Q2 2021 Abeona Therapeutics Inc Earnings Call

<unk> morning, ladies and gentlemen, thank you for holding your conference call will begin in just a couple of minutes. Once again. Thank you for holding your conference call will begin in just a couple of minutes.

Operator: Thank you for holding. Your conference call will begin in just a couple of minutes. Once again, thank you for holding. Your conference call will begin in just a couple of minutes.

Gregory Gin: Good day and welcome to the Abiona Therapeutics second quarter 2021 conference call. There will be a Q&A session after the presentation, and instructions will follow. As a reminder, today's conference is being recorded. I'll now introduce your host for today's conference, Greg Jinn, Vice President of Investor Relations and Corporate Communications at Abiona. Please go ahead.

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Yes.

Good day and welcome to the Abbvie on a therapeutics second quarter 2021conference call.

There will be a Q&A session. After the presentation and instructions will follow as a reminder, today's conference is being recorded on now introduce your host for today's conference, Greg Gin, Vice President of Investor Relations and corporate communications.

Gregory Gin: Thank you, Paul. Good morning, everyone. I would like to welcome and thank you for joining us on our second quarter 2021 conference call. The press release announcing the second quarter results and recent operational progress is available on our website at www.abionattheratherapeutics.com. On the call today with prepared remarks are Michael Amaroso, Chief Executive Officer of Aviona, and Ed Carr, Chief Accounting Officer.

I'll be on them. Please go ahead.

Thank you Paul.

Good morning, everyone I.

I would like to welcome and thank you for joining us on our second quarter 2021 conference call.

The press release announcing for the second quarter results and recent operational progress is available on our website at www dot.

Maybe on the therapeutics dotcom.

On the call today with prepared remarks are Michael MRO, So chief Executive officer of ABR on AR, and Ed Carr, Chief Accounting Officer.

Gregory Gin: After the prepared remarks, we will host the Q&A session. We are also joined by Dr. Vish Sashari, head of research and clinical development, and Dr. Brian Kavani, a lead research scientist working on our preclinical eye program. Before we start, I will review our Safe Harbor statement. Remarks made during today's call may contain projections and forward-looking statements regarding future events. Forward-looking statements are made pursuant to the Safe Harbor provisions of the federal securities laws. Forward-looking statements are based on current expectations and are subject to change, and actual results may differ materially from those expressed or implied in the forward-looking statements.

After the prepared remarks, we will host the Q&A session.

We are also joined by Dr. Vishal, sorry, head of research and clinical development.

Acacia Brian conveying.

On a lead research scientists working on our preclinical programs.

Before we start I will review, our safe Harbor statement.

Mark's made during today's call may contain projections and forward looking statements regarding future events forward looking statements are made pursuant to the safe Harbor provisions of the federal Securities laws. These.

<unk> looking statements are based on current expectations and are subject to change and actual results excuse me actual results may differ materially from those expressed or implied in the forward looking statements.

Gregory Gin: Various factors that could cause actual results to differ include but are not limited to those identified under the section entitled risk factors in the company's end report on Form 10K and quarterly reports on Form 10Q filed by the company with DST. These documents are available on the website at www. www.abionatherapeutics.com. And with that, I will now turn the call over to Michael. Thank you, Greg. Good morning, everyone.

Various factors that could cause actual results to differ include but are not limited to those identified under the section entitled risk factors in the company's annual report.

Port on form 10-K, and quarterly reports on form 10-Q filed by the company with the SEC.

Documents are available on our website at www dot if you're on a therapeutics dot com and with that I will now turn the call over to Michael Michael.

Thank you Greg good morning, everyone and thanks for joining.

Michael Amaroso: And thanks for joining us. We are excited to be with you today. I hope this call finds you and your loved one safe and that this is still an uncertain time.

We are excited to be with you today and I Hope this call finds you and your loved ones safe from the store on certain time.

Michael Amaroso: I'd like to begin this morning with a review of our three strategic priorities for this management team in 2021, bolstering our relevant operational experience, first and foremost for our management team, but also for our board members. Second, delivering operational excellence, both timely and fiscally disciplined, to make sure we advance our clinical programs with meaningful data toward regulatory miles. Third, prioritizing, executing, and advancing the preclinical pipeline toward the clinic, starting with a focus that we discussed on our last call about the I or our pharmacogenetics gene therapy program. Now that it's the midpoint of 2021, let's assess how we're doing. Priority one was accomplished.

I'd like to begin this morning with a review of our 3 strategic priorities for this management team in 2021.

First.

Bolstering our relative operational experience first.

First and foremost for our management team.

But also for our board members.

Second delivering operational excellence, both timely and fiscally disciplined.

To make sure we advanced our clinical programs with meaningful data toward regulatory milestones.

Third.

<unk> executing and advancing our free.

Preclinical pipeline towards the clinic, starting with a focus that we've discussed on the last call on the IDE.

On the gene therapy programs.

Now that's the midpoint of 2021, let's assess how were doing.

Priority 1.

Accomplish.

Michael Amaroso: We have added specific operational experience to our management team and our board of directors. As I noted on our Q1 call, we enhanced our board with the appointment of four new members, and, most importantly, we strengthened our management team with the appointment of Dr. Vishwashashadri, who joined us from a senior level position at BMS, to be our head of research and clinical development. In addition, we've added even more strength and experience to our clinical development program teams under VISH for EB and MPS.

We have added specific operational experience to our management team and our board of directors.

As noted on our Q1 call we enhanced our board with the appointment of for New members and most importantly, we strengthened our management team with the appointment of Dr. Vishal Shah.

Who joined us from a senior level position at BMS.

We are head of research and clinical development.

In addition, we've added even more strength and experience to our clinical development program on the teams under this for EDI and NPS.

Michael Amaroso: We've added relevant regulatory BLA experience, some of which has been paramount for our successful two Type B meetings over the last six months. Also, we continue to fortify our quality and technical operations teams in Cleveland as we move closer to BLA readiness skills. All of these teams have been strengthened in 2021 months fall.

We've added relevant regulatory BLA experience some of which has been paramount for a successful 2 type b meetings over the last 6 months.

Also we continued to fortify our quality and technical operations teams in Cleveland as we move closer to the BLA readiness skill sets.

All of these teams have been strengthened in 2021 months fall on.

Michael Amaroso: And we will continue to be opportunistic about adding the best talent in the market. Priority 2 on target. We are delivering and have delivered operational excellence in achieving significant clinical milestones in a fiscally disciplined and timely manner. Let's start with our pivotal programs in our debt, EB-101. I'm excited to tell you about the progress we made in patient enrollment, opening a second site for completing our registration trial, and ultimately, all driving towards a BLA in 2022.

We will continue to be opportunistic about adding the best talent from the marketplace.

<unk> priority to on target.

We are delivering and have delivered operational excellence and achieving.

Significant clinical milestones in a fiscally disciplined and timely manner.

Let's start with our pivotal program and our debt <unk> 101.

I'm excited to tell you about the progress.

We made and patient enrollment.

Opening a second site for completing a registration trial and ultimately all driving towards a BLA in 2022.

Michael Amaroso: I'm also excited to tell you about the progress made on our NPS 3A program, which we had a successful and collaborative type B meeting with the FDA last month, confirming that transfer A is the pivotal study for ABO 102 in MPS3A. Our third clinical program, MPS 3B, We are at the conclusion of enrollment at the high dose cohort three level and will be closing the transfer B study for further accrual, will continue to follow these patients to assess long-term safety and efficacy, specifically neurocognitive development over time. And then priority three, also on target: we are advancing our preclinical eye programs toward the clinic with great speed and precision. During Q2, we reported the results of two non-human primate studies.

I'm also excited to tell you about the progress made on our NPS program.

Which we had a successful and collaborative type B meeting with the FDA last month.

On confirming the transfer is the pivotal study for <unk> 102, and NPS 3 day.

Our third clinical program NPS, we'd be.

We are at the conclusion of enrollment at the high dose cohort 3 level and will be closing the transfer B study for further accrual.

We will continue to follow these patients.

With <unk> long term safety and efficacy, specifically neurocognitive development overtime.

And then priority 3 also on target with <unk>.

Michael Amaroso: We are on track to begin proof of concept studies in the second half of this year, and this will be toxicology study enabling into 2022 in some select upthalmic indications. Now, let's take a deeper dive into the progress of our clinical programs and preclinical programs. Starting DB 101, our lead pivotal phase three vital study for recessive dystrophic epistemolysis, or RDMALOSA, or RDF, We continue to build enrollment momentum and vitality. There continues to be a high and growing level of interest among patients and health care professionals, And we are very pleased to have recently activated a second clinical trial site at UMass Memorial Medical Center in Worcester, Massachusetts under principal investigator and world-renowned Dr. Wiss is a professor of dermatology and pediatrics at UMass Medical School, and she's the Director of Pediatric Dermatology.

We are advancing our preclinical programs towards the clinic with great speed and precision.

During Q2, we reported the results of 2 non human.

In Primate studies.

We are on track to begin proof of concept studies in the second half of this year and this will be toxicology study enabling.

Into 2022 on some select ophthalmic indications.

Now, let's take a deeper dive into the progress of our clinical programs and preclinical programs.

Starting with <unk> 101 on <unk>.

Lead pivotal phase III vital study for recessive dystrophic, epidermolysis <unk> or our debt.

We continue to build enrollment momentum and vital.

There continues to be high and growing level of interest among patients and health care professionals.

And we are very pleased to have recently.

Activated our second clinical trial site at Umass Memorial Medical Center in.

In the Worcester mass on the principal investigator and world renowned expert Dr. Karen West.

Michael Amaroso: We are excited to have the UMass team join the avi owner's mission of pursuing a standard of care for large and chronic RDEB. This is a significant and major milestone, and I want to congratulate the team on this timely execution and thank the staff and team at UMass. Now, in addition to our lead trial site at Stanford Medical Center in Palo Alto, California, we can provide convenient treatment locations for study participants on both the West and East Coasts, making travel logistics easier for patients and family.

Dr. <unk> is a professor of dermatology and pediatrics at Umass Medical school and she's the director of pediatric dermatology.

We are excited to have the Humana team joined <unk> on admission are pursuing a standard of care for large and chronic ardeb wounds.

This is a significantly a major milestone and I want to congratulate the team on this timely execution and thank for staff and team at <unk>.

Now in addition to our lead trial.

Stanford Medical center in Palo Alto, California.

Michael Amaroso: I'll remind our investment community, this was one of the major challenges we heard from the community in 2020, and thus far in 21, it seems to be opening up with our pandemic. The second site is paramount to our success. At the same time, we're expanding necessary physician experience with EB-101, as we plan for potential commercial launch in the U.S. We look forward to collaborating closely with the clinical team at UMS to screen in the role subjects in vital as soon as possible. They are ready to go.

We can provide convenient treatment locations for study participants on both the west and East coast, making travel logistics easier for patients and families.

Ill remind our investment community. This was 1 of the major challenges we heard from the community in 2021.2000.

'twenty and thus for in 'twenty, 1 it seems to be opening up with our pandemic. The second site. It is paramount to our success.

At the same time, we're expanding necessary physician experience with VB 101, as we plan for potential commercial launch in the U S.

Michael Amaroso: Next, we continue our progress toward completing patient enrollment in the vital study. We have successfully administered EB 101 to patient number five. As you may recall from our last call, this is the patient who opted to rebiopsy and make new products. We are extremely happy to report that the rebiopsy and manufacturing of EB-101 products were successful for this patient, and they have received their EB-101 administration. The patient will be followed as per our vitals protocol.

We look forward to collaborating closely with the clinical team at UBS.

The screen and enroll subjects and vital as soon as possible.

They are ready to go.

Net we continue our progress toward complete completing patient enrollment in the vital study.

We have successfully administered EV 101 to patient number 5.

As you may recall from our last call. This is the patient.

To re biopsy and make new product.

We are extremely happy to report that the re biopsy and manufacturing with VB 101 product was successful for this patient and they have received that VB 101 administration.

Michael Amaroso: Additional patients continue to be identified and pre-screened at both Stanford and now UMass to determine their eligibility for vital. As a reminder, the target for the Pivotal trial is the treatment of approximately 35 large chronic wounds across 10 to 15 patients. Today, I'm excited to report that we have treated more than half of the target number of randomized pairs of wounds thus far.

The patient will be followed as per our vital protocol.

Additional.

Additional patients continue to be identified on Prescreened at both Stanford and now Umass for determining eligibility for vial.

As a reminder, the target for the pivotal trial is the treatment of approximately 35 large chronic wounds across 10 to 15 patients today.

Michael Amaroso: Next, let's turn our attention to our AAB platform, our second Inc. clinic program, ABO 102, the San Felipe Syndrome type A, or MPS3A disease. Yesterday, we announced some very exciting news about our type B meeting with the FDA for the MPS 3A program. We had a successful, collaborative type B meeting and agreed with the FDA that the current single-arm transfer A study will serve as the pivotal study for ABO 102 and potentially support a biologic license application, of course, depending on the data.

Today I'm excited to report that we.

We have treated more than half of the target number of randomized payers are moving thus far.

Next let's turn our attention to our AAV platform, our second infinite program <unk> 102 for Sanfilippo syndrome type a or MPS III disease.

Yesterday.

Today, we announced some very exciting news about our type B meeting with the FDA for the MPS <unk> program.

Michael Amaroso: Since 2016, we have now treated 21 patients in the transfer A trial. We're excited about the safety and the magnitude of benefits seen with our investigational ABO 102 product in the younger children from the higher dose cohort, as we reported at the World Symposium earlier this year. We remain hopeful that if the more recently dosed children in cohort three display similar treatment effects as those already presented, we could have a valuable data set in 2022. The patients we serve have tremendous unmet need. They cannot wait.

We had a successful collaborative type b meeting and aligned with the FDA that the current single on trends for 8 study will serve as the pivotal study for <unk> 102.

And potentially support.

Logics at biologic license application of course, depending on the dataset.

Since 2016, we have now treated 21 patients in the transfer a trial.

We're excited about the safety and the magnitude of benefit seen with our investigational ABL, 1 or 2 product in the younger children from the higher dose.

Michael Amaroso: And we remain fully focused on operational excellence with the intent of now delivering two pivotal data packages in 2022, one for EB 101 and one now for ABO 102. At the type B meeting, we also aligned with the FDA on the definition of the primary endpoint for transfer A, which is a neurocognitive assessment using the raw score from the Bailey scales of infant and toddler development and the Calcment assessment battery for children. These scales will be used in sequence.

Violet as we reported at the World Symposium earlier this year.

We remain hopeful that if the more recently those children in cohort 3 display similar treatment effects as those already presented we could have in a valuable dataset in 2022.

The patients we.

Covid have tremendous unmet need they cannot wait and we remain fully focused on operational excellence with the intent of now delivery 2 pivotal data packages in 2022, 1 for <unk> 101, and 1 now for <unk>.

Michael Amaroso: This is data we're already collecting as secondary endpoints. They will move to primary and transfer to A. And Vish will tell you a little bit more about that shortly.

Michael Amaroso: We are grateful to the FDA for their guidance, and we look forward to continuing to work closely with the agency toward our goal of bringing potentially life-saving therapy to patients afflicted with MPS 3A. In the near future, we intend to share the type B meeting feedback with the EMA, followed by potentially other regulatory authorities around the world, to guide our development plans for NAA in the XUS market. Of course, the United States is our first focus. In addition to the guidance and clarity from the FDA on the regulatory front, we also shared some very encouraging new clinical data from TransferA that had not before been published this past weekend during an oral presentation at the 16th International Symposium on MPS and related diseases, our new MRI data.

At the type B meeting.

We also in line with the FDA on the definition of the primary endpoint for transfer rate, which is neuro cognitive assessment using the raw score from the bayley scales of infant and toddler development.

And the Kauffmann assessment battery for children.

These scales will be used in sequence. This is data we're already collecting a secondary.

We serve endpoints they will move to primary and transfer a ambitious we'll tell you a little bit more about that shortly.

Okay.

We are grateful to the FDA for their guidance and we look forward to continuing to work closely with the agency toward our goal of bringing potentially lifesaving therapy to patients afflicted with NPS 3 day.

And then in the near future, we intend to share the type be meeting feedback with the EMEA.

Michael Amaroso: The data indicates that ABO 102 increases gray matter, corpus, colosum, and amygdala volumes in the brain in three young patients with MPS3A at 24 months post-treatment compared to an afflicted patient without. Now, let's talk about this for a moment. Brain volume loss is characteristic in children with MPS 3A, and it's associated with long-term cognitive and physical disability. Specifically, gray matter is important for cognitive development, the corpus Colossum for motor function, and the amygdala for emotional learning as well as social and emotional development.

Followed by potentially other regulatory authorities around the world to guide on development plans for MAA, an ex U S markets.

Of course, the United States is our first focus.

In addition to the guidance and clarity from the FDA on the regulatory from we also shed some very encouraging new clinical data from transfer rate that had not before been published this past weekend during an oral presentation at the 16th International Symposium on M. P S and related diseases or new MRI data.

The data indicates that a b O 1 O 2 increases gray matter.

Corpus callosum and amygdala volumes in the brain and 3 young patients with M. P. S..3 8 at 24 months post treatment compared to on afflicted patient without too.

Michael Amaroso: We're excited about the MRI data, as are our clinicians. And it's consistent with previously reported results of preservation of neurocognitive development in the three younger children and the three younger children from cohort three that we presented from TransferA earlier this year with the longest follow-up. Moving onward to our last in-clin program, ABO 101, in the TransferB study for MPS 3B. As noted on the last quarterly call, the reported results from Transvae at the World Symposium in February, The results to date, Transfer B, the high dose cohort, like the high dose cohort in Transfer A, show the drug is safe and well-tolerated, eliciting a dose-dependent, sustained reduction in disease-specific biomarkers, denoting clear biologic effects.

Now, let's talk about this for a moment brain volume losses characteristic in children with M. P. S..3 yet and it's associated with long term cognitive and physical disability.

Specifically gray matter as important for cognitive development.

Corpus callosum for motor function.

And amygdala for feel learning as well as social and emotional development.

We're excited about the on the idea as a clinicians.

And it's consistent with previously reported result of preservation of Neurocognitive development and the 3 younger children that we in the 3 younger children from cohort 3 that we have that we have presented from transfer a earlier this year with a long follow up.

Michael Amaroso: As I've reminded you in the past, we absolutely want to see biomarkers moving in the right direction. The gold standard will be the collection of neurocognitive development data, and we need to let that mature into 2022. Previously, we shared the accrual and transfer B was paused after dosing four patients in the higher cohort because the drug products, again, supplied by nationwide children's hospital in Ohio, had reached their two-year shelf-life expertise. Some of our additional stability testing results showed that Specifications were not met for all parameters of the transfer B protocol. However, specifically physical tighter.

Moving onward to a lab and clinic program Aviall, 1 on 1 and the transfer <unk> study for M. P. S..3 day.

As noted on the last quarterly call reported results from transfer to be at the World Symposium on February.

The results to date transferred the high dose cohort liked the high dose for what can transfer 8 show the drug is safe and well tolerated listening a dose dependent sustained reduction in disease specific biomarkers.

Michael Amaroso: However, after reviewing the test results based on equivalent potency, infectious tighter, as well as the purity profile of the drug, the German health regulatory authority, along with our DSMB, deemed that the benefit of the drug outweighed the risk and endorsed the use of the product for those remaining patients with the highest unmet need through the German named patient program. The NPP is a compassionate use program in Germany that allows individuals to be treated at the request of the retreating physician and their families.

And clear biologic effects as I reminded you in the past, we absolutely want to see Biomarkers moving in the right direction, but the gold standard will be the collection of neurocognitive development data and we need to let that mature into 2022.

Previously we share the accrual and transferred <unk> was Paul.

After dosing for patient from a higher cohort because the drug product again supplied by nationwide Children's hospital in Ohio had reached its 2 year shelf life expert.

Michael Amaroso: We're thankful for the authority and the DSMB actions, acting quickly to get the drug to these patients. To date, three patients have been dosed in the German NPP, and a fourth is pre-screened and getting ready for treatment. The total number of patients treated now at the higher dose, 1 times 10 to the 14 vector genome per kilogram, between TransferB, cohort 3, and now the NPP program will soon be eight children collected. In parallel, we're in the process of closing enrollment in the Transfer B study.

Some of our additional stability testing results showed.

Pacification, we're not meant for all parameters of transfer B protocol.

However.

Specifically physical tighter however, after reviewing the test results based on equivalent potency infectious titer as well as the purity profile of the drug the German health regulatory authority on.

Along with our D. S M. A D SMB deem it the benefit of the drug outweighed the risk and endorsed the use of the product for those remaining patients with highest unmet need through the German named patient program. The NPP as a compassionate use program in Germany that allows individuals to be treated at the request for the retreating physician.

Michael Amaroso: And patients from both the Transfer B and the main patient use program will be monitored with the same rigor for ongoing safety and efficacy of the high dose EB 101 product as they would have been within the TransferB study. While early biomarker data is promising, neurocognitive preservation and development are the gold standard, as we've discussed.

And families.

Michael Amaroso: We look forward to seeing two-year neurocognitive data beginning in the first half of 22 for some of the first patients' doses in the higher dose cohort from TransferB. And subsequently, we'll determine next steps for the program once we have some of these important and essential data. As we await these data, I'll remind you that out of our wholly owned Cleveland non-CDMO dependent manufacturing facility, ABO 102 for MPS3A, commercial grade products are being made.

We're thankful for the authority.

And the <unk> actions.

Acting quickly to get drug to these patients.

To date 3 patients have been built in the German NPP and a fourth is prescreen and getting ready for treatment.

The total number of patients treated now at the higher dose 1 times 10 to the 14 infected genome for Kilogramme between transfer be cohort, great and now the NPP program will soon be 8 children collectively.

Michael Amaroso: Our experience in AAB production from our fully owned Eliza Lytton Center will be highly transferable if and when we decide to manufacture AB 101 for MPS 3B, of course, data dependent in 22. Finally, I'll give a brief update on preclinical, and I'll open it up to the group's questions. As previously noted, we conducted preclinical research with novel AAB capsids, including our abiona invented and partnered capsules in six undisclosed eye indications. These eye indications represent opportunities in the U.S. alone of about 5,000 to 15,000 patients with the highest unmet needs.

In parallel we're in the process of closing enrollment in the transferred <unk> study.

And patients from both the transfer B and the named patient use program will be monitored for the same rigour for ongoing safety and efficacy of.

Of the high dose 81 on 1 product as they would have been within the transfer <unk> study.

While early biomarker data is a promising neurocognitive preservation and development is the gold standard as we've discussed.

We look forward to seeing 2 year neurocognitive data beginning in the first half of 22 for some of the first patients dose on the higher dose cohort from transfer day and.

Michael Amaroso: This continues our EBOA identity as a fully integrated end-to-end gene therapy focused on high unmet needs. Please hold the line while I'll back out, and Michael has rejoined. Go ahead, Michael. Yeah, I'm sorry about that to the community.

And subsequently will determine next steps for the program once we have some of these.

Important and essential data points.

As we await these data I'll remind you that out of our wholly owned Cleveland non C D Mo dependent manufacturing facility.

Michael Amaroso: I'll pick up where I left off in the preclinical programs. In the second quarter, we reported preclinical data from Argo, 2021, and completed non-human primate studies. As a reminder, the NHP results showed that AAB 204, one of our in-licensed AIM CAPS programs, was superior to AAB 8 using a recently developed novel route of ocular administration. And Brian will be on the call to tell us about that. If you have any questions,

0102 for M. P S..3 a commercial great product.

Is being made our experience at AAV production.

From our fully owned Elisa Lytton center will be highly transferable, if and when we decided to manufacture 81 on 1 <unk> program of course data dependent and 22.

Michael Amaroso: In a separate NHP experiment, AAV214 and 214D5, two wholly owned adione caps, demonstrated nearly identical levels of transduction compared with AAB8 of photoreceptor and retinal pigmented epithelium cells, which are the cell types most frequently affected in inherited retinal diseases. These data are believed to be very important findings, as I will remind you the gold standard today in ophthalmic subretan So we're enthusiastic about the find. We're moving as we speak to proof of concept studies in the second half of this year, and this will enable toxicology studies in 2022. With that, I'm going to turn over to Ed, our chief accounting officer, to review our financial results. Please, Ed. Thank you.

Finally, I'll give a brief update preclinical on I'll open it up to the group of questions.

As previously noted we conducted preclinical research with novel AED capsid, including R. E. B on Ah invented partnered cabinets and 6 undisclosed indications. These.

These items key indications represent opportunities in the us alone for about 5 to 15000 patients with the highest on that need.

This continues R. I E b on identity as a fully integrated end to end gene therapy company focused on high unmet needs.

Oh, please hold the line on that out I can't come on.

And Michael has Regina go ahead myself.

Yeah, I'm, sorry about that to the community I'll pick up where I left off on the preclinical programs in the second quarter, we reported preclinical data from order of 2021.

Ed Carr: Thank you, Michael. I would like to remind everyone that Form 10Q is available on our website, where you can get additional details.

And completed nonhuman Primate studies as a reminder, the <unk> results show that a ritual for 1 of our in licensed in caps programs was superior to a V..8 using a recently developed novel root of ocular administration.

Ed Carr: on our financial results for the three and six months ended June 30, 2021. While pursuing the key strategic priorities outlined by Michael, we have thoughtfully and carefully managed our spending decisions. Across each function within the organization, there is a balanced approach to not only focusing on moving forward towards our key milestones but also using our cash resources prudently and on time to deliver results. Looking at research and development activities in the second quarter of 2021, we spent $7.4 million, which is consistent with the 7.2 million spent in the first quarter of 2021. Research and development spend includes the cost of the clinical development of

Brian will be on the call to tell us about that if you have any questions.

In a separate H P experiment 80, 214, and 214 D..5 2 wholly owned 80 on a captains demonstrated nearly identical levels of transaction compared with 88 photo receptor and retinal pigmented epithelium cells, which other cell types, most frequently affected and inherited retinal diseases.

These data are believed to be very important findings as will remind you the gold standard today and I'll call make sub retinal drug delivery is a V 8.

So we went through the ethic about departments we're.

We're moving as we speak to proof of concept studies in the second half of this year and this will enable toxicology studies in 2022.

Ed Carr: EB 101 and MPS programs, and the manufacturing of the drug products for EB 101 and ABO

Ed Carr: and our preclinical ophthalmic research activities. Our spend on general administrative activities was 5.5 million in the second quarter of 2019, down significantly from the 6.6 million spent in the first quarter of 2021. Generally, administrative spend includes the cost of personnel not working directly on clinical and pre-clinical activities, as well as professional fees, insurance, rent, and office space. The decrease in general administrative spend in the second quarter of 2021 results primarily from lower professional fees.

With that I'm Gonna turn it over to add on cheap accounting officer to review our financial results. Please that thank you.

Oh, Thank you Michael I would like to remind everyone that the from 10 cubic available on our website, which is where you can get additional details on our financial results for the 3 and 6 months ended June 30th.

2021.

While pursuing the key strike strategic priority as outlined by Michael we have thoughtfully and carefully manage our spending decisions across each function within the organization. There's a balanced approach to not only focusing on moving forward towards our key milestones, but also using our cash resources prudently and on time to deliver results.

Ed Carr: Turning to the financial resources on our balance sheet, we had cash, cash equivalence, and short-term investments of $77.6 million as of June 30, 2021, as compared to $86.8 million as of March 31, 2021. The change in cash resulted primarily from $11.5 million of cash used in operating activities, partially offset by $2.3 million of cash from financing, based on our existing cash, cash equivalence, and short-term investments, our ability to access additional financial resources, and our financial flex-flexers.

Looking at research and development activities in the second quarter of 2021, we spent $7.4 million, which is consistent with the 7.2 million spent in the first quarter of 2021.

Research and development spending cruise the cost of the clinical development of the E. B 1 on 1 and M. P. S programs the manufacturing of the drug products for easy 1 on 1 and a bureau, 1 O 2 and are preclinical ophthalmic research activities.

Are spent on general and administrative activities was $5.5 million in the second quarter of 21.

On significantly from the 6.6 million spent in the first quarter of 2021.

Ed Carr: ability to reduce operating expenses if required. We believe that we have sufficient resources to fund operations through at least the next 12 months. And with that, I'll turn the call back over to Michael. Michael?

Administrative spend includes the cost of personnel not working directly on clinical on preclinical activities as well as professional fees insurance for rent and office expenses.

The decrease in general administrative spend in the second quarter of 2021 results primarily from lower professional fees.

Michael Amaroso: We're committed to delivering operational excellence and bringing gene therapy to patients with no approved treatment. We continue to advance our clinical programs with great operational know-how, many of our pre-existing team and new higher talent, and with fiscal discipline. We've activated a second clinical trial site at UMAP, and we are moving toward completing enrollment for EB 101, the Phase 3 Vidal Study in our day. In MPS 3A, we've aligned with the FDA on TransferA as a pivotal trial and the primary endpoint, giving us great guidance and clarity on the potential regulatory path for ABO 102. We are focusing our resources on completing these registration-enabling studies and preparing for the potential of two BLA filings.

Turning to the financial races on resources on our balance sheet, we had cash cash equivalents and short term investments of 77.6 million as of June 30th 2021, as compared to 86.8 million as of March 31, 2021. The change of cash resulted primarily from $11.5 million of cash used in operating activities partial.

Oh, you're all set by $2.3 million of cash from financing activities.

Based on our existing cash cash equivalents in short term investments our ability to access additional financial resources and our financial flexibility authorities operating expenses. If required we believe that we have sufficient resources to fund operations through at least the next 12 months.

And with that I'll turn the call back over to Michael Michael.

Thank you very much.

Operator: The second quarter was a highly effective and productive quarter for Aviona, and I want to thank our patients, their families, and our teams, including our investors who have made this incredible drug development possible. With that, I turn it over to the operator to open up questions and answers. Thank you. Thank you. Ladies and gentlemen, the floor is now open for questions. If you have any questions or comments, please press star 1 on your phone at this time.

We're committed to delivering operational excellent for bringing the gene therapies to patients with no approved treatments.

We continue to advance on clinical programs with great operational know, how many of our pre existing team in new hire talent and with physical discipline.

We've activated a second clinical trial side at new match on.

Moving towards concluding enrollment E. B went on 1 page to be vital studying all day.

An M. P S..3 a with a line with the FDA on transfer it as a pivotal trial and the primary endpoint, giving us great guidance and clarity on the potential regulatory pathway the old 1 or 2.

Operator: We ask that while posing your question, you please pick up your handset if listening on speakerphone to provide optimum sound quality. Please hold while we poll for questions. And the first question is coming from Kristen Kluska from Cantor Fitzgerald. Kristen, your line is live.

We are focusing on resources on completing these registration, enabling studies and preparing for the potential of 2 BLA filings the.

The second quarter was a highly effective and productive for for a biana and I want to thank our patients their families and our team.

Kristen Brianne Kluska: Hi, good morning everyone. Congratulations on the type B outcome and thanks for taking the questions. The first one I have is, could you remind us about the latest efforts and the current database for natural history in MPS3B? And given that for MPS3A, you achieved the best results when treating early in the high dose cohort, how should we also be thinking about perhaps the long-term data in cohort two, given that these patients are actually receiving a higher dose than MPS3A?

Including our investors will make this incredible drug development possible.

With that I turned it over to the operators open up questions and answers. Thank you.

Thank you, ladies and gentlemen on the floor as normal for questions. If you have any questions or comments. Please press star 1 on your phone at this time, we asked how I'll post on your question you. Please pick up your handset is listening on speakerphone to provide optimum sound quality.

Please hold while we poll for questions.

Michael Amaroso: Thanks, Chris, good to hear your voice. I think what I'll do. Juan Ruiz is actually with us on the phone, my lead clinician and MD from the 3B program. I think we're asking about the national history registries that exist or repositories, if you will, that exist for 3B. And then, Chris, I'll ask you to clarify. Are we also asking about the expectation of the higher dose cohort from 3B and how if we're expecting similar similarities to 3A? I just want to clarify the second part of that question before I have one answer, please. Okay.

And the first question is coming from my Christian for Scott from Cantor Fitzgerald Kristen Your line of ice.

Hi, good morning, everyone. Congrats on the typing, meaning outcome and thanks for taking my question.

The first 1 I have is could you remind us about the latest efforts and the current database for natural history and M. P. S..3 b and given that for M. P. S..3 a the cheese the best for results when treating early in the high dose cohort how should we also be thinking about perhaps the longterm data and cohort too given that these patients are at.

Saint receiving a higher dose than M. P yesterday.

Kristen Brianne Kluska: Sure, but also, the focus was on cohort 2 for MPS3B, just given that the protocol for the MPS3B trial includes higher doses relative to what you're studying for MPS3A.

Thanks for some good to hear your voice I think what I'll do 1 of the reasons actually with us on the phone on my my lead to condition of M. D. From the 3 D program I think we're asking about the natural history registries that exist or repositories. If you will that exists for 3 D. And then crystal ask you to clarify on Ah We also.

Michael Amaroso: Ah, yeah, gotcha. Okay, so there's two doses in 3B that are actually, cohort 2 and 3, that are higher than the highest dose in 3A, obviously a different drug. And I think we also believe the data we showed in February was from cohort 3B, the highest dose, 1 times 10 to the 14th. But I'll let Juan address both of those.

Asking about the expectation of the higher dose cohort from 3 B and how if we're expecting similar similarities to 3 I just want to clarify the second part of that question before I have on on 1 answer please.

Sure, but also the focus was on cohort 2 for M. P. S..3 be just given that the protocol for the M. P. S..3 b trial includes higher doses relative to what you're studying for M. P. S..3 a.

Michael Amaroso: So, Juan, let me open it up to you to please address what natural history data exists for 3B and what we should be looking for from 3B, the arm we discussed, as far as expecting neurocognitive results in 2022. Please want.

Yep Gotcha, Okay. So there's there's 2 doses and 3 day that are actually the call or 2 and 3 that are higher than the highest dose and 3 a obviously a different drug and I think we also believe the day to we showed February was from cohort 3 also from 3 day. The highest goes 1 time center for 14th but I'll, let 1 address both of those for 1 let me open.

Juan Ruiz: Yes, thank you Michael and thank you Kristen for the question. Regarding NPS 3B, the nationwide children's hospital conducted a natural history study for 3A and 3B, so they used the information to inform the clinical trials. So there is already data gathered from nationwide on 3B patients. In addition, Ted Whitley at the University of Minnesota conducted a natural history study on 3B patients that has been published.

On it up to you to please address on what natural history did exist for 3 B and what we should be looking for from 3 B, which arm what we discussed at this point as far as expecting neurocognitive results in 2022. Please 1.

Juan Ruiz: So we have access to this information that we are using to compare the children in our study. And also, biomerane has released some data on a significant natural history study on 3B patients for their own programs. So this information has been collected, and it's been used, and we are using it in a similar way to the information collected for 3A for our transfer A program. So we are confident that this information collected for our transfer A program will be used for our transfer A program. So we are confident that

Yes. Thank you Michael I'll send you a Christian for the question.

We've got a b and B S V. A nationwide to the hospital for conducted on that what he said he studied for C. A on T V. So they're using for answers towards was home.

Can we have on file so that is already d'etats other from nationwide on C. D basins. In addition to the.

He said Widdly Ah the University of Minnesota.

Juan Ruiz: There will be a amount of information that is needed in order to make the comparisons between the evolution of the children in transfer B and the natural history data. Regarding doses in transfer B versus transfer A, I would like to remind first that the product that we are using in both trials, although based on AB9, they both have some differences. The transfer A, I mean the product for the 3A program, is a self-complementary AV9 versus the single stranded AV9 vector for transfer B.

Conducted that's what he said he study on T V basically because in publics totally have access to information that we are using to compare the 200 and our friends on.

And also by a marine has released some data on a significant graduate and she's studying study on T V basically for the on programs. So this information has been collected on these dangerous on what we have to just.

In a similar way to.

Juan Ruiz: And this has implications regarding the speed of gene transduction and also the amount of gene expression. So although the doses are different and three times 10 to 13 in transfer A versus one times 14 in transfer B, this is somehow compensated for by the higher expression derived for the self-complementary Aves. On that regard, yes, the cohort 2 that is using 5 times 10 to 13 in the transfer B program is similar to those higher baselines in cohort 3 in transfer A, but it is difficult to compare because of this explanation.

For the information collected for C. A for hours on for a brought out. So we are confident that there was an amount.

The amount of information for these movies in order to convey the comparisons between the 1 on some of the 2 lines on for the we'd have total he's pretty data regarding doses in terms for to be let's discuss for a I would like to remind for is that the the product says we are used in both styles or the base on a benign both of them.

Have some differences the day cause for a <unk> I mean, the product and for the security code on you Sir.

Complimentary a V 9 on <unk> was the singular standard 89 that for for the job.

Juan Ruiz: We are going to, we are continually collecting data from these children, and we will have data throughout the year, and they will complete two years of follow-up before the end of the year, and we'll be ready for the beginning of 2020. Thank you, Juan. Thanks for the excellent explanation.

It's gonna be on on this it has implications.

Implications regarding to dispute the transaction that also the the amount of inexpressive. So although the doses are are are different on on on 3 times to do associate in sales today, but it was 1 thing for 14 cents for a b.

Kristen Brianne Kluska: Yes, thank you very much. And then moving on to ABO 102, is there a specific time length of follow-up that you're looking to collect for the more recently treated patients in cohort 3 as it relates to your comments about having a potential pivotal package next year?

Somehow compensated.

However, the expression you know if it's for.

Michael Amaroso: Yeah, Kristen, great question. I'll take that one.

It says complementary.

The other presided and just the the cohort too that is used in the 5 times 10 to 15 in the transfer B program is <unk> kind of for them.

Michael Amaroso: So I think the timeline that you guys have heard me talk about for post-treatment, not that it's a perfect science, but I just want to remind you, that two-year time point, knowing that neurocognition and development and those comparisons versus the scale of Bailey and, hopefully, Calphman, and this will speak to that, I'm sure, coming up in another question, as Bailey turns to Calphman, as a But the bottom line here is two years, Kristen, at that time point we've talked about. Now, again, what does that relate to?

Similar to to do those either of those simple hopefully you can transfer a but is that it's difficult to compare index of this.

There's plenty of issue we are going to continue to collecting data from these children on we would have a data on.

On the year are on.

They will compete to just follow up before the end of the year whenever you're ready for the beginning of 2022.

Thank you 1 thanks for the ex 1 explanation.

Yes. Thank you very much and then moving on to a B O..1 O..2 is there a specific time line to follow up that you're looking to collect for the more recently treated patients and cohort 3 as it relates to your comments about having a potential pivotal package for next year.

Michael Amaroso: Basically, our youngest patients are around 12 months old. So when you really start to see the separation versus the historical controls out there, the natural history, it's that three-year time frame we've talked about, Kristen. So we want to make sure we've got at least two years of follow-up of a treated patient. Again, that was based on the youngest patient at the time being treated for about 12 months. You know, it could be less data, for example, if you're treating a patient at baseline who's two years old. You know, now at two years, they're going to be four. You should see a really clear delineation.

Yeah Christian Great question I'll take that 1.

So I think the time on that you guys are hardly talk about on on on post treatment not that is a perfect science dogs remind you is that that 2 year time point, knowing that neural cognition and development and those comparisons versus the scale of Bailey and ultimately hopefully Kaufman official speak about that I'm sure coming up on another question as Bailey turns to Kaufman has it.

Michael Amaroso: So we think two years is a little minimum follow-up that's really important. Kristen, by the fall of next year, with the majority of all the cohort three, the three times 10 to the 13th from for ABO 1 or 2, from transfer A, we'll have almost all patients will be past two years by the fall, and we'll have some patients up to about five years. So that's what we say based on the magnitude of effect, still being determined in the SAP with the FDA.

Games, a certain level of acceptable cognitive age, which is obviously good news if you're turning to that survey, but the bottom line here is 2 years Christian 2 years at that time point, we've talked about now again, what does that relate to.

Basically our youngest patients are around 12 months. So you when you really start to see the separation versus the historical controls out there on the natural history is that 3 year timeframe, we've talked about Kristen. So we want to make sure we've got at least 2 years.

Michael Amaroso: We talked a little bit about, you know, it'll be a review decision, which is great, that's okay. I think people are very confident in the results we see thus far. But we think we get past that two-year mark in around the fall of next year for almost all of the patients, and we think we can have an invaluable package that early. So we'll have between two and five years on those patients.

Most follow up on the treated a patient again that was based on the youngest patient of time being treated about 12 months.

You know it could be lesser data for example, if you're treating a patient at baseline who is 2 years old you know now or 2 years, they're going to be for you should see a real clear delineation. So we think 2 years as a minimum follow up is really important Christian by the fall of next year with the majority of all the cohort 3 the 3 times 10 to the 13th from Freebie on 1 or 2.

Kristen Brianne Kluska: And then the last question on the same program, in regards to the brain MRI data you recently shared, were there any other measurements conducted at time points besides 24 months? And then, just looking across these three patients in good detail now that you have some neurocognitive findings, biomarkers, and this data as well. Could you talk about how all of these endpoints are correlating with each other? Yeah, sure. I'm going to turn that back over the wand.

From transfer right.

We'll have almost all patient old almost all patients will be passed 2 years better for and we'll have some patients up to about 5 years. So that's what we say based on the magnitude of effect will be determined in the SAP with the F. D. A we talked a little bit about you know it'll be a a review decision which is great. That's okay. I think people are very confident the results we see thus far.

But we think we get past the 2 year Mark and around the fall of next year for almost all of the patients and we didn't get on the value of the package that early so we will have between 2 and 5 years on on those patients.

Michael Amaroso: Yeah, sure. I'm going to turn that back over to Juan because he can do better justice to it than I can. Juan, do you want to take that one, please?

Thanks, I appreciate that and then the last question on the same program in regards to the brain M. R. I D that you recently shared were there any other measurements conducted at time points sides 24 months and then just looking across these 3 patients in good detail on now that you have some nerve.

Juan Ruiz: Thank you. Yes, thank you, and this is a very important question. Yes, indeed we see a very good correlation between the biomarker data, showing a sustained decrease two years after treatment with CSF Herbalansulfate, and brain MRI data, where we see that compared to the brain atrophy that is progressing in children without treatment, the three children for which we have two years of follow-up have shown this increase in gray matter volume, amygdala volume, and also corpus calenium volume To mention just three areas of the brain, there are other data showing the same direction. So we are deviating from the brain. I mean, dine atrophy and loss of tissue in the child.

Cognitive finding biomarkers and the state as well could you talk about how all of these end points are correlating with each other.

Yeah sure I'm Gonna turn it back over to 1 because he he can do a better Jessie for that then I can 1 day you want to take that 1 please nice.

Yep. Thank you for this.

This is a very important question.

Yes, Indeed, we see a very good correlation between the biomarker data selling a sustained degrees.

Juan Ruiz: And this correlates with the cognitive evolution of these children that has been shown over two years. In fact, 30 months and 36 months in them, because we have two years and a half and three years later, they have shown continuous gains in cognitive skills, going beyond the ceiling of natural history and deviating clearly from what is expected according to natural history. Thank you, Juan. Thanks, Kristen. Thanks. Thank you. And the next question is coming from Marie Raycroft from Jeffries. Marie, your line is live.

2 years after treatment.

C S as for what else would fight Mmm.

Mmm brain M. R. I data what are we see that compare to the brain atrophy that is progressing.

Progress in children without treatment the 3 children for which we have to just follow up on this increase in gray matter volume mixed on a volume on also corpus callosum button to mention just 3 areas. So that they can get on on the Richter. So at the same day or is it. So we are we are.

Maurice Thomas Raycroft: Hi, good morning everyone. Congratulations on the progress and thanks for taking my question. I'll start off sticking with the MPS3A program. So for the neurocog time point, you mentioned both Bailey and Kaufman are used sequentially, and it sounds like Kaufman is used after Bailey. So I'm just wondering if you could talk more about this and the timing. And then, separately, can you provide specifics on how the two endpoints will be weighted in FDA's review? I guess a patient will have to improve on both measures or just one or the other in order to succeed?

Deviating from the that day.

Do I mean, they're not trophy on lots of P. C. <unk> correlates with the cognitive Williamson of these children.

On or 2 years and in fact for 30 months on 36 months and then because we have 2 years had a house on the Hill later of Sun continues gaming cause they do the screen. According to be on the ceiling of 70 network history, abbreviated including from what's expected that for.

Right into network you for the day.

Michael Amaroso: Hey, Maury, how are you doing? Good questions. I'm going to turn it over to Vish and have him answer. The short answer on the second is no, they're not like co-primary endpoints. They're used in tandem. But Vish, maybe you can walk the group through how Bailey and Kaltman kind of work together when the handoff occurs, and it will be really one seamless test, but not co-primary in any way. Please go ahead, Dish.

Thank you want.

Thanks Christian.

Thanks.

Thank you and the next question is coming from Mary Raycroft from Jeffries Mari your line of Fives.

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

I'll start off sticking with the Amp yesterday program. So for the the narrow cock time point, you mentioned, both Bailey and Hoffman argues sequentially and it sounds like Hoffman is us after Bailey.

Just wondering if you could talk more about based on the timing and.

Vishwas Seshadri: Sure, thanks Michael and thanks Marie for the question. Just to clarify, Bailey and Kaufman are used sequentially, as you pointed out correctly, and not in combination. Bailey is used in children until they reach the upper limit of the scale at about 42 months of development age. And after that upper limit is reached for Bailey, then Kosmman will replace it to continue the evaluation of children. So in the natural history studies in MPS3A to date, it's important to note that Kaufman was not implemented, mainly because the children never achieved a cognitive age close to that 42 months of development age, and that the upper limit observed was about 30-31 months.

And then separately could you provide specifics on how that you add points will be weighted and Fda's review I guess for a patient have to improve on both measures or 1 or the other in order to succeed.

Hey, Maureen how Ya doing good question I'm Gonna turn it over to fish.

Answer a short answer on the second is know that they're not like cold primary on point, they're used in tandem, but dish maybe you can walk to the group through how balian Kaufman kind of work together when the handle for curves and it will be really wanted to see more test did not not cool primary in any way. Please go ahead. This for.

Thanks for Michael and Thanks for money for the question just to clarify Balian Kaufman argues sequentially as you pointed out correctly and not in combination bally's using children until they reached the upper limit of the scale at about 42 months of the development age and after that upper limit is reached.

Vishwas Seshadri: So in Transfer-A, however, we are already collecting data with Kaufman, as children are reaching that 42-month cognitive age time point, which is something that's very interesting and we will continue to follow. So the short answer is they are not going to be combined, and they will be measured sequentially. I hope that clarifies your question, Marie.

Maurice Thomas Raycroft: Yes, yeah, it's really helpful. And so it sounds like any data that you get on Kauffman, there's probably not much natural history data to compare to. And so any data you get on Kauffman will be kind of like a bonus for FDA. Is that the right way to think? That's correct. That's correct. There's not very much natural history data for Kauffman.

For Bailey, then Kaufman was replaced the day I need to continue the evaluation of children. So on the Master history studies on M. P..3 8 to date, it's important to note that Kaufman was not implemented mainly because the children never achieved the cognitive age close to that 42 months of development age ended up on the limit observed was about 30 to 31.

Vishwas Seshadri: It will be descriptive for us. Got it. Okay, thank you. And then the other question was about EB-101. And you said you dosed more than half of the target, 35 wounds, and five patients. So just wondering if there's anything you can say about the types of wounds you're seeing, how they compare to the phase one experience. And then you've mentioned the potential to complete enrollment in 2021. At this point, can you put any more, I guess, finer points or clarity on timelines?

Months, so and transfer day. However, we are already collecting data of a cough medicine or not reaching debt 40 per month cognitive age time point, which is something that's a very interesting and we will continue to follow so the short answer is they are not gonna be combined there will be measured sequentially I hope that.

Clarifies Mary.

Justin.

Yes, yeah, it's really helpful and so it sounds like.

Maurice Thomas Raycroft: Yeah, Maury, thank you. I'll take that, Michael.

Any day to that you get on Kaufman, there's probably not much natural history data to compare to and so any day to you get on a coffin will be.

Michael Amaroso: First and foremost, yeah, past the halfway point on wounds. Large and chronic wounds, remember, guys, different types of EB out there. Just a quick reminder, R-Deb is the worst, unfortunately, the worst prognosis of all EB right now in terms of morbidity and mortality.

Kind of like a bonus for Fda's review that.

That's correct that's correct, there's not very much natural history day, though for Kaufman it'll be descriptive for us.

Got it okay. Thank you and then the other question was on you'd be 1 O..1 and so you said you just more than half for the target thirty-five orange and 5 nations and so just wondering if there's anything you can say about the types of orange, you're seeing how they compared to the phase once you experience and then you've mentioned potential to complete enrolled.

Michael Amaroso: The two different types of wounds that occur within R-Db are kind of, if you will, earlier in the chronology of the disease. Small, clustering recurrent wounds. Think about a patch of blisters that opens, close, open, and close.

Michael Amaroso: Some of the other life sciences companies are concentrating on such wounds, so we think that's great. We think that'll be super complementary and really very helpful for patients and our partner companies out there. And then where EB 101 kicks in, AB owner's work's been focused more, if you will, on kind of that last line of defense, the other half of the R-Dev wounds, which is when those wounds are no longer a current, small, open, closed cluster; they just become one continuous chronic wound. definition of large in the trial: 20 centimeters is greater.

2021.

At this point did you put any more I guess finer points or or clarity on timelines.

Yeah more thank you I'll take that Michael first and foremost yeah past that passed the halfway point on wounds large and chronic wounds remember guys different types of E. B out there just a quick reminder, ardeb is the worst unfortunately, the worst prognosis of all the B right now morbidity and mortality.

The the 2 different types of wounds that occur within Ardeb, what kind of you will earlier in the chronology of the disease small clustering. The current movies think about a patch of blisters that opens close open and closed some of the other life Sciences companies are are concentrating on such wounds. So we think that's great you think that'll be super complimentary and the looting very hard for patients.

Michael Amaroso: I'll remind everybody, we have entire legs, thighs, entire backs, hundreds of centimeters of wounds at times. And chronic, this is an important term. Chronic means the wound has now been open for six months or longer, and I can no longer close it.

And on a partner companies out there.

And then where he'd be 1 on 1 kicks. It may be on his works can focus more if you will on kind of that last line of defense. The other half of the Ardeb wounds, which is when those wounds are no longer with current small open close cluster. They just become 1 continuous chronicling the definition of large and the trial 20 centimeters of greater I'll remind everybody we have entire leg.

Michael Amaroso: That's where you need the regeneration of skin that we're obviously doing with the curatinocytes for EB-101 and surgical transplantation. So those are the wounds that we are focusing on in the R-DEP trial. I mean, more what I could tell you, obviously, it's an ongoing pivot, so we're not looking at data along the way. But I could tell you that feedback's been positive. I think what we're trying to replicate, and I think the consistency you'll be looking for here is what we see from phase one, too. I'll remind everybody that we just showed you durability data. of for almost six years.

<unk> sighs entire back hundreds of centimetres of wounds of times.

<unk> chronic because this is an important turned chronic means the wound has now been open for 6 months or longer and can no longer close itself.

That's where you need.

The regeneration of skin that we obviously doing with the cure genocides for he'd be on on 1 and the surgical transplantation. So those are the wounds that we're focusing on in vital they are debt trial I'd be more than what I could tell you. Obviously, it's an ongoing pivotal so we're not looking at data along the way I can tell you that feedback has been positive I think that what we're trying to <unk>.

Michael Amaroso: So this is really important, right? We know it's not a topical gel. We know there are, you've got to take some biopsies from patients. You've got to make these graphs, and you've got to put them on. And the reality for this drug product is, you know, it's got to be worth it. And we believe the key here is that in the worst of the worst wounds that lead to ultimate morbidity and mortality, durability will be super important.

Replicate and I think the consistency you'll be looking for here is what we see from the phase 1 to remind everybody would just Georgia durability data is almost 6 years. So this is really important right. We know it's not a topical jail. We know there's you gotta take some sort of biopsies from patients you Gotta make these graphs and you've got to put them on and the reality for this drug product.

Michael Amaroso: So, Maury, that's what we're looking for. Can't talk to you too much about results, safety, and efficacy because we are in pivotal. The second part of that, Maury, for you've got to be very, was, I'm sorry, remind me the second part of that question.

Is.

It's gotta be worth it and we believe the key here is on the worst of the worst wounds that lead to ultimate morbidity and mortality the durability will be super important. So that's what we're looking for can't talk to you too much about results safety and efficacy because we are on pivotal the second part of that Boy E. B was I'm, sorry remind me the second part of that question.

Michael Amaroso: Just based on if you have more clarity on timing at this time, greater than half. Yeah, thanks, Maury. So so far, we're not changing our kind of, I always said it was, we said the terms weren't guidance, but a bold goal we were setting for the team. Frankly, I joke, but because the patients really need us. So we're not changing our push to try to hit accrual by the end of this year.

Just based on if if you have more clarity on a tiny.

Yeah.

A greater than.

Yeah.

Yeah. Thanks for I. So so far we're not changing our our kind of I always said it was <unk>. We said the terms it wasn't guidance for a bit of bold goal, you'll put in for the team frankly, I joke book, because the patients really need us. So we're not changing our push to try to hit a cruel by the end of this year.

Michael Amaroso: We're still on that. It is a bold goal. We truly don't know what the run rate will be monthly now that UMass is onboarded, Maury, right? So really important. We've treated the patient five. We've got some candidates in the queue here.

We're still on that it is a bold goal we truly don't know what the run rate will be monthly now that you list your matches on board and Murray right. So really important we treat a patient 5 we've got some candidates in the queue here I won't say anything about the next patient just yet it's a little premature but now we've got 2 sites on the east and West Coast. So you've got to see how that plays out.

Michael Amaroso: I won't say anything about the next patient just yet. It's a little premature, but now we've got two sites on the east and west coasts. So we've got to see how that plays out. We can treat up to two patients a month in our facility right now, you know, while we're still in the Klinneddedge stage before we turn on kind of commercial manufacturing size. So that's really important to know.

We can treat up to 2 patients a month and on facility right now in a while was stolen condensed page before we turn on kind of commercial manufacturing size. So that's really important to know so right now we're still holding to our to our bold goal of end of the year. Later this year probably on on X Komura I can give you a better idea if it might spill into Q1 at all forget to get to a cool cause it is tough.

Michael Amaroso: So right now, we're still holding to our bold goal of the end of the year. Later this year, probably on our next call, I can give you a better idea if it might spill into Q1 at all, or forget to get to our accrual because it is tough to predict when patients kind of come in the queue for the trial. But we're very, very pleased with what we're seeing. We think getting past the halfway point is very important. And now we've got two sites.

To predict 1 patient has kind of come into cute for the trial, but we're very very pleased with we're seeing we think we're getting past. The halfway point is very important and now we've got 2 sites. They just think about it that could expedite and make a double the amount of volume I I think we could be getting towards the end really close just to remind you to the group once we accrue why that's so important.

Maurice Thomas Raycroft: If you just think about if that could expedite and we could double the amount of volume, I think we could be getting toward the end really close. Just a reminder to the group, once we've accrued, why that's so important is that from the last patient plus six months, that'll be when we have top-line data to say if it's a positive pivotal phase three at that point in time. So if we accrue at the end of this year, we're looking for positive top-line results mid next year, and I'm sorry, but that's not very helpful. Thanks for taking my question.

From the last patient plus 6 months that'll be when we have top line data to say if it's a positive pivotal phase 3 at that point in time. So if we accrue at the end of this year. We're looking for a positive top line results mid next year more.

Right. That's really helpful. Thanks for taking my questions. Thank.

Thank you.

[noise]. Thank you on the next question is coming from money for her for my speed Miller extra money. Your line is nice.

Moni Faruhar: Thank you, and the next question is coming from Moni Faruhar from SBB Lerink. Moni, your line is live. You guys, thanks for taking the question. I'm going to have a little more of a practical commercial one. We talk a lot about capacity in manufacturing as if it's a number of patients, but I want to narrow in on more of a volume, or I guess an area question. I mean, talking about large wounds, you're taught that sometimes they can scale, as you said, the entire backs, large parts of the chest.

Hey, guys. Thanks for taking my question I'm going on for a little more of a practical commercial 1 we talk a lot about capacity in manufacturing as this number of patients, but I'm on a narrow in on multiple volume quite okay for the area question and I'm talking about large willing to talk to some debt. Some heart from scale as you said the entire backs large parts of the chest.

Moni Faruhar: You have a very high percentage of body surface area. Can you help scale for us the absolute area of graft you could manufacture on an annualized basis and how to think about that? As some of these patients may require tremendous volumes of graft with implications for per patient costs, per patient required manufacturing volume, et cetera.

They're very high percentage of body surface area Uhm can you help scale for us.

The absolute area of draft, you could manufacture on an annualized basis and how to think about that at some of these patients may required tremendous volume of grass what day bookcases for procreation cost per page that required manufacturing volume et cetera.

Michael Amaroso: Yeah, Mike.

Yeah My.

Michael Amaroso: of my good question and thanks, and good to hear your voice. I'll take that one. So it's a great question that the practical now really meets you know the fact that having practical conversations is good news, right, as we get closer to patients. That's a really important point, so let's talk about that a little bit. Let me remind you about one product of EB 101. They are six sheets. One product is 6.40 centimeters squared, a little bit bigger than maybe the largest business card you've seen.

Good question and thanks, good to hear your voice I'll take that 1 so.

It's a great question that the the practical now really Matt if the fact of having practical conversations is good news right as we get closer to patients. That's a really important point. So let's talk about that a little bit let me remind you with 1 product if he'd be 1 on 1 is.

They are 6 sheets, 1 product is 640 centimeters square a little bit bigger than maybe the largest business card you've seen 40 centimeter squared sheets time 6 for 240 centimeters will be with 1 product deliberately is 1 product to transplantation.

Michael Amaroso: 40 centimeters squared sheets times six for 240 centimeters will be what one product delivery is, one product transplantation. I'll remind you how we got there. True empiricism, guys; that was how it was done at Stanford. And when we spoke to the FDA before starting the trial, of course, this is an investigational therapy. So it's not something that the FDA felt comfortable going even beyond that, of, you know, go head to toe or double the size of the graphs. We truly followed the empiricism of what started at Stanford.

I'll remind you how we got there true empiricism guys that was how it was done at Stanford and when we spoke to the F. D. A before starting to trial of course. This is an investigational therapy. So it's not something that the F. D. A felt comfortable going even beyond that you know go head to toe with double the size of the grass, we truly followed the empiricism on what started at Stanford.

Michael Amaroso: So there's no perfect science for that. Of course, our process development teams are looking at, you know, what's the next product follow-on? How do we enhance that?

So there's no perfect size for that of course on process development teams are looking at you know what's the next product follow on how do we enhance that but what I will tell you is if you look at the E. B 1 on 1 typical patient as we as we kind of thought about our forecasting and the capacities we're gonna need.

Michael Amaroso: But what I will tell you is, if you look at the EB-101 typical patient, as we've kind of thought about our forecasting and the capacities we're going to need, about 50% of their wounds, so think about 2,500 patients a year with RDEB in the U.S. specifically. It's not a concentrated disease. So you'd see something like this, for example, you could expect something similar in the EU5 and so on. So it's diffuse across the world.

About 50 per cent of their wounds. So think about 2000 for 2500 patients a year with our debt and the U S. Specifically, it's not a concentrated disease. So you'd see similar for example, you could expect similar in that you 5 and so on so it's diffuse across the world, but if you just think about 2000.2500 patients with our debt about for.

Michael Amaroso: But if you just think about 2,000, 2,000,000,000 patients with R-Db, about 50% of their wound burden at any given time is large chronic wounds, and the other 50% is small recurrent. Now, again, do we think that small recurrent could be addressed?

50 per cent of their wound burden at any given time is large chronicling the other 50 per cent of small recurrent now again do we think that small occurrence could be addressed that that's some phase for work will do what he'd be 1 on 1 first things first we want it to be the the line of defense for the the most problematic and troublesome moon, that's the positioning of the B 1 on 1.

Michael Amaroso: That's some phase four work we'll do with EB-101. First things first, we want it to be the line of defense for the most problematic and troublesome wounds. That's the positioning of the EB-101 product, durability, and the worst of the worst wounds.

Do ability and the worst for the worst wounds. So if you look at the Ardeb wound distribution of about 50 per cent on these patient at any given time.

Michael Amaroso: So if you look at the R-Deb wound distribution of about 50% in these patients at any given time, there's also a range of different afflicted wound surface area in these patients, and the best published literature shows about 30% of the body surface area with wounds at any given time. So think about half of that being large and chronic. So if you do the math on that, at 240 centimeters squared, this will be a repeat treatment.

There's also a range of different afflicted wound surface area money on these patients and the best published literature shows about 30% of the body surface area afflicted with wounds at any given time to think about half of that be large and chronic so if you can do the math on that at 240 centimeters square.

It will be a repeat treatment very important to understand this will be a therapy that you're looking at probably a medium for over a lifetime to treat the entire wound surface area large chronic wounds on the medium E. B 1 on 1 our debt patient. Okay. So I kind of walk you through some numbers. There are you thinking about 3 to for a little more.

Michael Amaroso: Very important to understand. This will be a therapy that you're looking at probably a median of four over a lifetime to treat the entire wound surface area of large chronic wounds on the median EB 101RD. Okay, so I kind of walked you through some numbers there. You're thinking about three to four, a little more than three, about four administrations over the lifetime.

3 about for administration over the lifetime. So you can imagine maybe there's 1 or 2 procedures a year, let's say 2 years in you've had your 3 or 4 procedures. You've now covered that full body surface area. We think that's super important because we're proving this drug on improvement in quality of life. When you really think about pain and the.

Michael Amaroso: So you can imagine maybe there are one or two procedures a year. Let's say two years in, you've had your three or four procedures, and you've now covered that full body surface area. We think that's super important because we're approving this drug based on improvement in quality of life when you really think about pain and the ability to close wounds. Mortality is something that we will have to look at. long term, as we follow these patients for a long term follow-up, how much body surface area do you need to close for how long?

Alrighty to close wounds mortality as something that will have to look at long term as we followed these patients on a long term follow up how much body surface area, you need to close for how long and so our goal here is to get to all of the large chronic wounds and then some of our face for work follow on work will will focus on maybe the small the current ones okay.

Michael Amaroso: And so our goal here is to get to all of the large chronic wounds and then some of our phase four work, follow-on work. We'll focus on maybe the smaller current ones. So Moni, I hope that gives you a little bit of a depiction. Thanks. That's really helpful. Thank you. There are no more questions in Q. I will hand the call back to the management team for any closing remarks. Paul, operator, I thank you for your help today.

So money hope that gives you a little bit of a depiction.

Yeah.

That's that's really helpful.

[noise]. Thank you and there are no more questions on queue I will have to call back to the management team for any closing remarks.

Oh, Paul operator, I. Thank you for your help today I think on investment community without your interest without you guys. Writing me analyses without your investments, we would not be able to to bring these potentially and hopefully lifesaving therapies for these patients.

Michael Amaroso: I thank our investment community. Without your interest, without you guys writing the analyses, without your investments, we would not be able to bring these potentially and hopefully life-saving therapies to these patients. I want to thank the patients and their families. And, as always, I want to thank my team. I think the ABODA team has really shown a lot of progress over the last, you know, nine plus months that I've been with them.

I want to thank the patient can families and as always I Wanna. Thank my team I think the a b on a team has has really shown a lot of progress over the last you know 9 plus months that I've been with him and you know I'm I'm very privileged to be part of this group I think we're doing a lot with a with a small mighty group of people, we're continuing to bring tally.

Michael Amaroso: And, you know, I'm very privileged to be part of this group. I think we're doing a lot with a small, mighty group of people. We're continuing to bring talent in, and we'll continue to talk to you about, you know, our three management team priorities: talent and operational excellence. And then, you know, of course, first and foremost, our in-clinic programs, two of which we're now in pivotal, and we're looking and tending to bring to registration. We could have valuable packages as early as next year for both.

<unk> and we will continue to talk to you about our you know our our 3 management team priorities talent operational Excellence and then you know of course first and foremost in our in clinic programs, 2 of which now where where in pivotal and we're looking intended to bring to registration we could have a valuable packages as early as next year for bold and patience really.

Michael Amaroso: And patients really, really need that. So we'll keep you up to date on that. And then again, the super progress that's been made in Brian's domain and Linus's domain and research under VISH and of bringing, really prioritizing first our core pre-clinical programs, the eye, and moving them closer to the clinic. So I thank the teams and the team. patients for all the work.

[noise] really need that so we'll keep you up to date on that and then against Super progress has been made in Brian's domain and Loomis is domain and research on dervish, and bringing really prioritizing first or or core frequent programs the eye and moving them closer to the clinic. So I think the teams and the patience for all the work.

Michael Amaroso: I thank the investment community for their interest, and I know I'll speak to some of you in follow-up. So again, thank you. Please be safe, everybody. Thank you, ladies and gentlemen. This does conclude today's conference call. You may disconnect your phone lines at this time, and have a wonderful day. Thank you for your participation.

I think the investment community for their interest and I know I'll speak to somebody can follow up. So again. Thank you please be safe everybody.

Thank you ladies and gentlemen, this does conclude today's conference call. You may disconnect. Your phone line to have this time and have a wonderful day. Thank you for your participation.

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