Q1 2021 Clearside Biomedical Inc Earnings Call

And ladies and gentlemen, this day conference operator, Elaine will be and music hold and for the Companys begins please continue to standby.

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Operator: Greetings and welcome to the Clearside Biomedical First Quarter Financial Results and Corporate Update Conference Hall. As a reminder, conference calls are being recorded. I'd like to introduce your host, Jenny Colbin, Clearside Investor Relations. And please go ahead.

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Greetings and welcome to the cleaner side biomedical first quarter financial results and corporate update conference call and that's a great.

This conference call and speaking recorded.

I would like to introduce your host Ms Jenny Colby.

Investor Relations Ma'am. Please go ahead.

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 Security Litigation Reform Act of 1995. However, actual results may differ materially from those indicated by these forward-looking statements as a result of many

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 and the risk factors section of our annual report on form 10-K for the year ended December 31, 2020 and our other SEC filings are available on our website.

Jenny R. Kobin: important factors, including those discussed in the risk factors section of our annual report on form 10K for the year ended December 31st, 2020, and our other SEC filings 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. 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.

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 and the future. We specifically disclaim any obligation to do so even if our views change.

Jenny R. Kobin: On today's call, we have George Lisek, our chief executive officer, Dr. Thomas Chula, our chief medical officer and chief development officer, and Charlie Degnan, 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.

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

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

George Lisek: Thank you, Jenny. Good afternoon, and thank you for joining us on the call today. We have made meaningful progress since we hosted our last earnings call in March. We resubmitted our Zypier new drug application to the U.S. Food and Drug Administration. Saipier is our proprietary suspension of the corticosteroid triumcinolome.

We have made meaningful progress since we hosted our last earnings call in March we resubmitted, our ZIP your new drug application to the U S food and drug administration.

<unk> is our proprietary suspension of the corticosteroid triamcinolone.

George Lisek: It's formulated for supercaroidal administration for the treatment of macular edema associated with UVIID, which is delivered by our patented SCS MicroonJack. This is an important milestone for our company and our shareholders for two reasons. First, Zypure approval would represent ClearSight's first commercial product approval. Second, it would be the first drug approved for delivery into the supercaroidal space, which is behind the patient's visual field. This innovative approach to ophthalmic drug delivery could be a major breakthrough for the treatment of retinal diseases, as it demonstrates the potential for a reliable, non-surgical, office-based method to deliver a variety of therapeutic products for a broad range of back-and-BI diseases. Our team has worked tirelessly throughout this Vipier NDA resubmission process, and I'd like to publicly recognize their efforts. They successfully transferred the technology to our new manufacturing partner in an incredibly short period of time.

And it's formulated for Super Choroidal administration for the treatment of macular edema associated with uveitis, which is delivered by our patented SCS microinjection.

This is an important milestone for our company and our shareholders for two reasons first XI pure approval would represent clear sites first commercial product approval.

It would be the first drug approved for delivery into the supercritical space, which is behind the patient's visual field.

This innovative approach to opt them, our ophthalmic drug delivery could be a major breakthrough for the treatment of retinal diseases.

As it demonstrates the potential for a reliable nonsurgical office based method to deliver a variety of therapeutic products for a broad range of back of the eye diseases.

Our team has worked tirelessly throughout this IPR NDA resubmission process and I'd like to publicly recognize their efforts.

They successfully accomplished the technology transfer to our new manufacturing partner and an incredibly short period of time.

George Lisek: The efficiency of this transfer process is a testament to the hard work, cooperation, and professionalism of both the Clearside team and the team at our new contract manufacturer. The Zypairn-NDA resubmission is a full and complete response to all of the items identified in the complete response letter we received from the FDA in October 2019. We anticipate FDA acceptance of the resubmission of the NDA within approximately 30 days of its submission date, and we believe this application will be considered a Class II resubmission with a targeted six-month review timeline under the Prescription Drug User Fee Act.

And the efficiency of this transfer process is a testament to the hard work cooperation and professionalism.

Both the clear side team and the team at our new contract manufacturer.

The Zip your NDA resubmission as a full and complete response to all of the items identified in the complete response letter we received from the FDA and October 2019.

We anticipate FDA acceptance of the Resubmission of the NDA within approximately 30 days of its submission date.

And we believe this application will be considered a class two resubmission with a targeted six month review timeline under the prescription drug user fee Act.

We will provide an update when we receive a resigned to do per day the potential.

George Lisek: We will provide an update when we receive our assigned Padua date; potential approval of Zypire will further validate our supercaroidal injection platform and its utility in delivering small molecule suspensions into the supercaroidal space. For the commercialization of Zypier, we have two outstanding global partners, Baushen-Lam and Arctic Vision.

Approval of <unk> will further validate our super choroidal injection platform and its utility and delivering small molecule suspensions into the Super cordon space.

For the commercialization of <unk>, we have two outstanding Global partners, Bausch and Lomb and Arctic vision.

Bausch health and Bausch and Lomb, its leading global eye health business is the exclusive license for commercialization and development of ZIP here in the United States and Canada as well exclusive options for the European Union, United Kingdom and other territories.

George Lisek: Bausch Health and Bausch and Loam, a leading global eye health business, have the exclusive license for commercialization and development of Zypire in the United States and Canada, as well as exclusive options for the European Union, United Kingdom, and other territories. We have maintained an ongoing dialogue with Bausch Health and Bausch and Loam as we prepared the Zypure NDA resubmission, and they provided input and support in connection with the filing. Our medical affairs, supply chain, and clinical teams have also worked closely with Bausch Health and Bauchin Lam as they prepare for the commercial launch of Zypier in the U.S. once approved. In Asia, Arctic Vision has the exclusive license for the commercialization and development of Zypire in Greater China and South Korea.

We have maintained and ongoing dialogue with Bausch health and Bausch and Lomb as we prepared the ZIP your NDA resubmission and they provided input and support and connection with the filing.

Our medical affairs supply chain and clinical teams have also worked closely with Bausch health and Bausch and lomb as they prepare for the commercial launch of <unk> in the U S. Once approved.

And Asia Arctic vision has the exclusive license for the commercialization and developed and the ZIP here and greater China, and South Korea, They announced in December that they obtained approval from the Chinese regulatory authority for their investigational, new drug application and UBI day macular edema.

George Lisek: They announced in December that they obtained approval from the Chinese Regulatory Authority for their investigational new drug application in UVIDIC macular edema. They currently expect to begin phase three clinical trials in that indication later this year. The second small molecule suspension for supercroyda delivery in our internal pipeline is CLSAX, our proprietary suspension of the tyrosine-kinase inhibitor exidinif. We're excited about this program because we believe that CLSAX may improve the treatment of neovascular age-related macular degeneration, commonly known as wet AMD, through potentially improved safety and efficacy, and by reducing the frequency of patient injection CLSAX is currently being evaluated in a U.S.-based phase 1-2A clinical trial entitled OAS. It is a multi-center, open-label study to evaluate safety and tolerability of escalating single doses of CLSAX in wet AMD patients.

Currently expect to begin phase III clinical trials in that indication later this year.

The second small molecule suspension for super chord of delivery and our internal pipeline CLS Ax, our proprietary suspension of the tyrosine kinase inhibitor exit.

We're excited about this program because we believe that C. L. S. A X may improve the treatment of Neovascular age related macular degeneration, commonly known as wet AMD.

Through potentially improved safety and efficacy and by reducing the frequency of patient injections with its prolonged durability.

C O S. A X is currently being evaluated and a U S based phase one to a clinical trial entitled Oasis.

It is a multicenter open label study to evaluate safety and Tolerability of escalating single doses of CLSA X and wet AMD patients. We have completed patient dosing in cohort one and we expect to announce cohort one results by the end of June after the last patient visit and data analysis.

George Lisek: We have completed patient dosing in cohort one, and we expect to announce cohort one results by the end of June after the last patient visit and data analysis. I'll now turn over the call to Dr. Tom Chula, our chief medical officer and chief development officer, to elaborate on CLSAX, our partnered programs, and recent data presentations.

I'll now turn over the call to Dr. Tom Ciulla, our Chief Medical Officer, and Chief Development Officer to elaborate on C. L. S. A X our partnered programs and recent data presentations.

And.

Thank you George.

Dr. Thomas Chula: Thank you, George. Our clinical and development teams are extremely excited about the milestone we achieved with the resubmission of our Zypier NDA. We look forward to our first potential product approval and further validation of the benefits of our supercordial injection platform. We are also pleased with the progress we have made with CLSAX, our lead development. As George mentioned, the CLSAX Phase 1-2 Oasis Clinical Trial is a U.S.-based single-dose escalation clinical trial consisting of three cohorts.

Medical and development teams are extremely excited about the milestone we achieved with the Resubmission of our XI peer NDA, we look forward to our first potential product approval and further validation of the benefit of our supercritical injection platform.

We are also pleased with the progress we have made with CLS Ax, our lead development assets as George mentioned, the CLSA ex phase one two our latest clinical trial is a U S. Based single dose escalation clinical trial, consisting of three cohorts. The primary endpoint for the trial will assess the C.

Dr. Thomas Chula: The primary endpoint for the trial will assess the safety and tolerability of CLSAX for three months following its administration. Secondary endpoints will evaluate the pharmacokinetics, visual function, ocular anatomy, and the need for additional treatment with intubitriol efflibersate. As we reported in March, we completed enrollment of cohort one on schedule.

<unk> and Tolerability of CLS Ax for three months following its administration secondary endpoints will evaluate the pharmacokinetics visual function ocular anatomy and the need for additional treatment with interdigital Flipper set.

As we reported in March we completed enrollment of cohort one on schedule.

Dr. Thomas Chula: Our primary objective for cohort one is to establish a floor for safety in this first inhuman trial using a low dose of.03 milligrams of COSAX as we are committed to proceeding prudently in developing a safe and well-tolerated treatment. We expect to announce data from cohort one by the end of June. Following that announcement, we then expect to begin recruiting patients in cohort 2. Late last year, as part of our overall regulatory strategy, we submitted a plan to the FDA to study a broader range of doses in OATs.

Our primary objective for cohort one is to establish a floor for safety and this first in human trial using a low dose of 0.03 milligrams of CLSA X and we are committed to proceeding prudently and developing a safe and well tolerated treatment.

We expect to announce data from cohort one by the end of June.

Following that announcement, we then expect to begin recruiting patients in cohort two.

Late last year as part of our overall regulatory strategy, we submitted a plan to the F. D. A to study a broader range of doses and a waitress based on our preclinical data the FDA and our institutional review Board recently accepted this approach.

Dr. Thomas Chula: Based on our preclinical data, the FDA, and our Institutional Review Board recently accepted this approach. Consequently, we plan to increase our CLSAX cohort 2 dose from 0.06 milligrams to 0.1 milligram, which was our originally planned cohort 3 dose.

Sequentially week, we plan to increase our CLSA X cohort two dosing from 0.06 milligrams to 0.1 milligram, which was our originally planned cohort three dose.

Overall, we are pleased with the with the trajectory of this trial to date and we believe CLSA X will be attractively differentiated combining the potential benefits of Pan VEGF inhibition with compartmentalize safety of Supercritical administration all.

Dr. Thomas Chula: Overall, we are pleased with the trajectory of this trial to date, and we believe CLSAX will be attractively differentiated, combining the potential benefits of PanVEGF inhibition with the compartmental safety of supercort administration. Ultimately, we believe that CLSAX may improve the overall patient experience with a more durable treatment and a favorable tolerability profile. With respect to our pre-clinical initiatives, we continue to advance our Integrant Inhibitor program with the focus on diabetic maculidema and macular degeneration, where specific integrins have been implicated in these diseases. Similar to what we have demonstrated with their other small molecule suspensions, excitinib and trine-sin-alone, we believe our supercordial delivery approach of an intricate inhibitor could provide targeting, compartmentalization, and durability advantages over other delivery approaches.

Ultimately, we believe that CLS ax may improve the overall pacemaker and patient experience with a more durable treatment and a favorable tolerability profile.

With respect to our preclinical initiatives, we continue to advance our integrin inhibitor program with a focus on diabetic macular edema, and macular generation, where specific and integral and tad and implicated and these diseases.

And with what we have demonstrated with their other small molecule suspensions exit and had been trying and sin alone. We believe our super <unk> delivery approach of and integrin inhibitor could provide targeting compartmentalization and durability advantages over other delivery approaches.

Dr. Thomas Chula: We are currently running preclinical studies with their intricate inhibitor suspension, and we expect to conclude these studies later this year. Our clinical development partners also continue to advance their programs, utilizing our SCS microinjector to deliver their agents. Regenix bio is currently conducting two phase two clinical trials evaluating the efficacy, safety, and tolerability of supercordal delivery of their gene therapy agent, RGX 314. The first trial, entitled 88, is targeting the treatment of patients with severe wet AMD who are responsive to anti-vege F treatment.

We are currently running preclinical studies with their integrin inhibitor suspension and we expect to conclude these studies later this year.

Our clinical development partners also continued to advance their programs utilizing our SCS microinjection to deliver their agents with Gen X bio is currently conducting two phase III clinical trials evaluating the efficacy safety and Tolerability of supercritical delivery of their gene therapy agent Archie ex free.

And 14.

The first trial entitled 88 is targeting the treatment of patients with severe wet AMD, who are responsive to anti VEGF treatment.

Dr. Thomas Chula: On their Q1 earnings call, Regenics Bio reported meaningful advancements in this trial and provided three key updates regarding superquittal delivery of gene therapy. First, they expect to report interim data from cohort 1 in the third quarter of this year. Second, they have completed dosing of patients in cohort 2 and expect to report interim data in the second half of 2021. And third, they have expanded the patient population for Aviate and have begun dosing a third cohort in patients who are positive for neutralizing antibodies. As a reminder, based on the protocol, patients are not receiving cortical steroids before or after administration of RGX314. Thus, the continued progress in this trial without immune suppressive therapy is very encouraging.

On your Q1 earnings call Rich and expire reported meaningful advancements on this trial and provided three key updates regarding supercritical delivery of gene therapy.

First they expect to report interim data from cohort, one and the third quarter of this year.

Second they have completed dosing of patients in cohort two and expect to report interim data and the second half of 2021 and third day of expanded the patient population for 88 and has begun dosing a third cohort and patients who are positive for neutralizing antibodies.

As a reminder, based on the protocol patients are not received and cortical steroids before or after administration of <unk> 314 thoughts and the continued progress and this trial without immune suppressive therapy is very encouraging.

The second RG X 314 clinical trial is a phase II trial for the treatment of diabetic retinopathy entitled altitude.

Dr. Thomas Chula: The second RGX 314 clinical trial is a phase two trial for the treatment of diabetic retinopathy entitled Alpitude. Regenics Bile continues to enroll patients in cohort one and expects to report initial data later this year. These Regenics Bio programs highlight the opportunity for an in-office super quarterly administered gene therapy. We are also excited about the recent new data from our oncology partner, Orobioscience. They are currently running a phase two clinical trial, evaluating their lead asset, AU011, delivered via our SCS microinjector into the supercordal space.

<unk> continues to enroll patients in cohort one and expect to report initial data later this year.

These <unk> bio programs highlight the opportunity for an in office Super quarterly administered gene therapy.

We're also excited about the recent new data from our oncology partner Aura Biosciences. The are currently running a phase II clinical trial evaluating near lead asset <unk> 011 delivered via our SCS microinject or into the supercritical space aliens 011 is a first in class <unk>.

Dr. Thomas Chula: AU011 is a first-in-class, virus-like drug conjugate therapy in development for the first-line treatment of corotomal melanoma, a rare and aggressive form of eye cancer that is the most common interocular cancer in adults. Recently, ORA has published promising preclinical data on AU01.

Iris like drug conjugate therapy in development from the first line treatment of choroidal melanoma, a rare and aggressive form of eye cancer that is the most common intraocular cancer and adults.

Recently Ora has published promising preclinical data on <unk> 011.

Dr. Thomas Chula: In April, data was published in the peer-reviewed Medical Journal Cancer Immunology Research, a journal of the American Association for Cancer Research, reinforcing the therapeutic advantage of their virus-like drug conjugate in treating cancer compared to other available treatments. In addition, at the recent Arvo conference, Gore presented promising data comparing the ocular distribution and exposure of AU011 with both intubitrial and superchoral administration in a rabbit model After Supercorral Administration, negligible levels of AU01111 were observed in the vitreous, while there were high exposure levels in the tumor and corroid retin.

And April data was published and the peer reviewed medical Journal cancer Immunology Research a journal of the American Association for cancer research reinforcing that therapeutic advantage of their virus like drug conjugate and treating cancer compared to other available treatments.

In addition at the recent ARVO conference were presented promising data comparing the ocular distribution and exposure of Au 011, with both Intrepid trio and supercritical administration and a rabbit model of human Uveal melanoma.

After Supercoil administration negligible level to a user of one one were observed from the vitreous, while they were high exposure levels in the tumor and choroid retina and.

Dr. Thomas Chula: In addition, when comparing supercroyal to individual administration, the exposure of AU011 in the tumor was approximately five times higher when AU011 was injected supraoroidally. These data suggest that supercroyal administration may have certain advantages compared to individual administration, including superior tumor distributions, higher tumor bioavailability, and less unintended exposure in the vitreous and other key ocular structures. We are extremely encouraged by this preclinical data and look forward to the continued progress from ORA on their phase two clinical trial. We've also been active in the retina physician community. We are pleased to have Clearside featured in several recent key industry events.

In addition, when comparing supercritical to individual administration the exposure of 8011 of the tumor was approximately five times higher when a user of one one was injected super quarterly.

These data suggest that Supercoil administration may have certain advantages compared to interventional administration, including superior tumor distributions and higher tumor bioavailability and less unintended exposure and the vitreous and other key ocular structures. We're extremely encouraged by this preclinical data and look forward to the continued per.

Progress from Ora on their phase II clinical trial.

We've also been active among the retina physician community and we're pleased to have clear sight featured and several recent key industry events.

Dr. Thomas Chula: At the WET AMD and DME Drug Development Summit, we participated in panel discussions entitled Ending the Burden of Monthly Treatments and Making Strides Forward in Drug Delivery and Dose. We also presented superquital drug delivery of CLSAX as a potential solution for treatment burden in patients with YAMD. During the Investing and Cure Summit, organized by the Foundation Fighting Blindness and its RD Fund, we were honored to have the opportunity to present our corporate profile.

At the wet AMD and D and need drug development summit, we participated and panel discussions entitled ending the burden of monthly treatments, and making strides forward and drug delivery and dosing.

We also presented supercritical drug delivery of CLSA acts as a potential solution for treatment burden and patients with wet AMD.

During the investing and tourists summit 2021 organized by the foundation fighting blindness, and it's R. D Fund, we were honored to have the opportunity to a per cent and our corporate profile.

Dr. Thomas Chula: At the recent Arvo 2021 annual meeting, we had multiple posters and presentations. These presentations highlighted the benefits of superclerital delivery in multiple settings and diseases. There are several key posters I'd like to mention from these data presentations. First, Dr. Alan Ho presented a multimodal imaging study on supercoyal injections across species. This project compared supercordal injections to individual injections using diagnostic imaging and demonstrated the uniquely differentiating compartmentalization and targeting of supercordial drug delivery.

At the recent ARVO 2021 annual meeting, we had multiple posters and presentations. These presentations highlighted the benefits of supercritical delivery and multiple settings and diseases. There are several key posters and I'd like to mention from these data presentations.

Dr. Allen Ho presented and multimodal imaging study and supercritical injections across species. This project compared supercritical injections to individual injections using diagnostic imaging and demonstrated that uniquely differentiate and compartmentalization and targeting a supercritical drug delivery.

Doctor Sumit Sharma presented on safety results of the supercritical injection procedure across three retinal disorders, and our clinical trial programs. This poster demonstrated that in humans. The safety profile of supercritical injections is broadly comparable to individual injections.

Dr. Thomas Chula: Dr. Sumit-Shama presented on the safety results of the supercortal injection procedure across three retinal disorders in our clinical trial programs. This poster demonstrated that in humans, the safety profile of supercoyal injections is broadly comparable to individualine. Our team also presented a poster on the ongoing supercortal injection procedure training we've been running with physicians during COVID-19. This training program is becoming increasingly important as we advance our CLSAX trials and prepare for the potential U.S. approval of Zyp.

Our team also presented a poster on the ongoing supercritical injection procedure training, we've been running with physicians. During COVID-19. This channel training program is becoming increasingly important as we advance our CLSA X trials and prepare for the potential U S approval and XI per.

Dr. Thomas Chula: Importantly, physicians who completed virtual or in-person training felt highly confident in their ability to perform the procedure in patients in the future. In addition, Dr. Varel Kinsara presented a poster where he showed that superchoretally delivered DNA nanoparticles containing the human Myo7 transgene produced durable levels of human Myel 7A protein in the RPE and corroy.

And importantly, physicians, who completed virtual and in person training, so highly confident and your ability to blend the procedure and patients in the future.

In addition, Dr. Brough Consol represented a poster where he showed that super quarterly deliver DNA nanoparticles containing the human miles seven transgene produce durable levels of human mile seven and a protein in the RPE choroid.

These data demonstrate that supercritical delivery has potential as an office based repeatable therapy for retinal disorders caused by defects and jeans too large to fit into an AAV vector approach.

Dr. Thomas Chula: These data demonstrate that supercoyal delivery has potential as an office-based repeatable therapy for retinal disorders caused by defects and genes too large to fit into an AV-V-V-V-approach. Links to these publications and presentations are available on our website in Science. In closing, we've had a productive start to 2021, and we look forward to continued progress as we advance our clinical and pre-clinical development program. I will now turn the call over to our CFO, Charlie Degnan, to review our financial results. Charlie?

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

In closing we've had a productive start to 2021 and we look forward to continued progress as we advance our clinical and preclinical development programs I'll now turn the call over to our CFO, Charlie Deignan to review our financial results Charlie.

Thank you Tom our financial results for the first quarter per published this afternoon, and our press release and are available on our website.

Therefore, I will summarize our current financial status.

Cash and cash equivalents as of March 31st 2021 totaled approximately $26 million. This includes approximately $14.4 million and aggregate net proceeds from our registered direct offering and use of our ATM facilities and January.

Charles A. Deignan: Thank you, Tom. Our financial results for the first quarter were published this afternoon in our press release and are available on our website. Therefore, I will summarize our current financial staff. Our cash and cash equivalence as of March 31, 2021, totaled approximately $26 million.

Our quarterly cash burn is primarily due to workout and the activities related to getting <unk> approved and our C. L S and X program.

Investments in our pipeline and are also incorporated into our operating plans.

Based on our current funding and planned spending we expect to have sufficient resources to fund our operations into the first quarter of 2022.

Charles A. Deignan: This includes approximately $14.4 million in aggregate net proceeds from our registered direct offering and use of our ATM facilities in January. Our quarterly cash burn is primarily due to work on the activities related to getting Zypere approved in our CLS-A-X program. Investments in our pipeline are also incorporated into our operating plan. Based on our current funding and plan spending, we expect to have sufficient resources to fund our operations into the first quarter of 2020. Importantly, this estimate does not include milestone payments we may receive under our current partnership agreement.

Importantly, this estimate does not include milestone payments, we may receive under our current partnership agreements is that here is that if approved we expect to receive up to $15 million from passion law and approval and prelaunch milestones. In addition, we would receive a milestone payment from Arctic vision of $4 million.

Thus, we are on track to receive nearly $20 million of non dilutive funding before the end of this year.

And we appreciate the interest and support from our shareholders and the broader investment community and we look forward to participating in the upcoming JMP and Raymond James' Investor conferences next month I will now turn the call back over to George for his closing remarks.

Charles A. Deignan: If Zipier is approved, we expect to receive up to $15 million from Bauchin Lomb in approval and pre-launch milestones. In addition, we would receive a milestone payment from Arctic Vision of $4 million. Thus, we are on track to receive nearly $20 million of non-deluda funding before the end of this year. We appreciate the interest and support from our shareholders and the broader investment community, and we look forward to participating in the upcoming JMP and Raymond James investor conferences next month. I will now turn the call back over to George for his closing remarks.

Thanks, Charlie.

We are optimistic as we look forward to reporting data next month from our Oasis trial and to the potential XI per U S. Marketing approval later this year.

There are currently four ongoing clinical trials with three novel product candidates administered into the supercritical space using our proprietary SCS microinjection.

Our extensive clinical experience with more than 1200 injections reinforces our belief that the S. E. S. Microjet injector has the potential to be a reliable non surgical office based method to access the super choroidal space for the treatment of a broad range of back of the eye diseases.

George Lisek: Thanks, Charlie. We are optimistic as we look forward to reporting data next month from our OAS trial and to potential Zypire U.S. marketing approval later this year. There are currently four ongoing clinical trials with three novel product candidates administered into the supercaroidal space using our proprietary SCS microinjector. Our extensive clinical experience with more than 1,200 injections reinforces our belief that the SES microinjector has the potential to be a reliable, non-surgical, office-based method to access the supercaroidal space for the treatment of a broad range of back-of-the-eye diseases.

We have clear side remained dedicated to making a difference for people suffering from potentially blinding diseases and we look forward to keeping you updated on our progress as the year unfolds.

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

Ladies and gentlemen, if you have a question at this time. Please press Star Sunday number one on your telephone keypad hip to your question and that's been answered or you wish to remove yourself from the queue. Please press the pound key.

Your first question is from Doctor said major law from Roth Capital Partners. Your line is open.

George Lisek: We at Clearside remain dedicated to making a difference for people suffering from potentially blinding diseases, and we look forward to keeping you updated on our progress as the year unfolds. I would now like to ask the operator to open the call up for questions. Ladies and gentlemen, if you have a question at this time, please press stars, Thunder Number 1 on your telephone keypad. If your question has been answered or you wish to remove yourself from the queue, please press the pound key.

Hi, guys. Thanks for taking my question just have a couple of quick ones and see I think the first one is just about the upcoming phase one two study I just wanted to clarify the patients that have been resolved I day anti bad you have to respond.

There is a non responders and I know you know what the purpose of Thanksgiving and I just wanted to get a sense if that Ah patient.

Tom you want to take that question.

Sure so ah patients to.

Dr. Segbejala: Your first question is from Dr. Segbejala, from Roth Capital Partners. Your line is open. Hi, guys. Thanks for taking my question. Just have a couple quick ones here. I think the first one is just about the upcoming phase one study. Just wanted to clarify the patients that have been enrolled. Are they anti-bedev responders or non-responders?

To be eligible and the trial.

And two have been treatment experience they had to have had to <unk>.

Higher injections within the four months preceding screening they receive.

And the flip herself inject and on screening and then.

CLS Ax injection a month later.

They have to have active.

Our expectation based on a masked reading center assessment.

So I would I would categorize these patients says digests dependent.

Dr. Thomas Chula: And I know, you know, the focus is safety, but I just wanted to get a sense of the patient. Tom, do you want to take that question? Sure. So patients to be eligible in the trial had to have treatment experience. They had to have had two prior injections within the four months preceding screening. They received a flibersep injection on screening and then a COSAX injection a month later. They have to have active exudation based on a masked reading center assessment.

Okay, Okay perfect.

And just a follow up here I know and I bet you present it at seven.

Information and your virtual training.

Training, a few Jason and just kind of wanted to get some more details on that and then to get a sense of how you expect backup of Haps and point you know your ability to actually train monetization is for future study.

That's a great question, we have a very robust training program or medical science lays on our biomedical engineers, who have helped with the validation of the original injector and.

Dr. Thomas Chula: So I would categorize these patients as VEGF dependent. Okay, okay, perfect. And then just to follow up here, I know at Arva you presented some information on your virtual training procedures, and I just kind of wanted to get some more details on that and then to get a sense of how you expect that to perhaps influence, you know, your ability to actually train more physicians for future studies. That's a great question.

Are they in conjunction with the medical Affairs team has designed a very robust training program.

We have a and I.

And artificial I, where physicians can practice.

And during COVID-19.

And honestly with travel restricted we actually are developing a virtual training program and it's a very clever.

Program, when we will ship out this artificial eye to the physician and able to actually do.

Dr. Thomas Chula: We have a very robust training program; our medical science liaisons are biomedical engineers who have helped with the validation of the original injector. And they, in conjunction with the medical theorist team, have designed a very robust training program. We have an artificial eye where physicians can practice.

Live training over the Internet.

We then as part of this project represented Toronto.

Looked at some metrics with respect to the training and physicians. We are overall quite pleased with both the virtual and in person training and and both the virtual and in person training felt.

And quite well trained and order to be able to deliver investigational products Super quarterly and the future.

Dr. Thomas Chula: And during COVID-19, obviously with travel restricted, we actually developed a virtual training program. It's a very clever program where we will ship out this artificial eye to the physician and are able to actually do live training over the internet. We then, as part of this project, presented Argo, looked at some metrics with respect to the training, and physicians were overall quite pleased with both the virtual and in-person training, and both the virtual and in-person training felt quite well trained in order to be able to deliver investigational products super quarterly in the future. Thanks, Tom.

Okay.

I'm looking forward to more updates on the program, including the data coming up and that and come back from that came on that and D. H P.

Thanks Deborah.

I appreciate it.

Your next question is from Annabel Sammy mean from Stifel. Your line is open.

Hi, guys.

And for taking my question and congratulations on the progress.

Couple questions and I guess.

And on Oasis and just want to.

I understand are you keeping and asphalt are gone.

Straight and <expletive>, one milligram, so that second cohort and are there going to be any additional cohort dosing cohort after that and looking at it now.

Dr. Thomas Chula: Looking forward to more updates on the program, including the data coming up. And congratulations to the team on the NDA for Zipe here. Thanks, Zubber. Appreciate it. Your next question is from Annable Sammy Me, from Steveung. Your line is over.

Higher and and.

How are you.

Beyond the three months, how are you looking for durability and beyond that.

And I'm just trying to understand what your intention is.

And what should.

Annabel Eva Samimy: Hi guys, thanks for taking my questions and congratulations on the progress. I had a couple questions. I guess first on Oasis, I just wanted to understand, are you skipping an actual dose and going straight into the one milligram for that second cohort, or are there going to be any additional doses after that, so you're looking to go higher? And then are you, beyond the three months, looking for durability data beyond that? I'm just trying to understand what your intention is for this dose escalation trial. And then I'll have another follow-up question. Okay, Tom, do you want to go ahead?

Hum and another follow up.

And.

Okay, and Tom and you wanted to go ahead with.

Sure, let me talk a little bit about the dosing and and the changes we've made.

And as I mentioned in the prepared remarks.

We approach the F D E and the IRB and ultimately because we wanted a broader range of dosing and more flexibility. So cohort one was unaffected.

0.03 milligram dose.

Cohort two is now 0.1 milligram dose, which was our originally proposed cohort three and.

And then.

For cohort three.

We plan to go to three milligrams.

Annabel Eva Samimy: Sure, let me talk a little bit about the dosing and the changes we've made. As I mentioned in the prepared remarks, we approached the FDA and the IRBs, ultimately, because we wanted a broader range of dosing and more flexibility. So cohort 1 was unaffected. It's the 0.03 milligram dose.

So that that youre going to which one.

Two 0.3, so so the dosing will range from 0.03.

Two 0.32.

Potentially from mine.

And for ethically net right.

And.

Of course, this will all be contingent on.

Dr. Thomas Chula: Cohort 2 is now the 0.1 milligram dose, which was our originally proposed cohort 3. And then for cohort three, we plan to go to 0.3 milagule. Sorry, so you're going to which one?

Cohort two results and review by the safety monitoring committee, but that's the current plan.

So in essence, we are skipping over the point.

Zero six milligram, so we've gone and we're going instead of going head to and from a twofold increase over cohort one we're going to a threefold increase over cohort one.

Dr. Thomas Chula: to 0.3. So the dosing will range from 0.03, to 0.3. So a potential 10-fold escalation. That's right.

And are you looking for.

Great and durability data from.

Sure.

Yeah. So the second with respect to the second question as we see.

Dr. Thomas Chula: And, Of course, this will all be contingent on cohort two results being reviewed by the Safety Monitoring Committee, but that's the current plan. So, in essence, we are skipping over the point, 06 milligram. So we're going, instead of going to a twofold increase over cohort one, we're going to a threefold increase over. Okay, and are you looking for greater durability data than just for three months? Yeah, so the second question, as we've said before, the cohort one dose is really to establish a floor of safety. It's a low dose, and we want to proceed prudently in escalating these doses. So we don't expect robust signs of biological efficacy from cohort one.

<unk> said before.

The cohort one dose is really to establish and for safety.

It's a low dose and we want to proceed prudently.

Escalating these doses so we don't expect.

And.

Robust signs of biologic efficacy from cohort one.

And ultimately as we escalate and we plan to.

Established and extension study, where we follow the patients for an additional three months beyond the originally planned three months. So we will be looking for durability and as we escalate the dose.

Okay, and then I had one.

One other question on <unk>.

I guess, the right from Jakafi and I'm thinking more conceptually.

And historically.

And so curious to me and responses central it for you and barrels that parents for gene therapy.

And.

And.

Thanks.

Surgery sparing.

Dr. Thomas Chula: And ultimately, as we escalate, we plan to establish an extension study where we follow the patients for an additional three months beyond the originally planned three months. So we'll be looking for durability as we escalate. And then I have one other question on the regenerative bio, and I'm thinking more conceptually, I guess historically there have been some serious immune responses to the delivery of viral Zuckers for gene therapy, I guess outside of being surgery-sparing, like delivering to the SCS space. Are there benefits to delivering the gene therapy super quietly in terms of an immune response? Is there anything that can help us understand that? That's a great question.

S based.

Are there benefits relative brain and gene therapy.

Currently in terms of and immune response and Mr.

And anything can help us understand about that.

And that's a great question so.

A two part question. So number one what are the potential benefits soup quintal delivery over and <unk>.

Sub retinal surgical delivery of gene therapy, and as you mentioned, obviously, we avoid the surgical risks of the Trek to me and general we also avoid the risk of creating a retina anatomy or a whole and the retina through which the gene therapies are injected and we also.

Avoid.

Avoid the risks of creating a bleb or sub retinal.

During the sub retinal injection.

And literally creating a small and retinal detachment and which of course can can cause harm to the photo receptors. So we avoid the risks of surgery.

Dr. Thomas Chula: So it's really a two-part question. Number one, what are the potential benefits of supercoyal delivery over subretinal surgical delivery of gene therapy? And as you mentioned, obviously, we avoid the surgical risks of the trectomy in general. We also avoid the risk of creating a retinotomy or a hole in the retina through which the gene therapy is injected. And we also avoid the risks of creating a bled, or subretinal, during the subretinal injection. You're literally creating a small retinal detachment, which, of course, can cause harm to the photoreceptors.

And also the distribution of supercritical delivery may be quite attractive for gene therapy, because we're able to potentially.

Potentially expose.

The retina, and choroid circumferential and peripheral language, which may be a very attractive way to treat inherited retinal diseases with Jonathan start and the retinal periphery.

And so those are the potential advantages of supercritical deliveries.

And then the second part of your question with the immune response.

And that's really an important key question, that's still being worked out.

And there's an increasing body of literature, suggesting that it is well tolerated.

Dr. Thomas Chula: So we avoid the risks of surgery. Also, the distribution of supercortal delivery may be quite attractive for gene therapy because we're able to potentially expose the retina in the corroid circumferentially and peripherally, which may be a very attractive way to treat inherited retinal diseases, which often start in the retinal periphery. So those are the potential advantages of supercroidal delivery. And then for the second part of your question with the immune response, and that's really an important key question. You know, that's still being worked out. There's an increasing body of literature suggesting that it is well tolerated and that the immune response is not insurmountable, and that it's overall a fairly favorable immune response.

And that the immune response.

Is is not insurmountable, but it's overall a fairly favorable immune response and I think the fact that <unk> bio is starting a cohort three these are patients.

Who actually have neutralizing antibodies as a very positive sign for supercritical gene therapy, and I just want to remind everybody that they are doing this without any.

Protocol mandated cortical steroids immunosuppressive therapy. So so I think we're still learning a lot about supercritical gene therapy administration.

But but but I think so far so good, especially with respect to some of the news coming from organic smile.

Great. Thank you.

Your next question is from Andreas <unk> from Wedbush Securities. Your line is open.

Dr. Thomas Chula: And I think the fact that Rogenix Bio is starting cohort three, these are patients who actually have neutralizing antibodies, is a very positive sign for supercordial gene therapy. And I just want to remind everybody that they're doing this without any protocol-mandated cortical steroid immunosuppressive agents. So I think we're still learning a lot about supercroyal gene therapy administration, but I think so far, so good, especially with respect to some of the news coming from Eugenic. Your next question is from Andreas Argyrites from Red Bush Securities. Your line is open. Good afternoon, Thanks for taking our question. This is Andrea Sonsoliana Musatos.

Good afternoon. Thanks for taking our question. This is andreas on fully autonomous autos.

Congrats guys also on the progress during the quarter.

But for for XI peer can you provide and update on the status of the preapproval manufacturing inspections, and then I have a follow up after that.

Sure I'll take that and this is.

George.

We're not sure what how the FDA is going to approach. This we've made our resubmission.

Two things that we've done and the Resubmission and actually was a full NDA resubmission that was responsive to all of the items and the CRM and as I mentioned in the prepared remarks.

Andreas Argyrides: Congratulations guys, also on the progress during the quarter. For Zypure, can you provide an update on the status of the pre-approval manufacturing inspections? And then I have a follow-up after that. Sure, I'll take that. This is George.

The most important thing that we had to provide to them was stability data three months stability data on our registration batches and we've done that secondly, and more to your question. We had to demonstrate that the procedure that we buy which we make the drug product with substantially the same as the previous CMO.

George Lisek: We're not sure how the FDA is going to approach this, but we've made our resubmission. Two things that we've done in the resubmission; actually, it was a full NDA resubmission that was responsive to all of the items in the CRL, as I mentioned in the prepared remarks. The most important thing that we had to provide to them was stability data, three-month stability data on our registration batches, and we've done that. Secondly, and more to your question, we had to demonstrate that the procedure that we used, by which we made the drug product, was substantially the same as the previous CMO. And we've done that as well.

And we've done that as well so it's really up to the F. D. A at this point and time, it's hard to predict how they're going to do any kind of inspection of our new contract manufacturer are they may decide to do and onsite inspection and they may.

And not because it's from COVID-19 backup and their shop. They may take a different approach, but I'm sure they'll let us know once we were engaged in conversations with the FDA regarding the NDA Resubmission. So right now that's up to them and we don't know exactly what they're going to do in terms of a pre approval inspection.

George Lisek: So it's really up to the FDA at this point in time, but it's hard to predict how they're going to do any kind of inspection. of our new contract manufacturer. They may decide to do an on-site inspection, or they may not because of some COVID backup in their shop. They may take a different approach, but I'm sure they'll let us know once we're engaged in the conversations with the FDA regarding the NDA resubmission.

Would that be would that be included and the six month timeline or do you think if they want to do and inspection that could push it out.

Well theyre going to do it if they do and onsite inspection, it's gonna be on whatever schedule and they have available and how they considered into their schedule, but we would anticipate that any inspection and including in and outside of inspection would be within that six month timeframe.

George Lisek: So right now, that's up to them, and we don't know exactly what they're going to do in terms of a pre-approval inspection. Would that be included in the six-month timeline, or do you think if they were to do an inspection that could push it out? Well, they're going to do it, if they do an on-site inspection, it's going to be on whatever schedule they have available, how they can fit it into their schedule. But we would anticipate that any inspection, including an on-site inspection, would be within that six-month time frame. I appreciate that; thanks. This is probably one for Tom.

I appreciate that thanks.

This is probably one for Tom.

And.

For for CLS Ax.

Anatomic benefit remains the biggest driver of positive outcomes. When do you think you guys will provide imaging that's fluid levels at what point. Thanks.

I'm, sorry, you broke up and the set and the last part of that.

He and I apologies so at what point do you think you would show any type of imaging of fluid levels that would give indication of the effectiveness of drawing etcetera. Thanks.

Andreas Argyrides: So for CLSAX, anatomic benefit remains the biggest driver of positive outcomes. When do you think you guys will provide imaging fluid levels at what point? I'm sorry, you broke up in the last part of that.

Sure.

As I mentioned, the first cohort is really geared towards safety and so we don't expect robust signs of efficacy from this first cohort and fat.

The primary endpoint is really to look at the safety and Tolerability, but of course, the secondary endpoints will include best corrected visual acuity and some of the anatomic features from OTT and and geography.

Andreas Argyrides: Yeah, apologies. So at what point do you think you would show any type of imaging of fluid levels that would give indication of the effectiveness of drying, etc., etc.? Sure. As I mentioned, the first cohort is really geared towards safety. So we don't expect robust signs of efficacy from this first cohort.

Once the final patients or patient visits are completed and we review the data we plan to report data from the first cohort and.

And we expect that will be and the next month.

And that will.

That will include.

The safety parameters as well as.

Some of them obviously.

Dr. Thomas Chula: In fact, the primary endpoint is really to look at safety and tolerability. But, of course, the secondary endpoints will include best-collective visual acuity and some of the anatomic features from OCT and angiography. Once the final patients are completed and we review the data, we plan to report data from the first cohort, and we expect that will be in the next month. And that will, you know, include safety parameters, as well as some of the, you know, obviously signs of biological activity like visual acuity and some of the OCT anatomy. Okay. Thanks for taking my questions. And congratulations to you guys. Your next question is from Serge Belanger, from Etherning Company. Your line is open. Hey, good afternoon.

Obviously signs of biologic activity light visual acuity and some of the.

OTT and atomic parameters.

Okay. Thanks for taking my questions and congrats again.

Your next question is from Serge Belanger from Needham and company. Your line is open.

Hey, good afternoon, and thanks for taking my questions.

The first one on and ZIP here.

So from a clear side standpoint.

What remains outstanding and with regards to this collaboration and.

Now that you submitted the D M D.

The collaboration and are you, referring the collaboration with Bausch health.

Yes, yes, yes.

And we'll be working with them.

During the review period to plan on success and they'll be working up there.

Hopefully their launch plans and anticipating that we'll also are our medical affairs team our supply chain people are working with their people too.

Serge D. Belanger: Thanks for taking my questions. Uh, first one on Zipier. Um, so from a clear standpoint, what remains outstanding with regard to this collaboration now that you submitted the D&A? The collaboration, are you referring to the collaboration with Bausch Health? Yes, yes, yeah.

Make sure the training is all buttoned up and ready to go they have a very aggressive training program that.

And that Theyre contemplating.

We will be talking to them about supply chain issues or just working working on those with them very cooperatively and.

George Lisek: Well, we'll be working with them during the review period to plan for success, and they'll be working up their Hopefully, there are launch plans anticipating that. We'll also, our medical affairs team, our supply chain people are working with their people to make sure the training is all buttoned up and ready to go. They have a very aggressive training program that they're contemplating.

We'll deal with any issues that may come up or any questions that came up with the F. D. A collaboratively so.

Once the once the IPR NDA is approved the there'll be a transfer of the NDA to Bausch and lomb.

And that's.

George Lisek: We'll be talking to them about supply chain issues. We're just working on those with them very cooperatively. And we'll deal with any issues that may come up or any questions that come up with the FDA collaboratively. So once the, once the IPRNDA is approved, there'll be a transfer of the NDA to Bosh and Lowe. So that's why we've been very cooperative with them. They've been great to work with, and we've worked very cooperatively on the resubmission package, and we'll continue to do so through the entire review process.

And that's why we have been very cooperative with them they've been great to work with and we've worked very cooperatively on the Resubmission package and we will continue to do so through the entire review process.

Okay.

And then on the licensing option for Europe, and the U K.

Is there any timelines associated with them on and when Bosch needs to get back to you and.

On the decision there or.

And something that Hasnt been and you haven't disclosed.

We yes, there is a timeline be.

George Lisek: And then on the licensing option for Europe and the UK, are there any timelines associated with him on when Bosch needs to get back to you on the decision there or something that hasn't been disclosed?

And this summer the end of August.

Unless for some reason the <unk> approved quicker than that.

But the decision will have to be.

Serge D. Belanger: We, yes, there is a timeline, the end of this summer, the end of August, unless for some reason Zyker gets approved quicker than that. But the decision will have to be, will have to be made before the end of August, and we'll be talking with Bouch about that. In the near future, or rather shortly, we'll start having those conversations with them now that the NDA has been resubmitted. So, again, we anticipate that they're going to be very good partners, but we'll have to talk to them about their plans outside of North America.

We will have to be made before the end of August and we'll be and comps are and we'll be talking with the bausch about that.

Beginning or rather shortly and we'll start having those conversations with them now that the NDA has been resubmitted. So.

And again, we anticipate that there can be.

Very good partners.

But we'll have to talk to them about their.

And there are plans outside of North America.

And that'll be ongoing over the next couple of months.

Okay.

And then on the I guess, a question for Tom and CLS Ax.

Serge D. Belanger: But that'll be ongoing over the next couple of years. And then, I guess, a question for Tom on CLSA, as you increase the dosing levels here. You talked about durability. What kind of durability do you think is possible?

And as you and.

Increase the.

Dosing levels here, you talked about durability.

It's what kind of durability do you think as is possible.

Serge D. Belanger: Could we see something as long as four to six months here, or not? I guess just based on your preclinical models, is that something that's possible? Thanks for the question.

Could we see something is as long as four to six months here or.

I guess just based on your preclinical models is that something that's possible.

Thanks for the Crusher and great question.

Dr. Thomas Chula: So we feel that supercurdily administered CLSAX is really attractively differentiated for several reasons, not just durability but first of all for safety because we're compartmentalizing the drug in the supercordial space. So we don't expect to have particle migration into the vitreous or into the visual axis. So we think there's a potential safety benefit. Number two, we think the panvegevient aspect of this for the differentiating it from other long-acting therapies that are really focused on VEG-F-A.

We feel that Super quarterly administered CLS Ax has really attractively differentiated for several reasons and not just durability, but but first of all for safety because we're compartmentalizing the drug and the supercritical space. So we don't expect to have particle migration into the vitreous rooms, and the digit visual access. So we think we think theres a potential safety benefit.

Number two we think the pan VEGF inhibition aspect of this.

Further differentiates it from other long acting therapies that are really focused on veg F E.

This has potential to be more efficacious and current anti VEGF therapies, and even long acting anti VEGF therapies, because because both preclinical and early clinical studies suggest that pan VEGF inhibition may be more efficacious with respect to visual acuity and or drawing and then third.

Dr. Thomas Chula: This has the potential to be more efficacious than current anti-VEG-F-A therapies and even long-acting anti-Vegg-FA therapies because both pre-clinical and early clinical studies suggest that pan-vege F in addition may be more efficacious with respect to visual acuity and or drying.

With respect to durability, we know from our preclinical models that we can have levels.

Dr. Thomas Chula: And then third, with respect to durability, we know from our pre-clinical models that we can have levels in the posterior segment for many months, many months above the IC50 for the VEGF2 receptor, which controls angiogenesis and leakage. So to answer your question, yes, we think that we can have, there's good potential to have beyond three to four months of durability, but we also may have a very nice safety profile and also potential for enhanced efficacy being a panveget inhibitor.

In the post or your segment.

And for many months many months above the IC 50 per the veg F two receptor, which controls and angiogenesis and leakage. So so to answer your question. Yes, we think that we can have.

Theres good potential to have beyond three to four months of durability, but we also may have a very nice safety profile and also potential for enhanced efficacy being a pan VEGF inhibitor inhibitor.

Okay.

Oh, Thanks look forward to seeing the data and excellent.

Again, if you have a question at this time. Please press Star then the number one on your telephone keypad.

Your next question is from John <unk> from JMP Securities. Your line is open.

Dr. Thomas Chula: Thanks. I look forward to seeing the data next month. Again, if you have a question at this time, please press star, then the number one on your telephone keypad. Your next question is from John Wallabin, from JMP Securities. Your line is open. Hey, thanks for taking the question and congratulations on the progress. Just a couple for me.

Hey, Thanks for taking my question and congrats on the progress just.

Just a couple from me first with CLSA ex with the sign off on going ahead to this 0.1 milligram dose I'm wondering what else is left before you'd start dosing. The patients I think you said youre going to wait till.

July to start dosing and I'm wondering if that could happen any sooner and when we could see data from that second cohort.

Well thanks for the question so as I mentioned once the final patient visits are completed and we review the data haven't really by the safety monitoring Committee, we were planned and plan to report data from the first cohort, we expect that city and June and then after that and we plan to start enrollment enrollment.

Jonathan Patrick Wolleben: First, with CLSAX, with the sign-off on going ahead to this 0.1 milligram dose, I'm wondering what else is left before you start dosing the patients. I think you said you were going to wait until July to start dosing, but I'm wondering if that could happen any sooner and when we could see data from that second cohort. Well, thanks for the question.

So.

We potentially could have.

A readout for the second cohort.

Six months after that.

And so I think.

The investigators have been very.

Eager to recruit.

Dr. Thomas Chula: So, as I mentioned, once the final patient visits are completed and we review the data, have it reviewed by the Safety Monitoring Committee, we are scheduled to report data from the first cohort. We expect that to be in June. And then after that, we plan to start enrollment; you know, we potentially could have a readout for the second cohort six months after that. So I think the investigators have been very eager to recruit operationally. The study has gone extremely well.

Operationally the study has gone extremely well and I also want to remind everybody. We started this trial during the pandemic during the holiday season, and we recruited a very robustly so.

And as I mentioned that the investigators are very enthusiastic about the program and about recruiting so.

So we hope to have.

That data readout from the first cohort and June and again, it's mostly going to be geared towards safety and the first cohort.

But we expect to begin recruitment and shortly thereafter from cohort two.

That's helpful.

And then with the integrin and inhibitors as you mentioned I think that you'd be completing preclinical work this year, but I'm just wondering when you might be publicly discussing those in more detail with any data and then if you could characterize which categories are going after.

Dr. Thomas Chula: And I also want to remind everybody that we started this trial during the pandemic, during the holiday season, and we recruited very robustly. So, as I mentioned, the investigators are very enthusiastic about the purpose of the program and about recruiting.

And then how you think about the opportunity there in <unk>.

You said <unk>.

Or do you are.

Versus expanding CLSA accident and to those indications.

Dr. Thomas Chula: So we hope to have that data readout from the first cohort in June. And again, it's mostly going to be geared towards safety in the first cohort, but we expect to begin recruitment shortly thereafter for another cohort. That's helpful.

I'll take the.

The latter two questions and let George discussed disclosure, but we've adopted as integrin inhibitor that.

Targets integrin Alpha.

Alpha the beta three alpha and beta five and Alpha five day to one and these are the key integrations that have been implicated in diabetic macular edema, diabetic retinopathy and <unk>.

Jonathan Patrick Wolleben: And then with the integrin inhibitors, you mentioned, I think, that you'd be completing preclinical work this year, but I'm just wondering when you might be publicly discussing those in more detail with any data and then if you've characterized which integrins you are going after. And then how you think about the opportunity there in, I think you said, DME or DR versus expanding CLSAX into those indications. I'll take the latter two questions and let George discuss disclosure, but we've adopted this integron inhibitor that targets integrins alpha V beta 3, alpha V, beta 5, and alpha 5 data 1. And these are the key integrins that have been implicated in diabetic maculidema, diabetic retinopathy, and A&D.

A N D.

As you know, there's there's been preclinical and early clinical data, suggesting a role for Anika inhibitors and these.

Large disorders.

So we're currently formulating our integrin inhibitor is a small molecule a suspension.

We're doing further preclinical testing to assess the ocular tolerability distribution and pharmacokinetics.

And.

We hope to share that sometime this year in terms of portfolio planning.

I will defer that to George in terms of how it fits in with C O X.

Well, John and I think.

You know you never can have enough shots on goal and so we think that we have an opportunity with integrin to have another shot on major retinal diseases take.

Take your point that you could be you.

Dr. Thomas Chula: As you know, there's been preclinical and early clinical data suggesting a role for antigrant inhibitors and these large disorders. So we're currently formulating our integron inhibitor as a small molecule suspension. We're doing further preclinical testing to assess the ocular tolerability, distribution, and pharmacokinetics, and we hope to share that sometime this year. In terms of portfolio planning, I'll defer that to George in terms of how it fits in with COFAC. Well, John, I think, you know, you can never have enough shots on goal.

Could consider something like a CLSA acts to go after some of the similar diseases, but where we're looking at different we're trying to diversify our pipeline based on mechanism of action as well as anything else and.

And we just think there's it makes perfect sense to us to be able to formulate integrin is a small molecule, it's our sweet spot and and research and development of our small molecule suspensions of molecules.

George Lisek: And so, you know, we think that we have an opportunity with Innegrin to have another shot at major retinal diseases. Take your point that you could consider something like CLSAX to go after some of those similar diseases. But we're looking at different, we're trying to diversify our pipeline based on mechanism of action as well as anything else. And we just think it makes perfect sense for us to be able to formulate Integrin as a small molecule. It's our sweet spot in research and development, our small molecule suspensions. of molecules that are relatively insoluble.

Molecules that are relatively and soluble and so it's another opportunity for us and it.

When we're talking about these kind of indications now that doesn't mean, that's where we're going to end up.

And Tom and I have a constant discussions about other potential applications for both of these products, both CLSA X and immigrant so where this.

This is where we're initially looking.

George Lisek: And so it's another opportunity for us. And, you know, when we're talking about these kinds of indications now, that doesn't mean that's where we're going to end up. Tom and I have constant discussions about other potential applications for both of these products, both CLSAX and Integrant.

But it may not be where we end up and so we have bus and pretty robust discussions about that.

And the company and as Tom mentioned in terms of the preclinical data, where we're hoping to have some preclinical data to be able to disclose before year end.

The integration.

George Lisek: So we're, this is where we're initially looking, but it may not be where we end up. And so we have some pretty robust discussions about that in the company. And as Tom mentioned, in terms of the preclinical data, we're hoping to have some preclinical data to be able to disclose before year end on the integrative. I am looking forward to it. Thanks again for taking the questions. Sure. Thank you. I'm showing no further questions at this time.

Perfect looking forward to and thanks again for taking the questions sure. Thank you.

I'm showing no further question at this time I would like to turn the conference back to CEO and Mr. Douglas Husky for closing remarks.

Yeah.

Thanks, well. Thank all of you for joining us on the call. This afternoon are we really appreciate your continued interest in clear side and what we're doing and we look forward to updating you on our progress throughout the rest of the year.

Operator, now you may disconnect the call and.

George Lisek: I would like to turn the context back to CEO Mr. George Lushevsky for closing remarks. Thanks. Well, thank all of you for joining us on the call this afternoon. We really appreciate your continued interest in Clearside and what we're doing. And we look forward to updating you on our progress throughout the rest of the year. Operator, you may disconnect the call now. And thanks again to everybody who participated. Ladies and gentlemen, this concludes today's conference call.

Thanks again for everybody participating.

Ladies and gentlemen. This concludes today's conference call. Thank you for your participation and have a wonderful day.

Okay.

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George Lisek: Thank you for your participation and have a wonderful day, and and so on and so forth, you know, and I'm sorry, and... I'm gonna be able to be. I'm gonna, and Thank you.

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