Q2 2020 Passage Bio Inc Earnings Call
Thank you for holding good morning, and well go to the passage bio second quarter 2020 financial and operating results.
Operator: Thank you for holding. Good morning, and welcome to the Passage Bio second quarter 2020 financial and operating results conference call. At this time, all participants are in a listen only mode.
Lets call at this time, all participants on the listen only mode.
Operator: Following the formal remarks, we will open the call up for your questions. Please be advised that today's conference is being recorded at the company's request. At this time, I'd like to turn the call over to Zoe Mita. Zoe, please proceed.
Following the formal remarks, we will open the call up for your question.
Please be advised that today's conference is being recorded at the company's request.
At this time I like the turn the call or because the only meta.
No. We please proceed.
Thank you operator. This morning, we issued a press release that outlines the topics you plan to discuss today. It's releases are available on the passage by a web site at Investor stop hostage bio dot com under the news and events section.
Zoe Mita: 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 at investors.passagebio.com under the news and events section. On today's call, Bruce Goldsmith, President and Chief Executive Officer, and Rich Morris, Chief Financial Officer, will review our second quarter 2020 financial results and discuss recent business highlights. Gary Romano, our Chief Medical Officer, and Jill Quigley, our Chief Operating Officer, will also be available for the Q&A portion of the call. 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 the timing of the execution of anticipated milestones, including the resolution of FDA feedback on INDs, the initiation of clinical trials and the availability of clinical 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 the underlying causes of their respective These forward-looking statements are based on assumptions that are subject to risk and uncertainties that could cause the company's actual results to differ significantly from those suggested by these statements.
On today's call preschool Smith, President and Chief Executive Officer, and Rich Morris Chief Financial Officer or have you. Our second quarter 2020 financial results and discuss recent business highlights Gary Romano, Our Chief Medical Officer, Joe quickly, our Chief operating Officer will also be available for the Q any portion of the call.
Where do you again. Please note that today's call may include a number of forward looking statements, including but not limited to comment on our expectations about tightening execution of anticipated milestones, including the resolution of FTC back on I, Indeed initiation of clinical trials and the availability of clinical data from such trials or expectations about her.
Collaborators and partners ability to execute key initiatives.
The ability of our lead product candidate to treat the underlying causes that their respective target mano genetic CNS disorders manufacturing plans and strategies trends with respect to financial performance in cash was the company's ability to fund research and development programs impacts of the Coca 19 pandemic on the company's operations and its ability to man.
Its costs along with other you should 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 getting these risks and uncertainties you should not place undue reliance on these forward looking statements.
Bruce Goldsmith: 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 the 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 after this call. It is now my pleasure to pass the call over to Bruce Goldsmith. Bruce?
Please refer to the company's filings with the FCC for information concerning 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 reflect events or circumstances.
It occur after this call. It is now my pleasure to pass the call over to Brian Goldsmith Bruce.
Bruce Goldsmith: Thanks, Zoe, and thank you all for joining us this morning. We began 2020 with the goals of continuing to build a premier gene therapy company focused on rare monogenic CNS disorders and advancing our pipeline to set the foundation for initial clinical trial data in 2021 from our LEAD program. We made important progress through the first half of the year, growing our internal team from 22 to 55 people, with a focus on bolstering our clinical and manufacturing capabilities, as well as strengthening several of our core operational competencies, including communications, commercial planning, and human resources. Doing so, along with continuing to engage with key partners who support our business, will enable continued growth and execution as we move closer to initiating clinical trials for our three LEAD programs.
Thanks, Joey and thank you all for joining us this morning.
We began 2020 with the goals of continuing to build Premier gene therapy company focused on rare monogenic CNS disorders, and advancing our pipeline just set the foundation for initial clinical trial data in 2021 from our lead programs.
We made important progress through the first half of the year growing or internal team from 20 to 55 people with a focus on bolstering our clinical and manufacturing capabilities as well as strengthening several of our core operational competencies, including communications commercial planning and human resources.
Doing so along with continuing to engage with key partners, who support our business will enable continued growth in execution as we move closer to initiating clinical trials for three lead programs.
We've made this progress despite the challenges posed by the cobot 19 pandemic.
Bruce Goldsmith: We've made this progress despite the challenges posed by the COVID-19 pandemic. I'm incredibly proud of the ingenuity and flexibility of our team as they continue to keep the needs of patients who are waiting for therapies like ours front and center. Currently, our employees are all working from home, and as a leadership team, we have decided that this will be the case at least until the end of this year because their safety and well-being are our top priority.
I'm incredibly proud of the ingenuity flexibility of Archie as they continue to keep the needs of patients were waiting for therapies like ours front and center.
Currently our employees all working from home and as a leadership team. We've decided that this will be the case at least until the end of this year, because their safety and well being our top priority.
Bruce Goldsmith: In order to secure our supply chain, we have begun limited site visits to our manufacturing partners and are taking the necessary precautions to ensure this can be done as safely as possible. With that, let me begin today's call with an update on our lead program, PBGM01, a next-generation HU68 AAV capsid designed to deliver a functional GLB1 gene directly to the central nervous system via intrasterna magna injection, or ICM, for the treatment of infantile GM1 gangliosidosis. As a reminder, GM1 is a rare monogenic recessive lysosomal storage disease caused by mutations in the GLB1 gene encoding the enzyme beta-galactosidase, with no current treatment options and a very rapid and severe disease course. Despite the pandemic and the unprecedented disruptions we are all living through, we are pleased to announce that we met our previously stated guidance with the June submission of our IND to FDA for the treatment of infantile GM1 in a Phase I-II clinical trial with PBGMO1.
In order to secure supply chain, we have begun limited site visits to our manufacturing partners and are taking necessary precautions to ensure this can be done safely as possible.
With that let me begin today's call with an update on our lead program PPG and a one and next generation HQ 68, Avi capsid designed to deliver a functional GLP ones directly to the central nervous system. The interest cisterna Magna injection, where I see him for the treatment infant.
Child G M ganglia seditious.
As a reminder, G. M. One is a rare monogenic recession lysosomal storage disease caused by mutations in the GLP one gene encoding the enzyme basic lucky Fridays with no current treatment options in a very rapid and severe disease course.
Despite the pandemic any unprecedented disruptions we are all living through we are pleased to announce that we met our previously stated guidance for the June submission of our eye and DHL FDA for the treatment of infant child G. M. In a phase one two clinical trial with P.G.M. Hawaiian.
We believe this accomplishment continues to demonstrate the effectiveness of the partnership between passage bio and the University of Pennsylvania as gene therapy program led by Dr., Jim Wilson.
Bruce Goldsmith: We believe this accomplishment continues to demonstrate the effectiveness of the partnership between Passage Bio and the University of Pennsylvania's gene therapy program, led by Dr. Jim Wilson. However, following discussions with FDA, we have been notified in a brief communication that the IUD has been placed on clinical hold because the delivery device we are proposing for ICM administration requires additional biocompatibility risk assessment and or testing.
However, following discussions with FDA, we have been notified in a brief communication that the idea has been placed on clinical hold because the delivery device. We're proposing for IC ATM administration requires additional biocompatibility risk assessment and or testing to be clear, we believe that the device we have front.
Bruce Goldsmith: To be clear, we believe that the device we have proposed for use in our trials utilizes components that are already approved by FDA for existing medical procedures and are highly similar to those in other gene therapy clinical trials using ICM delivery. We expect to receive formal written communication with additional information from FDA in the near future and plan to work with FDA in an effort to resolve all questions as promptly as possible. While we await the official clinical hold letter from FDA, we are working with external medical device and regulatory experts to evaluate options for additional risk assessment and testing that could be conducted to further demonstrate the compatibility of the device with the ICM injection procedure. Based on our own internal assessment, we are confident that we can respond rapidly to FDA regarding the biocompatibility risk of our ICM delivery device and that our device will ultimately clear FDA's biocompatibility requirements.
Post for use in our trials utilizes components that are already approved by FDA for existing medical procedures in our highly similar to those other gene therapy clinical trials using I see I'm delivery.
We expect to receive formal written communications with additional information from F.D.A. in the near future and plan to work with F.D.A. in an effort to resolve all questions as promptly as possible.
Well, we await the official clinical hold letter from FDA, we're working with external medical device and regulatory experts to evaluate options for additional risk assessment and testing.
Could be conducted to further demonstrate the compatibility of the device with the IC ATM injection procedure.
Based on our own internal assessment, we are confident that we can respond rapidly Jeff D.A. regarding the biocompatibility risk or I see him delivery device and that our device will ultimately clear ASCII age biocompatibility requirements.
Bruce Goldsmith: Despite the current clinical hold, we anticipate enrolling the first patient in the Phase 1-2 trial of pBGM01 late in the fourth quarter of 2020 or early in the early first quarter of 2021, and we expect to remain on track to report initial 30-day biomarker and safety data late in the first half of 2021. After discussions with FDA on the IND, we are revising the protocol for our Phase 1-2 trial in order to better understand the dose requirements and ensure safety for both early and late infantile GM1 patients. As a result of our discussions, FDA informed us in a brief communication that there were no further clinical information requests. As a reminder, this trial has been designed as an open-label dose-escalation study of pBGM01 administered by a single injection into the intercisterna magna in pediatric subjects with early and late-onset infantile GM1. Early-onset infantile GM1, which is the most severe and common form of the disease, is characterized by onset in the first six months of life, while late-onset infantile GM1 is characterized by onset between 6 and 24 months.
Despite the current clinical hold we anticipate enrolling the first patient in the phase one two trial TPG at my one late in the fourth quarter of 2024.
Early first quarter 2021.
And we expect to remain on track to report initial 30 day biomarker in safety data late in the first half of 2021.
After the discussions with FDA on the island D., we are revising the protocol for phase one two trial in order to better understand the dose requirements and ensure safety for both early and late infant child GM on patients.
As a result of our discussions ft informed us in a brief communication, but there are no further clinical information requests.
As a reminder, this trial has been designed as an open label dose escalation study of P.G.M., a one administered by a single injection into the interest cisterna Magnum in pediatric subjects with early and late onset infantile GM one.
Early onset Infratel GM, one which is the most severe and common form of the disease is characterized by onset in the first six months of life, while late onset infantile Jim one is characterized by onset between six to 24 months.
There are two key goals for the initial dose cohorts in the phase one two study our first goal is to demonstrate the P.G.M. a one is safe for patients with infantile Jim one.
Bruce Goldsmith: There are two key goals for the initial dose cohorts in the Phase 1-2 study. The first goal is to demonstrate that PBGMO1 is safe for patients with infantile GM1. Our second goal is to demonstrate increased beta-gal in both the CSF and sera. For the dose escalation portion of the trial, we have changed the design to specifically study early and late infantile patients in separate smaller cohorts. We will now be enrolling a total of four cohorts of two patients each with separate dose escalation cohorts for late-onset infantile GM1 and early-onset infantile GM1. We will initiate dosing with a low dose of PBGMO1 in the first cohort of late-onset infantile GM1. Safety in this first cohort will gate dosing in both the high-dose late-infantile cohort and the low-dose early-infantile cohort. Thereafter, dose escalation will occur independently in the early-onset and late-onset cohorts across his entire cohort.
Our second goal is to demonstrate increased beta gal in both the CSF and zero.
So the dose escalation portion of the trial, we have changed the design just specifically study early and late in child patients in separate smaller cohorts.
We'll now be enrolling a total of four cohorts to patients each.
Separate dose escalation cohorts for late onset infant child, Jim one.
Early onset can for child GM one.
We will initiate dosing with a low dose of PBG at my one in the first cohort of late onset Infratel G. M. Shifty in this first cohort will gate dosing in both the high dose late infantile cohort and low dose early infant child, Copart thereafter dose escalation.
Kurt independently in the early onset and lead on site.
As a child cohorts.
Bruce Goldsmith: Following these dose escalation cohorts, each patient population will be enrolled into a separate confirmatory cohort, and patients will be evaluated over two years for safety and efficacy, followed by an additional 36 months of long-term follow-up. The initial data readouts in the first cohort, which we expect to report late in the first half of 2021, will include safety data as well as key biomarker data, including change of baseline beta-galactosidase activity in both CSF and sera. Our teams are now working to prepare for enrollment in anticipation of the clinical trial initiation. In parallel with our site initiations, we recognize that patient identification and engagement of families are key tenets of successful rare disease therapeutic development programs. We are working with our partners at Penn, as well as with other external groups, such as our key opinion leaders and patient advocacy partners, to identify patients as rapidly as possible.
Following these dose escalation cohorts each patient population will be enrolled into a separate confirmatory cohort.
Patients will be evaluated over two years for safety and efficacy followed by an additional 36 months of long term follow up.
The initial data readout for the first cohort, which we expect to report late in the first half of 2021 will include safety data as well as key biomarker data, including change a baseline beta Kellogg societies activity in both CSF and serum.
Our teams are now working.
You prepare for enrollment in anticipation of the clinical trial initiation.
In parallel with our site initiations, we recognize that patient identification engagement of families are key tenants a successful rare disease therapeutic development programs.
We are working with our partners and.
As well as with other external groups such as our key opinion leaders and patient advocacy partners to identify patients as rapidly as possible.
In addition to our site preparations and patient identification initiatives.
Bruce Goldsmith: In addition to our site preparations and patient identification initiatives, we have also secured clinical stage manufacturing capacity for our gene therapy programs under our agreement with Catalan. We are excited to share that our GM1 clinical supply has been manufactured, and we have established a global clinical supply chain. We also expect our dedicated manufacturing suite to be functional by year end. Once it is up and running, the CGMP suite will be capable of meeting production requirements for our current lead product candidates through early commercialization. Having our own dedicated suite is an important step towards our goal of having increased control of the supply chain, which we believe will set us up for both clinical and commercial success by allowing for greater flexibility in terms of scalability and prioritization as we move products through development. To that end, we have also signed agreements with many suppliers for both upstream manufacturing components and service providers.
Also secured clinical stage manufacturing capacity for gene therapy programs under our agreement with catalyst.
We're excited to share that are Jim one clinical supply has been manufactured and we have established global clinical supply chain.
We also expect are dedicated manufacturing suite to be functional by yearend.
Once it's up and running but cgmp suite will be capable of meeting production requirements for our current lead product candidates clinical needs.
Through early commercialization.
Having our own dedicated suite is an important step towards our goal of having increased controller supply chain, which we believe will set us up for both clinical and commercial success by allowing for greater flexibility in terms of scalability and prioritization as we move products through development.
To that and we've also signed agreements with many suppliers for both upstream manufacturing components and service providers.
Across our company, we remain extremely excited to death PDG at my one toward the potential treatment of patients with substantial unmet medical needs and to enter into this new phase of developing as I said earlier, we're confident that we can address the questions raised by the FDA quickly and efficiently and we look forward to providing an update soon.
Bruce Goldsmith: Across our company, we remain extremely excited to advance PDG M01 toward the potential treatment of patients with substantial unmet medical need and to enter into this new phase of development. As I said earlier, we are confident that we can address the questions raised by FDA quickly and efficiently, and we look forward to providing an update soon. Before turning the call over to Rich to discuss our financial results, I also wanted to quickly review our extended pipeline of gene therapy candidates. Our next most advanced program, PBFTO2, is for the treatment of frontotemporal dementia, or FTD. PBFCO2 is an AAV1 capsid-based product that is designed to deliver to the brain a functional granulone gene encoding the progranulone protein. Preclinical studies have demonstrated the ability of PBFT02 to significantly increase progranulin above normal levels in the cerebral spinal fluid. Progranulin is a complex and highly conserved protein thought to have multiple roles in cell biology, development, and inflammation. However, emerging evidence suggests that progranulosome pathogenic contribution to FTD and other neurodegenerative disorders relates to a critical role in lysosomal function.
Before turning the call over to rich to discuss our financial results. I also wanted to quickly review our extended pipeline of gene therapy candidates.
Our next most advanced program PBF T O two is for the treatment of Frontotemporal dementia or FTD.
Maybe F T O two isn't easy one capsid based product designs. It delivers the brain functional granule in genes encoding the pro granular approach.
Unopposed studies have demonstrated the ability of PBF T O two to significantly increase progression yellen above normal levels in the cerebral spinal fluid.
From a granular and is complex and highly conserve protein tons have multiple roles and cell biology development and inflammation.
Emerging evidence suggests that programs pathogenic contribution to FTD and other neurodegenerative disorders relates to a critical role in lysosomal function.
As part of our preclinical studies, we tested I see I'm administration, the easy one capsid against other capsid types in non human primates and found that easy one provide the strongest or instruction and also achieved 50 times the normal human CSF levels for Brian one.
Based on the encouraging data from our completed preclinical toxicology studies.
We continue to advance the manufacturing as well as site selection.
We plan to initiate a phase one two trial in the first half that's 2021.
Bruce Goldsmith: As part of our preclinical studies, we tested ICM administration of the AAV1 capsid against other capsid types in non-human primates and found that AAV1 provided the strongest transduction and also achieved up to 50 times the normal human CSF levels of programming. Based on the encouraging data from our completed preclinical and toxicology studies, we continue to advance the manufacturing as well as site selection. We plan to initiate a Phase 1-2 trial in the first half of 2021. We have also completed our preclinical and toxicology studies and are undergoing manufacturing and site selection for our third program, PBKRO3, a potential treatment for infantile Crab A disease that utilizes the same next-generation AAVHU68 capsid used in the GM1 program. Infantile Crabbe disease is a rare and often life-threatening glycosomal storage disease that results in progressive damage to both the brain and peripheral nervous system.
We've also completed our preclinical toxicology studies and are on undergoing manufacturing and site selection for our third program P.B.K., our a three potential treatment for individual crabby disease that utilizes the same next generation Aviate you 68 capsid use in the GM one program.
If it's how crabby disease is a rare and orphan life threatening places on the storage disease that results in progressive damage to both the brain and peripheral nervous system.
TDK, our Threeg utilizes aviate, she 68 to deliver a functional galasie gene to increase kelcy enzyme activity and reduce CECO seen accumulation and restore mylan.
At the U.S. GCT conference in mid May preclinical data from the University of Pennsylvania as gene therapy program showcased the promising potential CSF vector administration to achieve robust scalable effects utilizing cross correction on central and peripheral nerve function.
These data demonstrated that the single injection of 88, she 68 carrying functional galaxy gene.
Bruce Goldsmith: PBKRO3 utilizes AAVHC68 to deliver a functional GALC gene to increase GALC enzyme activity and reduce cyclosine accumulation and restore myelin. At the ASGCT conference in mid-May, preclinical data from the University of Pennsylvania's Gene Therapy Program showcased the promising potential of CSF vector administration to achieve robust, scalable effects utilizing cross-correction on Central and Peripheral Nerve Function. These data demonstrate that a single injection of AAVHC68, carrying a functional GALC gene, resulted in normalization of GALC enzyme activity and improved all parameters in animal models of Crab A disease.
Resulted in normalization of Galasie enzyme activity and improved all parameters in animal models Krave disease. For example, treated crabby dogs showed nerve conduction normalization CSF psycho seen level normalization.
Proved brain histopathology phenotypic correction and increase survival.
We believe that PB care of three has the potential to be a life altering therapy that can address the underlying cause of disease and plan to initiate a phase one two trial and the first half of 2021.
Finally, our early stage pipeline programs in metre chromatic leukodystrophies.
Rich Morris: For example, treated Crab A dogs showed nerve conduction normalization, CSF psychosine level normalization, improved brain histopathology, phenotypic correction, and increased survival. We believe that PBKR03 has the potential to be a life-altering therapy that can address the underlying cause of the disease and plan to initiate a Phase I-II trial in the first half of 2021. Finally, our early stage pipeline programs in metachromatic leukodystrophy, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease type 2a are currently in discovery and at the candidate selection stage and continue to progress. And with that, I will turn the call over to Rich to give a financial and operations update. Thank you, Bruce. As we reported in our press release this morning, we ended the quarter with cash and cash equivalents of approximately $353 million, as compared to $159 million as of December 31st, 2019.
Trophic lateral sclerosis had charcoal Murray to disease type two way are currently and discovery and at the candidate selection stage and continue to progress.
And with that I will turn the call over to rich to give a financial and operations update.
Thank you Bruce.
As we reported in our press release this morning.
Ended the quarter with cash cash equivalents of approximately $353 million as compared to $159 million as of December 31st 2019.
We expect our current cash Brown to fund our operation into 2023.
R&D expenses were $19.9 billion for the quarter ended June thirtyth compared to $6.3 million for the same quarter in 2019.
The increase was primarily due to an increase of $8.5 million in R&D costs incurred with time in connection with the preparation of several I'd be filing.
An increase of $4 million in clinical manufacturing costs.
As well as an increase in other research costs.
$5 million as we prepare for clinical trials will begin in the second half of 20, Twond and early 2021.
We also had a 3.1 million dollar increase.
Rich Morris: We expect our current cash balance to fund our operations into 2023. R&D expenses were $19.9 million for the quarter ended June 30th, compared to $6.3 million for the same quarter in 2019. The increase was primarily due to an increase of $0.5 million in R&D costs incurred with Penn in connection with the preparation of several I&D filings, an increase of $4 million in clinical manufacturing costs, as well as an increase in other research costs of $0.5 million as we prepare for our clinical trials to begin in the second half of 2020 and early 2021. We also had a $3.1 million increase in personnel-related costs and a $0.1 million increase in facility and other costs due to increases in employee headcount in the R&D function.
Personnel related costs, and a point 1 million dollar increase in facility and other costs due to increases in employee head count in the R&D function.
DNA expenses were $7.4 million for the quarter ended June thirtyth compared to $1 million the same quarter 2019.
The increase was primarily due to a 4.7 million dollar increase and personnel related and share based compensation expense due to increases in employee headcount.
Oh professional fees and facility costs also increased $5.7 million and $1 million respectively.
As we expanded operations to support our research and development efforts.
Net loss was $27.2 million for the second quarter of 20, twond compared to $13.4 million and the same quarter of 2019.
Net loss per basic and diluted share was 67 in the second quarter of 20 point.
Compared to like $3, Nineteens <unk> net loss per basic and diluted share.
The second quarter 2019.
Now I'll turn the call back to Brown for closing remarks.
Thanks Rich.
The coming months will be transformative per passage bio as we continue to prepare for clinical stage development of three promising pipeline assets.
Our ultimate goal is to provide patients who currently has limited or no available treatment options with innovative safe and effective therapies.
Rich Morris: G&A expenses were $7.4 million for the quarter ended June 30th, compared to $1 million for the same quarter in 2019. The increase was primarily due to a $4.7 million increase in personnel-related and share-based compensation expense due to increases in employee headcount. Our professional fees and facility costs also increased by $0.7 million and $1 million, respectively, as we expanded our operations to support our research and development efforts. Net loss was $27.2 million for the second quarter of 2020, compared to $13.4 million in the same quarter of 2019, and net loss per basic and diluted share was $0.60 in the second quarter of 2020, compared to a $3.19 net loss per basic and diluted share in the second quarter of 2019.
As I shared earlier, where we were very excited to collaborate with the gene therapy program to file or I Andy in June.
As we work with FDA to resolve their questions regarding device biocompatibility, we anticipate treating or first patient in the phase one trial. The PBGA My one late in the fourth quarter of 2020 or early in the first quarter of 2021.
We continue to expect that we will remain on track to report initial 30 day biomarker and safety data for the first cohort late in the first half of 2021.
We look forward to providing further updates on the progress of PBGA My one phase one two study later in the year.
We also remain on track and moving our FTD incredibly programs towards clinical study initiation in the first half of 2021.
As I mentioned earlier, our head count continues to grow as we expand our clinical manufacturing and operations teams.
Support these programs along with future development of additional pipeline candidates all with the goal of helping patients suffering from serious life threatening rare monogenic central nervous system diseases.
Bruce Goldsmith: Now I'll turn the call back to Bruce for his closing remarks. Thanks, Rich. The coming months will be transformative for Passage Bio as we continue to prepare for the clinical phase development of three promising pipeline assets. Our ultimate goal is to provide patients who currently have limited or no available treatment options with innovative, safe, and effective therapies. As I shared earlier, we were very excited to collaborate with the gene therapy program to file our IMD and GA. As we work with the FDA to resolve their questions regarding device biocompatibility, we anticipate treating our first patient in the Phase 1-2 trial of PBGMO1 late in the fourth quarter of 2020 or early in the first quarter of 2021. We continue to expect that we will remain on track to report initial 30-day biomarker and safety data for the first cohort We look forward to providing further updates on the progress of the PBGM01 Phase 1-2 study later in the year. We also remain on track in moving our FTD and CRAB-A programs towards clinical study initiations in the first half of 2021.
At this time, we'd like to open the call up for your questions operator.
Thank you.
The asked the question you would need to press Star then one on your telephone to withdraw your question. Please press the pound King again that is star then one if you would like to ask the question.
Our first question comes on the line of a new Pan Rama with J.P. Morgan. Your line is now open.
Hey, guys. Thanks, so much for taking the question.
Can you clarify your comments on what components of the proposed ITM device are similar to two other administration of the same method and then like to be clear. This is a discussion with the FDA on GM, one specific right or does it a broader questions about.
The other programs using them as well.
That's our first question.
Hi on apartments for his thanks for thanks for joining the call. Thanks for the question.
So.
We believe that the components are highly similar to other devices. It's typically syringe, a Ah hey, connector and and then in an injection needle.
Thats typically has set up for a nice you have injection and and again, we believe that's highly similar to show how other approaches are given but obviously those are proprietary each other companies and other clinical studies. So we can only comment on what we believed to be the case based on but based on our device and our knowledge.
Operator: As I mentioned earlier, our headcount continues to grow as we expand our clinical, manufacturing, and operations teams to support these programs, along with future development of additional pipeline candidates, all with the goal of helping patients suffering from serious, life-threatening, rare, monogenic central nervous system diseases. At this time, we'd like to open the call up for your questions. Operator? Thank you. To ask a question, you will need to press star then 1 on your telephone.
The field.
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We don't have just wanted to emphasize that we don't have official written feedback from the agency. So you can't comment further on which particular component or the entire device. So what is the is that is the focus we think that they're either questions or technical in nature and.
Can be addressed or additional risk assessments and are testing, which we've already begun and we've also based this assessment I should note on certainly our internal capabilities, but input from multiple regulatory device experts some of whom have a significant experience with FDA and they're in their former.
Operator: To withdraw your question, please press the pound key. Again, that is star and then 1 if you would like to ask a question. Our first question comes from the line of Anupam Rama with J.P. Morgan.
Anupam Rama: Your line is now open. Hey guys, thanks so much for taking the question. Can you clarify your comments on what components of the proposed ICM device are similar to other administration of the same method? And then, like, to be clear, this is a discussion with the FDA about GM1, right? Or does it prompt broader questions about the other programs using ICM as well? That's our first question. Hi Anupam, it's Bruce.
Employment, so putting all that together, we think that we can respond rapidly to the FDA.
And so it does the answer to your first question. If you could repeat of second part Oh, sorry. The second part is whether this relates to GM. One. It is it is the G. M. I Indy filing so that's the only thing that we can comment on we obviously think that this.
You know, what's we resolve this that off this will increase the.
Bruce Goldsmith: Thanks for joining the call and thanks for the question. So, you know, we believe that the components are highly similar to other devices, typically a syringe, a connector, and an injection needle. That's typically the setup for an ICM injection.
The probability and likelihood of us moving forward smoothly with all of the other studies as well and that's why we're eager to resolve it for them to Jim on my Andy filing, but we obviously haven't haven't gotten feedback or are submitted yet for the other programs.
Great. Thanks for taking my question.
Absolutely. Thank you.
Bruce Goldsmith: And again, we believe that's highly similar to how other approaches are given, but obviously, those are proprietary to other companies and other clinical studies. So we can only comment on what we believe to be the case based on our device and our knowledge of the field. I just want to emphasize that we don't have official written feedback from the agency, so we can't comment further on which particular component or the entire device is the focus. We think that the questions, which are technical in nature, can be addressed through additional risk assessments and or testing, which we've already begun. And we've also based this assessment, I should note, on not only our internal capabilities but input from multiple regulatory device experts, some of whom have significant experience with the FDA in their former employment. So, putting all that together, we think that we can respond rapidly to the FDA. And so, you know, I think that's the answer to your first question. If you can, repeat the second part.
Thank you. Our next question comes on the line of Salveen Richter with Goldman Sachs. Your line is now open.
Thanks for taking your question Thats Andrea on her shopping maybe just one on your FTD program, but love to hear your comments on the competitive dynamics mistakes and how you get your approach is being differentiated thanks so much.
Sure Thanks, Andrea and.
I'm happy to take the question so for the FTD program. There a couple of different aspects of differentiation that we think no. One is it is obviously, we do think that the.
That the ongoing studies using the antibody approach to block. This are telling receptor are certainly interesting and we noted that theres a advancement into Oh randomized phase three program that are really show the actual efficacy of that approach in blocking the re uptake of program.
Bruce Goldsmith: Oh, sorry, the second part is whether this relates to GM-1. It is the GM-1 IND filing, so that's the only thing that we can comment on. We obviously think that once we resolve this, it will increase the probability and likelihood of us moving forward smoothly with all of the other studies as well, and that's why we're eager to resolve it for the GM-1 IND filing. But we obviously haven't gotten feedback or submitted them yet for the other programs. Great, thanks for taking our questions. Absolutely not.
And your lending through that receptor.
That's one point of differentiation, obviously, it's the modality.
The that's the frequency of administration, there, which is I believe monthly and obviously, it's the it's the difference between shifting in Dod Eunice levels are progressing tailwind from intercellular <unk> extra cellular potentially.
Versus versus creating a gene therapy that we'll obviously increase.
Operator: Thank you. Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open. Thanks for taking our questions. This is Andrea.
Regarding that will levels.
Through with here through the expression of proteins.
So the other parts that's that's out there that is.
Andrea: For Salveen, maybe just one on your FTD program. We'd love to hear your comments on the competitive dynamics in the space and how you view your approach as being differentiated. Thanks so much. Sure. Thanks, Andrea. I'm happy to take the question. So, for the FTD program, there are a couple of different aspects of differentiation that we think are interesting. Now, one is, obviously, we do think that the ongoing studies using the antibody approach to block the sirtelin receptor are certainly interesting. And we noted that there's advancement into a randomized phase 3 program that will really show the actual efficacy of that approach in blocking the reuptake of progranulin through that receptor. That's one point of differentiation. Obviously, it's the modality.
That has an I'd active is is looking at.
Using the JV nine approach.
Two through through nicely and injection and that's obviously had been been shown to be effective in preclinical models to increase.
CSF level, so pro gradual and through a gene therapy expression patterns gene therapy delivery and protein expression.
So we did note that the the levels of increases for gradual and appear to be in the approximately two to two and a household levels.
That's that's a that's certainly a interesting and it certainly hopeful.
Are you going back to our differentiation, which is using an AG one approach.
What we showed is that a b one actually can win delivered through I see.
Bruce Goldsmith: It's the frequency of administration there, which is, I believe, monthly. And obviously, it's the difference between shifting endogenous levels of progranulin from intracellular to extracellular, potentially, versus creating a gene therapy that will obviously increase progranulin levels through the expression of protein. So, you know, the other approach that's out there that has an IND active is looking at using the AAV9 approach through an ICM injection. And that's obviously been shown to be effective in preclinical models to increase CSF levels of progranulin through gene therapy expression—through gene therapy delivery and protein expression. We did note that, you know, the levels of increase in progranulin appear to be in the approximately two to two-and-a-half-fold range. And that's certainly interesting, and it's certainly hopeful.
Can actually ship programming a levels up to 50 times the levels of upper granular with.
Without concomitant systemic exposure.
So we do think that the and that has to do with specific transduction of clinical cells. So putting all this together.
The gene therapy approaches obviously different than doesn't anybody approach that is systemically administered number one and number two our approach based on a selection and missed centrally a comparison of 81 to other vectors shows that we can shift progressing on much higher than not and other gene therapies and that may be important in Steve.
Analyzing or potentially a it from a long term perspective stabilizing or hopefully addressing disease.
Thanks, so much.
Thank you.
Thank you as a reminder, if he would like to ask a question.
Bruce Goldsmith: Our—you know, going back to our differentiation, which is using an AAV1 approach, what we showed is that AAV1 actually can, when delivered through ICM, can actually shift progranulin levels up to 50 times the levels of progranulin without concomitant systemic exposure. So we do think that the, and that has to do with the specific transduction of ependymal cells. So, putting all this together, the gene therapy approach is obviously different than an antibody approach that is systemically administered, number one. And number two, our approach, based on selection and essentially a comparison of AAV1 to other vectors, shows that we can shift progranulin much higher than other gene therapies.
Please press Star then one on your telephone.
Our next question comes on the line of urine Werber with Cowen. Your line is now open.
Yeah, Hi, good morning, Thanks, so much for taking my question.
Bruce I've I've a couple of we should all one the first one is just a follow up on the last question and can you give us a sense in across your programs are you planning and using immuno suppressant. In addition to high dose steroids, maybe just give us a sense sort of well to the except as you can what's the steroid regimen more or less of these.
These are going to suppress and to reduce the adaptive immune response, and then I've a follow up.
Sure we understand the prompted the question and Thanks Your question John.
So I'll start and then maybe I'll turn it over to to Gary I'm not sure that we've given the specific operational details of of the of the immunosuppression regimen, but we do think it's important to have.
Bruce Goldsmith: And that may be important in stabilizing or potentially, from a long-term perspective, stabilizing or hopefully, addressing the disease. Thanks so much. Thank you. Thank you. As a reminder, if you would like to ask a question, please press star then 1 on your telephone. Our next question comes from the line of Euryn Werber with Cowan. Your line is now open.
At least at an approach that has a.
Brief course.
Of that and you know it's also important to note that we haven't seen.
Significant it means immune reactions.
Euryn Werber: Yeah, hi, good morning, and thanks so much for taking my question. Bruce, I have a couple if you don't mind. The first one is just a follow-up to the last question, and can you give us a sense across your programs whether you are planning on using immunosuppressants in addition to high-dose steroids? Maybe just give us a sense of, to the extent that you can, what's the steroid regimen, more or less, and do you use immunosuppressants to reduce the adaptive immune response? And then I have a follow-up. Sure, we understand the prompt of the question and thanks for your question, Yaron. So, I'll start and then maybe I'll turn it over to Gary.
In our non human Primate studies so.
I'll, Oh, I'll turn it over to Gary to talk about just a global approach that we think about immunosuppression in our studies for for for all of our programs.
Yes, Thank you Chris.
So yes, we do intend to use a prophylactic immunosuppression.
Beginning beginning with good steroid treatment and.
We're not going to go into the details of the immunosuppression Rigi regimen.
For each program, but I just want to so that it's going to be adaptive in the sense that if there were immuno related.
Good.
Adverse events that this could obviously be adjusted and.
By the investigator.
Two positions.
And Gary, but it sounds like it's going to be stewards, only or do you plan to using through all the most effective problem is one of those actual immuno suppressant.
Bruce Goldsmith: I'm not sure that we've given the specific operational details of the immunosuppression regimen, but we do think it's important to have at least an approach that has a brief course of this and, you know, it's also important to note that we haven't seen significant immune reactions in our non-human primate studies. So, I'll turn it over to Gary to talk about just the global approach that we take to immunosuppression in our studies for all of our programs. Yeah, thank you, Bruce.
Yes, good question. Thanks.
You know in Oregon, we haven't seen any evidence in any of our three toxicology studies across all the programs of immuno related.
Changes in pathology or clinical any clinical manifestations and so for that reason.
Our intention is to start with.
With switch steroid prophylaxis.
Which is on the on the on this scale maybe on the on the milder ends of the Immunosuppressants as you know there's many different regimens out there in Houston gene therapy programs and this is on the on the lighter and of course, we're watching carefully what's happening in the field and you know that could that could change for future programs based.
Gary Romano: So yes, we do intend to use prophylactic immunosuppression beginning with steroid treatment. And we're not going to go into the details of the immunosuppression regimen for each program, but I just want to say that it's going to be adaptive in the sense that if there are immuno-related adverse events, that this could obviously be adjusted by the investigator or, you know, treating physician. And Gary, but it sounds like it's going to be steroids only, or do you plan to use sirolimus or one of those actual immunosuppressants? Yeah, good question. Thanks. And we haven't seen any evidence in any of our three toxicology studies across all the programs of immuno-related changes in pathology or any clinical manifestations.
On emerging data.
Okay, Great and you mentioned I'm, just kind of shift back to a good Jim one.
Bruce you mentioned that there could be other additional testing that after you might be requiring an addition to buy bio compatibility can you give us a sense what are those additional testing.
Sorry, just to be clear the additional testing or risk assessment is taken from their brief communication and that all has to do with the biocompatibility. So the way that they phrase the clinical hold communication is that they are.
Gary Romano: And so for that reason, our intention is to start with steroid prophylaxis, which is on the scale, maybe on the milder end of immunosuppression. As you know, there are many different regimens out there in use in gene therapy programs, and this is on the lighter end. Of course, we're watching carefully what's happening in the field, and, you know, that could change for future programs based on emerging data. Great. And you mentioned—I'm just going to shift back to GM1—Bruce, you mentioned that there could be other additional testing that FDA might be requiring in addition to biocompatibility. Can you give us a sense of what those additional tests are?
Looking through looking at biocompatibility at the dice device.
And may require additional risk assessments and or testing.
So just to be clear that is that is not perfectly known yet to review the process and I think it's worthwhile. The clinical hold is it typically made by FDA guidelines by a brief communication either by telephone or in this case email.
With fall off a telephone call.
And then we expect a a full communication.
With fuel fuel.
Full written communication with an explanation.
Approximately within 30 days and we just want to be clear that we've received the initial feedback, but we have not received.
Bruce Goldsmith: Sorry, just to be clear, the additional testing or risk assessment is taken from their brief communication, and that all has to do with biocompatibility. So the way that they phrase the clinical hold communication is that they're looking at the biocompatibility of the device and may require additional risk assessments and or testing. And so, you know, just to be clear, that is not perfectly known yet. To review the process, and I think it's worthwhile, the clinical hold is typically granted by FDA guidelines by a brief communication, either by telephone or, in this case, email, with a follow-up telephone call.
You know the full feedback at this point so we're somewhat limited in what we can give you.
But what we have done then is reached out to all of our external experts and external experts and defined various risk assessments and testing that are very typical for four of medical device.
And that follows a range of testing.
As simple as for example sort of toxicity.
Of the device for example, because it comes in contact with with skin now some of this I will mention also as I said many of these devices that were using or all of them. We believe our are approved. So we're also gathering information on though is that could potentially address the uptick concerns. So it's a mix of risk assessment and potential.
Bruce Goldsmith: And then we expect a full written communication with an explanation within approximately 30 days. And we just want to be clear that we've received the initial feedback, but we have not received the full feedback at this point. So we're somewhat limited in what we can give you. But what we have done then is reached out to all of our internal experts and external experts and defined various risk assessments and testing that are very typical for a medical device. And that follows a range of testing, as simple as, for example, sort of toxicity of the device, you know, because it comes in contact with skin.
Testing that we are ready for when we're waiting for the F. dealer.
Okay, Great and then just a final question in terms of D.
DRG or sensory sort of testing as part of the consist the Clos concerns about a benign and can you give us a sense of what's going to be included in the phase one two thank you.
Sure and two points to that it's it's not just a benign that has the that DRG.
Jim I Wilson and his group at the Gene therapy program I presented at CCT and analysis across multiple a the sub types and showed that the DRG toxicity.
Bruce Goldsmith: Now, some of this I will also mention, as I said, many of these devices that we're using, or all of them we believe are approved, so we're also gathering information on those that could potentially address the FDA concerns. So it's a mix of risk assessment and potential testing that we are ready for when we're waiting for the FDA. Okay, great. And then just a final question, in terms of DRG or sensory sort of testing as part of the class concerns about AV9, can you give us a sense of what's going to be included in Phase I-II? Thank you. Sure, and I add two points to that. It's not just AAV9 that has the DRG. Jim Wilson and his group at the Gene Therapy Program presented at ASGCT an analysis across multiple AAV subtypes and showed that the DRG toxicity, which is just a pathology right now and doesn't look like it has clinical manifestation, actually occurs across multiple AAV subtypes.
Which is just a apology right now and it doesn't look like it has clinical manifestations.
Occurs actually.
Across multiple Avi subtypes, just wanted to make sure that that youre aware of that.
So what we're going to do it is a in all of our studies, but certainly in the GM on study is we're going to monitor.
The nerve conduction of of limbs of.
Make sure that.
And to see if we can detect any changes in nerve conduction studies and that follows the.
The assessment and in non human primates that we could see that.
Again without any clinical manifestations.
Great. Thanks, so much.
Thank you yeah.
Thank you.
Bruce Goldsmith: I just wanted to make sure that you're aware of that. So what we're going to do in all of our studies, but certainly in the GM1 study, is we're going to monitor the nerve conduction of limbs and make sure that we can detect any changes in nerve conduction studies. And that follows the assessment in non-human primates that we could see that, again, without any clinical manifestation. Great, thanks so much. Thank you. Thank you. Our next question comes from the line of Gabolo Musa with Chardon. Your line is now open.
Next question comes from the line of football and use that was Chardan. Your line is now open.
Hi, good morning, Thanks for taking my call. So just a quick one on the question of bio compatibility of the proposed IC ATM delivery device and forgive me for asking about external parties and I understand if you can't comment but are you aware of any similar clinical hold on I see I'm devices, what the issues, where and how quickly they.
They resolved.
Yeah. Unfortunately, I thought highball. This is the spurs. Thanks for your question.
Gabolo Musa: Hi, good morning, and thanks for taking my call. So just a quick one on the question of biocompatibility of the proposed ICM delivery device. And forgive me for asking about external parties, and I understand if you can't comment, but are you aware of any similar clinical holds on ICM devices, what the issues were, and how quickly they were resolved? Yeah, unfortunately, this is Bruce.
Unfortunately, we're not aware so they either obviously didn't occur or not disclosed and we we aren't sure which is the case and obviously that is subject to.
Proprietary discussions along the the pathway to I.M.D. between companies and the and the FDA. So Unfortunately, we can't comment what we what we do know go through a mix internal experience as well as talking to our experts is that the device that we are using.
Bruce Goldsmith: Thanks for your question. Unfortunately, we're not aware of them. So they either obviously didn't occur or were not disclosed. And we aren't sure which is the case.
Bruce Goldsmith: And obviously, that is subject to, you know, proprietor discussions along the pathway to IND between companies and the FDA. So, unfortunately, we can't comment. What we do know both from internal experience as well as talking to our experts is that the device that we are using, which is essentially, you know, three components of approved individual components, is highly similar to other companies. So, we're not, again, until we have the final kind of official letter, we're not clear exactly what the tests and risk assessments that are required, but we're hoping, based on precedent and based on our experts, that it'll be a fairly rapid back and forth between us and the FDA.
Which is essentially a you know multiple three components so have approved.
Individual components.
It is highly similar to other companies so.
We're not we're not again until we have the the final kind of official letter or were not clear exactly what the what the tests and.
And risk assessments that are required, but but we're hoping based on precedent and based on our experts that it'll be.
A fairly rapid back and forth between us and the FDIC, We're certainly looking Virgin working with them to results.
Great. Thanks, Chris.
Thank you.
Thank you.
I'm showing no further questions in the queue at this time.
Ladies and gentlemen, thank you for your participation in today's conference.
You may now disconnect.
Bruce Goldsmith: And we're certainly looking forward to working with them to resolve it. Great, thanks Bruce. Thank you. Thank you. I'm showing no further questions in the queue at this time. Ladies and gentlemen, thank you for your participation in today's conference. You may now disconnect. Everyone, have a great day.
Everyone have a great though.
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