Q4 2021 Clearside Biomedical Inc Earnings Call

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Operator: © BF-WATCH TV 2021, Good day and thank you for standing by. Welcome to the Clearside Biomedical Fourth Quarter 2021 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode.

Good day, and thank you for standing by welcome to the career side bio medical fourth quarter 2021 financial results and corporate update conference call. At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. And now, it is my pleasure to hand the conference over to your host today, Jenny Kobin with the Clearside Biomedical Investor Relations. Thank you. Please go ahead.

Can I ask a question you will need to press star one on your telephone if you require any further assistance. Please press star zero and now it's my pleasure to hand, the conference over to your host today, Jenny coping with the career side bio medical Investor Relations. Thank you. Please go ahead.

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

Good afternoon, everyone and thank you for joining us on the call today before we begin I would like to remind you that during today's call we will be making certain forward looking statements various remarks that we make during this call about the company's future expectations plans.

Fans and prospects constitute forward looking statements for purposes of the private Securities Litigation Reform Act of 1995.

Actual results may differ materially than those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our annual report on Form 10-K for the year ended December 31, 2020, and our other SEC filings are available on our website we expect.

Our 10-K for the year ended December 31st 2021 will be filed Tomorrow. 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 saw.

Jenny Kobin: We expect that our 10-K for the year ended December 31, 2021, will be filed tomorrow. 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.

Specifically disclaim any obligation to do so even if our views change on.

Jenny Kobin: 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 for your questions. I would now like to turn the call over to George.

On today's call, we have George Luecke, Becky, 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.

George Lasezkay: Thank you, Jenny. 2021 was a year of validation for Clearside and our Super Corridor Injection platform. Last quarter we achieved our first FDA approval with Zyper, which solidified our position as the leader in delivering drugs into the supracarotid space. We have developed a truly innovative therapeutic approach in treating retinal diseases that allows unparalleled access to the back of the eye to directly target the site of disease. Zyper is being commercialized in the U.S. by our partner, Bosch and Lohm, for the treatment of macular edema associated with UVitis.

Thank you Jenny.

2021 was a year of validation for clear site and our Super Choroidal injection platform.

Last quarter, we achieved our first FDA approval with XI pier, which solidified our position as the leader in the luby delivering drugs into the Super Choroidal space.

We have developed a truly innovative therapeutic approach in treating retinal diseases that allows unparalleled access to the back of the eye to directly target the site of disease.

<unk> is being commercialized in the U S by our partner Bausch alone for the treatment of macular edema associated with uveitis.

George Lasezkay: VIPIR is the first therapy approved for this indication, and we're honored to make a difference in the lives of these patients battling this potentially blinding condition. Bausch announced last month that they have launched Xypyr in the United States with focused physician training in the use of our proprietary SES microinjector. FAUSCH is a well-respected leader in our industry, and we're confident in the strength and capabilities of their commercial team to advance this therapy to patients in need.

<unk> was the first therapy approved for this indication and we're honored to make a difference in the lives of these patients battling this potentially blinding condition.

Bausch announced last month that they launched snipe here in the United States with focused physician training and the use of our proprietary SCS micro injector.

Bausch is a well respected leader in our industry and we're confident in the strength and capabilities of their commercial team to advance this therapy to patients in need.

George Lasezkay: During 2021, Arctic Vision, our China-based development and commercialization partner, also made great strides with Xypyr, which they refer to as ARBN001, and the brand name Arcadis. Last quarter, Arctic Vision initiated their confirmatory phase 3 trial in China in macular edema associated with uveitis. Their ultimate goal is to commercialize Arcadis, if approved, in their licensed regions of Greater China, South Korea, Australia, New Zealand, India, and 10 Southeast Asian countries.

During 2021, Arctic vision, our China based development and commercialization partner also made great strides with IPR, which they referred to as a or B 001, and the brand name Arcadis.

Last quarter Arctic vision initiated their confirmatory phase III trial in China, and macular edema associated with uveitis.

The ultimate goal is to commercialize arcadis, if approved and they're licensed regions of Greater China, South Korea, Australia, New Zealand, India and pin Southeast Asian countries.

George Lasezkay: In addition, last week, Arctic Vision announced that they have dosed the first patient in China in a Phase I clinical trial of ARVN001 for the treatment of diabetic macular edema. The Xipir-related milestones also strengthened our balance sheet. In total, we generated $20 million of non-dilutive funding in the fourth quarter from Bausch and Arctic Vision that will be utilized to advance our internal pipeline program. While Xypair is our first commercially available product, we also have a broad pipeline of internal programs and collaborations with our development partners, targeting multiple indications including macular degeneration, diabetic retinopathy, diabetic macular edema, and ocular cancer.

In addition last week, our vision announced that they have dosed the first patient in China in a phase one clinical trial of a RV and 001 for the treatment of diabetic macular edema.

The XI peer related milestones also strengthened our balance sheet in total we generated $20 million of non dilutive funding in the fourth quarter from Bausch and Arctic vision that will be utilized to advance our internal pipeline programs.

While <unk> is our first commercially available product. We also have a broad pipeline of internal programs and collaborations with our development partners targeting multiple indications, including macular degeneration.

<unk> retinopathy, diabetic macular edema and ocular cancer.

George Lasezkay: The approval of Xipyr in the U.S. validates our strategic approach to focus on small molecule suspension. Our lead internal pipeline product candidate, CLSA-X, combines our proprietary small-molecule suspension of the tyrosine kinase inhibitor Exidinib, with delivery by our SES microinjector. In 2021, we've reported positive data from cohorts 1 and 2 in our Phase 1-2a OASIS trial in patients with wet AMD. We achieved our primary safety endpoints in these first two cohorts as CLSAX was well-tolerated with no serious adverse events.

The approval of <unk> in the U S validates our strategic approach to focus on small molecule suspensions.

George Lasezkay: And we are making progress in Cohort 3 with the 0.5 mg dose of CLSAX, and we remain on track to report results from this cohort mid-year. As a reminder, OASIS is a dose escalating study to explore a broad range of doses to take into a Phase 2B clinical trial.

Our lead internal pipeline product candidate C. L. S. A X combines our proprietary small molecule suspension of the tyrosine kinase inhibitor with.

With delivery by our SCS microinjection.

In 2021 we've reported positive data from cohorts, one and two in our phase one two a oasis trial in patients with wet AMD.

We achieved our primary safety end points and these two first two cohorts at C. L. S. A X was well tolerated with no serious adverse events and we are making progress in cohort three with the 0.5 milligram dose of CLSA X and we remain on track to report results from this cohort midyear.

As a reminder, oasis is a dose escalating study to explore a broad range of doses to take into a phase two b clinical trial.

George Lasezkay: Based on the positive safety profile to date and input from our scientific and clinical advisors, we are planning to add a fourth cohort in this trial. Prior to moving forward with a higher dose in Cohort 4, we will review the preliminary one-month safety data from Cohort 3. Unless we see dose-limiting toxicities, we plan to initiate Cohort 4 promptly after the safety data review, at a higher dose than we used in Cohort 3. We expect both of these events to occur in the second quarter.

Based on the positive safety profile to date and input from our scientific and clinical advisors. We are planning to add a fourth cohort in this trial.

Prior to moving forward with a higher dose in cohort four we will review the preliminary one month safety data from cohort three.

Unless we see dose limiting toxicities, we plan to initiate cohort four promptly after the safety data reviews at a higher dose than we used in cohort three.

We expect both of these events to occur in the second quarter, because we will be conducting cohorts three and four and an overlapping schedule. We expect to complete the entire Oasis study and begin recruiting a larger phase two b clinical trial by the end of this year.

George Lasezkay: Because we will be conducting Cohorts 3 and 4 in an overlapping schedule, we expect to complete the entire OASIS study and begin recruiting a larger Phase 2B clinical trial by the end of this year. I also want to highlight that our gene therapy and oncology partners have made tremendous strides in their supercoital clinical trials. Our gene therapy collaborator, Regenexx Bio, continues to advance their two Phase II clinical trials with their asset, RGX314, delivered suprachoroidally with our SVS microinjector in patients with wet AMD and diabetic retinopathy.

I also want to highlight that our gene therapy and oncology partners have made tremendous strides in their supercoil clinical trials.

Our gene therapy collaborator rejects bio continues to advance their two phase II clinical trials with their asset RG X 314, deliberate supercool widely with our S. T S micro injector in patients with wet AMD and diabetic retinopathy.

George Lasezkay: Last month, Regenexx Bio reported positive interim data in patients with diabetic retinopathy, reporting that RGX314 continues to be well tolerated at six months, with nearly 50% of patients demonstrating a two or more step improvement from baseline compared to 0% of patients in the observational control. We look forward to additional data from both their wet AMD and diabetic retinopathy trials later this year. Our ophthalmology-oncology partner, Oura Biosciences, is utilizing our SES microinjector to deliver their viral-like drug conjugate, AU011, for the treatment of choroidal melanoma, the most common intraocular tumor in adults.

Last month, Regenesis bio reported positive interim data in patients with diabetic retinopathy reporting that RG X 314 continues to be well tolerated at six months with nearly 50% of patients demonstrating a two or more step improvement from baseline compare compared to zero percent of patients.

In the observational control.

We look forward to additional data from both their wet AMD and diabetic retinopathy trials later this year.

Our ophthalmology, our ophthalmology oncology partner or a biosciences is utilizing our SCS microinjection to deliver their viral like drug conjugate a 011 for the treatment of choroidal melanoma. The most common intraocular tumor in adults.

George Lasezkay: We expect Aura to disclose more data from its current supercoroidal clinical trials later this year. To date, we have presented and published promising pre-clinical data on our gene therapy program. And we are excited about the potential of our Super Corridor Injection Platform for both viral and non-viral gene therapy. Gene therapy remains an extremely promising approach to treating retinal disease, and the use of our proprietary SES microinjector offers the potential to deliver a variety of gene therapy constructs supercoroidally through a non-invasive, in-office procedure for the potential treatment of several ocular diseases.

We expect aura to disclose more data from their current Super Corrado clinical trials later this year.

To date, we have presented and published promising preclinical data on our gene therapy programs and we are excited about the potential of our Super colloidal injection platform for both viral and non viral vectors.

Gene therapy remains an extremely promising approach to treating retinal disease and the use of our S. Proprietary SCS micro injector offers the potential to deliver a variety of gene therapy construct supercoil, Italy through a noninvasive in office procedure for the potential treatment of several ocular diseases.

George Lasezkay: We believe that companies with specific gene therapy expertise will be able to advance these programs more rapidly. Therefore, in keeping with our strategic approach to focus on small molecule suspensions, we have decided to consider additional development and commercialization partners for gene therapy. Outside of the specific indications licensed to Regenexx Bio, we are in a position to partner with other companies working on gene therapy using non-viral vectors for any retinal disorder or viral vectors targeting inherited retinal disorders or retinal diseases that are not primarily treated with current anti-VEGF standard-of-care therapies such as geographic action. I will now turn over the call to Dr. Tom Chula, our Chief Medical Officer and Chief Development Officer, to discuss our clinical development programs and provide more detail around the data disclosed by our partners. Tom?

We believe the companies with specific gene therapy expertise, we'll be able to advance these programs more rapidly.

Therefore in keeping with our strategic approach to focus on small molecule suspensions, we have decided to consider additional development and commercialization partners for gene therapy.

Outside of the specific indications license to Regenesis bio we are in a position to partner with other companies working on gene therapy, using non viral vectors for any retinal disorder or viral vectors targeting inherited retinal disorders or retinal diseases that are not primarily treated with current anti VEGF standard of care.

Therapies, such as geographic atrophy.

I will now turn over the call to Dr. Tom Ciulla, our Chief Medical Officer, and Chief Development Officer to discuss our clinical development programs and provide more detail around the data disclosed by our partners.

<unk>.

Dr. Thomas Chula: Thank you, George, and good afternoon, everyone. I'd like to begin by saying that as a retina physician, I believe we have truly redefined the treatment of retinal disease. Clearside studied the supracortal space, developed the SCS microinjector device to offer unprecedented access to the back of the eye, achieved the first approval of a therapy delivered to the supracortal space, and, with our partners, developed therapeutics for supracortal delivery are being studied in multiple indications.

Thank you George and good afternoon, everyone.

Like to begin by saying that as a retina position I believe we have a true we are truly redefine the treatment of retinal diseases clear sight studied the supercars will things develop the SCS microinjection device to offer unprecedented access to the back of the eye achieved.

Let's see the first approval of a therapy delivered to the supercargo space and with our partners develop therapeutics cause supercritical living.

<unk> studied in multiple indications.

Dr. Thomas Chula: At the forefront of our accomplishments is Xipyr, the first FDA-approved product for supracortal administration. This is the first and only therapy for macular edema associated with uveitis, and we are proud to have developed an innovative treatment option for patients suffering from this serious and potentially blinding disease. Since Xypyr approval in October, we've been working very closely with Bausch & Lomb to support their commercial and medical affairs teams on Xypyr and the FCS microinjectors. Bausch's focus on educating U.S. retina specialists on the platform and training them on the injection procedure as part of their extensive product launch program. And Xipir is just the beginning.

At the forefront of our accomplishments and ZIP here the first FDA approved product for Supercoil administration. This.

This is the first and only therapy for macular edema associated with uveitis and we are proud to have developed an innovative treatment option for patients suffering from the serious and potentially blinding disease.

Since <unk> approval in October we've been working very closely with Bausch and lomb to support the commercial and medical affairs teams on site here in the S. Yes, Michael injector Bausch is focus on educating youth retina specialists on the platform and training them on the injection procedure as part of their extensive product launch program.

And dive here is just the beginning we've shown in preclinical models of small molecule suspensions are durable when delivered into the supercritical space. In addition to try and sell on a seat night, we've tested exiting at a complement inhibitor and a plasma caliban inhibitor that have also shown durable drug levels in the RPE choroid sclera.

Dr. Thomas Chula: We've shown in preclinical models that small-molecule suspensions are durable when delivered into the supracortial stage. In addition to trimelonacetanide, we've tested exitinib, a complement inhibitor, and a plasmacalcine inhibitor that have also shown durable drug levels in the RPE chloride sclera at 1,000 times higher than the respective in vitro IC50, standard use to describe the half-maximal inhibitory concentration. Our current lead development asset is a proprietary suspension of exitinib, a small molecule suspension that we have formulated for supercoil delivery.

At 1000 times higher than their respected in vitro IC 50, a standard used to describe the half maximal inhibitory concentration.

Our current lead development asset is our proprietary suspension of exiting a small molecule suspension that we have formulated for supercoil delivering well.

Dr. Thomas Chula: We made steady progress in our CLSAx program last year, and our efforts are continuing in 2022. As a reminder, CLSA-X combines the potential benefits of a pan-VEGF inhibitor with the targeting, compartmentalization, and durability of supracoidal delivery. Excitinib is a highly potent tyrosine kinase inhibitor and is shown to effectively inhibit corneal, retinal, and choroidal angiogenesis in numerous animal models.

We made steady progress in our CLS Ax program last year and our efforts are continuing in 2022.

As a reminder, CLSA X combines the potential benefits of our Panther GF inhibitor with a targeting compartmentalization and durability of supermodel delivering.

Exit and it is a highly potent tyrosine kinase inhibitor and is shown to effectively inhibit corneal retinal and choroidal angiogenesis in numerous animal models. We believe that Supercoil administration may further leverage these potential benefits of exit NIM by more directly targeting the affected retinal and choroidal tissues.

Dr. Thomas Chula: We believe that supracortial administration may further leverage these potential benefits of excitinib by more directly targeting the affected retinal and corital tissue. In December, we reported safety and tolerability data from Cohort 2, as well as the combined data on Cohorts 1 and 2 from our ongoing Phase 1-2a clinical trial with CLSA-X, entitled OASIS-2. OASIS is a multi-center, open-label study to establish the safety and tolerability of escalating doses of CLSA-X administered by supracortal injection in patients suffering from 1AMD.

In December we reported safety and Tolerability data from cohort two as well as the combined data on cohorts, one and two from our ongoing phase one to a clinical trial with CLSA ex entitled Oasis.

Our latest is a multicenter open label study to establish the safety and Tolerability of escalating doses of CLS ax administered by <unk> injection in patients suffering from wet AMD.

Dr. Thomas Chula: The primary endpoint for the trial is to assess safety and tolerability for three months following supercoronal administration of CLS-AS. To date, the primary endpoints have been met in Cohorts 1 and 2 of OASIS. CLSA-X was well-tolerated with no serious adverse events. There were no treatment of emergent adverse events related to a Fliverset, CLSA-X, or the supracorridor injection procedure, and there was no dispersion of drug into the vit- In addition, there were no adverse events related to intraocular pressure, inflammation, or vasculitis.

Primary endpoint for the trial is to assess safety and Tolerability for three months falling supercritical administration of CLS Ax.

Today, the primary endpoints Heather net in cohorts, one and two of Oasis.

Let's say accent, well tolerated with no serious adverse events there were no treatment emergent adverse events related to our whoever set CLSA X when a super choroidal injection procedure.

And there was no dispersion of drug into the vitreous. In addition, there were no adverse events related to inter ocular pressure inflammation of vasculitis.

Dr. Thomas Chula: In cohort 2, 5 patients were enrolled at a dose of 0.1 mg; all were heavily treatment-experienced with numerous injections of standard-of-care anti-VEGF treatments prior to entering the OASIS trial. At 3 months post-CLS-AX dosing, one patient did not require any retreatment, and one other patient was retreated per protocol-defined retreatment criteria. Two patients were treated at month two, and one patient was treated at month one. However, based on independent reading center assessment, the protocol-defined retreatment criteria were not met in these three patients.

In cohort two five patients were enrolled at a dose of 0.1 milligrams.

All were heavily treatment experienced with numerous injections of standard of care anti VEGF treatments prior to entering in the Oasis trial.

At three months post CLSA ex dosing, one patient did not require any recruitment.

And one other patient was treated per protocol defined recruitment criteria.

Two patients were treated at month true and one patient was treated at month, one although based on independent Reading Center assessment. The protocol defined recruitment criteria were not met in these three patients.

Dr. Thomas Chula: In combined cohorts 1 and 2, 11 patients were enrolled, and all were heavily treatment experienced prior to entering the OASIS trial. The mean best corrected visual acuity score and the mean change in central subfield thickness of the macula were stable in the combined cohort.

And the combined cohorts, one and 211 patients were enrolled and all were heavily treatment experienced prior to entering the Oasis trial.

The mean best corrected visual acuity score and the mean change in central subfield thickness of the macula, we're stable and the combined cohorts. We also saw promising signs of durability and this early part of the study in.

Dr. Thomas Chula: We also saw promising signs of durability in this early part of the study. In particular, four patients, or 36% of the total, went at least three months post-CLS-AX dosing without retreatment. Six patients, or 55% of the total, went two months without re-treatment, and one patient, or 9% of the total, was re-treated at month one. As George mentioned, we've made progress with cohort three of the trial. As a reminder, we've established stringent criteria in our protocol for patient enrollment.

In particular for patients or 36% of the total when at least three months post CLSA ex dosing without re treatment.

Six patients or 35% of the total when two months without re treatment and one patient or 9% of the total was retreated at month one.

As George mentioned, we've made progress with cohort three of the trial as a reminder, we've established stringent criteria in our protocol for patient enrollment. Unlike similar trials ongoing in the wet AMD space assessing teekay is a tyrosine kinase inhibitors, we are only enrolling treatment experienced patients with active disease based.

Dr. Thomas Chula: Unlike similar trials ongoing in the wet AMD space assessing TKIs or tyrosine kinase inhibitors, we are only enrolling treatment experience patients with active disease based on reading center confirmation. We remain on track to report results from Cohort 3 midyear. We also plan to add cohort for it to explore a blood range of doses to evaluate in a phase 2B trial. This decision was based on input from our scientific and clinical advisors, combined with the positive safety results, with no dose-limiting toxicities in cohorts 1 and 2.

On reading center confirmation.

We remain on track to report results from cohort three midyear.

We also plan to add cohort four to explore a blog range of doses to evaluate in our phase two b trial.

This decision was based on input from our scientific and clinical advisors combined with a positive safety results with no dose limiting toxicities in cohorts, one and two.

Dr. Thomas Chula: Prior to moving forward with the higher dose in Cohort 4, we will review the preliminary one-month safety data from Cohort 3. Unless we see dose limiting toxicities, we plan to initiate cohort 4 at a higher dose. We expect this data review and initiation of Cohort 4 to occur in the second quarter of this year, and therefore Cohorts 3 and 4 will overlap. We expect to report data from Cohort 4 later this year.

Prior to moving forward with a higher dose in cohort four will review the preliminary one months safety data from cohort three and.

Lessons think dose limiting toxicity, we plan to initiate cohort four at a higher dose. We expect this data review and initiation of cohort four to a court to occur in the second quarter of this year, and therefore cohort three and four overlap.

We expect to report data from cohort four later this year.

Dr. Thomas Chula: We've begun planning for our Phase 2b clinical trial, and we are targeting to open enrollment for this trial by the end of the year. We've also been working on another small molecule program utilizing supercoital administration of an integrin inhibitor suspension, which we are referring to as CLS 301. Integrins play a role in pathogenic processes such as inflammation, angiogenesis, and fibrosis.

We've begun planning for our phase two b clinical trial, and we are targeting to open opening enrollment for this trial by the end of the year.

We've also been working on another small molecule program utilizing Super quarterly administration of an integrant inhibitor suspension, which.

Which we are referring to as CLS 301.

Two things play a role in pathogenic processes, such as inflammation angiogenesis in fibrosis, we believe an integral inhibition may play a role in the treatment of certain diseases, including diabetic macular edema and macular degeneration.

Dr. Thomas Chula: We believe that integrin inhibition may play a role in the treatment of certain diseases, including diabetic macular edema and macular degeneration. We believe that intracranial inhibition could potentially serve as primary therapy, adjunctive therapy to anti-MHF agents, or secondary therapy in refractory cases of diabetic macular edema and macular degeneration. Supercoidal delivery of an integrin inhibitor suspension could provide targeting, compartmentalization, and durability advantages over topical individual delivery, similar to what we've observed in other preclinical studies of small molecule suspension.

We believe that integrating inhibition could potentially serve as a primary therapy of dunker pair of eating into the destinations or secondary therapy refractory cases of diabetic macular edema and macular generation.

Cornell delivery of an integrant inhibitor suspension could provide targeting compartmentalization and durability advantages over topical individual delivering similar to what we've observed in other preclinical studies of small molecule suspensions.

Dr. Thomas Chula: Therefore, we are assessing ocular tolerability, distribution, and pharmacokinetics of our intricate inhibitor supracortial suspension. Our initial preclinical data has shown that the agent is well-tolerated with favorable ocular distribution targeting the corneal retina, and we've seen encouraging initial signs of durability. We are optimizing the formulation and expect to start a second preclinical study soon. We expect to have results from this study in the second half of this year. Moving now to our partner program.

Therefore, we are assessing ocular tolerability distribution in pharmacokinetics of our integrin inhibitor supercritical suspension. Our initial preclinical data has shown that the agent is well tolerated with favorable ocular distribution targeting the corio retina and we've seen encouraging initial signs of durability.

We're optimizing our formulation and expect to start a second preclinical studies soon we can.

Expect to have results from this study in the second half of this year.

Moving now to our partner programs 2021 with them clinically impactful year for our Super quite a delivery platform as the first ever data was presented in both gene therapy and ocular oncology.

Dr. Thomas Chula: 2021 was a clinically impactful year for our supercoital delivery platform as the first ever data were presented in both gene therapy and ocular oncology. Furthermore, both of our development partners, Regenexx Bio and Aura Biosciences, have reported promising results from several trials using our SES microinjector to deliver their product candidates into the supracortal space.

Both of our development partners mechanics file an aura biosciences have reported promising results from several trial using our SCS microinjection to deliver their product candidates into the supercargo space.

I'll start with orogenic style.

Dr. Thomas Chula: We're not only excited about the promising early results from their GenX bioprials, but also the fact that supracortial injection may offer these patients the option for one-time gene therapy treatment with a simple in-office injection. Regenexx Bio is running two multi-center, open-label, randomized-control dose-escalation studies evaluating the efficacy, safety, and tolerability of supercoil delivery of RGX314. Importantly, patients in these trials do not receive prophylactic immunosuppressive corticosteroid therapy before or after administration of RGX314.

We're not only excited about the promising early results from their tax pilot trial, but also the fact that supercritical injection may offer these patients the option for onetime gene therapy treatment with the simple in office injection.

Which Alex bile is running two multi center open label randomized controlled dose escalation studies evaluating the efficacy safety and Tolerability of Supercoil delivery of RG X 314 importantly patients in these trials do not receive prophylactic immune suppressant corticosteroid therapy before or after administration of RG <unk>.

Spring 2014.

Dr. Thomas Chula: As reported in November for the ADA trial for the treatment of patients with wet AMD, supracortial delivery of RGX314 continues to be well-tolerated, and positive interim efficacy data was reported at six months for cohorts 1, 2, and 3. Last week, Regenexx Bio updated the enrollment status for AV8. Enrollment is complete in Cohort 4 and expected to be completed in Cohort 5 in the first half of 2022. Cohort 3 and Cohort 5 are evaluating RGX314 in patients who are neutralizing antibody positive.

As reported in November for the <unk> trial for the treatment of patients with wet AMD simple portal delivery of Rdx 314 continues to be well tolerated and positive interim efficacy data was reported at six months for cohorts, one two and three.

Last week <unk> by an update on the enrollment status for 88 enrollment is complete in cohort four and expected to be completed in cohort five in the first half of 2022 .

Heart rate in cohort five are evaluating RG extra 14th in patients who are who are neutralizing antibody positive.

Dr. Thomas Chula: In addition, last month at the Endogenesis Conference, Regenexx Bio updated their positive interim data from the Phase 2 Altitude Trial in patients with diabetic retinopathy and reported the following from Cohort 1 at six months. Supercoil delivery of RGXV-14 was well-tolerated in 15 patients with no drug-related serious adverse events and no intraocular inflammation observed. And importantly, 47 percent of patients demonstrated a two or more step improvement from baseline on standardized diabetic retinopathy severity scale at six months, compared to 0% of the patients in the observational control.

In addition last month at the end of Genesis Conference Mechanics filed updated their positive interim data from the phase two alpha two trial in patients with diabetic retinopathy and reported the following from cohort one at six months.

Dr. Thomas Chula: This is an increase from 33% of patients at the three month time. Enrollment is expected to be completed in the Altitude Trial in the first half of 2022 for Cohorts 2 and 3. Cohort 3 is evaluating RGX314 in patients who are neutralizing antibody positive.

Super quite unpleasant Archie X report 14 was well tolerated 15 patients with no drug related serious adverse events and no intra ocular inflammation observed.

And importantly, 47% of patients demonstrated a tour more step improvement from baseline on standardized diabetic retinopathy severity scale at six months.

<unk> zero percent of the patients in the observational control.

This is an increase from 33% of patients at the three month time point.

Enrollment is expected to be completed in the altitude trial in the first half of 2022 for cohorts two and three.

Cohort three is evaluating <unk> hundred 14, and pacing to a neutralizing antibody positive.

Dr. Thomas Chula: In addition, our partner, Oro Biosciences, presented the first set of data utilizing supercoital delivery to treat coital melanoma, the most common primary ocular cancer in adults. ORRA reported their interim Phase 2 safety data for AU011 delivered via our SES microinjector. The data showed a favorable safety and tolerability profile with no treatment-related serious adverse events, dose-limiting toxicities, or grades 3-4 adverse events. We expect ORCA to disclose more data from its current supercoital clinical trials later this year.

In addition, our partner Aura Biosciences presented the first set of data utilizing supercritical delivering to treat portal melanoma. The most common primary ocular cancer in adults.

Or reported their interim phase II safety data for <unk> 011 delivered via our SCS, Michael injector. The data showed a favorable safety and tolerability profile with no treatment related serious adverse events dose limiting toxicity or grade three four adverse events, we expect or to disclose more data from its current.

Supercritical clinical trials later this year.

Dr. Thomas Chula: The continued progress by Regenexx Bio and Aura Biosciences is very encouraging, and we look forward to their ongoing clinical trial results. 2021 was a year of extensive engagement with retina specialists, with attendance at eight medical congresses, featuring 30 presentations delivered on our supracortial injection platform and our clinical development program. Last month, I delivered a presentation entitled Supercoital Space and Supercoital Delivery for Clinicians to my physician colleagues at the Baskin-Palmer Eye Institute's Antigenesis, Exudation, and Degeneration Conference.

The continued progress biogenic bio in Aura Biosciences is very encouraging and we look forward to their ongoing clinical trial results.

2021 was a year of extensive engagement with retina specialists with attendance at medical Congresses, featuring 30 presentations delivering on our supercritical injection platform and our clinical development programs.

Last month, I delivered a presentation entitled Supercritical space and Super quite a delivering for clinicians to my physician colleagues at the Bascom Palmer Eye Institute Angiogenesis, Exudation and degeneration conference. The presentation described the preclinical and clinical data demonstrating the methodology and benefits of supercars delivery, including advantages of intervention.

Dr. Thomas Chula: The presentation described the preclinical and clinical data demonstrating the methodology and benefits of supercoital delivery, including advantages over intervictal delivery, the durability potential of small molecule suspensions, and the possible suitability of supercoital delivery for gene therapy.

Delivering the durability potential of small molecule suspensions and the possible suitability of supercritical delivering for gene therapy.

Dr. Thomas Chula: We plan to continue this momentum in 2022 as we engage and educate the retina community. I look forward to keeping you updated on our clinical progress this year. I will now turn the call over to our CFO, Charlie Deignan, to review our financial results. Charlie.

We plan to continue this momentum in 2022, as we engage and educate the retina community.

I look forward to keeping you updated on our clinical progress this year.

I'll now turn the call over to our CFO , Charlie Deignan to review our financial results.

Thank you Tom.

Charlie Deignan: Thank you, Tom. As George and Tom mentioned, Zypere's approval has had a broad impact on our company. Our financial results for the fourth quarter and full year were published this afternoon in our press release and are available on our website.

As George and Tom mentioned does that appears approval has has had a broad impact on our company our financial results for the fourth quarter and full year were published this afternoon in our press release and are available on our website. Therefore, I will summarize our current financial status.

Charlie Deignan: Therefore, I will summarize our current financial status. Our progress over the course of last year significantly strengthened our balance sheet with non-deletable funds. In 2021, we generated nearly $30 million in revenue, primarily from Zypier development and approval-related milestones. From Bausch and Lomb, we recorded a total of 20 million of revenues in 2021 related to milestones, including the recognition of the previously deferred revenue of $5 million from their upfront payment. On a cash basis, $5 million was received in 2021, and $10 million was received in quarter one 2022.

Over the course of last year significantly strength strengthened.

We strengthened our balance sheet with non dilutive funding in.

In 2020 , one we generated nearly $30 million in revenue, primarily from Zach peer development approval and approval related milestones.

From Bausch and Lomb, we recorded a total of $20 million of revenues in 2021 related to milestones, including the recognition of the previously deferred revenue of $5 million from their upfront payment.

On a cash basis 5 million was received in 2021 and $10 million was received in quarter one 2022.

Charlie Deignan: From our division, we received a total of approximately $9 million in 2021 based on the approval of XIPIR, their Phase III trial initiation in China, and the expansion of their licensed territory. Therefore, our cash-in-cash equivalence as of December 31, 2021 totals approximately $30 million.

So market vision, we received a total of approximately $9 million in 2020 one based on the approval of ZIP here their phase III trial initiation in China and the expansion of their license.

Territory.

Charlie Deignan: As a reminder, this does not include the $10 million, we received in the first quarter of 2022 from Bausch and Lomb related to the Ziphyr mouse. This additional capital will be utilized to advance our clinical development pipeline, led by CLSA. In 2022, our cash burn will focus on funding our current operations and plan spend on our broader research pipeline. And we expect to have sufficient resources to fund our operations into the second quarter of 2023.

Therefore, our cash and cash equivalents as of December 31, 2021 totaled approximately $30 million. As a reminder, this does not include the $10 million.

We received.

In first quarter of 2022 from Bausch and lomb related to the Zackfia milestone.

This additional capital will be utilized to advance our clinical development pipeline led by CLSA acts in 2022 our cash burn will focus on funding our current operations and planned spend on our broader research pipeline and.

And we expect to have sufficient resources to fund our operations into the second quarter of 2023.

Charlie Deignan: We remain very active in the investment community with participation in the healthcare conference earlier this week, and we look forward to joining the upcoming Roth and Medium conferences as well. We greatly appreciate the interest and support from all of our stakeholders as we obtained our first FDA approval last year, and we look forward to advancing our supracorridor injection platform in 2022. I will now turn the call back over to George for his closing remarks.

We remain very active in the investment community with participation.

In the health care Cowen Health Care Conference earlier, this week and we look forward to joining the upcoming Roth and Needham conferences as well we greatly appreciate the interest and support from all of our stakeholders as we obtained our first FDA approval last year, and we look forward to advancing our Super Choroidal injection platform in 2022, I will now turn the call back over to George for his closing.

<unk> remarks.

George Lasezkay: Thank you, Charlie. Clearside is revolutionizing the delivery of therapies to the back of the eye through the supracrital space. Our supracarotidal injection platform is a novel, patented approach for ocular drug delivery that offers numerous advantages over other types of administration. And now, with our first drug approved for supracarotidal administration and well over 1,200 clinical supracarotidal injections to date, we have validated the clinical utility of this innovative technology and demonstrated our leadership in this increasingly important space.

Thank you Charlie.

Clear sight as revolutionary revolutionizing the delivery of therapies to the back of the eye through the Super parental space.

Our Super Choroidal injection platform is a novel patented approach for ocular drug delivery that offers numerous advantages over other types of administration.

And now with our first drug approved for Super Choroidal administration, and well over 1200 clinical Supercoil injections to date, we have validated the clinical utility of this innovative technology and demonstrated our leadership in this increasingly important space.

George Lasezkay: But our work does not stop there. In conjunction with our partners, there are currently six ongoing clinical trials targeting multiple indications. We continue to advance CLSAx and expect to complete our OASIS trial this year, and we look forward to additional progress and data readouts from all of our development and commercialization partners throughout the year. Last week, we were also pleased to announce that Dr. Ben Yerxa has joined our Board of Directors. Ben was an initial founder of Clearside, and as the current CEO of Foundation Fighting Blindness, he brings deep scientific ophthalmic research and clinical development expertise to our board.

But our work does not stop there.

In conjunction with our partners. There are currently six ongoing clinical trials targeting multiple indications, we continued to advance CLSA X and expect to complete our Oasis trial this year and.

And we look forward to additional progress and data readouts from all of our development and commercialization partners throughout the year.

Last week, we were also pleased to announce the Doctor been Yerxa has joined our board of Directors. Then was an initial founder of clear side and as the current CEO of foundation fighting blindness blindness. He brings deep scientific ophthalmic research and clinical development expertise to our board.

George Lasezkay: He has a unique perspective on patient needs, the global retina disease treatment landscape, and our technology. We look forward to leveraging his expertise as we advance Clearside's internal pipeline and external strategic collaboration. In closing, I would like to thank all of our stakeholders, including the Clearside team, shareholders, and clinical investigators whose broad support helped us accomplish several major milestones last year. We are excited about the future and inspired to bring additional therapies to patients with faith-threatening diseases. I would now like to ask the operator to open the call up for questions. Thank you, sir.

He has a unique perspective on patient needs the global retina disease treatment landscape and our technology.

We look forward to leveraging his expertise as we advance clear sight internal pipeline and external strategic collaborations.

In closing I would like to thank all of our stakeholders, including the clear side team.

Our shareholders.

And clinical investigators who have broad support helped us accomplish several major milestones last year.

We are excited about the future and inspired to bring additional therapies to patients with sight threatening diseases.

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

Operator: We will now begin the question and answer session. As a reminder, to ask a question, you will need to press star 1 on your telephone. Again, that's star 1 on your telephone keypad.

Thank you Sir we will now begin the question and answer session. As a reminder to ask a question you will need to press star one on your telephone again, that's star one on your telephone keypad. However, if your question has been answered or you wish to withdraw from the queue. Please press the pankey standby really compile the Q&A roster.

Operator: However, if your question has been answered and you wish to withdraw from the queue, please press the PAN key. Standby while we compile the Q&A roster. Your first question is from Annabel Samimy with CFO, your line is open. Hi.

Your first question is from animal so meaning with Stifel. Your line is open.

Annabel Samimy: Thanks for taking my question. I just want to get a little bit more color around the decision to add the fourth cohort to CLSAx and how, at this point, you're going to choose the upper limit. So, in terms of the feedback you've gotten from your advisors, was it something that they saw in other exigentive trials? Is it strictly driven by safety? And should we read anything into this decision about it being a question of efficacy or duration that you're seeing in the first cohort? So, just a little color behind that decision would be great.

Hi, Thanks for taking my question.

Just want to.

Get a little bit more color around the decision to add a fourth cohort of CLS ax.

And how at this point youre going to choose the upper limit. So in terms of the feedback you've gotten from your advisors was.

Was it something that they that doesn't that it's on other ex switching if trials is it strictly driven by safety.

And should we read anything into this decision about it being a question of efficacy of duration that youre seeing in the first cohort. So just a little color behind that decision would be great. Thank you and then.

I'll follow up after that.

George Lasezkay: Thank you. And then I'll follow up with a second after that. Okay, well, thanks, Annabel, for the questions. This is George.

Okay, well, thanks, Annabel for the question since George.

George Lasezkay: I'll let Tom give you the details on that, on the questions that you're asking around Cohort 4. We think this is an important move on behalf of the whole overall program, and I'll let Tom explain to you the rationale and where we are in that.

I'll, let Tom give you the details on that on the questions that you're asking around cohort four.

We think this is an important move on behalf of the whole overall program.

And I'll, let Tom explained to you the rationale and where we are in that Tom.

Dr. Thomas Chula: Sure, thanks for the question. You basically shouldn't; I won't read too much into this. Since we haven't seen any dose-limiting toxicities to date, we wanted to explore the broadest range of doses that would be most effective, as we consider Phase 2B and the take-in to Phase 2B. Given the positive safety profile in Cohorts 1 and 2, and, as you alluded to, the input from our scientific and clinical advisors, we simply decided to add a fourth cohort to continue the dose escalation. And we're going to do this while we continue to evaluate the cohort 3 dose. So there'll be an overlapping schedule, I think, as George mentioned.

Sure. Thanks for the question you basically said.

Read too much into this.

Since we haven't seen any dose limiting toxicities to date.

We wanted to explore the broadest range of doses that would be most effective as we consider.

Phase two b and to take into phase two.

Given the positive safety profile in cohorts, one and two and and as you alluded to and input from our scientific and clinical advisors, we simply decided to add a fourth cohort to continue the dose escalation and we're going to do this while we continue to evaluate the cohort three.

So there'll be an overlapping a schedule I think as George mentioned.

Dr. Thomas Chula: You know, throughout the process of initiating and conducting OASIS, we've highlighted that there is room to escalate dose levels further if we believe it's appropriate. We believe the FDA and IRB is supportive of a wider range of doses, based on our preclinical toxicity data. And as I allude to, the decision is not based on any information from cohort three. We're still enrolling in dosing patients in cohort three. Okay, got it.

You know throughout the processes of initiating and conducting awakedness. We've highlighted that there is room to escalate dose levels. Further if we believe it's appropriate.

We believe the F D a to IRB supportive of a broader range of doses.

Based on our preclinical toxicity data and as I alluded to the decision is not based on any information from cohort three we're still enrolling and dosing patients in cohort three.

George Lasezkay: And then just the bigger picture, as far as the wet AMD landscape is concerned, I guess there's quite a bit of development in what AMD is doing, a number of programs in pan-VEGF, there's bi-specific antibodies, gene therapy. So, how do you see this market by focusing on who's appropriate for VEGF treatment versus gene therapy, and do you have any sense as to how things might break down, assuming that these are successful? Yeah, that's a great question as well.

Okay got it.

And then just bigger picture as far as the wet AMD landscape is concerned.

I guess, there's quite a bit of development, and then and what AMD a number of programs in Pan VEGF Bispecific antibodies gene therapy. So.

How do you see this market bifurcate in.

Tween who's.

So it is appropriate for vent that J F Pan VEGF treatment versus gene therapy, and do you have any sense as to how things might breakdown I'm assuming that these are successful.

Yeah, that's a great question as well.

Dr. Thomas Chula: You know, there's been some major failures and commercial issues with WED-AMD treatment lately, and, You know, if you'd asked me a few years ago, I wouldn't have predicted some of these. So, it's hard to predict going forward, but I think that what we have is differentiated from many of the therapies out there because Japan VEGF inhibition has the potential to show better efficacy. Excitinib is a small molecule, and we expect it to continue to be very safe with less potential for an immune response like you'd see with a biologic or a gene therapy.

You know theres been some.

Some major.

Failures and commercial issues with.

Wet AMD treatments.

Lately and.

You know if you had asked me a few years ago I wouldn't have predicted some of these.

So it's hard to.

Predict going forward, but.

I think that what we have is differentiated from many of the therapies out there because.

Pan VEGF inhibition has potential to show better efficacy.

<unk>.

It's sitting in a small molecule and we expect it to be to continue to be very safe.

With less potential for an immune response like you'd see with a biologic or a gene therapy.

Dr. Thomas Chula: We also think that supercortical delivery will leverage some of these features even further because we can target the affected core retinal tissues and get very rapidly high levels that may potentiate efficacy. We can compartmentalize the treatment away from the front of the eye to potentially enhance safety.

We also think that supercritical delivery.

We will leverage some of these features even further because we can target the affected core reputation you can get a.

Very rapidly high levels that may potentially efficacy.

We can compartmentalize away from the front of the eye to potentially.

Dr. Thomas Chula: And we know from our preclinical studies that we have potential for many months of durability. So I think overall, Going forward, our therapy is very differentiated, not only as a mechanism of action being hand-to-jab, but also because of the potential safety benefits being a small molecule, less potential for immune response, and of course, supercortical delivery with the potential for the targeting compartmentalization and durability. So, you know, ultimately it could be used, you know, as maintenance therapy in patients who have ongoing established therapy.

Enhance safety.

And.

We know from our preclinical studies that we have potential for many months of durability. So.

I think overall.

Going forward, our therapies is very differentiated.

Not only as a mechanism of action being Tien <unk> Jeff.

But also because of the potential safety benefits being a small molecule less potential for immune response and of course soup supercoil, delivering but with the potential for the targeting compartmentalization and durability benefits. So.

Ultimately it could be used.

As maintenance therapy in patients who have <unk>.

Ongoing established therapy.

Dr. Thomas Chula: It could potentially be used for patients who are somewhat refractory to current anti-FHFA-focused therapy, and it could even be used as primary monotherapy. And, you know, we're still obviously sorting that out with this dose escalation study. As far as gene therapy is concerned, is there a population that would be more appropriate for gene therapy versus just traditional therapy?

It could be potentially used as for patients who are somewhat refractory to current.

Anti VEGF, a focus therapy and it could even be used as primary monotherapy in <unk>.

We're still obviously sorting that out with this dose escalation study.

Got it and as far as gene therapy is there a population that would be more appropriate for gene therapy versus just traditional.

Sure.

Dr. Thomas Chula: and SETREP therapy. Well, you know, I think some of the inclusion and exclusion criteria from some of the gene therapy, programs are somewhat telling because, you know, patients have to be treatment responsive to current therapy. And so, and potentially, you know, So, the ideal patient for gene therapy would be a patient that, as I mentioned, you know, is responsive to current therapy and is highly dependent. Supercoroidal CLSAX, potentially could serve that role with its durability, but there's potential for a broader role because of the pan-VEGF inhibition, that it may, you know, as I mentioned, have, better efficacy.

Such a therapy.

Well I think.

Some of the inclusion and exclusion criteria for from some of the gene therapy.

Our programs are somewhat telling because pace.

Patients have to be treatment responsive to current therapy.

And so.

And potentially.

Shipment dependent so so the ideal patient for a gene therapy would be a patient death.

As I mentioned you know.

Is responsive to current therapy, and it's highly dependent.

Super Choroidal CLSA X.

Candidly could serve that role with it but there's durability, but there's potential for a broader role because of the pan VEGF inhibition that it may.

As I mentioned have better efficacy it may be used for treatment of refractory patients.

Dr. Thomas Chula: It may be used for treatment-refractory patients, and the durability has the potential to be quite attractive. We think that having dosing somewhere between three and six months intervals is consistent with the Current Practice Model and Retina Specialist Practice, and we even think that our therapy could potentially be, you know, adjuncted to patients who have undergone gene therapy and have breakthroughs, for example. That's about it.

And the durability.

<unk> has potential to be quite.

Yes.

We think that having a dosing somewhere between the three and six months.

Intervals.

Is consistent with.

The current practice model and retina specialists practice.

And we even think that.

Arthur if he could potentially D adjunct to patients who have undergone.

Gene therapy have breakthrough for example.

Got it great. Thank you.

Operator: Your next question is from Andreas Argyrides with Redbush. Your line is open. Good afternoon, and thanks for taking our questions. I have a couple here.

Your next question is from Andres argue readers with Wedbush. Your line is open.

Good afternoon, and thanks for taking our questions I have.

Andreas Argyrides: So to start, with phase 2b in planning, does that suggest you're getting close to finding a go-ahead dose, or is there a possibility of adding a fifth cohort if safety is positive and you can potentially maximize efficacy? And then, with the details, what details of the design of phase 2b can you share at this moment?

A couple of here. So just start with the phase II B implanting does that suggest you're getting close to finding a go ahead dose or is there a possibility of adding a fifth cohort if safety.

It was positive and you can potentially maximize efficacy and then with the detail what details of the design of the phase two b.

Can you share it.

At this moment and then lastly.

Andreas Argyrides: And then lastly, do you also plan to present data from the extension study at the same time you present cohort three results? Thanks. Tom, I think you can take all of those questions right up here. Okay. Sorry, Tom. If you can't, I will, but I think you can do that.

Do you also plan to present data from the extension study at the same time you present cohort three results. Thanks.

Tom I think you can take all of those questions.

Okay.

Sorry, Tom.

If you can't I will but I think you can push back.

Dr. Thomas Chula: Well, I think you asked about dosing. So, you know, we have, as I mentioned, we want to have the broadest range of possible doses. And if you recall, we started at 0.01.

Well I think you asked about the dosing so you know.

We have as Ed mentioned, we want to have the broadest range of possible doses and if you recall, we started at zero point Jerald one.

Dr. Thomas Chula: Thank you. So, we've actually escalated, you know, quite meaningfully already and even higher in cohort four. And we expect to see a, you know, some biologic response. We expect that cohort three or cohort four dosing, one or the other would be what we would potentially use in a phase two B. So, we don't anticipate adding a fifth cohort at this point. I think your next question was a little bit about the Phase 2b trial design, and we're still in the planning phases for that.

So we've actually escalated.

Quite meaningfully already.

Even higher in cohort four.

And we expect to see it.

Some biologic response, we expect it.

That cohort three cohort four dosing will one or the other would be what we would potentially use in our phase two b.

Study.

So we don't we don't anticipate adding a fifth cohort at this point.

I think your next question was a little bit about.

The phase two B trial design and we're still in the planning phases for that it would be premature to comment on it.

Dr. Thomas Chula: It would be premature to comment on it. And I think your final question was on extension study results, and we would plan to release the extension study results from Cohort 2 when we announce Cohort 3 data in mid-2020. Okay, great. Thanks, Tom. Your next question is from Yi Chen with HC Wainwright, your line is open. Hey, this is Chait on behalf. We just have three quick questions.

And I think your final question was on.

Extension study results and we would plan to release the.

<unk> extension study results from.

Cohort two.

When we announced cohort three data in mid 2022.

Okay, great. Thanks, Tom.

Your next question is from Chen with H C. Wainwright Your line is open.

Hey, this is a cheat on behalf of <unk>.

We just have two quick questions.

Yi Chen: So based on your initial conversations with Bosch and Lomb, any feedback from physicians? Any immediate feedback from physicians? during their educational program? Lange Plank, And the second question...

Have you seen your initial conversations with Bosch alone.

Any feedback from physicians and immediate feedback from physicians during the educational programs.

Launch plans.

And the second question is.

Yi Chen: In your OASIS study, what can we expect from cohort 3 data presentation later this year compared to the data that you've shown, and and, I'm sorry if I missed this, but do we know the potential dose that you would want to explore in cohort 4? And lastly, I know you spoke about potential licensing agreements. Are you in contact with them, or are you in discussions with them? Potential, and companies already. Thank you so much.

This study what can we expect from the cohort three data presentation later this year.

Compared to the data that you've shown so far.

And.

I'm sorry, if I missed this but do we know the potential dose that you would want to explore.

In cohort four.

And lastly.

You spoke about potential licensing agreements.

Are you doing.

Intact or are you in.

Discussions with.

Potential.

Companies already thank you so much.

George Lasezkay: Tom, do you want to comment on the first question, which had to do with the Bausch reaction and more specifically on what you've done with Bausch in terms of their training and what we know about how they intend to roll out this training and the reaction of the physicians in the training program in particular. Sure, absolutely. Great question.

Tom do you want to comment on the I think the first question has to do with the Bausch reaction and more comment specifically on what you've done with Bausch in terms of their training and.

What we know about how they intend to rollout this training.

And the reaction to the physicians in the training program and particularly sure.

Absolutely.

Great question so.

Dr. Thomas Chula: So we've been very involved with Bausch and Lomb, assisting with the development of their training program. They developed a very nice, robust program. Their goal is to train all of the retina specialists and uveitis specialists in the United States. They've adopted a train-the-trainer program, so it'll be a peer-to-peer program.

We've been very involved with with Bausch and lomb assess.

Assisting with the development of their training program.

They developed a very nice robust.

Program.

Their goal is to train all of the retina specialists and uveitis specialists in the United States.

They have adopted a train the trainer program. So it'll be a peer to peer program, though your retina specialists training other retina specialists.

Dr. Thomas Chula: The retina specialist training other retina specialists. So the Clearside team was involved, with some of these initial sessions in which... Some of the key retina-specialist trainers were trained, and that went extraordinarily well. They're very excited and positive about the training.

So.

Clear Psi team was involved.

But some of these initial sessions and which.

Some of the key trainers retina specialist trainers were trained.

And that went extraordinarily well.

We're very excited and positive about the training they feel its various sectors.

Dr. Thomas Chula: They feel it's very effective. And then they, in turn, will then train retina specialists regionally. And we've gotten very positive feedback from the program. Physicians feel that well-trained and feel quite capable of being able to administer supracortial therapies in the hospital.

And then they in turn will then train retinal specialists regionally.

And we've gotten very positive feedback from the program.

Physicians feel that.

Ah well trained and feel quite.

Quite capable of being able to administer.

Supercritical therapies in the office.

Dr. Thomas Chula: I think your second question was the formatting or the sort of results, you know, we can expect from cohort three. So, so I think the format of those results be similar to what, you know, we've we've presented previously, you know, just a reminder. This single-dose escalating study is really about safety, and that's what the focus has to be and will be. But we'll be presenting similar data sets as to what we've presented previously. I think you asked about... Go ahead, I'm sorry. No, no.

And I think your second question was the format and.

Or the sort of results, we can expect from cohort three.

So I think the format of those results with similar to what.

We presented previously just a reminder.

This single dose escalating study is really about safety.

And that's what the focus has to be it will be but we will be presenting.

Similar.

Datasets as to what we presented previously.

I think I'll stick out.

Go ahead, I'm, sorry, no no I was going to say, Tom I think the other one was.

Dr. Thomas Chula: I was going to say, Tom, I think the other one was, have we decided on a dose for COVID? Right. And we have not finalized that yet. It'll be higher than cohort three. But we have not, Thank you so much for that.

Have we decided on a dose for cohort four.

Right and we have not finalized that yet it'll be higher than cohort three.

But we have not finalized that.

<unk>.

Thank you so much for that.

George Lasezkay: The last one on potential licensing agreements, have you already started a discussion? Well, I would answer that one and I'd say, listen, we have interest from... A number of companies contact us and talk about potential licensing. So it's a regular feature of our ongoing business. I've said before that partnering going forward is not, immediately critical strategically for us. But as we also said in our remarks, for gene therapy. This is something that if we're going to go any farther in gene therapy than we've done with Regenexx Bio or our biosciences, it would have to be with a partner. That is not something we're going to focus on as part of our internal pipeline.

The last one on potential licensing agreements are you are you have you already started discussions.

What I would answer that one and I'd say listen we are we have interest from.

A number of companies contact us and talk about potential licensing.

So it's a regular feature of our ongoing business.

I've said before that partnering going forward.

Is not.

Immediately critical strategically for us, but as we also said in our remarks.

For gene therapy.

This is something that if we're going to go any farther than gene therapy than we've done with <unk> or aura biosciences.

It would have to be with a partner that is not something we're going to focus on as part of our internal pipeline.

George Lasezkay: So all I can tell you is we do have discussions from time to time and we're exploring possible relationships but it's just a matter of ongoing business like any company in our position would do. We're not, I can't make any more comments than that except that we do talk to people and we are talking to multiple people about potential collaborations. Great. Thank you so much.

So.

All I can tell you is we do have discussions.

From time to time, and we're exploring possible relationships, but it's just a matter of ongoing business like like any company in our position would would do.

We're not.

I can't make any more comments on that except that we do talk to people and we are talking to multiple people about potential collaborations.

Collaborations.

Sure.

Great. Thank you so much sure.

<unk>.

Zegby Jalaw: Sure. Your next question is from Zegby Jalaw with Roth Capital Partners, your line is open. Thank you for taking my question, and congrats on the progress. I think a lot of the questions have been asked, so I'm just going to ask a couple of cheeky ones here.

Your next question is from Zigbee July with Roth Capital Partners. Your line is open.

Thank you for taking my question and congrats on the progress I think a lot of the questions have been asked so I'm just going to ask a couple of chunky months here and I think that the first one for me. This is trying to get a good understanding of best leisure.

Zegby Jalaw: And I think the first one for me is just trying to get a good understanding of the exposure that's being achieved with the dose being used in cohort 3, meaning are you, you know, saturating your receptors with cohort 3, and could you really get much more by going higher? Well, Tom, you want to attempt to answer Zegla's question? Sure, no, that's a great question, and, There's two aspects of the dose escalation, well three, obviously safety is number one, but You know, efficacy, as you alluded to, but the other thing, the other aspect that we need to think about is, The supracortal space acts like a natural drug reservoir.

That's being achieved with the dose being used in cohort three meaning are you saturating the receptors with cohort three could you round it got much more by going higher.

Well, Tom you want to.

Tempt to ask answer Zabows question.

Sure No segment, it's a great question.

And.

There's two aspects of the dose escalation will free obviously safety is number one but.

Efficacy as he alluded to but the other thing the other aspect that that we need to think about us.

The Super portal space acts like a natural drug reservoir.

Dr. Thomas Chula: And it is possible as we escalate, you know, we may achieve, we may saturate, Inhibition of the tyrosine kinase receptors and may not be able to inhibit more but as we add more drugs, We're basically filling the reservoir further, and that has the potential to provide us more durability. So we have to look at safety, obviously, efficacy, or in this case, biologic effect in the small but also as we escalate the dose, there's potential for more and more durability.

And it is possible as we escalate.

We may achieve we may saturate.

<unk>.

Inhibition of the tyrosine kinase receptors and it may not be able to inhibit more but as we add more drug to the space, where basically filling the reservoir.

Further and that has potential to provide us more durability.

So we have to look at safety obviously.

Efficacy or in this case biologic effect and the small.

No single dose escalating study, but also as we escalate the dose with potential for more and more durability one of the.

Dr. Thomas Chula: Fascinating features of Exitinib is that it's a very highly potent tyrosine kinase inhibitor. It's more potent than some of the other tyrosine kinase inhibitors that have been assessed and are being assessed currently. The interesting part of that is that that also can facilitate durability because, you know, as we continue to dose escalate, and ultimately over time as the drug levels start to decay on a, you know, microgram per microgram basis, we still have efficacy because of the high potency. So, to answer your question, even if we do potentially saturate in terms of the potential for efficacy, we also have potential to enhance durability with a greater dose.

Fascinate features of exiting that business are very highly potent tyrosine kinase inhibitor.

It's more potent than some of the other tyrosine kinase inhibitors that have been assessed and are being assessed.

Currently.

And.

The interesting part of that is that that also can facilitate durability because.

As we can as we continue to dose escalate.

And ultimately over time is that the drug levels.

Strike a decay.

On it.

Microgram per microgram basis, we still have.

Efficacy because of the high potency. So so to answer your question.

Even if we do potentially saturate.

Terms of the potential for efficacy, we also have potential to enhance durability with a greater dose.

Dr. Thomas Chula: Thanks, Tom. And as a follow-up here, for Cohort 3, is the point to show some efficacy, or is it similar to Cohort 2, where you're just wanting to show some kind of clean safety profile? Well, I think I think, you know, obviously, we have to focus on safety; we want to show a clean safety profile. It would also be helpful to see some Biologic Science, and you may recall that we had a web conference at the end of the cohort, too, and had Peter Kaiser, who's a well-respected KOL retina specialist, on with us. And he observed that even between cohorts one and two.

Thanks, Tom and then as a follow up here for cohort three is deploying to show some efficacy or is it similar to cohort two where are you just wanting to show.

I'm kind of clean safety profile.

Well I think I think you know obviously, we have to focus on safety, we want to show a clean safety profile.

It would also be.

Helpful to see some buyer.

Biologic sign and.

You might recall.

That we had a web conference at the end of.

Cohort, two and head Peter Kaiser who says.

Accordingly, well respected.

Okay, well retina specialists on with us.

And he observed that.

Even between cohorts, one and two.

Dr. Thomas Chula: There was potentially already a bit of a dose response, because he felt that the CSTs, you know, we provide subject-level data, and he felt that the CSTs appeared to be more stable in Cohort 2 than in Cohort 1, and he thought that may suggest the beginnings of a dose, So as we escalate, you know, we think we're in that dose-response curve, and we may start to see more and more signs like that, which would be, you know, helpful as we start to think about doses for Phase 2. Thanks, Tom.

There was potentially already a bit of a dose response, because he felt that the C. S T.

Subject level data and he felt that the C S cheese.

Appeared to be more stable in cohort two and cohort one and he thought that may suggest the beginnings of a dose response, so so actually escalate.

<unk>.

We think we're in that dose response curve and we may start to see more and more.

Signs like that which would be helpful. As we start to think about doses for the phase II.

Dr. Thomas Chula: And related to that, as it relates to efficacy, is the goal really to show superiority over ATLEA or to show maintenance of efficacy being achieved by ATLEA, but with longer durability? You know, something like you said, Dr. Kaiser mentioned, just maybe even better or just slightly better maintenance in CSP or something like that, but with greater durability.

Thanks, Tom and then related to that as it relates to efficacy.

Well need to show superiority of that Leah why T cell maintenance of efficacy.

Being achieved by rehab, but with longer durability.

And you know something like you said that the Kaiser mentioned is maybe even.

Better I'm, just slightly backup maintenance in CSP or something like that but with me like Youre about me.

Zegby Jalaw: You know, with such a small study and even smaller numbers per cohort, it's hard to really make any inferences to compare this to ILEA. So I think really we want to focus on safety. We'd like to see the beginnings of some biologic effect, which would help guide us in terms of, you know, dose selection. But really, you know, the comparison to ILEA, although, you know, it's intriguing to speculate, we really can't make any inferences with just such small sample sizes and really without a.., you know, a control group. I guess what I'm trying to get at is trying to understand what you need to see to kind of feel confident that you have a program with a differentiated profile.

Yeah.

But such a small study in an even smaller numbers per cohort.

It's hard to really make any entrances to compare this to two eylea.

So I think really we want to focus on safety, we'd like to see the beginnings of some biologic effect, which should help guide us in terms of dose selection.

But but really you know the comparison to eylea, although it's intriguing to speculate.

We really can't make any any entrances with just such a small sample size isn't really without it you know.

A control group.

I guess, what I'm trying to get out of.

China understand.

What you need to see to kind of so confident that you have a program with a differentiated profile.

Dr. Thomas Chula: Well, I think we're going to have to, you know, in Phase IIB study, but bear in mind, you know, as I mentioned in my prepared remarks, we are selecting patients in a way who are refractory. So these are patients who are generally highly treatment experienced. And as you recall, they have to have had two prior doses within the four months of the study entry. And then at screening, they have to have reading center-confirmed activity.

But I think we're going to have to.

Study that further in phase II B study, but bear in mind.

You know as I mentioned in my prepared remarks.

We are selecting patients.

In a way who are refractory. So these are patients who are generally highly treatment experience.

And as you recall they had to have had two prior doses within the four months.

To study entry.

And then at screening they have to have reading center, if confirmed activity so in a way.

Dr. Thomas Chula: So in a way, we're selecting patients who are .., almost by definition, treatment refractory. And, you know, as, As we if we see a biologic effect I think that, You know, it could potentially be very exciting because these patients represent the 30 to 40 percent of patients who respond sub-optimally to current therapy. And that's what we're essentially selecting.

We're selecting patients who are.

Almost by definition treatment refractory.

And.

Yeah.

So as we if.

If we see a biologic effect.

I think that.

It could potentially be very excited because these are these are these patients represent the 30% to 40% of patients who respond sub optimally to current therapy and that's that's where essentially selecting there are other trials currently that don't require reading center confirmation of activity, but our study does and this will help us.

Dr. Thomas Chula: There are other trials currently that don't require, you know, reading-centered confirmation of activity, but our study does. And this will help inform us a bit about Phase 2B. So to answer your question, I think... You know, we're confident that this approach, you know, has potential for nice safety, given the fact that this is a well-characterized molecule. It's a small molecule.

Form us a bit about phase III.

Yeah to answer your question I think.

We're confident that this approach.

Has potential for for nice safety given the fact that this is a well characterized molecule. It's a small molecule it's not a biological potential for immune response and as you know immune response has been a big deal and recent AMD trials and then the Pan VEGF inhibition.

Dr. Thomas Chula: It doesn't have the biological potential for immune response. And as you know, immune response has been a big deal in recent AMD trials. And then the pan-VEGF, in addition, you know, really may have a potential, particularly in these patients who are treating refractory. And then we think the durability potential is there.

Really may have.

Potential, particularly in these patients who are treatment refractory and then we think the durability potential is there.

We published.

Data recently.

Showing that we can achieve levels several log orders above the IC 50, and a rabbit model.

Zegby Jalaw: As you know, we've published data recently showing that we could achieve levels, several log orders above the IC50 in a rabbit model for up to six months. So we think the safety, the efficacy, and the durability of this approach are quite attractive. And this could be a really very helpful therapy for retina specialists who deal with patients with wet AMD. Thanks, Sam.

For up to six months. So so we think the safety efficacy and the durability.

This approach are quite attractive and this could be a really.

Very helpful.

<unk> therapy for retinal specialists, who deal with patients with wet AMD.

Zegby Jalaw: I think that's what I was trying to get at, you know, in terms of how refractive these patients are and the magnitude of efficacy, the magnitude of response that investors can kind of hope to see because it may not be as high because of the patient population you're working with. And then my last question here is just about the Phase 2B. I know you haven't really made any plans yet, but, you know, as we're talking about this, you know, heavily appreciative patient population and then thinking about that relative to a naive patient population, you know, regarding your decision as to whether or not you should go into a pretreated or naive setting, what are some things that you think, you know, might be prioritized? Maybe there's another question for George.

Thanks, Tom I think that's what I was trying to get at you know in terms of how you factor. These patient died the magnitude of efficacy or magnitude of response that investors can kind of hope to see because it may not be as high because of the patient population it'll work and in that and then my last question you asked about the phase two B I know you haven't really.

He made any plans yet, but you know as we're talking about this you know.

Heavily pretreated patient population and then thinking about that relative to a naive patient population you know regarding your decision as to whether or not you should go into pre treat a naive setting what are some things that you think.

Zegby Jalaw: Is it going to be the size of the market opportunity, you know, the indication or the patient population that can lead to a faster path to market? You know, what are some things that you think you'll be prioritizing to kind of help make that decision? Well, I think Zegbe, you just listed all the ones that we have to consider.

It might be prioritized that maybe there's a better question for George is it going to be the size of the market opportunity.

The indications are that the patient population that can lead to a faster path to market. You know like I said, some things that you think you'll be prioritizing to kind of help make that decision.

Well I think Doug that you just listed all the ones that we have to consider we obviously have to consider.

George Lasezkay: We obviously have to consider, we have to look at competition, we have to look at size of market, we have to look at, is there a better path forward? You know, we go through, you know, do you, you know, going for a moonshot? Do you try to get something that's approved?

I have to look at competition, we have to look at size of market, we have to look at.

Is there a better path forward.

We go through June .

Going for a moonshot do you try to get something Thats approved there's a lot of things that are going to go into the decision around phase two b, which will lead to hopefully.

George Lasezkay: There's a lot of things that are going to go into the decision around phase 2b, which will lead to hopefully setting up phase phase 3 clinical trials. As you said, as we've said, you know, we're in the middle of that planning now. We have not finalized the Phase 2B plan yet, but we have lots of input. We're considering a lot of different.., factors in deciding how we want to approach Phase 2B with ultimate approval in mind, you know. So you have to be, you have to be very sensitive and take into account all of the things that you've just mentioned.

Setting up the phase III phase III clinical trials.

As you said as we've said we're in the middle of that planning now.

We have not finalized the phase two b plan yet.

But we have lots of input we are considering a lot of different.

Factors.

In deciding how we want to approach phase two b.

Ultimate approval in mind so.

You have to be you have to be very sensitive and take into account all of the things that you've just mentioned, which one is more important that'll be which one decides is the deciding factor.

George Lasezkay: Which one's more important, that'll be, which one decides, is the deciding factor, that's going to be, that's still, we're still having that conversation and and waiting for some of the data that comes out of the OASIS trial to, to, you know, make a final determination of that. Tom, if you have anything to add to that. Yeah, perfect. And congrats on all the progress. Nice to have all this optionality regarding licensing the platform.

That's gonna be that's still we're still having that conversation and and waiting for some of the data that comes out of the Oasis trial.

To make a final determination of it.

Tom if you have anything to add to that.

Yeah, perfect and congrats on all the package, it's nice to have all this optionality regarding licensing.

Licensing.

That's fine.

Zegby Jalaw: Well, thank you, Zagbuffet. We always appreciate your support. Your next question is from Rohit Basin with Needham, your line is open. Hi, this is Rohit on for Surge.

Thank you Zach we always appreciate your support.

Yes.

Your next question is from Rohit <unk>.

<unk> with Needham Your line is open.

Hi, This is Robert on for Serge. Thanks for taking my question in regards to the Arctic vision trials can you provide some color about the studies.

Rohit Basin: Thanks for taking my question. In regards to the Arctic Vision Trials, can you provide some color about the studies and if the trials are doing anything different? And then for the Integrin Inhibitor Program, what indications are you looking to market with this mechanism of action? Well, I'll let Tom comment. He's probably closer to what Arctic's doing than I am, but regarding integrin, you know, that's still very early stage, and we have a number of ways we could go in terms of indications.

If you had the trials or doing anything different.

And then for the integrity inhibitor program, what indications are you looking to market with this mechanism of action.

Well, let me I'll, let Tom comment he is probably closer to what Arctic doing than I am but regarding.

Rohit Basin: Currently, we're thinking of diabetic macular edema, but that's not necessarily carbon style. We think that integrin, as we carry that forward, could have some other potential opportunities to be pursued. So, that's still, that's not a well-defined or a decision that's been, you know, carved in stone at this point in time.

Integrin.

That's still very early stage and we have a number of ways. We could go in terms of indications currently we're thinking of diabetic macular edema, but.

That that's not necessarily carbon style, we think that the integrin as we carry that forward could have some other potential opportunities to be pursued so that's still that's.

That's not a well defined or a decision thats been carved in stone at this point in time, but Tom do you want to comment on Arctic vision on there are two trials.

Tom: But Tom, do you want to comment on Arctic Vision on their two trials that they've started in China? Sure. So, so the, They're doing a uveitic macular edema trial in China, and it's essentially very similar to our Peachtree registration, and that's underway. I believe they've announced dosing of their first patient. They've also announced dosing of a patient in their diabetic macular edema trial. And this is a phase one study, so it's still early for them.

They've started in China.

Sure. So so the.

They're doing a <unk>.

<unk> macular edema trial in China, and it's essentially a.

Very similar to our Peachtree registration trial.

And that's underway and I believe they announced dosing of the first patient.

They've also announced dosing of a patient in their diabetic macular edema trial.

And this is a phase one study so it's still early for them.

Tom: I believe they're calling it a pharmacokinetic study. But. As you know, corticosteroids have been approved for the treatment of diabetic macular edema. Their use is often.., limited because of the potential to cause cataract progression and ocular hypertension, we think by compartmentalizing the corticosteroid in the supracortal space and away from the front of the eye, we can minimize the risk of ocular hypertension and cataract development.

I believe they're calling a climate go kinetic study.

But.

As you know.

Corticosteroids.

Have been approved for the treatment of diabetic macular edema, they're used as often.

Limited because of the potential to cause.

Cataract progression and ocular hypertension, we think by compartmentalized into corticosteroids in the supermarket space and away from the front of the eye, we can minimize the risk of <unk>.

Ocular hypertension and counteract development so.

Tom: So there's potential for.., and Xi Peer to have a role in diabetic macular edema in addition to uveitic macular edema. We're very excited about the trials, have a great relationship with Arctic Vision. Our clinical teams and biostatisticians, you know, have to open dialogue with them. It's an excellent relationship, and we wish them lots of success.

There is potential for.

Yes.

XI appear to have a role in diabetic macular edema. In addition to <unk> macro demand we're very excited.

About the trials we.

Uh huh.

Have a great relationship with Arctic vision.

Our clinical teams and Biostatistician has.

The open dialogue with them, it's an excellent relationship.

We wished him lots of success.

George Lasezkay: And I'll just echo what Tom said about Arctic Vision, they've been a.., a very engaged and a terrific partner. And we're very happy to be working with them. They're very aggressive, but appropriately so.

Yeah, and I'll, just echo what Tom said about Arctic vision, they've been a.

A very.

Barry engaged been a terrific partner and we're very happy.

To be working with them. They are very aggressive about appropriately so and I think they see the potential.

George Lasezkay: And I think they see the potential Zyper, they call Arcadis, in their territories. And so I think we have a terrific partner in the overall Asia, Australia and New Zealand region. They've been, they've just been really wonderful to work with. Very happy about that.

<unk> they call our cadence.

In their territories and so I think we have a terrific partner.

In the overall Asia, Australia, and New Zealand region.

They've been.

They've just been a really wonderful to work with very happy about that.

Great. Thank you.

Rohit Basin: Great. Thank you. And your last question is from John Wolleben with JMP Securities. Your line is open. Hey, thanks for taking the question. Just two for me.

And your last question is from John while they've been with JMP Securities. Your line is open.

Hey, Thanks for taking the question just two for me you talked about the phase II b in wet AMD, but wondering what expansion first tariff accident. The other indications might look like and then also with Zeiss here wondering if we should expect any meaningful.

John Wolleben: You talked about Phase 2B and wet AMD, but I was wondering what expansion for CLS-AX and the other indications might look like. And then also, with Xyp here, wondering if we should expect any meaningful royalties this year. If I remember right, the first $450 million is royalty-free. Just hoping to confirm that for expectations for this year.

Royalties this year, if I remember right the first $450 million.

Royalty free just opened they confirm that for expectations for this year. Thanks.

John Wolleben: Thanks. Thanks, John. Charlie, you want to take the royalty question first? Hey, John. Yeah. The first $45 million you write is royalty free for Bausch.

Thanks, John Charlie you want to take the royalty question first.

Charlie Deignan: So I can't talk about their guidance, but we'll start earning royalties once we get a dollar past $45 million in their sale. And then, Tom. John asked about other potential indications for a phase IIb trial for CLSA-X. I believe that was it, John. And currently, you know, currently our thinking in OASIS, obviously we're doing it in wet AMD patients. Yeah, absolutely. So there's potential in diabetic macular edema. Diabetic Retinopathy, and, you know, retinal vein occlusion-related maculodema.

Hey, John Yeah.

First $45 million, you're right is royalty free for Bausch health.

Can't talk about their guidance and but they definitely will start earning royalties once we get a dollar passed $45 million in their sales.

And then Tom.

Tom: Those are sort of the other, you know, classic indications for this sort of therapy. So, you know, we. Those, we discussed those and haven't made any firm decisions at this point. Those are all basically VEGF-mediated disorders, correct Yes, absolutely. They're all VEGF-inhibited disorders.

John asked about other potential indications for our phase two b trial for CLSA X I believe that was a chunk and.

Tom: And, you know, we think with the durability potential, of this approach, and also the targeting, particularly the peripheral retina, we think there's real potential here for diabetic retinopathy as well. You know, we. We can get targeted high levels to the retinal periphery where diabetic retinopathy tends to start.

Currently.

Currently our thinking and Oasis, obviously, we're doing at wet AMD patients.

Yeah, absolutely so theres potential andi.

In diabetic macular edema.

Diabetic retinopathy.

And retinal vein occlusion related master the game of those are sort of the other classic indications for this sort of therapy.

So we.

Those we discussed those in.

Haven't made any.

Firm decisions at this point.

Those are all basically VEGF mediated disorders.

Correct.

Yes, absolutely, they're all veg ethanol use disorders, and we think.

With the durability potential.

Of this approach.

And also that the targeting particularly the peripheral retina.

We think there's real potential here for diabetic retinopathy as well.

Yeah.

We can get targeted high levels to the retinal periphery, where diabetic retinopathy tends to stop.

So so.

Tom: There's a lot of potential with this approach, and again, we haven't made any, you know, obviously any firm decisions yet. We might have lost John. That was the last question. Yeah, George, why don't you give your closing remarks. Okay, all right. Well, all right, since that was the last question, I want to thank everyone 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.

There's a lot of potential but this approach and again, we haven't made any box.

Obviously any FERC decisions yet.

Okay.

We might have lost John .

Yeah.

I was the last question.

Yes, George wanted to give you a closer remarks, okay, alright, well alright since that was the last question I want to thank everyone for joining us on the call. This afternoon. We appreciate your continued interest in clear side and we look forward to updating you on our progress.

George Lasezkay: Operator, you may now disconnect the call. Thank you. Thank you. Thank you, sir. As a reminder to all participants, you may now disconnect. Have a good day, stay safe, and well. [music]

You may now disconnect. The call. Thank you. Thank you. Thank you Sir is there a reminder to all participants you may now disconnect have a good day stay safe and well.

Okay.

[music].

Sure.

[music].