Q2 2020 Clearside Biomedical Inc Earnings Call

Ladies and gentlemen, Lisa me on your line.

Operator: Ladies and gentlemen, please remain on your line. Your Clearside Biomedical 2nd Quarter 2020 Financial Results and Corporate Update conference call will begin momentarily. Thank you for your patience.

Hi, Biomedical second quarter, 2025, natural resource and corporate update conference call well begin momentarily. Thanks for your patience.

[music].

Music: ??? ??? ??? ??

Operator: Good afternoon, ladies and gentlemen, and welcome to the Clearside Biomedical Second Quarter 2020 Financial Results and Corporate Update Conference Call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star, then zero on your touchtone telephone. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Speaker Jenny Kobin, Investor Relations for Clearside. Please go ahead, Madi.

Good afternoon, ladies and gentlemen, and welcome could appear side by a medicals second quarter 2025, an awesome falls in corporate update conference call.

At this time, all participants are in listen only mode.

Peter We will conduct a question answer session and instructions will follow at the time.

And he wants to be quite assistance during the conference. Please press Star then zero on your touched on telephone as a reminder, this conference call is being recorded.

I would now like to turn the conference over to your House Speaker, Jenny Kobin Investor Relations for clear sight. Please go ahead Mike.

Jenny R. Kobin: Good afternoon, everyone, and thank you for joining us on the call today. Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements. Various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our annual report on Form 10-K for the year ended December 31, 2019, our quarterly report on Form 10-Q for the quarter ended June 30, 2020, and our other SEC filings available on our website.

Good afternoon, everyone and thank you for joining us on the call today.

Before we begin I would like to remind you that during today's call, we will be making certain forward looking statements.

Various remarks that we made during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factor section of our annual report on form 10-K for the year ended December 31st 2019, our quarterly report on form 10-Q.

You for the quarter ended June Thirtyth, 2020, and our other SEC filings available on our website.

Jenny R. Kobin: In addition, any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent dates. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change. On today's call, we have George Lasezkay, our Chief Executive Officer, Dr. Thomas Chula, our Chief Medical Officer and Chief Development Officer, and Charlie Deignan, our Chief Financial Officer. After our formal remarks, we will open the call to your questions. I would now like to turn the call over to George.

In addition, any forward looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date.

While we may elect to update these forward looking statements in the future, we specifically disclaim any obligation to do so even if our views change.

On today's call we have George was asking our Chief Executive Officer, Dr., Thomas Our Chief Medical Officer in Chief Development Officer.

Charlie Deignan, our Chief Financial Officer.

After our formal remarks, we will open the call for your question I would now like the turn call over to George.

Thank you Johnny good afternoon to everyone. Thank you for joining us on the call today.

George M. Lasezkay: Thank you, Jenny. Good afternoon to everyone, and thank you for joining us on the call today. Over the past year, we've worked hard to execute our strategy to reorient Clearside from a single product company to one that has multiple innovative and relevant opportunities targeting unmet medical needs through the supercoronal space. As a result, we are initiating a new clinical program targeting a large and growing market through suprachoroidal injection of a tyrosine kinase inhibitor. We are also advancing our supercoronal gene therapy and small molecule preclinical programs. These actions represent important progress, creating value through the expansion of our internal pipeline, which we'd like to highlight this afternoon.

Over the past year, we've worked hard to execute our strategy to reorient for side from a single product company to one that has multiple innovative and relevant opportunities targeting unmet medical needs through the super cooler space.

That's a result, we are initiating a new clinical program targeting a large and growing markets from Super choroidal injection of a tyrosine kinase inhibitor.

We're also advancing Osha recordable gene therapy, and small molecule preclinical programs.

These actions represent important progress creating value through the expansion of our internal pipeline, which was like the highlights and shopping.

Also we have selected the new very experienced in highly motivated me stretch from <unk> to.

George M. Lasezkay: Also, we have selected a new, very experienced, and highly motivated manufacturing partner to help us obtain our first commercial product approval. I'll begin with our new clinical program and lead development asset, CLS-AX, which is our proprietary suspension of extended reciprocal injectors. We are pleased to announce that our investigational new drug application was accepted by the FDA. With this open IND, we are now able to progress CLS-AX into human clinical trials. We are targeting the initiation of our Phase 1-2A clinical trial by the end of this year in patients with neovascular age-related macular degeneration, typically referred to as WET-AMD. As many of you know, wet AMD is a serious type of macular degeneration leading to central vision loss that occurs when a protein called vascular endothelial growth factor, or EGF, causes abnormal blood vessels to grow and leak in the back of the eye.

To help us up to the first part will probably.

I'll begin with active clinical program to lead development assets, CLS, Mdx, which is our I'm very suspension.

She took roedl injection.

We're pleased to announce the her investigational new drug application was accepted by the FDA.

With this open on Monday, we are now able to progress CLS, he actually infusion in clinical trials.

We are targeting the initiation box phase one two way clinical trial by the end of this year in patients with Neovascular age related nice energy generation.

Typically referred beat was wet AMD D.

As many of you know what TMT serious type back to their degeneration, leading to central vision loss that occurs when the protein called vascular endothelial broke.

Badger.

Causes abnormal what else was to grow and bleak in the back of the army.

In looking at the treatment landscape for wedding empty either four key factors that are considered boxes issuance in their patient safety efficacy duration of action he should be.

George M. Lasezkay: In looking at the treatment landscape for wet AMD, there are four key factors that are considered by physicians and their patients, safety, efficacy, duration of action, and patient convenience. The most common treatment options currently used by physicians to slow vision loss from wet AMD are anti-vegetative intravitreal injections given every four to eight weeks, which help stop the bleeding and leaking of blood vessels in the back of the eye. These treatments have shown good efficacy and safety but have a limited duration, thus requiring frequent injections. In clinical practice, however, most patients have difficulty complying with the need for such frequently scheduled appointments.

Most common treatment options currently used by physicians to so that he was somewhat danby our anti VEGF.

The trailing directions, giving you do you have in every four to eight weeks, which helped stocked with leading easily blood tests the yard.

These treatments you've shown good efficacy and safety.

Limited duration, that's recurring frequent injections.

Local practice, however, most patients have difficulty complying with the need for such frequently schedule appointments.

George M. Lasezkay: Therefore, compliance is a real-world issue in patients suffering with MED-MD. CLS-AX could fit very well in the wet AMD treatment landscape. We believe that a small molecule tyrosine kinase inhibitor, or TKI, could provide safe and efficacy comparable to, or better than, current standard of care by delivering a TKI into the supracoital space using our in-office SCS microinjector. We may also potentially extend duration of therapeutic action and enhance patient compliance. Our Phase 1-2A clinical trial will begin by the end of this year to assess the safety of supra-coroidal administration of CLSA-X. We look forward to reporting initial safety data from the first cohort in mid-2021.

Therefore compliance is a real world issue patients suffering from anybody.

CLS <unk>.

Very well and the wet AMD de treatment landscape, we believe that a small molecule tyrosine kinase inhibitor or teekay on.

Could provide safety and efficacy portable too well better than current standard of care.

Like delivering it you can.

Super cooler space, using or you don't see us micron Chuck.

We've also potentially extend duration of therapeutic actually.

Enhance patient compliance.

Phase one two way clinical trial will begin by the end of this year to assess the safety. So widely administration those yellow say acts.

We look forward to reporting initial safety data from the first cohort.

In mid 2021.

Building on the momentum of RCR lets say its program and the growing data interest and Super credit space.

George M. Lasezkay: Building on the momentum of our CLS-VX program and the growing data and interest in supercoronal space, we are expanding our internal pipeline with promising preclinical programs. The first is our Therapeutic Bioplankton Program, which is based on the supercoital administration of non-viral vector gene therapy for retinal disease. This is the second gene therapy preclinical program in our superb paroidal pipe. This biofactory program is designed to cause the expression and secretion of an anti-VEGF therapeutic protein from Red Mountain.

We are expanding our internal pipeline with promising preclinical programs first is our therapeutic Biofire program, which is based on Super coiled administration non viral back gene therapy.

Jesus.

The second gene Arab preclinical program in our Super core looks like.

This bio factory program is designed to cause the expression its accretion of an anti VEGF therapeutic probes.

Retinal cells. This approach potentially provides versatility to deliver not only anti vegetarians James.

George M. Lasezkay: This approach potentially provides versatility to deliver not only anti-vegetarian... but also a variety of different transgenes leading to the expression of other clinically relevant therapeutic proteins in the back of the eye. We are encouraged by our early research and preclinical data. Second, we've initiated another small molecule program utilizing supercoil administration of an integrin inhibitor suspension that will initially be focused on diabetic macular degeneration. While it's still early days for these programs, we are excited about expanding our preclinical pipeline to leverage the benefits of supercoordinated delivery. We will continue to advance these new programs through additional preclinical studies and, hopefully, on towards clinical trials. Tom will provide some additional detail on the scientific rationale for these programs in his report.

But also a variety of different transgene, leading to the expression.

Click relevant therapeutic proteins in the back of the yard.

We are encouraged by our early research and preclinical data programs.

Second we have initiated another small molecule program utilizing Super coil administration Integrase inhibitor suspension. It will initially be focused on diabetic macular edema.

Well, it's still early days for these programs, we are excited about expanding or preclinical pipeline to leverage the benefits of supercritical delivery.

We will continue to advance these new programs through additional preclinical studies and hopefully on towards clinical trials.

Tom will provide some additional detail on scientific rationale for these programs his remarks.

George M. Lasezkay: Next, I have an update on our plans for Zyphyr, our potential treatment option for patients suffering from macular edema associated with UVI. We announce today that we have secured a new commercial manufacturing partner for Zyper. Our previous contract manufacturing organization recently notified us that they are no longer willing to serve as our commercial supplier, and they are uncertain about being fully prepared for an FDA pre-approval inspection on our timeline. As a result, we were left with no workable options to continue with the previous CMO. After working closely with the CMO for many years, this news was unexpected and disappointing both to us and our Xipyr commercial partners. However, given previous disclosed delays due to manufacturing and facility issues, we had been proactively evaluating alternative manufacturing.

Next I have an update on her plans for sightseer potential treatment options for patients suffering from Mexico dealer associated with you I guess.

We announced today that we have secured a new commercial manufacturing partner for cycle.

A previous contract manufacturing organized organization recently notified us that you're no longer willing to sure I sort of commercial supplier and they are uncertain about being fully prepared for an F.D.A. preapproval inspection on our timeline.

As a result, we will have put no workable options to continue with the previous CMO.

We're working closely with the CMO for many years. This news was unexpected and disappointing to us and I'd like to commercial partners.

However, given previous disclose the delays due to manufacturing facility issues, we had been proactively evaluating alternatives manufacturers.

Therefore, therefore upon receiving this means we were able to quickly identify and engage with their CMO and it already initiated the process of transferring this high school manufacturing technology.

George M. Lasezkay: Therefore, upon receiving this news, we were able to quickly identify and engage a new CMO, and we have already initiated the process of transferring this high-pure manufacturing technology. During this transfer period, however, our previous CMO has agreed to manufacture initial clinical supplies of Xipyr for our greater China partner, Arctic Vision, to support its IMD filing in China and for use in clinical trials in China planned to start early next year. Our new CMO has an established track record with respect to FDA inspections, and they have extensive experience with the production of small molecule suspensions, steroids, and ophthalmic products. We believe this transition is a positive step forward to achieving Xipyr approval as the new CMO provides us with a very experienced, high-quality, and motivated partner for manufacturing Xipyr. With significant and relevant operating expertise and an experienced staff, we believe they will prove to be a collaborative and dependable partner to manufacturers like ours.

During this transfer period. However, a previous CMO has agreed to manufacture initial clinical supplies upside here for greater China partner Arctic mission to support its R&D filing in China and for use in clinical trials in China plant to start early next year.

Our new CMO has an established track record with respect to FDA inspections, and they have extensive experience with a production small molecule suspensions steroids and ophthalmic products.

We believe this transition has a positive step forward to achieving secure approval.

Oh provides us with a very experienced high quality and motivated partner for manufacturing site.

With significant relevant operating expertise and experience there we believe they will prove to be a collaborative dependable partner manufacturers like.

Well the transfer of the manufacturing thought process, we'll pause a short term delay we are convinced it will allow for a more efficient predictable process for Andy a resubmission and review.

George M. Lasezkay: While the transfer of the manufacturing process will cause a short-term delay, we are convinced it will allow for a more efficient and predictable process for NDA resubmission and review. We look forward to resubmitting the Xipir NDA as quickly as possible after the technical transfer to the new CMO is completed and the required stability data are generated. Although we are still in the process of finalizing the timelines with the new CMO, our current expectation is that resubmission will occur no later than the first half of 2021. We expect the FDA will review the NDA within six months of the resubmission date. We believe the strategy and timing of this transition is the most reasonable and prudent option for Clearside to successfully move forward with Xipair. We believe this change is in the best long-term interests of Clearside, as well as our commercial partners through Xipair, Bosch Health Companies, and Arctic Vision. We have discussed the transition with both companies, and they understand the circumstances and the rationale for making this change.

We look forward to resubmitting pure energy as quickly as possible after the technical transferred to the new CMO was completed and the required stability data or generate.

Although we are in still in the process of finalizing the timelines with the new CMO.

Our current expectation is that Resubmission will occur no later than the first half 2021.

I expect the FDA will review the Andy within six months other new submission date.

We believe the strategy and timing of this transition is the most reasonable imprudent option Clearsight can successfully moved forward type here. We believe this change isn't the best long term interest.

Your side as well as our commercial partners, whose I figure well Bausch help companies and party vision.

We have discussed the transition companies and they understand the circumstances and the rationale for making this change in Cmos.

I'll wrap up my initial remarks today with a number on corporate governance.

George M. Lasezkay: I'll wrap up my initial remarks today with a note on corporate governance. During the second quarter, we enhanced our board of directors with the addition of Dr. Nancy Hudson. With over 25 years of R&D leadership at Pfizer, Nancy brings a deep understanding of the pharmaceutical industry, coupled with an in-depth knowledge of research, clinical drug development, and dynamic business situations. She has also served on a number of biopharmaceutical company boards over the past 10 years, so she has a broad perspective on the industry. Nancy is already highly engaged in our strategic planning, and we are pleased to have her input as we advance our internal pipeline. With that, I will now turn the call over to Dr. Tom Chula, our Chief Medical Officer and Chief Development Officer, to expand more on CLSAx and our other research programs.

During the second quarter, we enhanced our board of directors make the addition of Dr. Nancy Hudson.

With over 25 years of R&D leadership advisor Nancy brings a deep understanding of the pharmaceutical industry.

With an in depth knowledge of research clinical drug development dynamic dynamics business situations.

She has also served on a number of biopharmaceutical company Gourdes over the past 10 years. So she has a broad perspective on the industry.

She is already highly engaging our strategic planning and we're pleased to have input as we advance or internal pipeline.

With that I'll now turn the call over dock to Dr., Tom Ciulla, or Chief Medical Officer, and Chief Development officer to expand more on CLS, eightx and or other research programs.

Thank you George.

Dr. Tom Chula: Thank you, George. I'm eager to start by diving a bit deeper into our CLS-AX clinical trial plans, and then I'll summarize our other pipeline programs. As George mentioned, we were pleased to announce today that our IND was accepted by the FDA. With this open IND, we are now able to progress CLSAx into human studies and initiate our phase 1, 2a clinical trial in patients with 1AMD by the end of the year. We are excited to advance this asset for its intrinsic characteristics that can be further leveraged through supercortical delivery. First, as a tyrosine kinase inhibitor, or TKI, exsitinib is designed to achieve pan-VEGF inhibition, and independent preclinical studies showed that exsitinib more potently inhibited neovascularization than either focused anti-VEGF-A inhibition or other

You go to start by diving deeper.

Interest CLS ex clinical trial plans and then I'll summarize our other pipeline programs.

As George mentioned, we were pleased to announce today that our idea was accepted by the FDA.

With us open I. Indeed, we are now able to progress CLS, hey exit to human studies.

Initiate our phase one two a clinical trial in patients with wet AMD D by the end of year.

We're excited to advance this asset for its intrinsic characteristics that could be further leveraged through super Cornel delivery.

First as a tyrosine kinase inhibitor or T.K., our exit and it was designed to achieve Pan JAK inhibition and independent preclinical studies show that accident and more importantly, inhibited neovascularization that either focused anti VEGF pathway inhibition, well other T.K. eyes.

Second Super quarterly administered CLS CX demonstrated targeted high drug concentration in the retina inquiry with lower concentration in the vitreous, leading to effective reduction of foreseen leakage and new vessel growth versus controls and models of wedding empty.

Dr. Tom Chula: Second, suprachoroidally administered CLSA-X demonstrated targeted high drug concentrations in the retina and choroid with lower concentrations in the vitreous, leading to effective reduction of fluorescein leakage and new vessel growth versus controls and models of wet AMD. Third, in animal models, CLSA-X demonstrated some compartmentalization benefits when administered supracortally, sparing the anterior chamber of the eye and the systemic circulation. It was well tolerated with no signs of toxicity at the intended clinical dose.

Third in animal models, CLS CX demonstrated some compartmentalization benefits when administered Super quarterly sparing the church, Kimberly I and the systemic circulation.

It was well tolerated with no signs of toxicity at the intended clinical dose.

Dr. Tom Chula: And finally, CLSAx administered supracortyly showed multi-month durability in animal models. This supports the potential to address treatment burden in wet AMD, a large and current unmet need. We look forward to starting our first human clinical trials with CLSA-X. We are planning our Phase 1-2A clinical trial in wet AMD patients to be an open-label dose-escalation study to assess the safety and tolerability of a single dose of CLSA-X administered through supracortial injection. Eligible patients are those who demonstrate stable visual acuity following two or more previous injections with an individual anti-VEGF agent. For this trial, we plan to use Flibersep as our anti-VEGF agent. The primary endpoint for the trial will be to assess the safety and tolerability of CLSA-X in these wet AMD patients.

And finally seal I say ex administered Super quarterly showed no Piedmont durability in animal models. This supports the potential to address treatment burden in wet AMD D. A large incurring unmet needs.

We look forward to starting our first human clinical trials with CLS Eightx, we're planning our phase one two way clinical trial in wet AMD patients to be an open label dose escalation study to assess the safety and Tolerability of a single dose subsea lets say ex administered can supercritical injection.

Eligible patients are those who demonstrate stable visual acuity falling to a more previous injections with an individual anti VEGF agents, but this trial, we plan to use aflibercept answer anti VEGF agents.

The primary endpoint for the trial will be to assess the safety and Tolerability I feel FX and these wet AMD patients secondary endpoints will evaluate the pharmacokinetics visual function macular anatomy and the need for additional treatment with Intravitreal aflibercept.

Dr. Tom Chula: Secondary endpoints will evaluate pharmacokinetics, visual function, ocular anatomy, and the need for additional treatment with intravitreal flippers. The study design is targeted to include 3 cohorts of 5 patients each for a total study population of approximately 15 patients. Eligible patients will receive a 2 mg individual injection of a further separate screening, followed by one supercortical injection of CLSA-X at baseline a month later. Patients return for three further visits for assessments on safety, tolerability, visual function, ocular anatomy, and the potential need for additional treatment with a flipper set. All patients will be followed through the fifth visit, regardless of whether additional therapy is given.

Study design is target to include three cohorts of five patients each for a total study population of approximately 15 patients.

Eligible patients will receive a two milligram intravitreal injection up a herceptin screening followed by one supercritical injection of the seal FX at baseline a month later.

Patients return for three for the visits for assessments on safety Tolerability visual function occupy anatomy and the potential need for additional treatment with aflibercept.

All patients we follow through the first as it regardless of whether additional therapy is given.

Dr. Tom Chula: For CLSA-X, the study design calls for dose escalation in each of the three cohorts. Cohort 1 will start at the lowest dose of 0.03 milligrams of acetamide delivered by supracoronal injection. Dose escalation will then proceed following review and recommendation of the safety data by the Safety Monitoring Committee to advance the next higher dose cohort. With the timeline for each cohort at approximately six months, we expect initial safety data from the first cohort in mid-2021.

For CLS they ex the design study the study design call for dose escalation in each of the three cohorts cohort one will start at the lowest dose of 0.03 milligrams of except in a deliberate super cool by delivered by supercritical injection.

Dose escalation will then proceed following the review and recommendation of the safety data by the safety monitoring committee to advance the next higher dose cohort.

But the timeline for each cohort at approximately six months, we expect initial safety data from the first cohort and mid 2021, we were excited about can to catch up with CLS say acts as a long acting therapy for wedding empty and this phase one two way trial is our first step to reach that goal.

Dr. Tom Chula: We are excited about the potential for CLSA-X as a long-acting therapy for wet AMD, and this Phase I-IIa trial is our first step to reach that goal. Internally, our research and discovery teams continue to advance our preclinical programs. We have a DNA nanoparticle biofactory gene program in preclinical development for our internal pipeline. There is well-established literature supporting subretinal DNA nanoparticle gene therapy in preclinical models of retinal disease. DNA nanoparticles can transfer genes that are too large for common viral vectors like AAV. In addition, since they lack viral capsid antigens, DNA nanoparticles are less immunogenic than viral vectors and could potentially undergo repeated office-based dosing via a supercoital approach.

[noise] internally, our research and discovery teams continue to advance our preclinical programs, we have a DNA nanoparticle bio factory gene program in preclinical development for internal pipeline, there as well established literature supporting sub retinal DNA nanoparticle gene therapy in preclinical models of retinal disease.

DNA nanoparticles can transfer genes that are too large for common viral vectors like Avi.

In addition, since they lack viral caps and antigens DNA nanoparticles, a less immunogenic and viral vectors it could potentially undergo repeat office based dosing the super Cordele approach.

Dr. Tom Chula: In a recently published paper, researchers at Johns Hopkins demonstrated that supercortical injection of non-viral nanoparticles can yield expression of a reporter gene in rat photoreceptors and RTE throughout the eye for at least eight months. They have also shown successful expression of an anti-VEGF protein with supercoital administration of non-viral nanoparticles containing the corresponding genes. With this therapeutic biofactory approach, they were able to suppress VEGF-induced vascular leakage and experimental neovascularization in their preclinical model. Furthermore, we have previously shown that supercortical administration of DNA nanoparticles yields similar marker gene activity compared to subretinal administration. Over the last year, we've been working with DNA nanoparticles containing therapeutic transgenes in a preclinical model. We have observed that supracortial administration is better tolerated clinically than intravitreal administration in this animal model.

In a recently published paper researchers at Johns Hopkins demonstrated that supercritical injection of non viral nanoparticle can yield expression of a reporter gene and rat photo receptors and arty throughout the eye for at least eight months.

They have also showed successful expression of an anti VEGF protein, what's supercard administration of non viral nanoparticles containing the corresponding gene.

What this therapeutic bio factory approach they were able to suppress that Jeff induced asker leakage and experimental neovascularization in their preclinical model.

We have previously shown that Super credit administration of DNA nanoparticles yields similar marketing activity compared to sub retinal administration.

Over the last year, we've been working with DNA nanoparticles containing therapeutic trans jeans, and a preclinical model.

We have observed a super Cordele administration is better tolerated clinically than Intravitreal administration and this animal model. We have also images supercard of space opening post yearly all the way to the optic nerve after Supercard administration of DNA nanoparticles supporting the potential to address both macular and peripheral retinal disorders.

Dr. Tom Chula: We have also imaged a supracortial space opening posteriorly all the way to the optic nerve after supracortial administration of DNA nanoparticles, supporting the potential to address both macular and peripheral retinal disorder. And, most importantly, we have seen preliminary signs of protein expression for the duration of the studies for three months and are in the process of more thoroughly quantifying these results.

<unk>.

And most importantly, we have seen preliminary signs of protein expression for the duration of the studies to three months and are in the process of more thoroughly quantitative these results.

Super Cordele administration of DNA Nanoparticle gene therapy has potential as an office space repeatable gene therapy without the risk of attracted me surgery in sub retinal ministration.

Dr. Tom Chula: Supercoital administration of DNA nanoparticle gene therapy has potential as an office-based repeatable gene therapy without the risk of vitrectomy surgery and subretinal administration. Furthermore, as demonstrated by the Johns Hopkins team, there is potential to swap out the transgene to address different targets and disorders. We are excited about the potential of this platform using our SCS microinjector for both a biofactory and native gene replacement approach. Next, I want to discuss another preclinical program targeting a potential important pathway in retinal disease; we have recently added an integrin inhibitor to our early preclinical development program. Integrins represent a novel target with limited competition. Integrins are multifunctional cell adhesion molecules that regulate critical cell processes such as adhesion, migration, proliferation, invasion, survival, and apoptosis. Most importantly, they play a role in pathologic processes such as inflammation, angiogenesis, and fibrosis.

Furthermore, as demonstrated by the John Hopkins team.

There is potential the swap out the transgene to address different targets and disorders. We are excited about the potential this platform using our FCS Michael injector for both a bio factory in native gene replacement approach.

Next I want to discuss another preclinical program targeting a potential important pathway in retinal disease. We have recently added an integrated inhibitor to our early preclinical development program.

Integrys represent a novel target with limited competition.

Integrates a multifunctional cell adhesion molecule to regulate critical self processes, such as adhesions migration proliferation invasion survival in Aptoses.

Most importantly, they play a role in pathlogic processes, such as inflammation answered Genesis in fibrosis.

Integrate inhibition has had some recent validation in preclinical models and an early clinical studies of diabetic macular edema, and Mac and the generation.

Dr. Tom Chula: Integrant inhibition has had some recent validation in preclinical models and in early clinical studies of diabetic maculodema and macular degeneration. Given their unique mechanism of action, endocrine inhibition could potentially serve as primary therapy, adjunctive therapy to anti-VEGF agents, or secondary therapy in refractory cases of diabetic macular edema and macular degeneration. Supercortical delivery of an intricate inhibitor suspension may provide targeted compartmentalization and durability advantages over intravitreal or topical delivery, just as we have seen with small molecule suspensions of triaciniloneacetanide clinically and except in preclinical studies. Given the potential to address the pathologic processes in diabetic macular edema and macular degeneration, we're planning a series of additional preclinical studies with our integr Next, I would like to touch briefly on the plans from our development partners.

Given their unique mechanism of action interconnect in addition could potentially service primary therapy.

Junk of their therapy to enter the Jeff agents, and where secondary therapy in refractory cases of diabetic macular edema and macular degeneration.

Super Cornell delivery of an intricate inhibitor suspension may provide targeted compartmentalisation and durability vantages open intravitreal, a topical delivery justice, we've seen with small molecule suspensions of trying some alone the seed and I'd clinically an exceptional preclinically.

Given the potential to address the pathlogic processes, and diabetic macular edema, and Immaculate generation, We're planning a series of additional preclinical studies, what their integrase inhibitor suspension.

Next I would like to touch briefly on the plans from our development partners. We're very pleased with the progress of our oncology partner or a bottle sciences.

Dr. Tom Chula: We are very pleased with the progress of our oncology partner, Ora Biosciences. Aura has a worldwide licensing agreement for the use of our SCS microinjector to deliver its proprietary drug candidates into the supracortal space for the potential treatment of certain ocular cancers. At Arvo in June, ORA presented preclinical research regarding the ocular distribution and efficacy of their asset, AU011, delivered via our SCS microinjector. According to Aura, the data show distribution of AU011 in the supracortal space and very impressive necrosis of tumors following laser activation in a rabbit model of cortomelanoma.

It has a worldwide licensing agreement for the use of our SCS micro injector to deliver as proprietary drug candidates into the supercar it'll space for the potential treatment of certain occupier cancers at ARVO in June or presented preclinical research regarding the articulate distribution the efficacy of their asset you use your ROE one one liberty our S.

Yes, micro injector. According to aura the data show distribution of you 011 in the Suprachoroidal space and very impressive necrosis of tumors falling laser activation in a rabbit model of Accordo melanoma.

Dr. Tom Chula: Preclinical studies have been completed, and ORA expects to initiate a phase two clinical trial evaluating supercordial delivery of AU011 during the third quarter of 2020. Regenexx Bio is utilizing our proprietary SCS microinjector to deliver RGX314 to two different patient populations with the hope of offering non-surgical, in-office access to their one-time gene therapy treatment. They announced last week that their Phase 2 trial is active and is entitled AVIH. The trial will evaluate supracortial delivery of RGX314 in patients with wet AMD. ABA will enroll 40 patients with severe wet AMD who are responsive to anti-adverse treatment. They plan to begin dosing patients this quarter and expect to report interim data from their first cohort of this trial by the end of 2020.

Preclinical studies have been completed and we're expects to initiate a phase two clinical trial evaluating supercritical delivery of eight zero on one during the third quarter of 2020.

Our Avi gene partner.

We don't expire utilizing our proprietary SCS, Michael injector to deliver Rdx 314 to two different patient populations with the help of offering nonsurgical in office access to the onetime gene therapy treatment.

They announced last week that their phase two trial is active and as entitled Aviate.

The trial will evaluate supercars living at RPX 314 in patients with wedding empty.

Aviate will enroll 40 patients with severe wedding empty, who responsive to anti VEGF treatment.

They plan to begin dosing patients this quarter and expect to report interim data from their first cohort of this trial by the end of 2020.

In addition to wedding empty, which annex bio also expects to initiate a phase two trial for Rx Gx, we 14, using supercritical delivery in diabetic retinopathy in the second half 2020.

Dr. Tom Chula: In addition to WET-AMG, Regenexx Bio expects to initiate a Phase II trial for RGX314 using supercortical delivery and diabetic retinopathy in the second half of 2020. Importantly, and despite the current pandemic environment, we continue to stay top of mind with the ophthalmic and retina communities, with over 20 posters and publications presented at the virtual annual meetings for the Association for Research in Vision and Ophthalmology and the American Society of Retina Specialists. At these events, several wetness specialists presented data on Excitative, our Super Cholera Delivery Platform, our Early Gene Therapy Programs, and Zytape. We continue to receive positive feedback from clinicians on how our supercordial treatment approach could target unmet needs for their patients. To leverage this input, we recently formed a scientific advisory board comprised of five world-renowned retina physicians to tap into their expertise as we advance our pipeline development plan. I will now turn the call over to our CFO, Charlie Deignan, to review our financial results.

Importantly, despite the current pandemic environment, we continue to stay top of mind with the ophthalmic and retina communities with over 20 posters and publications presented that the virtual annual meetings for the association for research and vision in Ophthalmology and the American Society of retina specialists at these events several retina specialists presented data on.

Accepted our super clear of delivery platform. Our early gene therapy program insight here, we continue to received positive feedback from clinicians and how our super cradle treatment approach could target unmet needs for their patients.

To leverage this input we recently formed a scientific advisory board comprised of five world renowned retinal physicians to tap into their expertise as we advance our pipeline development plans.

Ill now turn the call over to our CFO, Charlie Degnan to review our financial results.

Thanks, Tom.

Charles A. Deignan: Thanks, Tom. Our financial results for the second quarter were published this afternoon in our earnings press release and are available on our website. Therefore, I will summarize our current financial status. As we reported, our cash and cash equivalents at the end of June 2020 totaled $15.1 million. During the second quarter of 2020, we elected to pay off our outstanding bank loan due to various restrictions and other limiting covenants in the. The total amount paid was $5.3 million and included the remaining principal balance, accrued interest, and final payment. As a result, we now have a very clean balance.

Financial results for the second quarter Republish. This afternoon, and our earnings press release, it and are available on our website. Therefore, I will summarize our current financial status.

As we reported our cash and cash equivalents at the end of June 2020 totaled $15.1 million. During the second quarter 2020, we elected to pay off our outstanding bank loan due to various restrictions and other limiting covenants in agreement. The total amount paid was $5.3 million and included the remaining principal balance accrued interest.

And final team.

As a result, we had we now have a very clean balance sheet.

We are continually assessing options to preserve cash in our monitoring anticipated revenue from near term partner milestones. We are evaluating the most advantageous ways to fund our programs get to our approval milestones and meet our future financial needs.

Charles A. Deignan: We are continually assessing options to preserve cash and are monitoring anticipated revenue from near-term partner milestones. We are evaluating the most advantageous ways to fund our programs, get to our approval milestones, and meet our future financial needs. We will monitor market conditions and be opportunistic about increasing our capital resources in multiple ways, while always remaining cognizant of maintaining shareholder value with the goal of raising money at the lowest cost of capital. We are controlling expenses tightly and continue to prioritize gaining approval for Xipyr while also expanding our internal pipeline. The planned investments in our near-term clinical and preclinical work are incorporated into our operating plans, and we currently expect to have sufficient resources to fund planned operations into the second quarter of 2021. We look forward to presenting at the Webb-Bush-Packrow Virtual Health Care Conference tomorrow. And I will now turn the call back over to George for his closing remarks.

We will monitor market conditions and be opportunistic about increasing our capital resources in multiple ways, while always remain cognizant of maintaining shareholder value with the goal of raising money at the lowest cost of capital.

We're controlling expenses tightly and continue to prioritize gaining approval as IP or while also expanding our internal pipeline. The planned investments in our near term clinical and preclinical work are incorporated into our operating plans and we currently expect to have sufficient resources to fund planned operations into the second quarter 2021, we.

Look forward to presenting at the Wedbush pack grow virtual health care Conference Tomorrow.

Ill now turn the call back over to George for his closing remarks.

Thank you Charlie.

George M. Lasezkay: Thank you, Charlie. To sum up, we believe strongly in the versatility of our super-coil injection platform and its use in small molecules in gene therapy. We have an array of valuable assets: our proprietary SCS microinjector, lead clinical development program, CLS-AX, multiple preclinical programs, as well as our lead commercial product, Zyphus. All a bunch of well-protected, but related, intellectual property.

To sum up we believe strongly in the versatility of our Super coil injection platform.

And it's juice small molecules such there.

We are ready to valuable assets, our proprietary SCS micro injector lead clinical development program CLS X.

Multiple preclinical programs as well as our lead commercial Probugs life here.

All of what you well protected books related intellectual property.

Operator: We lead the industry with our experience targeting the supracarotid space and maintaining strong relationships with researchers and clinicians in the ophthalmic community. We continue to transition from a one product company to an ophthalmology company with exciting clinical collaborations and an innovative and expanding internal pipeline. Importantly, there will be three novel assets delivered via our SCS microinjector in four clinical trials by the end of this year. We are positioning ourselves to have a strong year in 2021 with potential FDA approval of Xipir and the initial data from our Phase 1-2a CLS-AX clinical trial in wet AMD, as well as progress on our other preclinical programs. Our team is very energized and optimistic about our growing pipeline and the potential to improve patient outcomes through our innovative super coroidal technology. I would now like to ask the operator to open the call to questions.

The industry with our experienced a targeting the suprachoroidal space and maintaining strong relationships with researchers and clinicians in the ophthalmic community.

We continue to transition one product company or not the models you company with exciting clinical collaborations and an innovative and expanding internal pipeline importantly, there will be three novel assets delivered via our SCS micro injector for clinical trials by the end of this year.

We're positioning ourselves to have a strong year in 2021 with potential 50 approval Xavier and the initial data from our phase one two a CLS X clinical trial in wet AMD deep as well as progress on or other preclinical programs. Our team is very energized and optimistic about our growing pipeline there.

Central to improve patient outcomes through our innovative Super cool technology.

I would now like to ask the operator to open the call for questions.

Ladies and gentlemen, if you have a question at this time. Please press the star and then the number one key young attached telling telephone you've addressed in its been answered all your wish through live yourself from the Kim Please press the Heskey.

Shweta: Ladies and gentlemen, if you have a question at this time, please press the star and then the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the hash key. First, the line is from the line of Liana Moussaros of Redbush. Your line is open. This is Shweta for Leanna.

First question is from the line of Liana Moussatos of Wedbush.

Ladies open.

This is my thoughts on Deanna Oh, Thanks for taking my question and congrats on all the programs.

Some of this that's remaining slowed resubmission of the MD and how long it takes what the new CMO to manufacture registration batches.

George M. Lasezkay: Thank you for taking my question and congratulations on all the progress. What are some of the steps remaining for the resubmission of the DiPure NDA, and how long will it take for the new CMO to manufacture registration batches? And has COVID-19 had any impact on the new CMO's daily operations? Thank you.

The 19 had any impact on the new Cmos BT operation. Thank you.

Okay. Thanks Liana.

I'll take that question first of all.

The best of our knowledge and our discussions with the new CMO coated has not had any significant impact on their operations. So that does not seem to be.

George M. Lasezkay: Okay, thanks Liana. I'll take that question. First of all, to the best of our knowledge, in our discussions with the new CMO, COVID has not had any significant impact on their operations. So that does not seem to be a significant factor.

You can factor.

Secondly, what needs to be done is we need to rich we need to manufacture registration batches and put them on three months real time stability in order to resubmit R. and D.A. <unk>.

George M. Lasezkay: Secondly, what needs to be done is we need to manufacture registration batches and put them on three-month real-time stability in order to resubmit our NDA. And we're working with the CMO now, the new CMO, on a very aggressive timeline to make that happen. And as I said, we're still working out those details of exactly when the registration batches will be made, but they've given us a very aggressive timeline, and there are incentives in place to go even faster. We're moving as fast as we possibly can, and they can, to get the registration batches made. As has been indicated already, the technology transfer is already underway. We've purchased the necessary equipment. It wasn't too much, but we purchased that equipment. It's already on site, and the teams are already working to put it in place and start to make batches.

We're working with the CMO now the new CMO on a very aggressive timeline to make that happen and this has said we're still working out those details exactly when the registration batches will be made but they've given us a very aggressive timeline and there's incentives in place to go even faster, we're moving as fast as we.

We can and they call it again, because the registration batches made there can be indicated already the technology transfer is already underway.

We purchased a necessary equipment Watson too much but we purchased equipment. It's already on site and the teams are already working to put it in place and start to make batches.

Thank you.

Your next question comes from the line of Annabel Summing up Stifel. Your line is open.

Avatar Jones: Thank you. Your next question comes from the line of Annabel Samimy of Stifel. Your line is open. Hey everyone, this is Avatar Jones on behalf of Annabel. Congratulations on all the new developments. We have two questions, if you could. First, on exit mode. Are you actively exploring partnership opportunities, or has there been any interest externally?

Hi, everyone. This is avatar Jones on for Annabel Congrats on all the new developments, we have two questions. If you may.

First is on exit.

Are you actively exploring partnership opportunities or has there been any interest externally.

And secondly regarding opex.

George M. Lasezkay: Regarding OPEC,

How should we or what are your expectations for R&D expenses through 2020, and 2021 now that there are multiple programs underway. Thanks.

Avatar Jones: How should we, or what are your expectations for R&D expenses through 2020 and 2021 now that there are multiple programs?

George M. Lasezkay: programs underway. Okay, let me take the first part of that question, and then, Charlie, you can answer the second part of that question.

Okay. Let me take the first part of that question and then Charlie you can answer the second part of that question.

Currently at this point in time, we have not explored partnership relationships around accident, we intend to push accident the forward into clinical trials.

George M. Lasezkay: Currently, at this point in time, we have not explored partnership relationships around Exidnib. We intend to push Exidnib forward into clinical trials by ourselves at this point in time. So we have not had those discussions. We've not sought those discussions at this time. Charles, do you want to answer the second part of that question?

By ourselves at this point in time, so we've not had those discussions weve not sought those discussions.

At this at this time.

You want to answer the second part of that question.

Sure, Yes, as I said on the call.

We have 15 million up just over $50 million in cash currently well well be receiving.

Charles A. Deignan: Sure, yeah, as I said on the call, you know, we have 15 million, just over 15 million dollars in cash. Currently, we'll be receiving, potentially, some milestones from our partners. So I would look at R&D, you know, spending. The trials are, the SITNIP trials are not, you know, they're Phase 1, 1A, 2A studies, not big, significant studies, 35 patients. So I wouldn't expect a dramatic increase in R&D, you know, slight increases, and we'll also see some of the manufacturing costs are starting to decline next year. So I wouldn't see a big, big jump. We can, you know, manage the programs as well we have getting into Q2 of next year.

Potentially got some milestones from.

Our partners.

So I wouldn't look at R&D spending.

The trials that shouldn't have trials or not you know their phase one.

182 way studies not significant Big studies 30, 35 patients. So I wouldn't expect a dramatic increase in R&D slight increases in and we'll also see some of the many to manufacturing cost is starting to decline next year. So.

I wouldn't see a big big jump we can.

You know manage the the programs with what we have getting into.

Q2 of next year.

Awesome, Thank you and congrats again.

Thank you. Thank you.

Next question from the line of Boris Peaker Cowen Your line is open.

Avatar Jones: Awesome, thank you, and congratulations again. Thank you. Thank you. Next question is from the line of Boris Beaker of Colvin. Your line is open.

Great. My question I was on the on the C. Unless a x. I mentioned that initial data is expected in the middle of next year I'm just curious how many patients.

Boris Beaker: Great. My question is on CLSAX. You mentioned that initial data is expected in the middle of next year. I'm just curious, how many patients should we expect to see? And also, is it reasonable based on this number of patients to see some initial efficacy as well?

Should we expect to see and also is it reasonable based on this patient number to see some initial efficacy as well.

Tom I think that's your question too damn sure.

Dr. Tom Chula: Tom, I think that's your question, too.

Well. Thank you for the question boards as you know what phase one two a study.

Dr. Tom Chula: to Ammo. Well, thank you for the question, Boris. As you know, it's a phase 1, 2A study, and the primary endpoints are really geared around safety. This is the first time in man that exitinib has been injected suprachoroidally, and so, again, the primary endpoint will be safety. Obviously, we're going to start at the lowest dose, but we will be looking at, as safety signals, some of the usual signals that you might base efficacy on. For example, the need for retreatment, visual acuity, and central subfield thickness are some of the parameters that we'll be assessing.

The primary endpoints are really geared around safety. This is the first time and then that exit and it has been injected supercool, Italy, and so again the primary.

And plant will be safety, obviously, we're going to start at the lowest dose, but we will be looking at.

Safety signal some of the usual signals that you might face efficacy on for example, the need for Retreatment of visual acuity and central Sellafield thickness. So some of the parameters that will be assassin.

Gotcha and Uh huh.

In terms of the actual number of patients Uh huh.

There will be five patients per cohort, okay, and there will be three cohorts is what we're planning gotcha great. Thank you very much for taking my question.

Boris Beaker: Gotcha. And, uh... In terms of the actual number of patients,

Dr. Tom Chula: There'll be five patients per cohort, and there will be three cohorts, is what we're planning.

Thank you for the question.

Next question comes from the line of Jonathan will then of JP Security. Your line is open.

Boris Beaker: Gotcha. Great. Thank you very much for taking my question.

Jonathan Patrick Wolleben: Thank you for the question.

Hi, good afternoon. Thanks for taking the questions just another follow up on I feel if they act.

Jonathan Patrick Wolleben: The next question comes from the line of Jonathan Wolleben of JP Security. Your line is open.

What are you expecting going in that study as far as the durability of response of the single injection and then also I guess.

Jonathan Patrick Wolleben: Hi, good afternoon. Thanks for taking the questions. Another follow-up on CLSAx. What are you expecting going into the study as far as the durability of response with a single injection and then?

Onset of responses something that you're going to be able to see in this interim readout from first cohort maybe second.

I guess I'm again, yeah sure that's your stuff.

Jonathan Patrick Wolleben: And then also, I guess, onset of responses is something that you're going to be able to see in this interim readout, if not from the first cohort, maybe the second.

So a couple of things about exiting the first of all as a tyrosine kinase inhibitor. It has hint that Jeff inhibition and there's been numerous independent.

Preclinical studies assessing it and animal models of retinal.

Dr. Tom Chula: I guess I'll do that again.

Dr. Tom Chula: Yeah, sure, that's your spot.

Dr. Tom Chula: So, a couple of things about exsitinib. First of all, as a tyrosine kinase inhibitor, it has pan-VEGF inhibition, and there have been numerous independent preclinical studies assessing it in animal models of retinal, corneal, and choroidal neovascularization, and it shows very robust inhibition of neovascularization. It shows inhibition of leakage, and there's actually one study where not only does it cause inhibition, but it actually causes regression of established choroidal neovascularization. There are studies suggesting that it's a more potent inhibitor of neovascularization than other TKIs, and other studies suggesting that it's a more potent inhibitor of neovascularization than a focused anti-VEGF-A approach. So intrinsically, it has some very desirable qualities, and we're going to leverage that further with suprachoroidal delivery, where we know we can get very high levels targeted to the affected tissues, such as the retina and choroid.

Corneal and choroidal Neovascularization and it shows very robust inhibition of Neovascularization. It shows. An addition of leakage is actually one study where not only does it cause an addition, but actually causes regression of established choroidal neovascularization.

Their study, suggesting that its more it's a more potent inhibitor of neovascularization other teekay eyes, and other studies, suggesting that its a more potent inhibitor of neovascularization than a focused anti VEGF. They approach. So intrinsically. It has some very desirable caught a qualities and we're going to leverage that further with superior.

Total delivery, where we know we can get very high level targeted to the affected tissue to the retina. Corey we know we can compartmentalize the drug there and keep it away from the anterior segment to minimize any off target effects that we've seen with other teekay is it a previously been a fast.

And.

We know in our own animal model that we have multi month durability. So so we're hoping that this will be a very durable various efficacious therapy and I think the second part of your question as you know what can we expect out of this first cohort or even the second cohort and as I. Just mentioned you know it's really geared toward safety. This is a first time.

Dr. Tom Chula: We know we can compartmentalize the drug there and keep it away from the anterior segment to minimize any off-target effects that we've seen with other TKIs that have previously been assessed. And we know from our own animal models that we have multi-month durability. So we're hoping that this will be a very durable, very efficacious treatment. And I think the second part of your question is, you know, what can we expect out of this first cohort or even the second cohort? And as I just mentioned, it's really geared towards safety. This is the first time in a man exhibit, and it's been injected suprachoroidally. But I think we'll have some... some signals as to its potential efficacy. I don't know if that'll be with the lowest dose or with the next dose, but we're eagerly looking forward to starting this trial because we think this is truly a differentiated or has the potential to be a differentiated therapy in terms of its pan-VEGF inhibition, its durability, and potential safety benefits due to the fact that it's compartmentalized and targeted to the affected tissues.

And then accidents in the injected Supercross, Italy.

But I think we'll we'll have some some.

Some signals as to its potential efficacy.

I don't know that will be with the lowest dose of with with the next dose but were easily looking forward to starting this trial because we think.

This is truly a differentiated or has potential to be a differentiated therapy in terms of panda. Jeff. In addition, the durability.

Potential safety it benefits due to the fact is compartmentalised.

In targeted to be affected tissues.

Got it that's helpful and then.

A quick question on the preclinical programs, we announced today I'm wondering what what are their work needs to get done before we can get isn't like clinic and could that be something we see and maybe next year. Thanks.

Well I'll strike that and George can can finish here. These are preclinical programs.

We're very excited about the bulk of potential as you know integrate inhibitor has some very early validation and some early clinical trials, if the novel target and retinal diseases.

Due to its unique mechanism of action it actually may have a rule.

In patients who are.

I don't respond well to enter digest could be adjunct to enter that Jeff.

Jonathan Patrick Wolleben: Got it. That's helpful. And then a quick question on the preclinical.

So we're very excited about that.

Jonathan Patrick Wolleben: I'm wondering what other work needs to get done.

But again these are just preclinical programs and.

Have a data driven approach to progression of that as well as the DNA nanoparticle gene therapy programs in Georgia may be able to give more specifics about.

Jonathan Patrick Wolleben: done before we can get these in that clinic, and could that be something...

Jonathan Patrick Wolleben: Next year. Thanks.

Dr. Tom Chula: Well, I'll start that, and George can finish. Sure. These are preclinical programs. We're very excited about the potential. As you know, endocrine inhibitor has some very early validation and some early clinical trials. It's a novel target in retinal diseases. Due to its unique mechanism of action, it actually may have a role in patients who don't respond well to anti-FHF. It could be adjunctive to anti-

Plans intentions.

Well the time I just I just echo what you said is that they are preclinical where you have to do some more work there maybe some more optimization that's required but we have come strong scientific underpinnings to these programs. So we really think that there is the potential to do something very interesting with.

Sure well certainly with the therapeutic bio factory approach and integration has.

Dr. Tom Chula: So we're very excited about that. But again, these are just preclinical programs, and we'll have a data-driven approach to the progression of that, as well as the DNA nanoparticle gene therapy programs. George may be able to give more specifics about plans and intentions.

Reasonable validation as a target so we think that those two programs in particular.

Have a lot of promise, but we're we're being very upfront about these are early preclinical programs. We're encouraged we think there good direction for us to go but.

George M. Lasezkay: Well, Tom, I just echo what you said is that they are preclinical. We have to do some more work. There may be some more optimization that's required, but we have kind of strong scientific underpinnings for these programs. So we really think that there is the potential to do something very interesting with the therapeutic biofactory approach, and Integrin has reasonable validation as a target. So we think that those two programs in particular have a lot of promise, but we're being very upfront about these are early preclinical programs. We're encouraged. We think they're a good direction for us to go, but it's going to take some additional preclinical work before we know whether we can really take these things on and start any kind of clinical trial. So I think it's a little premature to discuss that seriously right now. I got it.

It's going to take its going to take some additional preclinical preclinical work before we know whether.

We can really take these things aren't and start any kind of clinical trial. So I think that's it's a little premature to discuss that seriously right now.

Got it alright. Thanks, Thanks again for taking my question.

Next question from the line of like.

July from Roth capital more partners. Your line is open.

Good afternoon. Thanks for taking my question and congrats on the I'm.

I'm just a couple of questions you up I mean, I started with a C. Oleksiak just kind of one of you know what additional steps required before you can be in treating patients at the end of the here and how many sites do you plan to activate things like that and then a follow up question years, who manufacture as Phil.

Jonathan Patrick Wolleben: Got it. All right. Thanks. Thanks again for taking the time to answer the question.

Yeah, so you're going to be used and then use CMO that's doing as I address.

Zegbu Jalla: The next question is from the line of Zegbu Jalla from Roth Capital Partners. Your line is open. Good afternoon, thanks for taking my question and congratulations on the IMD.

Yes, I have here manufacturing or who's gonna be handling that and then at another follow up question with regards to the study design just wanted to know why I flip wish that is being as a baseline treatment, which I think is interesting, but any clarification, there and finally here.

Zegbu Jalla: Just a couple of questions here for me, starting with CLX-AX. Just kind of wanted to know what additional steps are required before you can begin treating patients at the end of the year, and how many sites you plan to activate, things like that. And then a follow-up question here is, who will manufacture CLX-AX? Are you gonna be using the new CMO that's doing your Zydra, not Zydra, but Zypyr, you know, manufacturing, or who's gonna be handling that? And then another follow-up question with regard to the study design, just wanted to know why AflibriSAP is being used as the baseline treatment, which I think is interesting, but any clarifications there? And finally, here, if there are any limitations on what you can use or what indications you can explore for your gene therapy nanoparticle delivery, since you do have some existing agreements, I was just wondering if that provided any limitations, and then maybe if you could even provide any ideas about what indications might be pursued initially.

There any limitations on what you can use it or what indications you can explore boy gene therapy nanoparticle delivery. Since you have some existing agreements I was just wondering if that provided any limitations and then maybe if you can't even provide any idea as to what indications might be pursued initially.

Well.

Thanks for four partner.

[laughter] I hope Tom Tom was writing as fast as I was writing there.

Let me take several parts of that question, then I'll turn it over to Tom first of all in terms of the the manufacturer for CLS a acts that has a different entirely different CMO. It is not the previous CMO through life here and it's not the new CMO. That's a completely separate CMO that we've been working with some time very happy with.

George M. Lasezkay: Well, Zegba, thanks for a four-parter.

How things are working there so that will be a different contract manufacturing organization that will manufacture CLS a acts.

George M. Lasezkay: I hope Tom was writing as fast as I was writing there. Let me take several parts of that question, then I'll turn it over to Tom. First of all, in terms of the manufacturer for CLS-AX, that is an entirely different CMO. It is not the previous CMO for Zyphyr, and it's not the new CMO. That's a completely separate CMO that we've been working with for some time, and I'm very happy with how things are working there. That would be a different contract manufacturing organization that will manufacture CLS-AX. The I've already forgotten one part of your question that I was going to answer.

The I've already forgotten one part of your question than it was going to answer Oh about bought the indications.

We we we're going to proceed and we'd we're not.

We are not very restricted in terms of how we can proceed using or non viral vector.

Therapy in terms of the indications we could explore.

And decide to go after its our preclinical data supports it.

We're fairly.

George M. Lasezkay: Oh, about indications. We, we, we're going to proceed, and we are not, We are not very restricted in terms of how we can proceed using our non-viral vector therapy in terms of the indications we could explore and decide to go after if our preclinical data supports it. We're fairly open to where we can go. We're not as restricted as you might think in terms of potential indications as long as we're in the non-viral vector area. So I'll let Tom, if he was writing down, answer the other two parts of your question. And if you require more amplification on that, I'm glad to give it to you.

Fairly open to where we can go we're not as restricted as you might think in terms of.

Potential indications.

As long as we're in the non viral vector.

Area.

So I'll, let Tom if he was writing down to answer the other two parts of your question and if you require more amplification on that I'm glad to give it to you signaled now that was helpful. Thank you perfect.

Yeah. Thanks for the questions. So I'll I'll take I think the first question.

Essentially you were asking about steps.

Required to get to the phase one a true to try to a trial by the end of the here so.

Gone through a number of steps we did the other preclinical work has been completed on we filed the R&D, we've announced acceptance on we finalized the protocol already.

George M. Lasezkay: No, that was helpful. Thank you. Perfect.

Dr. Tom Chula: Thanks for the questions, Zegba. So I'll take, I think, the first question.

That protocol husband were reviewed by our S&P, which I mentioned on my remarks earlier, a great cohort of the world renowned retina specialists, who found the trial designed to be a very appropriate.

Dr. Tom Chula: And essentially, you were asking about steps required to get to the phase 1, 2A trial by the end of the year. So we've gone through a number of steps. We did all the preclinical work. It's been completed. We filed the IND. We've announced acceptance. We have already finalized the protocol. That protocol has been reviewed by our SAB, which I mentioned in my remarks earlier. A great cohort of world-renowned retina specialists who found the trial design to be very appropriate. In terms of going forward, we've identified sites. They've filled out site feasibility questionnaires. What we've looked for in sites are sites that are experienced with phase 1 trials, experienced with wet AMD trials, and sites that are experienced with supracaroidal injection. Many of these sites were previous sites in our prior trials with Zyperis, so they're familiar with supracaroidal injection, very familiar with it. And then we have to get IRB approval for a site initiation study. And we feel confident that we can initiate this trial before the end of the year.

In terms of going forward, we've identified sites there they fill that site feasibility questionnaires, what we what we look for insights are sites that have experienced with phase one trials experience with wedding de trials.

Sites that are experienced with supercross it'll injection many of these sites where previous sites in our prior trials with type here, so they're familiar with supercritical injection very familiar with it.

And then.

We have to have IR be approval.

A site initiation study and we feel confident that we can initiate.

This trial before the end of year.

Awesome and then Tom just a follow up here outlets with regards to use that well be SAP as a baseline therapeutic goal that trial.

Dr. Tom Chula: And then, Tom, just a follow-up here with regard to using a Flipperswap as the baseline treatment for the trial.

Yes. So the trial design is it's very similar to other.

Dr. Tom Chula: Yes, so the trial design is very similar to other sponsors that have done wet AMD trials with new assets. So, we've spoken about Regenexx Bio. Their trial design involves an initial anti-VEGF injection to assess responsiveness. Our primary goal initially, because we feel this may be a very durable treatment, is really to assess durability and maintenance of visual acuity after anti-VEGF therapy. And so that's the reasoning for that. Again, it's very similar to what other companies have done. And, as I mentioned, the protocol was reviewed carefully by our SAB, and they found it to be very acceptable and appropriate.

Sponsors that have done went in the trials with.

New assets.

So we've spoken about Oragenics bio their trial design and you know involved.

Initial into that and Jackson to assess responsiveness.

Our primary goal initially because we feel this may be a very durable.

Treatment is really to assess durability and maintenance of visual acuity after anti VEGF therapy initially.

And so that's the reasoning for that again, it's very similar to what other companies have done and as I mentioned the protocol was reviewed carefully buyer FCB and they found it could be a very acceptable when appropriate.

Thank you appreciate it.

Dr. Tom Chula: Thank you. I appreciate it. Your next question comes from the line of Serge Belanger of Mid Ham. Your line is open.

Your next question comes from the line of search for the larger need hair. Your line is open.

Hey, Thanks for the question. This is 10 officers and congrats on the progress.

Serge D. Belanger: Hey, thanks for the question. This is Tien Ong for Surge, and congrats on the progress. I just had a couple of questions. So, the first one is about Zypeer.

Just had a couple of questions for the first one is on site here in terms of the FDA review timeline. So I guess based on the new CMO are you still expecting a six month review or could it be.

Tien Ong: In terms of the FDA review timeline, so I guess based on the new CMO, are you still expecting a six-month review, or could it be faster? Just, you know, thinking about the potential likelihood of approval and how this might impact your agreement with Bosch. And then in terms of the milestone payments, I think you've got about $15 million tied to pre-launch and regulatory milestones with Bosch. Is there any, I guess, impact from the fact that you're using a new CMO on your ability to get this milestone payment? Thank you.

Fast there just thinking about the potential likelihood.

For the approval and how this might impact your agreement with Bosch.

And then in terms of the milestone payments I think.

You've got about 15 million that are tied to pre launch and regulatory milestones with Bosch.

Is there any I guess impact from the fact that using a new CMO.

Our ability to to get this milestone payment. Thank you.

George M. Lasezkay: Thanks, Serge. I'll take the first part of that, and then I'll kind of share the second part with Charlie, because it does go to the CACHE runway. In the first part, we believe that if we transfer essentially the same process that was in existence at our previous CMO, which is exactly what we intend to do, the conditions that we need to meet and the requests that were made in the CRL that we received last year will remain the same. And the most important one there is the three-month real-time stability on the registration patches. So, we have a very strong belief that as long as there's no significant change in the manufacturing process that exists today, once it goes into the new CMO, the requirements of the CRL will hold, and we'll be able to submit with three-month real-time stability.

Thanks surge I'll take the first part of that and then I can assure the second part with with Charlie because it does go to other cash runway in the first part of we believe that we transfer essentially the same process that was in existence at our previous CMO, which is exactly what we didn't.

Tend to do that the conditions that we need to meet in the request that were made in the CRL that we received last year will remain the same and that the most important one there is three months real time stability on the registration batches. So we have a very strong beliefs that.

As long as there's no significant change in the manufacturing process that exist today.

Once it goes into the new CMO that the CRL will be the requirements of the CML C.R.L. will hold and we'll be able to submit with three months real time stability data.

The second question about the milestone payments you're right.

George M. Lasezkay: On the second question about the milestone payments, you're right. Just from Bausch, we expect a round of financing to get in approximately 15 million bucks from them and some additional monies from other partners. Obviously, we do expect that we'll get a six-month review date as well after we resubmit. That's, you know, the issue about getting to that, getting to the point where we can collect that milestone. I'll let Charlie talk to you about how we, how we intend to do that, manage our cash runway. So we're, we're sure to get there.

Just from Bausch, we expect a round approval to get in approximately 15 million Bucks.

From them and some additional monies from other partners.

Obviously, if the Oh, we do expect that we'll get a six month review data as well.

After we submit.

So.

That's.

The issue about to getting to that getting to the point, where we could collect that milestone I'll, let Charlie talked to you about how we Oh, we intend to do that manager cash runway. So we're we're sure to get there.

Yeah. Thanks shorts, yeah, so as we said.

Charles A. Deignan: Yeah, thanks, George. Yeah, so as you know, we said, you know, we'll Depending on when our approval is, and at this point we don't know when that is, we do get north of $15 million in from those approval milestones, um you know but until until we know uh you know when we get this resubmitted I you know I can't predict, When approval is, hopefully, like you said, it is faster than six months, but we can't commit to that. And we're monitoring our expenses and, you know, looking at our runway and doing everything we can to... And we'll be up. Yeah.

Well.

The depending on when approval isn't at this point, we don't know when that is we do get north of $15 million.

From those approval milestones.

But until until we know.

When we get this resubmitted I can't predict.

When when approval. This hopefully you'd like you said it is faster than six months, but we can't commit to that in and where we're monitoring our expenses and you know looking at our runway in doing everything we can to weigh extended.

Got it will be up.

Yes. Thanks.

All right. There are no further questions I will turn to call back over to Dr. Love.

Charles A. Deignan: All right, there are no further questions. I will turn the call back over to Dr. Lasezkay.

This guy.

George M. Lasezkay: Thank you. Once again, I want to thank all of you for joining us on this call this afternoon. I think you can tell we're excited about some of the new developments that have taken place here at Clearside. We certainly appreciate your continued interest in Clearside and look forward to updating you on our progress. Operator, you may now disconnect the call. And thanks again.

Thank you once again I want to thank all of you for joining us on this call. This afternoon. I think you can tell we're excited about some of the new developments that have taken place here a clear side. We certainly appreciate your continued interest in clear sight.

Look forward to updating you on our progress.

Operator, you may disconnect the call and thanks again.

Ladies and gentlemen, this concludes today's conference.

Thank you for your participation have a wonderful day you may all disconnect.

Operator: Ladies and gentlemen, this concludes today's conference. Thank you for your participation. Have a wonderful day. You may all disconnect.

[music].

Music: ??? ??? ???