Q3 2022 Passage Bio Inc Earnings Call

November 10, 2022

[music].

Thank you for holding and good morning, and welcome to the passage Bio's third quarter 2022 financial and operating results conference call. At this time all participants are in a listen only mode. Following the formal remarks, we will open the call up for your questions. Please be advised this call is being recorded at the company's request now I'd like to turn the call over to Stuart Henderson, Vice President corporate develop.

Investor Relations Stuart. Please proceed.

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 and news on.

On today's call. Our recently appointed Chief Executive Officer will Chu, who will review our third quarter 2022, and recent business highlights Mark Forman, Our Chief Medical Officer will review, our clinical programs and Simona King Our Chief Financial Officer will review, our third quarter 2022 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 progress of clinical trials and the availability of clinical data from such trials, our expectations about our collaborators and.

Partners the ability to execute key initiatives the ability of our lead product candidates to treat their respective target CNS disorder manufacturing plans and strategies, our expectations with respect to cash runway in 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.

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 its 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 reflect events or circumstances that occur.

On this call.

It is now my pleasure to pass the call over to Bill.

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

Before providing an update for the quarter I want to take a moment to say how thrilled I am to have joined the talented team here at passage bio.

I've worked with genetic medicines for the last eight years and as a physician everyday I continue to be inspired and motivated by the dramatic impact east therapies can have on patients and their families.

Humbled by the opportunity to lead path is through our next phase of development as we work to bring life transforming therapies to patients with CNS disease.

Over the past year passages built real momentum in advancing our portfolio.

The core value proposition of our programs remains compelling and in the face of a difficult external market, we have a strong.

To support our operations.

As we pursue our ambitious mission, we must continue to be thoughtful in our resource allocation to ensure we can successfully deliver meaningful clinical data across our programs and maintain a best in class pipeline.

With these goals in mind and after conducting a thorough review of our business, we will be refocusing our efforts and streamlining our operations in the following ways.

We will continue to focus on clinical trial execution and advancing our imagine one clinical trial for <unk> ganguly doses in our uplifted clinical trial for Frontotemporal dementia.

Both of which have the potential to make a differential impact on patients' lives.

We will prioritize advancing our preclinical programs in <unk> terrific lateral sclerosis, and Huntington's disease through our ongoing partnership with Penn Gene therapy program.

We will continue to leverage our strong in house analytical capabilities at our CNC lab at Princeton West as we believe these capabilities provide a competitive advantage and are critical to support ongoing and future clinical development of our programs.

Due to financial considerations, we are stopping further clinical development of PV <unk> III for krabbe disease.

We understand this is disappointing for the patient communities and for the healthcare providers caring for patients with <unk> disease, and we are committed to exploring strategic alternatives to advance this program.

As well as our PV MLR for program for Medicare Medic, lipid dystrophy, which received IND clearance earlier this year.

Operationally, we will streamline our organization via a 23% workforce reduction and decreased operating expenses.

As a result of these changes we now expect our existing cash resources to fund operations into the first half of 2025.

These prioritization decisions were difficult because of their impact on patients their families and providers and on the many talented people at passage bio who work to move these programs forward.

That said these changes put our company in a strong position to succeed in bringing our most advanced programs to patients in need.

We have built strong momentum in our GM, one FTE programs throughout 2022 and continued to build upon that momentum.

We have established a global network of trial sites with active sites in the United States, Brazil, Canada, and the U K.

For GM, one we've dosed a total of seven patients and expect to complete treating patients in dose ascending phase of our phase one two study by year end.

We plan to report initial safety and biomarker data from cohorts two and three from the GM One program in December .

As we move into 2023, we expect initial data from cohort four to become available and we plan to engage with the regulatory agencies to align on the Registrational pathway for this program.

In August we were excited to dose the first patient in our uplifted trial for Frontotemporal dementia.

We are encouraged by the increase in genetic testing observed as a result of our patient identification of initiatives and look forward to continued enrollment in this study.

The changes we are making will allow us to focus our efforts on continuing the positive momentum into 2023.

I am excited by the path ahead for passage.

We have a mission to bring life transforming therapies to patients with CNS disorders, and we plan to deliver on that mission.

With that I will now turn it over to mark to discuss our clinical programs.

Thank you will.

Let me begin with our lead program <unk>, one for <unk> Gangliosidosis.

<unk> is a fatal neurological lysosomal storage disease.

<unk>, one 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 to mortality within several years.

Patients with Gen. One are rare and underserved population and there are no disease modifying therapies for the disorder currently.

Our imagine one clinical trial focuses on the early and late infantile form of <unk>, which are the most severe forms of the disease.

The dose escalation portion of this global Phase <unk> trial is an open label study with <unk>, one enrolling four distinct cohort divided by age and dose level.

Our approach uses a next generation proprietary AAV <unk> 68 caps it administered via the cisterna Magna to deliver a codon optimized <unk> transgene to increased beta galactosidase enzyme activity in the brain and peripheral tissue.

Interim data presented from cohort one show that <unk> is well tolerated with a positive safety profile demonstration of functional transgene expression and meaningful gains in developmental milestones.

As previously discussed we have experienced strong momentum in our imagine one trial.

To date, we have dosed a total of seven patients in the study.

We have completed dosing of cohorts, one two and three representing the low dose cohorts in both early and late infantile patients and the high dose late infantile cohort.

We're also pleased to have dose the first patient in cohort four high dose early infantile.

This is the final cohort in the dose ascending phase of the study and we remain on track to complete dosing in this cohort by year end.

As will mentioned we plan to host a webcast to report initial safety and biomarker data from cohorts two and three in December and we'll also update cohort one data to crude additional follow up at that time.

The components of these data will be similar to what we have previously reported for cohort, one including safety and Tolerability beta galactosidase enzyme activity levels, and CSF and serum and initial clinical development assessments on the Vineland II Bailey III scales.

As data from the study continues to mature into 2023, including initial data from cohort four we look forward to better understanding how dose and patient populations relate to treatment effect and plan to engage with the regulatory agencies to align on the registrational pathway for the program.

Next let me discuss Pbf's T O two for frontal temporal dementia with granular mutations.

<unk> is a devastating form of early onset dementia affecting patients between the ages of 40% to 65.

The form of the disease, we are seeking to treat with our therapy is caused by a granular or GRN gene mutation, which results in a deficiency of pro granular.

It is estimated that about 5% to 10% of SCD is caused by a GRM mutation.

We are utilizing the AAV, one capsid to deliver a functional copy of the GRM gene by ICM delivery to the CSF.

The goal of this treatment and delivery approach is to potentially provide higher than normal levels of the <unk> proteins to the CNS to overcome the <unk> deficiency in GRN gene mutation carriers.

Our uplifted clinical trial investigating two dose levels of <unk> and its sequentially enrolling two cohorts.

Based on the results of the first two cohorts, we have the optionality for a third dose level cohort the.

The primary endpoint of the study is to evaluate the safety and Tolerability of <unk> <unk>.

Secondary endpoints include disease, Biomarkers and clinical outcome measures.

In August we are excited to report that we dosed the first patient in the study following the improved momentum experienced throughout patient identification and recruitment initiatives.

Patient identification remains a key focus for us and we continue to employ a variety of initiatives, including efforts to increase genetic testing among STD patients through our partnership with informed DNA.

This partnership provides no cost genetic counseling and testing for adults who are diagnosed by their physicians with FTE.

These efforts have increased genetic testing among STD patients over the last few months.

We look forward to sharing clinical data from this program as patient enrollment in that cohort continues to adapt with that I will now turn the call over to Simona to review our financials.

Thank you Mark.

We reported in our press release. This morning, we ended the third quarter with approximately $213 $8 million in cash cash equivalents and marketable securities compared to $239 3 million as of June 32.

<unk> 2022.

On <unk>, our operations and further prioritizing our research and development effort. We expect these existing cash resources to fund operations into the first half of 2025.

R&D expenses were $15 $4 million for the quarter ended September 32022, compared to $26 6 million for the same quarter in 2021.

The decrease was primarily due to a decrease of $8 $8 million in clinical and manufacturing expenses, which relates to the timing of our manufacturing activities to support our clinical trial area.

There is other expenses had a net decrease of $2 4 million dollar.

G&A expenses were $10 $7 million for the quarter ended September 32022, compared to $15 million towards the same quarter in 2021.

The decrease was primarily due to a $4 million decrease in personnel related and share based compensation expense related to our March 2020 to mark parts reduction and a zero point $4 million decrease in our professional fees facilities and other expenses.

Net loss was $26 7 million for the quarter ended September <unk> 2022, compared to $46 $9 million for the same quarter in 2021.

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

Thank you Simona.

I'm thrilled to be leading passage bio through our next phase of development as we focus on execution and continuing to generate meaningful clinical data from our lead programs in GM, one an FPGA.

For <unk>, we look forward to reporting initial safety and biomarker data from cohorts two and three of our imagine one trial in December and we also plan to provide an update on cohort one at that time.

As we move into 2023 and the data from our clinical programs matures, we look forward to aligning on the Registrational pathway for GM, one and continuing to enroll additional patients in our uplifted trial.

Prior to taking your questions I would like to thank the patients families trial investigators our colleagues at the gene therapy program and importantly, all of the employees at passage bio who provided their support and dedication to achieving this mission.

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

Operator.

Ladies and gentlemen, if you have a question or a comment at this time. Please press star one on your Touchtone telephone, we will pause for a moment, while we compile our Q&A roster.

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

Hey, guys. Thanks for taking our question. This is rob on for Madhu.

First are there any safety issues that led to the discontinuation of the <unk> program and in terms of FTE D. How are you thinking about competing with other per granular and replacement drugs and the FTC space for patient recruitment and how.

How many of these patients are you looking to treat before disclosing data. Thanks.

Great. Thanks for the question so.

To answer your first question. This was a very difficult decision to stop a clinical program anytime you do that we understand the impact on patients and their families.

The decision to stop the <unk> program was purely a resource driven decision we had to make a hard financial decision and this is the one we made to advance our most advanced clinical programs, which are <unk> and SPD.

To answer your second question on FTB I think your question was about competitive recruitment.

I will give two pieces to that one.

As you know screening for this mutation is important part of recruitment for all all competitors in this space and so.

The more people that are out there talking about screening the better it is overall to improve the overall rate of screening.

So that's one thing the second thing I'll say is just in general in my experience with early clinical trials as trials gather more data and are able to share more data with trial sites.

<unk> improves I will say, we're very pleased with where we are in terms of we have three sites open for FTE. We have more sites opening in Q1 of next year and we have multiple patients with the <unk> mutation in the process of enrollment.

At our sites.

Okay.

I think the last part of your question was disclosing so we will we will look forward to sharing more data from cohort one of the uplift to trial in 2023.

Thank you one moment for our next question.

Our next question comes from your own Weber with Cowen Your line is open.

Hi, guys. Thanks, Thanks for taking the questions. This is brendan on for your own just a couple of quick ones from US first can you maybe remind us what the actual mechanism of action for the gene therapy at AOS.

Are using how are you actually looking to functionally correct with <unk> 72, pathology I know theres a couple of different ways people have tried.

And then wondering when we might actually get to see some preclinical data from that program.

And then.

Similarly for Huntington's, obviously, one concern some of these other.

People using genetic therapies in this space have run into is kind of penetration into some of the deeper brain structures. So assuming youre planning ICM administration for that as well what maybe it gives you confidence you'll be able to avoid.

Some of those pitfalls.

Yes, so we're really excited with the progress we've made together with our colleagues at GTP on our preclinical programs and Alice in Huntington's disease.

We're looking forward to sharing more milestones as we get them.

I'm going to turn it over to Mark to answer your question about our mechanistic approaches.

Yes.

Alright, thanks for the question so.

Our approach is using the gene therapy.

To reduce the expression of the pathological forms of the <unk> org.

As well as instead of a knockdown and replace strategy as well as provide a functional copy that we can use to restore function again the mechanism of action for.

So the mechanism pathophysiology of the disease of the of the C&I North mutations is not known so we believe that using a knockdown and replace strategy allows us the best chance of correcting.

The potential different.

Pathophysiological mechanism in the disease.

Okay great.

Just on Huntington's you Havent been in that you are able to get into the deeper branch structure. So far is that something youre seeing pre clinically.

Okay.

Alright.

Okay.

Yes, we're going to explore the effects of our route of administration and we will be we'll be happy to share more data as it emerges next year.

Okay. Thanks, very much guys.

One moment for our next question.

Our next question comes from Neil <unk> with regard with Citi. Your line is open.

Hey, guys. Thanks for taking the question so on PBF tier Q&A said earlier that you do have multiple patients with <unk> mutations in the process of enrolling at.

The three sites that you have opened so far I guess can you clarify are those patients.

Jeff.

Likely to actually.

To meet the enrollment criteria in the screening criteria and ultimately get dosed I'm, just trying to kind of understand the timing for potential data next year.

Yes, so thanks for the question so.

As will said earlier.

Our patient identification efforts have led to we feel a fairly robust funnel of individuals identified with STD and granular in gene mutations and.

And where we are now as those patients are being evaluated for suitability for enrollment in the trial.

And and and.

And so that will.

As we get further along I think that's what we're prepared to disclose at this time and we will as.

As we have a cohort of data later, we'll be happy to disclose more information.

Okay got it thank you.

One moment for our next question.

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

Hey, good morning, guys. Thank you very much for taking the question I just have three so on STD.

I might follow up and ask the question a little bit differently, but can you remind us what are your assumptions around screening failure rate for <unk> patients and then number two.

In the second cohort is there that same 60 day waiting period between enrollment of different subjects and lastly, just one on <unk>.

What areas specifically of alignment are you looking to get from regulators I guess any any clarity in terms of how youre thinking about that and whether a U S launch may come second to other geographies. Thank you.

So see if I can keep the questions asked right. So the first question was regarding the assumptions on the screen failure rate.

In the <unk> trial and.

<unk>.

In the <unk> trial, I mean, the credit the inclusion criteria that we currently are utilizing allow patients.

Okay.

A relatively broad for this first in human trial, which is really focused on safety.

So as long as patients are able to live in the community. They are eligible for enrollment in the trial. So in general we expect for patients that are identified with SPD and and program human gene mutations we expect the vast majority of them to be eligible for enrollment in the trial unless they meet specific exclusion.

Criteria regarding its craig's other health conditions.

The second question can you remind me.

Yes, yes, yes, just with respect to the FTE enrollment I believe in the first cohort.

60 days spacing between enrollment of subjects enrolled one way at 60 days.

Not necessarily clear it's in the subsequent cohort do you still have that 60 day weight between subs.

Subject enrollment.

Alright, so in the yes, so for all of the patients currently for the entire for the <unk> trial in the first.

PBF deal.

Protocol one.

There is a 60 day waiting period for all patients.

As we enrolled.

That trial.

Both in cohort, one and other and higher dose cohorts, we believe that's important.

As we need to establish safety at the higher doses as we escalate. So yes. There is a 60 day waiting period for all of our patients in the trial.

And the third question.

Was on.

Yes.

Okay.

Yes, so in terms of.

I think there are a number of things that we need that we would like to align with the health authorities.

<unk>.

As we as we gear up to initiate the Registrational study, which is.

Yes.

The use of our external cohorts to support the registration of that study and the study design itself and making sure that we have alignment with the agencies before we proceed with initiating that trial so that.

It will meet the.

Meet the requirements that the agencies are expecting in order to support a registrational study.

Thanks very much.

One moment for our next question.

Our next question comes from Danielle Brill with Raymond James Your line is open.

Hi, guys. Good morning, Thanks for the question.

A couple of bigger picture questions. Here first just can you walk us through how you decided which program to prioritize in the considerations that you made and then.

Pertaining to the <unk> program I'm, just curious what's the biggest.

Bottleneck here the challenge with Roku mandated opening sites identifying suitable patients are.

Motivating them to enroll in the study given competition. Thank you.

Yes.

Sure. So let me take the first question. So this was a difficult decision in terms of prioritizing our programs. Let me start by saying that all four of our clinical stage programs and I'm, including MLD and crab and this all four of our click.

<unk> stage programs have the potential to transform patients' lives.

We looked hard at all of the programs and where they where we made the decision to move forward with our most advanced clinical programs and that is GM, one and FTB.

Looking at our preclinical program or our partnership with Dr. Wilson and his team at GTP is critical to what makes passage bio passage bio and so we also have prioritized the most advanced programs there.

And in terms of our manufacturing capabilities, having our own in house analytical capability. We believe is a competitive advantage and allows us not only future success registration only but success in terms of executing on our clinical programs right now.

The second question was.

Bottlenecks.

Mark answer that but I will say that all of the things that you mentioned were focused on so you have to go across the board with reaching the patients keeping the patients all the way through the process getting more screening and of course getting more sites started so.

What we are going to be laser focused on this year is execution around all aspects of our clinical programs.

And we're going to be pushing on all of those aspects.

Alright.

Thanks, Jeff.

Just to sort of.

To go a little bit deeper.

As will said I think the two the two big things you had a patient identification specifically patients with GRN mutation has been one of the bottlenecks. The other is getting sites opened and we were as low as talked about we're focused on getting sites sites that we havent multiple sites open and we're looking to add multiple more sites in the coming months.

In addition, we have launched sort of a multi pronged effort to enhance our sort of patient identification activities, including efforts sort of locally set of site specific tailored activities that are that are around each of our individual or individuals sites.

Secondly, we have broad outreach to health care providers, who are who are caring for SCD patients to enhance their understanding of disease and the role of genetic testing to really increase the genetic testing throughput and the third thing is we're involved with a number of advocacy groups to really at a pre competitive level to once again increase awareness on <unk>.

<unk> testing and genetic counseling and the availability and the understanding of what.

There are multiple clinical trial activities and options there are for patients if they happen to test positive for it yet.

Various mutant gene mutations so all of those we believe have really started to bear fruit as we've mentioned a few times theirs.

We now have a funnel of patients that we feel that our recruitment and enrollment is going to proceed efficiently going forward.

Yes and.

Thanks, Mark and let me just remind everyone as Im sure you know our preclinical data and STB is quite strong we've shown.

We've been able to achieve super physiologic levels of program inland in the CSS and we are very much looking forward in 2023 to see how that preclinical data translate into the clinic as I mentioned before.

And we've seen this in GM one.

The more data that you actually generate the more interest.

The trial and so we're looking forward to seeing that effect also.

Our FTE trial.

Okay. Thank you so much I appreciate your additional color.

One moment for our next question.

Our next question comes from coal mine restarted your line is open.

Hi, Good morning, this is calling on for cooler two from us.

So for the <unk> program.

And you will no longer be providing an update.

Later this year and for the preclinical portfolio can you talk about factors that you're weighing in to prioritize advancing these programs.

Programs with with the GTP and all of the available options that you have left can you remind us of the timeline for opting in and selection of high tea, we have given that new strategies.

Okay.

Sure sure.

So first your first question on <unk> as we are no longer enrolling patients in this trial, we will no longer be reporting data from it.

We will continue to follow the first patient as per outlined in our clinical protocol.

Yes.

On the preclinical portfolio the prioritization was.

Was really our most advanced programs. So we're furthest along with both ALS and Huntington's and we have eight options remaining through 2026.

Yes.

Thank you one moment for our next question.

Our next question comes from you and so on with <unk>. Your line is open.

Hi, Good morning, Thank you very much for taking the questions. So the first question is a follow up question on credit program.

I understand that the TSMC deep the safety finding to be potentially related to study treatment or study procedures.

I wonder if you're able to make a conclusion, whether that was the case in <unk>.

That was the case I understand their accreditation probably have a higher risk.

Hydrocephalus, but do you think Jim one patient it will potentially FTP patient will.

This kind of risk as well given the same procedure I have a follow up question.

So thanks for the question so.

So.

With regards to the <unk> trial I mean.

The.

The SAE of acute hydrocephalus has been assessed as possibly related to treatment.

There is evidence in the literature that.

Hydrocephalus is observed in <unk> patients, but because of the temporal association relative to the administration of drug.

<unk>.

We couldnt rule out that it was related to our treatment.

So it remains unknown.

Can we get it's impossible you cant draw a definitive conclusion, one way or the other as definitive causality, but we assumed from a safety perspective, and a trial perspective that it's related as the most conservative approach.

We don't have any reason to believe that.

But this that there is evidence of hydrocephalus in in FTE.

Risk of acute hydrocephalus. So we don't believe that that's a risk in a note that we haven't seen any of evidence of acute hydrocephalus in our GM, one trial, where we've dosed again seven patients. So so we don't think its a procedure related we can't completely rule that out but it doesn't given both our experienced and the literature throughout.

Using the ICM procedure for gene therapy, where it has not been reported by any of our any.

Any of the other companies that are working in this space, we don't believe that.

Generally related to the study procedure itself and the ICM administration.

Okay, Great and second question is when you reported.

Clinical update in December from the gym. One study is it reasonable to expect that we will be able to see functional measures from early infantile patients and do you think vineland and also bailey would be the most appropriate measures to.

Look at the functional.

10 points please.

Sure. So let me tackle that one at a high level and then I'll turn it over to Mark So.

I think it's important to remember what the goals of this phase one two trial are so first we want to establish the safety profile of the product. We also want to establish the dose that we will take forward to the pivotal stage of the program and then importantly, we want to identify patient populations that could be.

Better benefit from the product and in December we look forward to sharing our progress towards all three of those goals.

To your specific question I'm going to turn it over to Mark.

Thanks will yes, so what we anticipate disclosing in December is similar to what we've disclosed for cohort one data previously.

Obviously focus on safety and Tolerability as well just described we also will provide data on.

Beta galactosidase.

Activity so evident.

What I would call a target engagement that drug is getting into the targets that we're looking at beta galactosidase activity in both the CSF in the periphery as well as clinical development milestones, including both the Bally in Vineland scale.

<unk>.

So thats really what we anticipate providing as an update in the at the December when we disclosed data in December .

Okay.

Great. Thank you very much.

Okay.

And I'm showing no further questions in the queue at this time, ladies and gentlemen, thank you for participating in today's conference. This does conclude your program and you may now disconnect everyone have a great day.

The conference.

<unk> will begin shortly to raise your hand during Q&A you can dial star one one.

[music].

Hum.

<unk>.

Okay.

Yes.

Okay.

Yes.

Yeah.

Okay.

Yes.

[music].

Okay.

Yes.

Sure.

<unk>.

Yes.

[music].

Yes.

Okay.

Yes.

Sure.

Okay.

Yes.

Okay.

Yes.

Okay.

Sure.

Okay.

[music].

Yes.

Great.

Okay.

Yes.

Sure.

Okay.

No.

Okay.

Thanks.

Yes.

Okay.

Yes.

Sure.

Okay.

Sure.

Okay.

Sure.

Yes.

[music].

Okay.

Yes.

Yeah.

Okay.

Yes.

Okay.

Sure.

Yes.

Sure.

Okay.

[music].

Okay.

Yes.

Okay.

Yes.

Okay.

Yes.

Okay.

Sure.

Okay.

Yes.

Okay.

Sure.

Yes.

[music].

Yes.

Okay.

Yes.

Okay.

<unk>.

Yes.

Okay.

[music].

Great.

Sure.

Yes.

Okay.

Yes.

Okay.

Yeah.

Okay.

Yes.

Okay.

Sure.

[music].

Yes.

Okay.

Yes.

Okay.

Yes.

Okay.

Yes.

Sure.

Okay.

Yes.

Okay.

Yes.

Okay.

Yes.

Okay.

Sure.

Yes.

Okay.

Sure.

Yes.

Okay.

Yes.

Yeah.

Okay.

Yes.

Okay.

Yes.

Sure.

Yes.

Okay.

Sure.

Okay.

Thanks.

Okay.

Yes.

Thanks.

Okay.

Yes.

Okay.

Yes.

Okay.

Yes.

Okay.

Sure.

Yes.

Thanks.

Yes.

Okay.

Yes.

Thanks.

Yes.

Sure.

Okay.

Sure.

Okay.

Yes.

Okay.

Right.

Yes.

Okay.

Sure.

Okay.

Yes.

Okay.

Yes.

Okay.

Yes.

Okay.

Sure.

Okay.

Yes.

Okay.

Yeah.

Okay.

Yes.

Okay.

Yes.

Okay.

Yes.

Okay.

Yes.

Thanks.

Yes.

Thanks.

Okay.

Yes.

Okay.

Yes.

Okay.

Great.

Okay.

Yes.

Okay.

[music].

Okay.

Sure.

Yes.

Okay.

Yes.

Okay.

Sure.

Yes.

Okay.

Sure.

Okay.

Sure.

Yes.

<unk>.

Yes.

Sure.

Thanks.

Okay.

Thank you for holding and good morning, and welcome to the passage Bio third quarter 2022 financial and operating results conference call. At this time all participants are in a listen only mode. Following the formal remarks, we will open the call up for your questions. Please be advised this call is being recorded at the company's request now I would like to turn the call over to Stuart Henderson, Vice President of corporate development.

Investor Relations Stuart. Please proceed.

Partners ability to execute key initiatives the ability of our lead product candidates to treat their respective target CNS disorder manufacturing plans and strategies, our expectations with respect to cash runway in 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.

Except 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.

For this call.

It is now my pleasure to pass the call over to Bill.

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

Before providing an update for the quarter I want to take a moment to say how thrilled I am to have joined the talented team here at passage bio.

I've worked with genetic medicines for the last eight years and as a physician every day I continue to be inspired and motivated by the dramatic impact. These therapies can have on patients and their families.

Humbled by the opportunity to lead passage through our next phase of development as we work to bring life transforming therapies to patients with CNS disease.

Over the past year passages built real momentum in advancing our portfolio.

The core value proposition of our programs remains compelling and in the face of a difficult external market, we have a strong to support our operations.

With these goals in mind and after conducting a thorough review of our business, we will be refocusing our efforts and streamlining our operations in the following ways.

We will continue to focus on clinical trial execution and advancing our imagine one clinical trial for GM, one ganguly two doses in our uplifted clinical trial for frontal temporal dementia.

Both of which have the potential to make a differential impact on patients' lives.

We will prioritize advancing our preclinical programs in <unk> terrific lateral sclerosis, and Huntington's disease through our ongoing partnership with Penn's gene therapy program.

We will continue to leverage our strong in house analytical capabilities at our CMC lab at Princeton West as we believe these capabilities provide a competitive advantage and are critical to support ongoing and future clinical development of our programs.

Due to financial considerations, we are stopping further clinical development of PV <unk> three for krabbe disease.

As well as our PV MLR for program for Medicare Medic, Lipodystrophy, which received IND clearance earlier this year.

Operationally, we will streamline our organization via a 23% workforce reduction and decreased operating expenses.

As a result of these changes we now expect our existing cash resources to fund operations into the first half of 2025.

These prioritization decisions were difficult because of their impact on patients their families and providers and on the many talented people at passage bio who work to move these programs forward.

That said these changes put our company in a strong position to succeed in bringing our most advanced programs to patients in need.

We have built strong momentum in our GM one in FTE programs throughout 2022 and continued to build upon that momentum.

We have established a global network of trial sites with active sites in the United States, Brazil, Canada, and the U K.

For GM, one we've dosed a total of seven patients and expect to complete treating patients in dose ascending phase of our phase <unk> study by year end.

We plan to report initial safety and biomarker data from cohorts two and three from the GM One program in December .

As we move into 2023, we expect initial data from cohort four to become available and we plan to engage with the regulatory agencies to align on the Registrational pathway for this program.

In August we were excited to dose the first patient in our uplifted trial for Frontotemporal dementia.

We are encouraged by the increase in genetic testing observed as a result of our patient identification initiatives and look forward to continued enrollment in this study.

The changes we are making will allow us to focus our efforts on continuing the positive momentum into 2023.

I am excited by the path ahead for passage.

We have a mission to bring life transforming therapies to patients with CNS disorders, and we plan to deliver on that mission.

With that I will now turn it over to mark to discuss our clinical programs.

Thank you we'll let.

Let me begin with our lead program <unk>, one for Jim one ganglia Pseudocyst.

<unk> is a fatal neurological lysosomal storage disease caused by a <unk> one 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 to mortality within several years.

Patients with GM, one are rare and underserved population and there are no disease modifying therapies for the disorder currently.

Our imagine one clinical trial focuses on the early and late infantile forms of GM, one which are the most severe forms of the disease.

The dose escalation portion of this global Phase one two trial is an open label study with <unk>, one enrolling four distinct cohort divided by age and dose level.

Our approach uses a next generation proprietary AAV <unk> hundred 68, capsid administered via the cisterna Magna to deliver a codon optimized <unk> transgene to increase beta galactosidase enzyme activity in the brain and peripheral tissue.

As previously discussed we have experienced strong momentum in our imagine one trial.

To date, we have dosed a total of seven patients in the study.

We have completed dosing of cohorts, one two and three representing the low dose cohorts in both early and late infantile patients and the high dose latest pentyl cohort.

We are also pleased to have dosed the first patient in cohort four high dose early infantile.

This is the final cohort in the dose ascending phase of the study and we remain on track to complete dosing in this cohort by year end.

As will mentioned we plan to host a webcast to report initial safety and biomarker data from cohort two and three in December and we'll also update cohort one data to include additional follow up at that time.

Next let me discuss <unk> for frontal temporal dementia with granular mutations.

<unk> is a devastating form of early onset dementia affecting patients between the ages of 40% to 65.

A form of the disease, we are seeking to treat with our therapy is caused by a granular or GRN gene mutations, which results in a deficiency of pro granular.

It is estimated that about 5% to 10% of SCD is caused by a GRM mutation.

We are utilizing the AAV, one capsid to deliver a functional copy of the GRM gene by ICM delivery to the CSF.

The goal of this treatment and delivery approach is to potentially provide higher than normal levels of the pro granular proteins to the CNS to overcome the <unk> deficiency in GRN gene mutation carrier.

Our uplifted clinical trial investigating two dose levels of <unk> and a sequentially enrolling two cohorts.

Based on the results of the first two cohorts, we have the optionality for a third dose level cohort.

The primary endpoint of the study is to evaluate the safety and Tolerability of <unk> <unk>.

Secondary endpoints include disease, Biomarkers and clinical outcome measures.

In August we were excited to report that we dosed the first patient in the study following the improved momentum experienced throughout patient identification and recruitment initiatives.

This partnership provides no cost genetic counseling and testing for adults who have been diagnosed by their physicians with FTE.

These efforts have increased genetic testing among STD patients over the last few months.

We look forward to sharing clinical data from this program as patient enrollment in that cohort continues to with that with that I will now turn the call over to Simona to review our financials.

Okay.

Thank you Mark.

Reported in our press release. This morning, we ended the third quarter with approximately $213 8 million in cash cash equivalents and marketable securities compared to $239 $3 million as of June 32.

2022.

Three mining our operations and further prioritizing our research and development effort. We expect these existing cash resources to fund operations into the first half of 2025.

R&D expenses were $15 4 million for the quarter ended September 32022, compared to $26 6 million for the same quarter in 2021.

The decrease was primarily due to a decrease of $8 $8 million and clinical manufacturing expenses, which relates to the timing of our manufacturing activities to support our clinical trial area.

Other expenses had a net decrease of $2 4 million dollar.

G&A expenses were $10 $7 million for the quarter ended September <unk> 2022, compared to 15 1 million for the same quarter in 2021.

The decrease was primarily due to a $4 million decrease in personnel related and share based compensation expense related to our March 2020 to mark parts reduction.

<unk> zero point $4 million decrease in our professional fees facilities and other expenses.

Net loss was $26 7 million.

The quarter ended September <unk>, 2022, compared to $46 $9 million for the same quarter in 2021.

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

Thank you Simona.

I'm thrilled to be leading passage bio through our next phase of development as we focus on execution.

And continuing to generate meaningful clinical data from our lead programs in GM, one an FPGA.

For <unk>, we look forward to reporting initial safety and biomarker data from cohorts, two and three of our imagine one trial in December .

And we also plan to provide an update on cohort one at that time.

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

Operator.

Ladies and gentlemen, if you have a question or a comment at this time. Please press star one on your Touchtone telephone, we will pause for a moment, while we compile our Q&A roster.

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

Hey, guys. Thanks for taking our question. This is rob on for Madhu.

How many of these patients are you looking to treat before disclosing data. Thanks.

Great. Thanks for the question so.

To answer your first question. This was a very difficult decision to stop a clinical program anytime you do that we understand the impact on patients and their families.

To answer your second question on STD I think your question was about competitive recruitment.

I will give two pieces to that one.

As you know screening for this mutation is an important part of recruitment for all all competitors in this space and so.

The more people that are out there talking about screening the better it is overall to improve the overall rate of screening.

So that's one thing the second thing I'll say is just in general in my experience with early clinical trials as trials gather more data and are able to share more data with trial sites.

<unk> improves I will say, we're very pleased with where we are in terms of we have three sites open per FTE. We have more sites opening in Q1 of next year and we have multiple patients with the <unk> mutation in the process of enrollment.

At our sites.

Okay.

I think the last part of your question was disclosing so we will we will look forward to sharing more data from cohort one of the uplift the trial in 2023.

Thank you one moment for our next question.

Our next question comes from your own Weber with Cowen Your line is open.

Hi, guys. Thanks for taking the question. This is Brendan on for your own just a couple of quick ones from US first can you maybe remind us what the actual mechanism of action for the gene therapy at AOS.

Using how are you actually looking to functionally correct Athena in Europe , 72, pathology I know Theres a couple of different ways people have tried.

And then wondering when we might actually get to see some preclinical data from that program.

And then.

Similarly for Huntington's, obviously, one concern some of these other.

So Paul Thanks.

Yes, so we're really excited with the progress we've made together with our colleagues at GTP on our preclinical programs in ALS and Huntington's disease.

We're looking forward to sharing more milestones as we get them.

Im going to turn it over to Mark to answer your question about our mechanistic approaches.

Great. Thanks for the question so.

Our approach is using the gene therapy.

To reduce the expression of the pathological forms of the <unk>.

As well as its sort of a knockdown and replace strategy as well as provide a.

Functional copy that we can use to restore function again the mechanism of action.

For the.

So the mechanism pathophysiology of the disease of the senior North mutations is not known so we believe that using a knockdown and replace strategy allows us the best chance of correcting.

The potential different.

Pathophysiological mechanism in the disease.

Okay great.

Just on Huntington that you haven't been that Youre able to get deeper brain structures. So far is that something you are seeing pre clinically.

Okay.

Alright.

Okay.

Yes, we're going to explore the effects of our route of administration and we will be we'll be happy to share more data as it emerges next year.

Okay. Thank you very much.

One moment for our next question.

Our next question comes from Neil <unk> with regard with Citi. Your line is open.

Hey, guys. Thanks for taking my question. So on PBS Q&A, you said earlier that you do have multiple patients with germline mutations in the process of enrolling at.

The three sites that you have opened so far I guess can you clarify or are those patients.

Jeff.

Likely to actually.

To meet the enrollment criteria in the screening criteria and ultimately get dosed I'm, just trying to kind of understand the timing for potential data next year.

Yes, so thanks for the question so Ed.

As will said earlier.

Our patient identification efforts have led to what we feel are fairly robust funnel of individuals identified with STD and granular in gene mutations.

And where we are now as those patients are being evaluated for suitability for enrollment in the trial.

And and and.

So that will.

As we get further along I think that's what we're prepared to disclose at this time and we will.

As we have a cohort of data later, we'll be happy to disclose more information.

Okay got it thank you.

One moment for our next question.

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

Hey, good morning, guys. Thank you very much for taking the question I just have three so on STD.

I might follow up and ask the question a little bit differently, but can you remind us what are your assumptions around screening failure rate for <unk> patients and then number two.

And the second cohort is there that same 60 day waiting period between enrollment of different subjects and lastly, just one on the GM one.

So see if I can keep the questions Austria. So the first question was regarding the assumptions on the screen failure rate.

In the STD trial and.

In the <unk> trial, I mean, the inclusion criteria that we currently are utilizing allow patients.

Is.

A relatively broad for this first in human trial, which is really focused on safety.

So as long as patients are able to live in the community they're eligible for enrollment in the trial. So in general we expect for patients that are identified with SPD and any program human gene mutations we expect the vast majority of them to be eligible for enrollment in the trial unless they meet specific exclusion.

Criteria regarding is craig's other health conditions.

The second question can you remind me.

Yes, yes, yes, just with respect to the FTE enrollment I believe in the first cohort.

60 days spacing between enrollment of subjects enrolled one way at 60 days.

Not necessarily clear and the subsequent cohorts do you still have that 60 day weight between subs.

Subject enrollment.

Right. So in the yes, so for all of the patients currently for the entire for the FDA trial the first.

PBF deal.

Protocol one.

There is a 60 day waiting period for all patients.

We enrolled.

The trial.

Both in cohort, one and other and higher dose cohorts, we believe that's important.

As we need to establish safety at the higher doses as we escalate. So yes. There is a 60 day waiting period for all of our patients in the trial.

And the third question.

Was on.

Yes.

Okay.

Yes, so in terms of.

I think there are a number of things that we need that we would like to align with the health authorities.

As we as we gear up to initiate the Registrational study, which is.

Yes.

It will meet the.

Meet the requirements that the agencies are expecting in order to support a registrational study.

Thanks very much.

One moment for our next question.

Our next question comes from Danielle Brill with Raymond James Your line is open.

Hi, guys. Good morning, Thanks for the question.

A couple of bigger picture questions. Here first just can you walk us through how you decided which program to prioritize in the considerations that you made and then.

Pertaining to the <unk> program I'm, just curious what's the biggest.

Bottleneck here the challenge with recruitment opening sites identifying suitable patients are.

Motivating them to enroll in the study getting competition. Thank you.

Yes.

<unk> stage programs have the potential to transform patients' lives.

When we looked hard at all of the programs and where they where we made the decision to move forward with our most advanced clinical programs and that is GM, one and FTB.

The second question was on bottlenecks.

I'll, let mark answer that but I will say that all of the things that you mentioned.

We're focused on so you have to go across the board with reaching the patients keeping the patients all the way through the process getting more screening and of course getting more sites started so.

What we are going to be laser focused on this year is execution around all aspects of our clinical programs.

And we're going to be pushing on all those aspects.

Alright.

Thanks will.

Just to sort of.

To go a little bit deeper.

As will said I think the two the two big things patient identification, specifically patients with GRN mutations it's been one of the bottlenecks. The other is getting sites opened and we were as low as talked about we're focused on getting sites sites that we havent multiple sites open and we're looking to add multiple more sites in the coming months.

In addition, we have launched sort of a multi pronged effort to enhance our sort of patient identification activities, including effort sort of locally set of site specific tailored activities that are that are around each of our individual individual sites.

Lee we have broad outreach to health care providers, who are capable of caring for SCD patients to enhance their understanding of disease and the role of genetic testing to really increase the genetic testing throughput and the third thing is we're involved with a number of advocacy groups to really at a pre competitive level to once again increase awareness on genetic.

Testing and genetic counseling and the availability and the understanding of what.

There are multiple clinical trial activities and option to offer patients if they happen to cash positive ticket for various mutant gene mutations. So all of those we believe have really started to bear fruit as we've mentioned a few times theirs.

We now have a funnel of patients that we feel that our recruitment.

And enrollment is going to proceed efficiently going forward.

Yes.

Thanks, Mark and let me just remind everyone as Im sure you know our preclinical data and STB is quite strong we've shown.

We've been able to achieve super physiologic levels of programming inland in the CSF and we are very much looking forward in 2023 to see how that preclinical data translate into the clinic as I mentioned before.

And we've seen this in GM one.

The more data that you actually generate the more interest.

The trial and so we're looking forward to seeing that effect also.

Our FTE trial.

Okay. Thank you so much I appreciate your additional color.

One moment for our next question.

Okay.

Our next question comes from Morningstar. Your line is open.

Hi, Good morning. This is growing also cooler two from us.

So for the <unk> program.

And you will no longer be providing an update.

Later this year and for the preclinical portfolio can you talk about factors that you're weighing in Q prioritize advancing these programs.

Programs with with the GTP and all of the available options that you have left can you remind us of the timeline for opting in and selection criteria given the new strategies.

Okay.

Sure sure.

So first your first question on <unk> as we are no longer enrolling patients in this trial, we will no longer be reporting data from it.

We will continue to follow the first patient as per outlined in our clinical protocol.

Yes.

On the preclinical portfolio the prioritization was.

Was really our most advanced programs. So we're furthest along with both ALS and Huntington's and we have eight options remaining through 2026.

Yes.

Thank you one moment for our next question.

Our next question comes from <unk>, Zhang with <unk>. Your line is open.

Hi, Good morning, Thank you very much for taking the questions. So the first question is a follow up question on credit program.

I understand that the TSMC deep the safety finding to be potentially related to study treatment or study procedures.

I wonder if you're able to make a conclusion, whether that was the case in <unk>.

That was the case I understand the patient probably have a higher risk.

Hydrocephalus, but do you think that Jim one patient will potentially FTP patient.

This kind of risk as well given the same procedure I have a follow up question.

So thanks for the question so.

So.

With regards to the <unk> trial.

<unk>.

The.

The SAE of acute hydrocephalus, who has been assessed as possibly related to treatment.

There is evidence in the literature that acute hydrocephalus is observed in <unk> patients, but because of the temporal association relative to the administration of drug.

No.

We couldnt rule out that it was related to our treatment.

So it remains unknown.

It's impossible you cant draw definitive conclusions, one way or the other as definitive causality, but we assumed from a safety perspective, and a trial perspective that it's related.

The most conservative approach.

We don't have any reason to believe that.

<unk>.

So that there is evidence of hydrocephalus in in FTE.

The risk of acute hydrocephalus. So we don't believe that that's a risk and I'd note that we haven't seen any evidence of acute hydrocephalus in our GM, one trial, where we've dosed again seven patients. So so we don't think its a procedure related we cannot completely rule that out but it doesn't given both our experienced and the literature throughout <unk>.

Using the ICM procedure for gene therapy, where it has not been reported by any of our.

Any of the other companies that are working in this space, we don't believe that.

Generally related to the study procedure itself and the ICM administration.

Okay, Great and second question is when you reported.

Look at the functional.

10 point please.

Sure. So let me tackle that one at a high level and then I'll turn it over to Mark.

Better benefit from the product and in December we look forward to sharing our progress towards all three of those goals.

To your specific question Im going to turn it over to Mark.

Thanks, well so yes, so what we anticipate disclosing in December is similar to what we've disclosed for cohort one data previously.

Obviously focused on safety and Tolerability as well just described third we also will provide data on.

Beta galactosidase.

Activity so evident.

What I would call like target engagement that drug is getting into the targets that we're looking at beta galactosidase activity in both the CSF in the periphery as well as clinical development milestones, including both the daily in Vineland scale.

<unk>.

So thats really what we anticipate providing as an update in the at the December when we disclosed data in December .

Okay.

Great. Thank you very much.

And im showing no further questions in the queue at this time, ladies and gentlemen, thank you for participating in today's conference. This does conclude your program and you may now disconnect everyone have a great day.

Q3 2022 Passage Bio Inc Earnings Call

Request a DemoDemo

PASG

Passage BIO

Earnings