I think, from the frontal temporal dementia perspective, just knowing that ICM is gaining in traction, not only in the adult populations but also pediatric. But the real read-through, I think, has been in the CREB-A population. We've certainly been in touch with our investigators but also at the World meeting, spoke to a variety of groups that support from an advocacy perspective the CREB-A community. And, again, the ICM, the HE-68, it's a lysosomal storage disease.

But the real read through I think has been in the <unk> population, we've certainly been in touch with our investigators, but also at the World meeting spoke to a variety of groups that support from an advocacy perspective.

<unk> community and the again, the ICM to <unk> hundred 68, its a lysosomal storage disease, we're looking for treating children and of course. The developmental gains are all received is extremely promising. So we actually have seen quite a lot of positive feedback from the <unk> community and.

Bruce Goldsmith: We're treating children and, of course, the developmental gains are all perceived as extremely promising. So we actually have seen quite a lot of positive feedback from the CREB-A community and hope that reads through to accelerating the study and getting patients on the therapy. Great, thanks so much for the color.

I hope that reads through to accelerating the study and getting patients on monotherapy.

Great. Thanks, so much for the color.

Thank you.

Operator: Thank you. Thank you. Our next question comes from Yun Zong with BTIG. Your line is open. Hi. Good morning.

Thank you. Our next question comes from Yun Zhong with <unk>. Your line is open.

Yun Zong: Thank you for taking the question. So, on the GM1 data readout in the second half of 2022, is it reasonable to expect that the data readout will only be coming from one patient, from the high-dose cohort and the early infantile patient? And sorry for asking the same question, although it's on GM1 program.

Hi, Good morning, and thank you for taking my question. So Jim one data readout in the second half of 2022 is it reasonable to expect that the data readout will only be coming from one patients from the high dose cohort and the early infantile patient and sorry for asking the same question, although it sounds <unk>.

Bruce Goldsmith: Have you identified the second patient for each cohort? And I just wanted to confirm that the dosing of the second patient, it's not dependent on data from the first patient, is that correct? Great.

Graham.

<unk> the second patient for each cohort and just wanted to confirm that the dosing of the second patient.

Not dependent on data from the first patient is that correct.

Bruce Goldsmith: Thanks for the question. So, first, we expect to report by the end of the year is cohort level data on cohorts two and three, which would be, again, two patients in those cohorts each. And that's, and the anticipation is, is that we are going to be able to enroll the second patient in both cohort with, you know, as quickly as possible. And to your point, each patient right now, under the FDA guidance, has a 60-day interval in between dosing.

Great. Thanks for the question. So first week, we expect to report by the end of the year is a cohort level data on cohorts, two and three which would be again to patients in those cohorts each.

And the anticipation is is that we are going to be able to enroll sect.

The second patient in both cohort.

With.

As quickly as possible and to your point each patient right now under the FDA guidance has a 60 day interval in between dosing that allow us for the Biomarkers at 30 days similar to cohort one as well as the safety follow up through the end of day <unk>.

Bruce Goldsmith: That allows for the biomarkers at 30 days, similar to cohort one, as well as the safety follow-up through the end of day 60. So that would, that's required before we dose our second patient in each of these cohorts. And then any subsequent cohort, cohort four, for example, would require an IDMC and then move it forward.

So.

So that would that would.

That's required before we dosed our second patient in each of these cohorts and then any subsequent cohort cohort for for example would require an <unk> and then moving forward. So what we're expecting to report out as two patients from the high dose late infantile and two patients from the low dose early infantile.

Bruce Goldsmith: So what we're expecting to report out is two patients from the high-dose late infantile and two patients from the low-dose early infantile. And your last question is the quote-unquote identification of patients. So we are, I think as we mentioned at some point, we are having a significant interest in this study, which is fantastic, and we're trying to get patients identified, adjudicated for the potential of enrolling and then enrolling as quickly as possible after that 60-day interval.

We do.

And your last question is is the quote unquote identification of patients. So we are.

I think as we mentioned at some point.

We are having a significant interest in this study which is fantastic and.

We're trying to get patients identified adjudicated for the.

The potential of enrolling and then enrolling as quickly as possible after that 60 day interval.

Bruce Goldsmith: Okay, so the first release had safety and biomarker, but given the fast disease progression maybe in the early infantile patient, do you think, for example, the six-month data could allow you to report some efficacy signal as well by year-end? It's a great question.

Okay. So the press release had safety and biomarker, but given the disease progression maybe early infantile patients do you think for example, the six months data could allow you to report some efficacy signal as well by year end.

Bruce Goldsmith: So similar to what we did in cohort one, we will make that decision kind of when we when we see what the data is in the data maturity. You know, similar to what we said in December, we had six months follow up on one patient and only two months follow up 60 days on the on the second patient. Then we reported clinical efficacy data on both when we actually got to that three month time point, which was the first evaluation of both the Bayley and Vineland.

It's a great question. So similar to what we did in cohort one we will make that decision kind of when we when we see what the data is in the data maturity.

Similar to what we said in December we had six months follow up on one patient and only two months follow up 60 days on the on the second patient.

And then we reported epic clinical efficacy data on both when we actually got to that three month time point, which was the first evaluation of both the Bally in Vineland. So we don't want to commit to that but we're certainly.

Bruce Goldsmith: So we don't want to commit to that, but we're certainly, you know, we just have to let them data mature. It is possible that we would have data by the end of the year as longer term follow up. It really just depends on when those visitors are scheduled, when those databases, you know, come in house and when we can get enough comfort that we understand the data.

We just have to let them data mature it is possible that we would have data by the end of the year as longer term follow up it really just depends on when those visitors are scheduled when those databases come in house and when we can get enough comfort that we understand the data. So we're committing only 230 day biomarker and 60 day safety state.

Bruce Goldsmith: So we're committing only to 30 day biomarker and 60 day safety. Stay tuned and we'll update you as we go through the year. Great, thank you very much. Thank you. And I'm currently showing no further questions at this time. Ladies and gentlemen, thank you for participating in today's conference. You may now disconnect. Everyone have a great day. Thank you. Music

Stay tuned and we'll update you as we go through the year.

Great. Thank you very much.

Thank you.

And Im currently showing no further questions at this time, ladies and gentlemen, thank you for participating in today's conference. You May now disconnect everyone have a great day. Thank you.

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Okay.

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