Q4 2020 Clearside Biomedical Inc Earnings Call

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 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 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.

George M. Lasezkay: Thank you, Jenny. Good afternoon, and thank you for joining us on the call. 2020 was a year of progress for Clearside, and we've continued this momentum into 2021. Despite the uncertainties brought on by the global pandemic, our internal team and our board of directors remained focused throughout the year, and we were able to successfully execute on our key initiatives. The broad applicability of our supercoroidal injection delivery technology continues to grow as our programs advance both internally and with our partners.

George M. Lasezkay: To date, more than 1,200 injections have been performed in clinical trial patients using our novel SES microinjectors, delivering multiple therapeutic products, small molecules, viral gene therapies, and virus-like drug conjugation. These injections have been performed in a number of different retinal diseases, including uveitis, neovascular age-related macular degeneration, diabetic retinopathy, and choroidal melanoma This extensive clinical experience reinforces our belief that the SES microinjector has the potential to be a reliable, non-surgical, office-based method to access the supracaroidal space for the treatment of a broad range of retinal diseases.

Greetings and welcome to the clear side biomedical fourth quarter and year end financial results incorporate update conference call.

As a reminder, this conference call is being recorded.

And I'd like to introduce your host Jenny Kobe.

And Investor Relations. Please go ahead.

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 and about about the company's future expectations plans and prospects constitute forward looking statements for.

Purposes of the private Securities Litigation Reform Act of 1995.

George M. Lasezkay: In addition to our clinical injection experience, we have a comprehensive intellectual property portfolio that protects our novel SES microinjector, as well as the treatment of various conditions with supracaroidal administration of certain therapeutic products. We have 22 U.S. patents and more than 50 European and internationally issued patents. Our granted patents provide exclusivity for our delivery technology and product candidates into the mid-2030s. And, if granted, our pending applications would extend exclusivity beyond 2040.

Actual results may differ materially from those indicated by these forward looking statements.

As a result of various important factors, including those discussed and the risk factors section of our annual report on form 10-K for the year ended December 31st 2019, our quarterly report on form 10-Q for the quarter ended September 30th 2020 and our other SEC filings are available on our website.

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.

George M. Lasezkay: We continually monitor the activity of competitors who have recently initiated development programs related to supercorridor administration. Given our patent estate and extensive clinical experience, we feel confident that we will be able to successfully protect and have our assets commercialized if they are approved and go to market. Now, I'd like to discuss the specifics of our internal product pipeline, starting with Zypress.

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

On today's call, we have George Lisowski, our Chief Executive Officer, Dr. Thomas Ciulla, Our Chief Medical Officer, and Chief Development Officer, and Charlie Wagner, and our Chief Financial Officer.

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

George M. Lasezkay: Cypher is our proprietary suspension of triamcinolone acetonide, a corticosteroid formulated for supercoroidal injection using our SCS microinjector for the treatment of macular edema associated with uveitis. We remain on track to resubmit our new drug application for Zypyr in the second quarter of 2021, which is in line with our prior guidance. We anticipate that the FDA will review the NDA within six months of the resubmission date. The NDA filing is supported by data from the Phase III Peach Tree Clinical Trial that demonstrated significant and clinically meaningful improvement in vision for patients with macular edema associated with non-infectious uveitis. That improvement was achieved across all anatomical sites of uveitis.

Yeah.

Thank you Jenny and good afternoon, and thank you for joining us on the call today.

2020 was a year of progress for clear sight and we continued this momentum into 2021. Despite the uncertainties brought on by the global pandemic, our internal team and our board of directors remain focused throughout the year and we were able to successfully execute on our key initiatives.

The broad applicability of our Super Choroidal injection delivery technology continues to grow as our programs advance both internally and with our partners to date more than 1200 injections had been performed and clinical trial patients using our novel SCS microinjection for delivering multiple therapeutic products small.

<unk> viral gene therapies, and Viruslike drug conjugates.

George M. Lasezkay: Also, in patients with active inflammation at baseline, resolution was achieved in more than two-thirds of those treated with Zypyr across three commonly used measures of inflammation, vitreous haze, anterior chamber cells, and anterior chamber flare. Based on these data, we believe Xipir, administered supracoroidally, has the potential to be a novel treatment that improves the lives of patients suffering from macular edema associated with uveitis Also, for Xypher, we have two strong partners in Bausch & Lomb and Arctic Vision. Baoshan Lam has the exclusive license for the commercialization and development of Zyper in the United States and Canada and an exclusive license for Europe and the United Kingdom, Australia and New Zealand, South America, and Mexico.

These injections have been performed a number of different retinal diseases, including uveitis and <unk>.

Vascular age related macular degeneration, diabetic retinopathy and choroidal melanoma.

This extensive clinical experience reinforces our belief that the S. T. S. Micro injector has the potential to be a reliable nonsurgical office based method to access the Super Choroidal space for the treatment of a broad range of retinal diseases.

In addition to our clinical injection experience, we have a comprehensive intellectual property portfolio that protects our novel S. E S microinject or as well as the treatment of various conditions with Super Choroidal administration of certain therapeutic products, we have 22 U S patents and more than 50 European and internationally issued patents.

George M. Lasezkay: Arctic Vision has the exclusive license for the commercialization and development of Zypyr in Greater China and South Korea and has announced the approval of their investigational new drug application for a Phase III clinical trial in China. We appreciate the continued support and input from our partners as we look forward to potential U.S. marketing approval for Xipir and the initiation of a Phase III trial in China before the end of this year.

Granted patents provide exclusivity for our delivery technology and product candidates into the mid twenties thirties, and if granted or pending applications would extend exclusivity beyond 2040.

We continually monitor the activity of competitors, who have recently initiated development programs related to Super quarterly administration.

Given our patent estate and clinical extensive clinical experience, we feel confident that we will be able to successfully protect and have our assets commercialized if they are approved and come to market.

George M. Lasezkay: As we announced last week, we have completed patient dosing in the first cohort of OASIS, the phase 1-2A Clinical Trial for CLS-AX in patients with wet AMD. CLSA-X is our proprietary suspension of the tyrosine kinase inhibitor Exidinib for supercoronal injection. We believe CLS-AX can improve the treatment of wet AMD in three important ways. First, it may offer safety benefits by compartmentalizing the drug away from the vitreous and the anterior segment. Second, it may improve efficacy by directly targeting affected chorio-retinal tissues with high drug levels.

Now I'd like to discuss the specifics of our internal product pipeline starting with <unk>.

<unk> is our proprietary suspension of triamcinolone.

See Tonight, a corticosteroid formulated for Super Choroidal injection, using our SCS micro injector for the treatment of macular edema associated with U B S.

We remain on track.

For to resubmit, our new drug application for <unk> and the second quarter of 2021, which is in line with our prior guidance.

George M. Lasezkay: And third, it may reduce patient treatment burden due to prolonged durability of the small molecule suspensions in the suprachoridal space, thereby reducing the frequency of injection. Our differentiated approach with CLSAx combines the high-potency and pan-VEGF attributes of oxydenib with supercoroidal delivery by our SCS microinjector to potentially deliver these benefits.

We anticipate that the FDA will review the NDA within six months of the Resubmission date.

The NDA filing is supported by data from the phase III Peachtree clinical trial that demonstrated significant and clinically meaningful improvement and vision for patients with macular edema associated with non infectious uveitis.

And that improvement was achieved across all anatomical locations of uveitis.

George M. Lasezkay: OASIS is a U.S.-based, open-label, single-dose escalation trial to assess the safety and tolerability of CLSAx in wet AMD patients. Our continued progress on OASIS is important as we continue to expand our pipeline with new aspects and indications, and we look forward to reporting initial safety data from Cohort 1 by mid-year. Oasis Clinical Trial and the programs run by our strategic partners. There are currently four ongoing U.S.-based clinical trials with three different novel candidates administered into the supracorridor space using our proprietary SES microinjection.

Also in patients with active inflammation at baseline resolution was achieved and more than two thirds of those treated with <unk> across three commonly used measures of inflammation.

Vitreous haze anterior chamber cells and anterior chamber flare.

Based on these data we believe zipcar administered Super currently has the potential to be a novel treatment and improves the lives of patients suffering from macular edema associated with uveitis.

Also for XI peer, we have two strong partners and Bausch and Lomb and Arctic vision.

Ocean loans has the exclusive license for the commercialization and development of Syp here, and the United States, and Canada, and and exclusive license for Europe, and the United Kingdom, Australia, and New Zealand, South America and Mexico.

George M. Lasezkay: I will now turn over the call to Dr. Tom Chula, our Chief Medical Officer and Chief Development Officer. Tom will elaborate on our internal development pipeline featuring CLSA-X and our integrin inhibitor program. He will also provide an update on our partnership programs with Regenexx Bio and Aura Biosciences.

Arctic vision has the exclusive license for the commercialization and development of <unk>, and greater China, and South Korea, and as announced the approval of their investigational new drug application for a phase III clinical trial in China.

Tom Chula: Thank you, George. 2020 was a very productive year for us from a research and development perspective, and I'm excited to highlight some of these accomplishments for you today. We initiated our Phase 1-2a clinical trial in WebAMD with CLSAx, and as we reported last week, we made progress in completing enrollment in the first cohort. This achievement was made possible through the combined efforts and commitment from patients, investigators, advisors, and our internal team. The reception and interest in our program from the retina community have been amazing.

We appreciate the continued support and input from our partners as we look forward to the potential U S marketing approval for XI Pierre.

And the initiation of a phase III trial, and China before the end of this year.

As we announced last week, we have completed patient dosing in the first cohort of Oasis our phase one two a clinical trial for C. L. S. A X in patients with wet AMD.

C O S. A X is our proprietary suspension of the tyrosine kinase inhibitor accident for Super Gorilla injection.

Tom Chula: Ultimately, we believe that CLSAx can improve the overall patient experience with longer-lasting treatment and a favorable tolerability profile. Over the course of the last year, our discovery and research team has also made meaningful progress. We are continually utilizing our capabilities to develop proprietary suspensions of various agents to utilize our SCS microinjector in diseases where we can make a difference in the lives of patients. Our preclinical work with our integrin inhibitor program is ongoing, and we expect to conclude these studies this year. Together with our partners, significant progress has been made in expanding the use of our SCS injection technology into the gene therapy space and into new diseases.

We believe C. L. S. A X can improve the treatment of wet AMD and three important ways first it may offer safety benefits by Compartmentalizing drug away from the vitreous and the anterior segment.

Second it may improve efficacy by directly targeting affected corio retinal tissues with high drug levels, and third and may reduce patient treatment burden due to prolonged durability of the small molecule suspensions and the supercritical space, thereby reducing the frequency of injections.

Injections.

Our differentiated approach with approach with C. L. S. A X combines with the high potency and Pan Badger attributes of Big Sydney with Super Choroidal delivery by our S. T S micro injector to potentially deliver these benefits.

Tom Chula: Our partner Regenexx Bio is investigating the delivery of their gene therapy asset into the supracoretal space in two indications, and our partner Oro Biosciences has expanded the pipeline into the oncology space as they assess the supracoretal delivery of their product candidate for coretal melanoma. The use of our SCS microinjector in these clinical trials allows us to broaden the reach of our technology and potentially treat more patients. We have also made important progress within the medical community with over 35 presentations delivered over the last 14 months at the leading ophthalmology and retinal medical congresses.

Oasis is a U S based open label single dose escalation trial to assess the safety and Tolerability of CLSA X and wet AMD patients.

Our continued progress on Oasis is important as we continue to expand our pipeline with new assets and indications and we look forward to reporting initial safety data from cohort one by mid year.

With our CLS Ax.

Oasis clinical trial and the programs run by our strategic partners. There are currently for ongoing U S based clinical trials with three different novel candidates.

Tom Chula: These presentations and ongoing interactions with the leaders in the field have increased the interest in the supracortal space and the potential to adopt this procedure into their practices when available. We believe that excitement about our technology is evidenced by the quick enrollment of our initial clinical trial in wet AMD. I will now delve into each of these topics a bit more.

[noise] administered into the Super Gorilla space, using our proprietary SCS microinjection.

I will now turn over the call to Dr. Tom Ciulla, our Chief Medical Officer, and Chief Development Officer Tom.

Tom will elaborate on our internal development pipeline featuring C. L. S. A X and our immigrant inhibitor program. We will also provide an update of our partners program with rejects bile and Aura Biosciences Tom.

Tom Chula: First CLSAF. CLSAx combines a proprietary suspension of exitinib delivered via our SCS microinjector. We believe that there are several synergies for this approach to yield potential safety, efficacy, and durability benefits. But first, let's discuss safety.

Thank you George 20, Tani was a very productive year from for us from a research and development perspective, and I'm excited to highlight some of these accomplishments for you today.

Tom Chula: Excitinib is a tyrosine kinase inhibitor, or TKI. Because it is a well-characterized small molecule instead of a novel, complex biologic, there is potential for less immune response and inflammation compared to some new contemporary biological agents. Also, compared to other TKIs, Exitinib has shown better biocompatibility with ocular cells, including retinal pigment epithelial cells, which may potentially translate to safety benefits. Importantly, we believe that our unique route of SES administration for CLSAx, which is compartmentalized to the site of disease, may minimize treatment-related adverse events such as vitreous floaters, snow globe, or corneal off-target effects seen with other TKI administration techniques.

We initiated our phase one two a clinical trial in wet AMD with CLSA X and as we reported last week, we made progress and completed enrollment and the first cohort. This achievement was made possible through the combined efforts and commitment from patients investigators and advisors and our internal team.

The reception and interest and our program from the retina community has been amazing.

Ultimately, we believe and CLS ax and improve the overall patient experience with a longer lasting treatment and a favorable tolerability profile.

Over the course, and the last year and <unk>.

<unk> and research team and its also made meaningful progress we are continually and utilizing our capabilities to develop and powertrains suspensions and various agents to utilize our SCS microinjection diseases, where we can make a difference and the lives of patients our preclinical work with or integrin inhibitor program is ongoing and we expect to conclude these studies this year.

Tom Chula: Second, with respect to efficacy, current anti-VEGF treatments target VEGF-A, while excitinib shows pan-VEGF inhibition through broad receptor blockade. There are preclinical and clinical studies that suggest that broad VEGF blockade may have advantages over focused VEGF-A block. Furthermore, Exitinib has demonstrated more than 10 times the in vitro potency and more complete inhibition of preclinical angiogenesis compared to other TKIs being assessed for wet AMD. In addition, in preclinical models, Exitinib not only inhibited, but also regressed neovascularization, which is clinically relevant.

And <unk>.

Together with our partners significant progress has been made and expanding the use of our S. E S and Jackson technology and to the gene therapy space and into new diseases.

And our partner with you and X files investigating the delivering on their gene therapy asset and to the supercritical space and two indications and our partner Aura Biosciences has expanded the pipeline into the oncology space as they assess the soup crowds and living on their product candidate for choroidal melanoma, the use of our SCS micro injector and these clinical trial.

Tom Chula: While it is not surprising that TKIs have shown biological effects in wet AMD clinical trials and are delivered systemically, topically, and individually, each of these routes of administration has been associated with off-target effects. Consequently, the issue with TKIs is likely one associated with delivery of the drug and not the result of the mechanism of action.

<unk> allows us to broaden the reach of our technology and potentially treat more patients.

We also made important progress within the medical community with over 35 presentations delivered over the last 14 months at the leading ophthalmology and retinal medical Congresses.

These presentations and ongoing interactions with the leaders in the field and have increased the interest and the super portal space and the potential to adopt this procedure and to their practices when available and we believe and excitement about our technology is evident by the quick enrolment of our initial clinical trial in wet AMD Island.

Tom Chula: In preclinical studies with Dar-CLSVX suspension of exitinib delivered via supracortial injection, we have shown up to 11 times higher drug levels in affected tissues versus individual administration of the same dose of exitinib. Therefore, supracortial delivery of CLSA-X not only compartmentalizes therapy away from unaffected tissues for potential safety benefits, but also targets the affected chorioretinal tissue layers for potential efficacy benefits Third, with respect to durability, supracaroidal CLSAx has shown prolonged duration in preclinical pharmacokinetic studies.

Ill now delve into each of these topics a bit more.

First CLSA ex CLS Ax combines our proprietary suspension of exit net delivered via our SCS microinjection or we believe that there are several synergies for this approach to yell potential safety efficacy and durability benefits first lets discuss safety exit and there was a tyrosine kinase inhibitor or T. K.

Tom Chula: This could lead to longer-lasting, highly effective treatment that may reduce the number of treatments and visits required for patients to achieve optimal results. Our first CLSAx study is a Phase I-IIa clinical trial called OASIS, which is based in the United States. It is a multi-center, open-label trial in wet EMD patients. Because this is a first-in-human trial, our primary objective is to assess the safety and tolerability of CLSA-X administered by supracortal injection.

On the kind of.

And it is a well characterized small molecule and instead of a novel complex biologic, there's potential for less immune response and inflammation compared to some new contemporary biologic agents also compared to other teekay is exciting and has shown better biocompatibility with ocular cells, including retinal pigment epithelial cells, which may.

Tension translate to safety benefits and importantly, we believe that our unique route and SCS administration from CLSA ex wishes compartmentalize and decided disease may minimize treatment related adverse events, such as vitreous floaters Snow club on corneal off target effects seen with other TK I administration techniques.

Tom Chula: We'll be dose escalating to determine the optimal dose to advance into phase two testing, and we also have the capability to do an extension study as needed in later cohorts. As a reminder, our key inclusion criteria include active subfoveal coronary vascularization secondary to AMD, two or more anti-VEGF treatments with a meaningful response in the four months preceding the screening visit, and specifics related to patient's best corrected visual acuity to ensure patient stability after anti-VEGF treatment. Patients are then assessed at weeks 4, 8, and 12.

Second with respect to efficacy current anti VEGF treatments target day, Jeff, Hey, Wow accent, and <unk> Pan VEGF inhibition through broad receptor blockade.

There are preclinical and clinical studies that suggest that broad VEGF blockade may.

May have advantages over focus that Jeff a blockchain.

Tom Chula: If needed, patients would be retreated with FlibriSep based on a loss from best measurement of 10 or more letters and best corrected visual acuity with associated exudation, or an increase in central subfield retinal thickness greater than 75 microns, or the presence of a vision-threatening hemorrhage due to their AMD. All of these are criteria typical for chronic trials. The primary endpoint for the trial was set to be the safety and tolerability of CLSA-X for three months following its administration.

Furthermore, exit and it has demonstrated more than 10 times the in vitro potency and more complete inhibition of preclinical angiogenesis compared to other teekay is being assessed for wet AMD.

In addition, and preclinical models exit and have not only inhibited, but also regress near vascularization, which is clinically relevant.

Well and it's not surprising that teekay ice have shown biologic effect and wet AMD clinical trials and delivered systemically topically and individually each of these routes of administration have been associated with off target effects. Consequently, the issue with T. Cash is likely one associated with delivery of the drug and not a result on the mechanism of action.

Tom Chula: Last week, we announced that our first cohort of patients is fully enrolled. Based on the trial design, each patient received a FlivrSep at their first visit and a single dose of CLSAx at their second visit one month later.

And preclinical studies for a Dar CLS ax suspension of except nib delivered for the F. Super Kreidler injection, we have shown up to 11 times higher drug levels and affected tissues versus individual administration of the same goes for VIX hitting them. Therefore, supercritical delivery of CLSA acts not only compartmentalize this therapy and away from unaffected.

Tom Chula: Overall, we are very pleased with the rapid progress we've made in enrolling patients. Compared to other individually delivered therapies, we believe SCS administration of CLSAx is attractively differentiated, potentially providing synergistic safety, efficacy, and durability benefits. We look forward to reporting initial safety data from Cohort 1 of OASIS midyear and continuing with Cohort 2 at a higher dose in the second half of the year. With respect to our other research efforts, we continue to explore opportunities to expand our internal development pipeline through new molecules and disease applications.

Tissues for potential safety benefits, but also targets the affected Korea retinal tissue layers for potential efficacy benefits.

And with respect to durability Super Choroidal, CLSA X has shown prolonged duration and preclinical pharmacokinetics studies this could lead to longer lasting highly effective treatment that may reduce the number of treatments and visits required for patients to achieve optimal ourselves.

Tom Chula: Over the course of last year, we advanced our integrin inhibitor program with a focus on the area of diabetic macular edema and macular degeneration, where specific integrins have been implicated in these diseases. Integrins are multifunctional cell adhesion molecules that regulate cell processes and play a critical role in pathologic processes such as inflammation, angiogenesis, and fibrosis.

Our first CLSA X study is a phase one to a clinical trial called Oasis, which is based on the United States. It is a multicenter open label trial in wet AMD patients.

And as I first in human trial, our primary objective is to assess the safety and Tolerability of CLS Ax administered by <unk> injection will be dose escalating to determine the optimal dose to advance into phase II testing and we also have the capability to do and extension study as needed and later cohorts as a reminder, our key inclusion criteria and.

Tom Chula: Integrins also represent a novel target with limited competition, and we believe that given their unique mechanism of action, our proprietary suspension could serve as a primary therapy, an adjunctive therapy to anti-VEGF treatments, or as a secondary therapy in refractory cases. Similar to what we have demonstrated with our other small molecule suspensions, excitinib and triaciniloneacetonide, we believe our supercorridor delivery approach of an integrin inhibitor could provide targeting, compartmentalization, and durability advantages over other delivery approaches.

<unk> active sub ferrovial coordinate vascularization and secondary to a M D two or more anti VEGF treatment with a meaningful response and the four months preceding the screening visit and specifics related to patient best corrected visual acuity to ensure patients stability after anti VEGF treatment.

Patients are then assessed at weeks for eight and 12, if needed patients would be retreated with a flavor set based on a loss from best measurement of 10 of our letters and best corrected visual acuity with associated expectation or an increase and central subfield retinal thickness greater than 70, 575, microns or the presence of a vision.

Tom Chula: Our preclinical studies are ongoing with our proprietary intervent inhibitor suspension to preliminary assess the ocular tolerability, distribution, and pharmacokinetics as we look to address the pathologic processes in AMD and diabetic macular demyelination. We expect to conclude these studies this year, and we look forward to reporting relevant data.

Threatening hemorrhage due to their E M D and.

All of these are criteria typical for current trials.

The primary endpoint for the trial will assess the safety and Tolerability of CLSA X for three months following its administration.

Last week, we announced that our first cohort of patients is fully enrolled.

And the trial design each patient has received a flavor SAP at their first visit and a single dose of our CLS ax at their second visit and one month later overall.

Tom Chula: Gene therapy remains an extremely promising approach to treat retinal diseases, particularly those that are inherited, and we believe that our SCS technology can enhance the benefits of this approach. We are excited about the advancements made by our partner Regenexx Bio and their gene therapy program utilizing our SCS microinjectors. Regenexx Bio is currently conducting two Phase II clinical trials evaluating the efficacy, safety, and tolerability of supercoronal delivery of their agent, RGX314. We are very encouraged by these Regenexx Bio clinical trials for two important reasons. First, office-based supercrew administration potentially avoids the risks associated with paraspinopetrectomy, retinotomy, and subretinal injection, especially in AMD and diabetic retinopathy patients.

Overall, we're very pleased with the rapid progress he made enrolling patients compared to other individually delivered therapies. We believe SCS administration of CLSA access attractively differentiated potentially providing synergistic safety efficacy and durability benefits. We look forward to reporting initial safety data from cohort one of Oasis Mickey.

Air and continuing with cohort two at a higher dose and the second half for the year.

With respect to our other research efforts, we continue to explore opportunities to expand our internal development pipeline with new molecules and D disease applications.

Over the course of last year, we advanced our integrin inhibitor program with a focus on the area of diabetic macular edema, and macular generation, where specific integration have been implicated in these diseases integral into a multi functional cell adhesion molecules have Brexit shall processes and play a critical role and pathologic processes, such as inflammation angiogenesis and <unk>.

Tom Chula: Second, the ability for physicians to treat patients in their offices could substantially increase patient access to care compared to the current model of referring patients to regional ocular gene therapy surgical treatment centers. The first trial, entitled AVIATE, is targeting the treatment of patients with severe wet AMD who are responsive to anti-FHF treatment. They have completed enrollment in the first cohort and expect interim efficacy data in Q3 2021. Eugenics Bio has reported that RGX314 has been well-tolerated to date in the AV8 trial.

Yes.

And it's also represent a novel target with limited competition and we believe that given their unique mechanism of action our proprietary suspension could serve as a primary therapy and adjunctive therapy to anti VEGF treatment or as a secondary therapy and refractory cases.

Similar to what we have demonstrated with our other small molecule suspensions exit and they've been triamcinolone Acetonide, we believe our supercritical and liberty approach or an integral and inhibitor could provide targeting compartmentalization and durability advantages over other delivery approaches.

Tom Chula: This is quite encouraging as they are not only using, as they are not using prophylactic steroid treatment in the trial, and the tolerance of supercordially administered gene therapy in humans would represent an important sign of progress. Regenexx Bio has also begun enrollment in Cohort 2 and expects enrollment completion for that cohort in the second quarter of this year. The second RGX 314 clinical trial is for the treatment of diabetic retinopathy. This trial, entitled Altitude, is ongoing, and initial data is expected in 2021.

Our preclinical study for ongoing with our proprietary integrin inhibitor suspension to preliminary assess the ocular tolerability distribution and pharmacokinetics and we look to address the pathologic processes and a empty and diabetic macular edema.

We expect to conclude these studies this year and we look forward to reporting relevant data.

Gene therapy remains at an extremely promising approach to treat retinal diseases, particularly those that are inherited and we believe that our SBS technology can enhance the benefits for this approach.

We are excited about the advancements made by our partner rich and expire and their gene therapy program utilizing our SCS microinjection.

Tom Chula: We are excited about this groundbreaking approach, and we look forward to the important safety signals from these first-in-man dose cohorts of a super-quarterly-administered gene therapy. Meanwhile, our oncology partner, Oro Biosciences, continues to enroll their Phase II clinical trial evaluating their proprietary virus-like drug conjugate, AU011, delivered via our FCS microinjector into the supracortal space. The trial is assessing the safety and primary efficacy of AU011 in patients with choroidal melanoma, a rare and aggressive form of eye cancer that is the most common type of interocular cancer in adults.

<unk> bio is currently conducting two phase III clinical trials evaluating the efficacy safety and Tolerability of Supercrat overlay free up their agent Archie extra 14th we are very encouraged by the rejects bio clinical trials for two important reasons first office day Super CRO administration potentially avoid the risks associated with price kind of attract.

And my retinal enemy and sub retinal injection, especially and A&D and diabetic retinopathy patients and.

And second the ability for for physicians to treat patients and their offices could substantially increased patient access to care compared to the current model of referring patients to regional ocular gene therapy surgical treatment centers.

Tom Chula: We look forward to continued progress from AURA, and we are encouraged by the potential for AU011 to treat this devastating disease and improve the lives of cancer patients. I will close today with a brief overview of our recent interactions with the retina physician community. Despite all of the meetings being held virtually over the last year, our medical affairs team continues to make meaningful connections at conferences and through numerous publications.

The first trial entitled Aviate is targeting the treatment of patients with severe wet AMD, who are responsive to anti VEGF treatment there.

We have completed enrollment and the first cohort and expect interim efficacy data and Q3 2021.

And expire as reported that Archie X 314, its been well tolerated date and the Aviate trial. This is a quite this is quite encouraging and say no I don't.

Tom Chula: Most recently, we presented at the annual Immaculate Society meeting, as well as the Angiogenesis, Exudation, and Degeneration 2021 program. At the Macular Society, leading retina physicians presented a wide variety of information on our programs, including presentations on CLSAx, XiPIR, and supracortial administration of small molecule and nanoparticle suspension. Importantly, data were also presented on the safety of the supracortial injection procedure utilizing our SCS microinjector across three retinal disorders, demonstrating the broad applicability of our injection platform.

Only using and if they are not using prophylactic steroid treatment and the trial and the tolerance for Super Credibly administered gene therapy, and humans would represent an important sign of progress.

Rich and expire on has also begun enrollment in cohort two and expect enrollment completion for that cohort and the second quarter of this year.

The second Archie X 314, clinical trial and for the treatment of diabetic retinopathy. This trial entitled altitude is ongoing and initial data expected in 2021 work.

Tom Chula: The angiogenesis presentation highlighted several of the key attributes of excitinib in Clearside supercortical delivery of the agent, including the ease of administration as demonstrated in the video of a clinical trial patient undergoing the office-based supercortical delivery procedure. In addition to these medical meetings, we have also had multiple papers accepted for publication. In February of this year, the peer-reviewed British Journal of Ophthalmology published a paper on our Azalea clinical trial, which is an open-label, prospective, multi-center study evaluating the local and systemic safety of zycare in subjects with non-infectious uveitis with and without macular edema. Azalea corroborates and augments a successful Phase III P3 trial in which Zypia was observed to be well tolerated over the 24-week period.

We are excited about this groundbreaking approach and we look forward to the important safety signals from these first in man dose cohorts of our Super quarterly administered gene therapy.

Our oncology partner Aura Biosciences continues to enroll their phase II clinical trial evaluating their proprietary virus like drug conjugate au zero and one one delivered via our SCS microinject here into the Super core it'll space the trial assessing the safety and primary efficacy of a use hero <unk> and <unk>.

Patients with choroidal melanoma, a rare and aggressive form of eye cancer that is the most common intraocular cancer and adults.

We look forward to continued progress from Ora and we are encouraged by the potential for and use your own one one to treat this devastating disease and improve the lives of cancer patients.

I will close today with a brief overview of our recent interactions with the retinal physician community.

Tom Chula: And our Xipir phase 3 extension study, Magnolia, was also recently accepted for publication in the British Journal of Ophthalmology. In January of this year, in the online publication Expert Opinion on Drug Delivery, there was an in-depth analysis of the biomechanics of supracortal drug delivery. This focused on how compartmentalizing therapies away from the unaffected tissue can help prevent, along with fluid transport properties and formula customization for pharmacologic agents may allow for a more tailored treatment of diseases affecting coronary retinal tissue.

Despite all of the meetings being held virtually over the last year. Our medical affairs team continues to make meaningful connections at Congresses and drew numerous publications and most recently, we presented at the annual Macula Society meeting as well as the angiogenesis exudation and degeneration 2021 program.

At Mac and the society, leading retina physicians presented a wide variety of information on our programs and putting presentations on CLSA X XI pear and Super quarterly administration of small molecule and nanoparticle suspensions.

And importantly data was also presented on the safety of the supercritical injection procedure utilizing our SCS microinject or a cross screen retinal disorders, demonstrating the broad applicability of our injection platform.

Tom Chula: And finally, in December of 2020, there was a paper in Translational Vision Science and Technology regarding how supercoitally delivered DNA nanoparticles transfected the retina and retinopigment epithelium in choroids in rabbits. Links to these publications and presentations are available on our website in the science section. In closing, given our extensive experience with over 1,200 patient injections performed to date in a robust training program, we believe our SCS microinjector could be readily adopted in clinical practice. We look forward to continued progress in 2021 and updating you as the year unfolds. I will now turn the call over to our CFO, Charlie Deignan, to review our financial results. Charlie.

The angiogenesis presentation highlighted several of the key attributes and except nib and clear sight cheaper credit delivery up the agent and credit and the ease of administration as demonstrated in net video of a clinical trial patient undergoing the office based super quite old delivery procedure.

In addition to these medical meetings, we have also had multiple papers et cetera for the application and February of this year. The peer reviewed British journal of Ophthalmology published a paper on our Azalea clinical trial, which was an open label prospective multicenter study evaluating the local and systemic safety of XI per in subjects with non infectious.

The items with and without Mcadoo Redeemer and.

Failure, Collaborates and augment and a successful phase III Patriot trial, and which sites here was observed to be well tolerated over the 24 week period.

Charles A. Deignan: Our financial results for the fourth quarter and full year 2020 were published this afternoon in our press release and are available on our website. Therefore, I will summarize our current financial status.

And our XI per phase III extension study and Magnolia, which also recently accepted for publication and the British Journal of Ophthalmology and January of this year and the online publication and expert opinion on drug delivery. There was an in depth analysis of the biomechanics and supercritical drug delivery. This focus on how compartmentalized and therapies away from.

Charles A. Deignan: Our cash and cash equivalents as of December 31st, 2020 totaled approximately $17 million. This includes $6.9 million of funds raised in the fourth quarter through our at-the-market or ATM facility. In January 2021, we raised aggregate net proceeds of $14.4 million from a registered direct offering and our ATM facility. Based on this additional funding, we currently expect to have sufficient resources to fund planned operations into the first quarter of 2020. This estimate does not include additional development and approval milestone payments we may receive under our current partnership agreement.

Unaffected tissues, along with fluid transport properties, and forming our customization for pharma because logic agents may allow for a more tailored treatment of diseases affecting corvette and all tissues and finally in December of 2020. There was a paper and translational vision science and technology regarding house Super correlate deliberate DNA net.

Particles, transfected, retina, and retinal pigment epithelium, and choroid and Rabbit Lake.

And thanks to these publications and presentations are available on our website and the science section.

And closing given our extensive experience with over 12 pancreatic patient injections per for them to date and a robust training program. We believe our SCS microinjection could be readily adopted and clinical practice and we look forward to continued progress and 'twenty 'twenty, one and updating you as the year unfolds I will now I will turn the call over to our CFO, Charlie Deignan to review our.

Charles A. Deignan: Our current quarterly CASPER is primarily related to work on Xipir manufacturing, NDA resubmission, and the CLS-AX clinical trial. The planned investments in our preclinical work are also incorporated into our operating plan. In summary, we expect that our current financial resources will enable us to potentially reach multiple value-creating events over the next 12 months. We appreciate the interest and support of the investment community and look forward to participating in the upcoming Roth and Needham Conferences. I will now turn the call back over to George for his closing remarks.

Financial results Charlie Thank you.

Tom.

Financial results for the fourth quarter and full year 2020 were published this afternoon and our press release and are available on our website.

And while I will summarize our current financial status and our cash and cash equivalents as of December 31, 2020 totaled approximately $17 million.

George M. Lasezkay: I'd like to wrap up our formal comments today with a few final points. First, as the pioneers in treating back-of-the-eye diseases through the supercoronal space, we continue to demonstrate that our injection technology platform can be utilized for a range of potential optomic conditions and with multiple therapeutic entities. Second, we have considerably expanded the clinical use of our first-in-class proprietary SES microinjection. In just the last six months, four clinical programs using our SCS microinjector have been initiated, both from our internal pipeline and from partner-led efforts.

This includes $6 $9 million of funds funds raised in the fourth quarter through our aftermarket or ATM sales.

And January 'twenty 'twenty, one we raised aggregate net proceeds of $14 $4 million from a registered direct offering.

And our ATM facility.

Based on this additional funding we currently expect to have sufficient resources to fund planned operations into the first quarter of 2022. This estimate does not include additional development and approval milestone payments, we may receive under our current partnership.

Treatments.

Our current quarterly cash burn is primarily related to work on site for your manufacturing NDA Resubmission and the CLS Ax clinical trial.

George M. Lasezkay: That is in addition to our Xipir program that we expect to reach the development finish line later this year and then be ready for commercial launch. Finally, I'd like to thank the entire Clearside team, who, together with our many valued partners, have proven that even in a global environment faced with uncertainty and restrictions due to COVID-19, much can be accomplished in a short time with focused and dedicated efforts and the desire to make a difference for patients suffering from potentially blinding diseases. We appreciate and value this important opportunity. And with that, I'd now like to ask the operator to open the call for questions. Alright, so as a reminder...

And investments in our preclinical work on also incorporate into our operating plans and summary, we expect and our current financial resources will enable us to potentially reach multiple value creating events over the next 12 months.

We appreciate the interest and supportive and the investment community and I look forward to participating in the upcoming Roth and Needham conferences I will now turn the call back over to George for his closing remarks.

Yeah.

Thanks, Charlie.

I'd like to wrap up our formal comments today with a few final points.

First as the pioneers intriguing back of the eye diseases through the Super Choroidal space.

Operator: All right, so as a reminder, to ask the question, you will need to press star 1 on your telephone. To resolve your question, press the pound key. Again, that is star 1 on your telephone. Please stand by, we will compile the QNA roster. First question comes from the line of Andreas Argyrides from Wedbush Securities. You are now live.

We continued to demonstrate that our injection technology platform can be utilized for a range of potential ophthalmic conditions and with multiple therapeutic entities.

Second we have considerably expanded the clinical use of our first in class proprietary SCS micro injector and just the last six months for clinical programs using our SCS micro injector had been initiated both from our internal pipeline and from partner led efforts.

Andreas Argyrides: Thank you, Operator. Good afternoon, team. This is Andreas Anteliano-Masatos. Our first question is, with initial data from other pan-VEGF inhibitors now becoming available, what would you like to see as far as rescue rates at three months in the upcoming readout of OASIS?

That is in addition to our XI peer program that we expect to reach the development finish line later this year and then be ready for commercial launch.

Finally, I'd like to thank the entire clear side team, who together with our many valued partners has provided that it is proven that even in a global environment faced with the uncertainty and restrictions due to COVID-19, much can be accomplished and a short time with focused and dedicated efforts and the desire to make a difference for patients suffering from.

George M. Lasezkay: Tom, I think that's your question.

Tom Chula: Oh, thank you for the question. So the question has to do with potential or projected Rescue Rates in the Upcoming OASAS Study, and I just want to backpedal a bit and remind everybody that this study is really, at least the first cohort, really geared towards safety. This is the first time a tyrosine kinase inhibitor has been injected into man suprachoroidally, and so really, the first cohort is geared towards safety. We want to make sure it's well-tolerated before we escalate.

Potentially blinding diseases.

We appreciate and value for this important opportunity and with that I'd now like to ask the operator to open the call for questions.

Alright, so as a reminder.

And that's a question you will need to press star one on your telephone to resolve your question crashed it down and Keith again that is star one on your telephone please standby will be composite for any roster.

Tom Chula: Um, so, you know, with that in mind, we have absolutely no prior data on what we can expect with this mode of delivery, and it's very difficult to do cross-trial comparisons from other TKI studies where the TKI is packaged in a sustainable delivery device and injected individually. So it's really hard at this point without any data for me to speculate. And that's really, you know, the whole goal of the study is to collect that initial data, again, geared toward safety with the first cohort and thus escalate thereafter.

First question comes from the line and yes.

<unk> rights from Wedbush Securities sure and all light.

And.

Thank you operator, good afternoon team.

This is andres on for me on them and sought those.

Andreas Argyrides: And I'll just ask one follow-up question and then jump back in the queue. How are the higher doses in the second and third cohorts being determined? Are they predetermined or on a result-based basis?

Our first question is with initial data from other Pan VEGF inhibitors, and that'll be coming available what would you like to see as far as rescue free rates at three months and the upcoming readout of Oasis.

Tom I think that's your question.

Oh. Thank you for other question. So the question has to do with.

Tom Chula: That's a great question. The question was doses for the upcoming cohort. So, as we've noted on clinicaltrials.gov, the initial dose will be 0.03 milligrams. Cohort 2 will be 0.06 milligrams, and cohort 3 will be 0.1 milligrams. But your point's well taken. So, these are pre-specified, but obviously we have the ability to amend the protocol and adjust.

Potential are projected.

Rescue rates and the upcoming Oasis study and I.

Just one on backpedal, a bit and remind everybody that.

This study is really at least the first cohort is really geared towards safety. This is the first time, a tyrosine kinase inhibitor has been injected and man.

Quarterly and so really the first cohort is geared towards safety and go on and make sure it's well tolerated for fully escalate.

Andreas Argyrides: Okay, thank you, and congrats on the quarter.

Operator: Next one on the queue is Annabel Samimy from Stifo. You are now live.

So.

With that in mind, we have absolutely no prior data on what we.

Annabel Eva Samimy: Hi all, and congratulations on the progress. There is a lot going on with your proprietary and your partnered programs. I had a couple here.

We can expect with this mode of delivery and it's very difficult to do cross trial comparisons.

Annabel Eva Samimy: So, I guess first with CLSAX, I guess I'm not going to ask you to comment on the gray bug data. But, you know, there are a number of... Tampa just trials that are ongoing, starting, or about to start. And I'm just wondering, from a competitive perspective, would you imagine SDS delivery might speed up or possibly slow down the development relative to competitors? For example, if you have a longer duration, could this be a problem competitively? I guess it won't matter if you have better data, but how do you think about the development pathway? Is it a race? And how do you expect to sort of manage that?

And from other TK I studies, where.

Petechiae as package and a sustained delivery device and injected individually. So it's really hard at this point with without any data for me to speculate.

And that's really the whole goal of the studies is to collect that initial data.

And again geared towards safety with the first cohort and Telstra escalate thereafter.

Understood.

And just ask one follow up and then jump back and you too.

How are the thinking about the higher doses and in the second and third cohorts how are those doses being determined and have been.

Are they pre determined or on a well.

Results.

Thank you.

Tom Chula: I guess I'll take that to start. So that's a great question, and I think you mentioned other programs.

That's a great question. The question was up a day.

<unk> for the upcoming cohort so actually as we've noted.

Tom Chula: So, as I mentioned in my prepared remarks, supercortical delivery of a tyrosine kinase inhibitor is well differentiated from other modes of delivery. We believe there are synergies between the intrinsic properties of Xitinib and the Attractive Features of Supercortical Delivery. So, first, for exitinib, as you may know, it's a pan-VEGF inhibitor, it's one of the most highly potent tyrosine kinase inhibitors, and it's been shown in preclinical studies to have better compatibility with ocular cells and other TKIs.

And on clinical trials Gov. The initial dose will be zero point share.

<unk> three milligrams cohort to be zero points here on six milligrams and and cohort three will be 0.1 mill.

Milligrams, but your point's well taken so these are pre specified.

But obviously, we have the ability to and.

And then protocol and adjust accordingly.

Yeah.

Tom Chula: So there may be not only an efficacy benefit intrinsically with Exitinib due to its potency, but potentially a safety benefit as well. And then we think we can leverage that further with supercordial delivery. So we know that when we inject small molecule suspensions supercordially, we can compartmentalize them in the supercordial space. We get very high levels in that space and very, very low levels in the vitreous, basically undetectable. The limited checks in the aqueous.

Okay. Thank you and congrats on the quarter.

And excellent on a Q is annabel Sammy from Stifel Your and our lives.

Hi, Al and.

Graduations on progress.

A lot going on and with their proprietary and your partner program and I had a call.

For here.

And so I guess first with a CLO.

Hum.

And so to comment on on.

On a go grab and go at all.

Tom Chula: So we think by compartmentalizing the drug in the supercordial space, we're going to minimize the risk of any snow globe effects or any off-target effects. And then, in terms of efficacy, by achieving very high levels in that space, we can further potentially enhance the efficacy of Exitinib. And finally, from the work we've done with several small molecule suspensions, we have multi-month durability.

But you know.

There are a number of.

And that just trials there.

Ongoing are starting about to start and I'm, just wondering from a competitive perspective.

Would you envision I guess delivery might mean on for possibly slow down the development and.

Relative to competitor for example, if you have a longer duration could this be a problem competitive play and I guess it won't matter. If he has the other data, but how do you think about the development pathway.

Tom Chula: So, we think that supercortical delivery of a TKI, a potent TKI like Exitinib, is very well differentiated and clearly, potentially separates us from other TKIs. And I might add that, as you know, TKIs have been assessed topically, systemically, and individually. And in many of these cases, there's been a biological effect. So, we think that TKIs probably work, and it's not a matter of mechanism of action but really one of delivery. And we think we've solved that problem.

On a race and how do you.

Expect to sort of manage that.

But I guess I'll take that to start.

It's a great question.

And I think you mentioned other programs so and.

And I mentioned in my prepared remarks.

Supercritical delivery of a tyrosine kinase inhibitor.

It is well differentiated from other.

Annabel Eva Samimy: Great, and then if I could ask the second question, I guess it's regarding Regenexx Bio, their program 314. So we saw the long-term results from the subretinally administered R-JX through 14, and the durability seemed really good, and I guess that was measured partly by also measuring the rejection of the anti-vege f, by the reduction of anti-vegef injections. I guess maybe, and some of it went out quite long, and I guess maybe you can help us understand what expectations would be for supercorroidally delivered 314 based on what you saw from the subretinal durability. And what is the possibility of that higher protein expression being repeated in humans? I think you saw that preclinically already. So maybe you can talk a little bit about that.

Most of the delivery.

We believe there are synergies between the intrinsic properties of exiting it.

And the.

The the attractive features of supercritical delivery, so first for exit and a S.

You May know it is a pan VEGF inhibitor. It's one of the most highly potent tyrosine kinase inhibitors and it's been shown in preclinical studies to have better.

Compatibility with orchid herself and other TK I. So there may be it not only on the efficacy benefit intrinsically except net due to its potency for potentially a safety benefit and then we.

They can leverage that further with Super court on delivery. So we know that when we when we inject small molecule suspension super correctly, we can compartmentalize them and the Super corridor stays and we get very high levels and that space and.

Tom Chula: Sure, so it's a great question. And, you know, Regenexx Bio is in phase two for wet AMD and diabetic retinopathy. They've announced that they have completed enrollment of patients in cohort one, their initial dose, and they expect interim efficacy data from cohort one in the third quarter of this year.

Very very low levels, and the vitreous and and basically on undetectable at the limited Texan and the aqueous so we think by compartmentalize and the drug and the supercritical space, we're going to minimize the risk of any snow globe effects or any off target effects and then in terms of efficacy by by achieving very high levels and that space we can.

Tom Chula: And they've already begun enrollment in cohort two. But I want to, again, backpedal a bit and just remind everybody that, once again, this is the first in man that a viral vector gene therapy has been injected supracolloidally. And I think that their announcement, that it's been well-tolerated to date, is really a huge step forward. Because, as you know, viral vectors can be associated with inflammation when delivered individually

And further potentially enhance the efficacy of exit and it and finally, we know from from the work we've done with several small molecule suspensions, we have multi month durability. So so so so we think that Ah soup.

Supercritical delivery of a T. K I have potent teekay I like exit and it is very well differentiated and clearly potentially it separates us from other TK ice and I might add that as.

As you know teekay either been assessed.

Topically systemically and individually and in many of these cases, there has been a biologic effect. So we think that.

Tom Chula: And the fact that they've already announced that it's been well-tolerated again is a step in the right direction. So I think, you know, just like our first cohort of our CLSAx study, their first cohort of supercarroidal delivery of their vector, RGX314, is, I would speculate, really geared toward safety. And the fact that it's been well tolerated to date is a huge step forward, not just for Regenics Bio and RGX314, but really the entire field of viral vector gene therapy, particularly for biofacts.

Teekay is probably work and it's not a matter of us.

Mechanism of action, but really one of delivery and we think we solve that problem.

Yes.

Great and then if I could ask a second question or I guess, it's for regarding rich and expire.

Their programs for one for them. So we saw the.

The long term results from the retina Lee administered.

Ourselves for one for and the durability really good and I guess that was measured partly by the also by the reduction on the anti VEGF.

Tom Chula: And, you know, obviously, they're going to dose escalate, as they've already done in Cohort 2. And I think, just as they did with their subretinal program with five cohorts, they'll escalate until they find a dose that's not only safe but also efficacious. So I think we're in the early innings, but I think it looks very promising so far.

Reduction of anti that's all from collection I guess, maybe.

Some of it we're now quite long and I guess, maybe you can help us understand what expectations would be for.

Super Corrado delivered three one for based on what you saw from the sub retinal and durability and.

Annabel Eva Samimy: Okay, one last question, if I may. Is there any work that's being done? I know that Sabaash is controlling the commercialization of Zipair, but have you established or have they established some kind of training program for physicians given that SCS, I mean, I imagine that the SCS delivery would be, Zyper would be something that you would want to use as the launchpad in training for all the other programs that are coming down the pike, so can you talk about the training program that's being established for that?

And.

What is the possibility of that higher person expression repeated and humans.

On preclinical and already.

And so maybe you can talk a little bit about that.

Sure. So it's a it's a great question and you know as.

As you know rich.

<unk> bio and phase II for wet AMD and diabetic retinopathy.

They've they've analysis completed and enrollment of patients in cohort one and their initial dose they expect interim efficacy data from cohort one and the third quarter of this year and they've already begun.

George M. Lasezkay: Yeah, I think, Tom, you can speak to what MedAffairs has done with Bausch training, at least for Bausch employees.

Tom Chula: Sure. So we have a very robust training program. And actually, during this pandemic, we've actually developed a hybrid virtual program where we can ship our artificial eyes to physician investigators, and we can then be with them virtually via webinar and train them. And we found that that's gone really well. We are actually looking at this with surveys.

Enrollment in cohort two.

But I want to again, backpedal, a bit and just remind everybody that.

Once again this is first in man.

<unk> vector gene therapy has been injected Supercool, Italy and.

And on I think that their announcement gotta spend and well tolerated to date is really a huge step forward because as you know.

<unk> vectors can be associated with inflammation when delivered individually and the fact that they've already announced that its been well tolerated.

Tom Chula: and we're presenting this at Arvo as a means of physician training, virtually. We also have a very robust in-person training program, and I can tell you that it's been extraordinarily well received by physicians. We recently published what I call our procedure performance paper, it's available on our website, which indicates that the procedure itself is very well accepted by physicians. And our interactions with Bausch, as well as with GenX Bio and Aura in terms of training have been really stellar.

Again, it is a step on the right direction. So I think just like our first cohort of our CLSA X study.

Their first cohort of Super.

Super Choroidal delivery of their character Archie ex free 14 on.

Yes.

I would I would speculate is really geared towards safety and and the fact that it's been well tolerate to date I think it's a huge step forward not just for <unk> bio and our Jack St and 14, but really and the entire field and viral vector gene therapy, particularly for bio factory, and obviously theyre going to dose escalate as there is it already time and cohort two.

Tom Chula: We've had great experiences with these companies. We have some injection videos on our website, and I think if you have a chance to view those, I would encourage you to do so, because they demonstrate how easy physicians can become with injecting. We actually have an injection video of CLSCX, and you can see from the video that it seems to be well-tolerated; it seems to be fairly quick and efficient. So we're really confident that this procedure could be readily adopted in clinical practice when it's approved, especially in the retina community, where these physicians love gadgets and love procedures.

And I think just as they've done with their sub retinal program with five cohorts.

And bill escalate until they find.

A dose that's not only safe, but also on efficacious. So I think were and the early innings, but but I think.

You know it looks very promising so far.

Okay and one last question if I may is for any.

Work, that's being done and I know that bausch is confined to the commercialization of life here, but how do you establish them.

Or have they established from kind of a training program for physicians given that.

Yes, I mean, I imagine that that SaaS delivery would be.

Something that you would reside here would be something that you would want to use the launch pad and training for all the other programs for the coming down the Pike. So can you talk about the low training program.

Annabel Eva Samimy: Great! Thank you so much.

Operator: Great. So again, if you would like to ask a question, please press star 1 on your telephone. Again, that is star 1. Next one on the queue is John Wolleben from JMP Securities. You are now live.

And being established for that.

I think Tom you can speak to what Medicare has done with with Bausch on training.

Jonathan Patrick Wolleben: Hey, good afternoon, and congratulations on all the progress. Just a couple of questions from me as well on CLSAx. Tom, you mentioned a few times that the focus for this first readout midyear is going to be on safety, but you are collecting a few different efficacy endpoints. So I was hoping you could let us know specifically what data to look forward to midyear on the efficacy front.

And at least the Bausch employees.

Sure. So we have a very robust training program and actually during this pandemic, we've actually developed a.

Our hybrid virtual.

Program, where we can ship.

Our artificial ice to physician investigators and are.

Tom Chula: Well, sure. You know, we hate to even call these endpoints efficacy endpoints with only five patients, but your point's well taken. They tend to be traditional efficacy endpoints. And again, they're all listed on clinicaltrials.gov.

We then can be with them virtually via webinar and.

And train them and we found that that's gone really well, we actually are looking at this with surveys and will be presenting this at ARVO.

As a means of a.

Physician training.

Tom Chula: But they'll be the usual endpoints that most companies report. So, of course, we'll have best corrected visual acuity. We'll be looking at the need for rescue. We'll be looking at anatomic features on OCT angiography and OCT angiography, particularly central subfield thickness. And of course, again, because it's mostly geared towards safety, we'll be looking at adverse events, treatment emergent adverse events, and serious adverse events.

Virtually we also have a very robust in person training program and I can tell you that it's been extraordinarily well received.

By physicians, we recently published.

What I call our price.

Procedure performance on paper.

It's available on our website, which and.

Indicates that the day procedure itself is is.

He is very well accepted by on physicians.

And our interactions with bausch and as long as with <unk> bio and aura in terms of training has been really stellar and we had great experiences with these companies.

Jonathan Patrick Wolleben: That's helpful. And I think you mentioned that the plan is to start the second cohort in the second half of this year. So I'm wondering how much safety fault have you designated that's necessary before dose escalating, and is that the same between cohorts two and three as well?

And and finally I wanted to mentioned net.

We have some injection and videos on our website and I think if you get a chance to a few of those I would encourage you to do so because they demonstrate how.

Tom Chula: Great question. So, as you know, patients will be followed for three months after their CLSX injection, and we'll essentially tabulate the results, present them to the Safety Monitoring Committee, and they'll help us decide whether it's safe to move on or not. We plan to start recruitment at... just at the beginning of the second half of this year and potentially have results from cohort two by the end of the year.

Relatively.

Facile physicians can become with injected and we actually have an injection and video of CLSA acts and.

And you can see from the video that it seems to be well tolerated it seems to be fairly quick and efficient. So we're really confident that.

This procedure could be readily adopted and clinical practice.

When it's approved especially and the retina community where.

Jonathan Patrick Wolleben: Terrific. And, shifting gears, one last one from me.

These physicians love gadgets and loved procedures.

Jonathan Patrick Wolleben: On the preclinical integrin platform, you mentioned that wrapping up the preclinical work this year is the goal. Will we be seeing any of that data this year? And is the expectation to have a lead candidate or multiple? How are you thinking about next steps for the integrin platform?

Great. Thank you for much.

So again, if you would like to ask a question. Please press star one on your telephone and again that is star one.

Next one on the Q is John Walden from GMP Securities your and all that.

Tom Chula: We've adopted an integrin inhibitor. We're very excited about this particular integrin inhibitor because it targets the alpha V beta 3, alpha V beta 5, and alpha 5 beta 1, which have been indicated in some of these important retinal diseases like diabetic macular edema, AMD, and diabetic retinopathy.

<unk>.

Hey, good afternoon, and congrats on all the progress just a couple for me as well on CLS Ax and Tom.

Tom You mentioned, a few times that the focus for the first readout midyear is going to be on safety, but you are collecting a few different efficacy endpoints and I was hoping you could let us know specifically what data to look forward to mid year on the upstream on the excuse for them.

Tom Chula: We're currently formulating this as a small molecule suspension, and it is currently undergoing pre-clinical testing to assess ocular tolerability, ocular distribution, and pharmacokinetics. As you know, we've done a significant amount of work with small molecule suspensions, and we expect them to be well tolerated to show favorable distribution, that is, high levels in the targeted corteretinal tissue layers and low levels anteriorly, and to have multi-month durability. So we will hopefully be wrapping those studies up this year and sharing some of those results with the retina community and the investment community.

Oh sure we hate to even called these endpoints.

Efficacy endpoints with only five patients, but but your point's well taken and they tend to be traditional efficacy endpoints and again, they're all listed on clinical trials dot Gov, but it'll be the usual and points that most companies are.

Report so of course, we'll have.

And the best corrected visual acuity will be looking at the need for rescue will.

And we'll be looking at anatomic features on OTT, and geography, and O C T and geography, particularly central subfield thickness and.

And of course Oh.

And because it's mostly geared towards safety will be looking at adverse events treatment emergent adverse events and serious.

Jonathan Patrick Wolleben: Great. Thanks for taking the questions and congrats on the progress again. Thank you.

Adverse events.

Operator: And There are no further questions at this time. I will now turn it over back to Dr. Lasezkay.

That's helpful and I think you mentioned that the players who started the second cohort and the second half of this year. So I'm wondering how much safety follow up have you designated.

George M. Lasezkay: Well, thank you for joining us on the call this afternoon. We appreciate your continued interest in Clearside, and we look forward to updating you on our progress. Operator, you may now disconnect the call.

Necessary before dose escalating and and is that the same between cohorts two and three as well.

Great question. So as you know patients who will be followed for three months after their CLS ax injection.

And then will essentially.

Operator: Thanks again.

Tabulate the results.

<unk> presented for safety monitoring committee and they'll help us design and decide whether it's safety and move on or not.

We plan to start on recruitment.

And then just at the beginning of the second half of this year.

And potentially have for results from cohort two by the end of the year.

Terrific and then just shifting gears and one last one for me on the preclinical integrin platform you mentioned.

Wrapping up the preclinical work. This year is the goal we'd be seeing any of that data. This year and is the expectation and have a lead candidate or multiple how are you thinking about next steps for the integrated platform.

And we've adopted.

And the integrin inhibitor and we're very excited about this particular integrin inhibitor because it targets the alpha the beta three alpha and beta Fiat and Alfa five beta one which have been indicated and some of these.

Important retinal diseases like diabetic macular edema, a M D and diabetic retinopathy.

Were currently formulating this is a small molecule suspension.

Its currently undergoing preclinical testing to assess the ocular tolerability, the ocular distribution and pharmacokinetics.

As you know we've done.

Significant amount of work with with small molecule suspensions and we expect it to be well tolerated to show favorable distribution that has to be.

High level from the us and the targeted Corey retinal tissue layers and low levels anteriorly and to have multi month durability. So we will hopefully be wrapping those studies up this.

This year and sharing some of those results with the retina commodity and the investment community.

Great. Thanks for taking my questions and congrats on the progress again.

Thank you for your interest.

And there are no further question at this time and I'll now turn it over back to the Doctor Lizzie ski.

Yeah.

Well, thank you for joining us on the call. This afternoon. We appreciate your continued interest and clear side and we look forward to updating you on our progress.

Operator, you may now disconnect the call.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.

And.

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And.

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Yeah.