Q3 2021 Clearside Biomedical Inc Earnings Call

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Operator: Good day, thank you for standing by, and welcome to the Clearside Biomedical Q3 2021 Financial Results and Corporate Update 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. To ask a question during that session, you will need to press Star 1 on your telephone keypad. If you require any further assistance, please press Star Zero. Thank you. I would now like to hand the floor over to your speaker today, Ms. Jenny Colvin, Clearside Investor Relations. The floor is yours.

Yeah.

Good day, Thank you for standing by and welcome to the career side biomedical accused to be 2021 financial results and corporate update 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.

Can I ask a question during that session you will need to press star one on your telephone keypad. If you require any further assistance. Please press star zero.

I would now like to hand, the conference over to your Speaker today and this is Johnny Colvin decide investor relations the floor is yours.

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

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.

Remarks that we make during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by these forward looking statements as a result of various important.

Factors, including those discussed in the risk factors section of our annual report on Form 10-K for the year ended December 31, 2020, and our other SEC filings available on our website.

Jenny R. Kobin: In addition, any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change. On today's call, we have George Luzeske, our chief executive officer, Dr. Thomas Chula, our chief medical officer and chief development officer, and Charlie Dedman, our chief financial officer. After our formal remarks, we will open the call to your questions. I would now like to turn the call over to George.

In addition, any forward looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date, while we may elect to update these forward looking statements in the future. We specifically disclaim any obligation to do so even if our views change.

On today's call we have George was SK, our Chief Executive Officer, Dr. Thomas Ciulla, Our Chief Medical Officer, and Chief Development Officer, and Charlie Deignan, Our Chief Financial Officer. After our formal remarks, we will open the call for your questions I would now like to turn the call over to George.

Thank you Jenny.

George Luzeske: It's our pleasure to join you on the call today to discuss clear size accomplishments in the last two months. Simply put, we've achieved an impressive number of firsts.

It's a pleasure to join you on the call today to discuss clear signs of accomplishments in the last two months simply put we've achieved an impressive number of firsts.

George Luzeske: The FDA's recent approval of Zypier is the first commercial product developed by Clearside and the first product approved for injection into the supercaroidal space. In addition to being an exciting accomplishment for Clearside, we believe this approval represents a potential game change, as we have developed a truly innovative therapeutic approach in the field of retinal diseases. Our superkoroidal injection platform is a novel, patented approach that provides unparalleled access to the back of the eye that precisely administers drugs at the site of disease. With our proprietary SCS microinjector, we have developed a clinically tested, non-surgical, repeatable microinjection platform designed to unlock the potential clinical benefit of supercaroidal administration.

With the Fda's recent approval ZIP here is the first commercial product developed by clear side and the first product approved for injection into the Super Choroidal space.

In addition to be an exciting accomplishment for clear side. We believe this approval represents a potential game changer as we have developed a truly innovative therapeutic approach in the field of retinal diseases.

Our Super Choroidal injection platform as a novel patented approach, providing unparalleled access to the back of the eye that precisely administers drug at the site of disease.

With our proprietary SCS micro injector, we have developed a clinically tested nonsurgical repeatable micro injection platform designed to unlock the potential clinical benefits of <unk>.

Supercoil administration.

George Luzeske: Further, Zypire is now the first therapy approved for patients suffering from macular edema associated with uveitis, and I am proud of the fact that we are able to make a difference in the lives of these patients battling this potentially blinding condition. With approval, we are redefining the treatment of macular edema associated with UVitis. Zipir will be commercialized in the U.S. by our partner, Bausch and Lans. Bouch is a well-respected leader in our industry and has been a tremendous partner throughout this process.

Further <unk> is now the first therapy approved for patients suffering from macular edema associated with uveitis and I am proud of the fact that we are able to make a difference in the lives of these patients battling this potentially blinding condition.

With this approval we are redefining the treatment of macular edema associated with uveitis.

Xavier will be commercialized in the U S by our partner Bausch and Lomb.

Bausch is a well respected leader in our industry has been a tremendous partner throughout this process.

George Luzeske: We now expect to receive $15 million in approval and pre-launch milestones from Bouch. We continue to work closely and cooperatively with the Bouch team as they prepare to launch DIPIR and educate retinal specialists on the use of our SDS microinjecture. Boush expects to launch Zypere in the first quarter of 2022. Also, during the quarter, we expanded our Zypier licensing agreement with Arctic Vision, a Chinese-based biotechnology company focused on ophthalmic therapy. Based on Arctic's commitment and belief in the product, we agreed to expand their licensed territory from Greater China and South Korea to also include Australia, New Zealand, India, and 10 Southeast Asian countries. We will receive $3 million and upfront payments as consideration for the expanded territory, and we also expect to receive $4 million based on our recent U.S. approval of Zyp.

We now expect to receive $15 million in approval and prelaunch milestones from Bausch, we continue to work closely and cooperatively with the Bausch team as they prepare to launch the <unk> and educate retinal specialists on the use of our SCS micro injector.

Bausch expects to launch <unk> here in the first quarter of 2022.

Also during the quarter, we expanded our XI pure licensing agreement with Arctic vision, a Chinese Chinese based biotechnology.

Oh Gee company focused on ophthalmic therapies.

Based on Arctic commitment and belief in the product we agreed to expand their license territory from greater China and South Korea to also include Australia, New Zealand, India, and Tim South East Asian countries.

We received 3 million in upfront payments as consideration for the expanded territory.

And we also expect to receive $4 million based on our recent U S approval of its IPO.

George Luzeske: Arctic Vision is planning to initiate a confirmatory phase three clinical trial in macular edema associated with UVitis in China by the end of this year with the ultimate goal of commercializing Zypire, if approved, in their licensed region. In addition, in the past two months, our clinical development partners reported promising results utilizing our SCS microinjector to deliver their therapeutics into the super-coroidal space. Regenics Bio reported initial data from two phase two clinical trials, which represents the first data ever presented utilizing gene therapy delivered into the supercuroidal space.

Arctic vision is planning to initiate a confirmatory phase III clinical trial in macular edema associated with uveitis in China by the end of this year with the ultimate goal of commercializing <unk>, if approved and they're licensed regions.

In addition in the past two months, our clinical development partners reported promising results utilizing our SCS micro injector to deliver their therapeutics into the super cooler space.

<unk> bio reported initial data from two phase II clinical trials, which represents the first data ever presented utilizing gene therapy delivered into the Super cooler space.

George Luzeske: We look forward to Regenics Bio reporting additional phase two data at the upcoming American Academy of Optomology Meeting later this week. And our partner, ORABiosciences, reported the first data ever presented in ocular oncology with their viral-like drug conjugate administered by supercaroidal injection to treat caroidal melanoma. We're very excited about the progress to date from our partners, and we look forward to future results from these trials. Finally, our lead clinical development candidate, CLSAX, continues to progress in our Phase 1-2A Oasis trial in patients with wet AMD.

We look forward to reject smile reporting additional phase two data at the upcoming American Academy of Ophthalmology meeting later this week.

And our partner Aura Biosciences reported the first data ever presented an ocular oncology.

With their viral like drug conjugate administered by Super Choroidal injection to treat choroidal melanoma.

We're very excited about the progress to date from our partners and we look forward to future results from these trials.

Finally, our lead clinical development candidate CLSA X continues to progress in our phase one two way Oasis trial in patients with wet AMD.

George Luzeske: CLS-AX combines our proprietary suspension of the tyrosine kinase inhibitor, Exidinib, for suprachoroidal use with our SCS microinject. We have completed enrollment in cohort 2 and expect to report safety and tolerability data from this cohort by the end of this year. With the Panvege F attributes of Exidinib delivered into the supercaroidal space, we have the opportunity to improve the treatment of patients with wet AMD, as we believe CLSAX may offer improved safety and efficacy, as well as prolonged durability by reducing the frequency of patient injections. With an approved product and four ongoing clinical trials utilizing three distinctly different therapeutics, we are revolutionizing the delivery of therapeutics to the back of the eye through Tom?

C. L S. A X combines our proprietary suspension of the tyrosine kinase inhibitor exiting them.

For Supercoil use with R. F C S micro injector.

We have completed enrollment in cohort two and expect to report safety and Tolerability data from this cohort by the end of this year.

With the Pan VEGF attributes of exit nib delivered into the Super Gorilla in the space, we have the opportunity to improve the treatment of patients with wet AMD as we believe C. L. S. A X may offer improved safety and efficacy as well as prolonged durability by reducing the frequency of patient injections.

With an approved product in four ongoing clinical trials utilizing three distinctly different therapeutic assets.

We are revolutionizing the delivery of therapeutics to the back of the eye through the Super Choroidal space.

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

Thank you George and good afternoon, everyone before I discuss our clinical development programs I would like I would just like to take a moment to recognize the excitement and momentum created by the approval of the Ikea.

This is a tremendous achievement for our dedicated employees as they have worked diligently to bring the first drug approval to fruition.

Dr. Thomas Chula: Thank you, George, and good afternoon, everyone. Before I discuss our clinical development programs, I would just like to take a moment to recognize the excitement and momentum created by the approval of Zyp. This is a tremendous achievement for our dedicated employees, as they have worked diligently to bring the first drug approval to fruition. As a retina physician, I'm truly thrilled that my colleagues and their patients now have a new, innovative treatment option for those suffering from utheic macular edema, a serious, potentially blinding disease.

As a physician I am truly thrilled that my physician colleagues and their patients now have a new innovative treatment option for those suffering from youth Yearick macular edema is serious potentially blinding disease retina physicians love adopting new technologies, and embracing new therapy to add to their treatment Arsenal and as many of our meeting.

Presentations and publications have shown there was strong interest in a cyclic delivering platform within the retina community.

In fact, our published study evaluating the use of our SCS microinjection highlighted that supercritical injection was well accepted by physician investigators with potential for rapid adoption into clinical practice.

Importantly, our micro injector has been clinically tested in multiple disorders with over 200, <unk> injections and a favorable safety profile and clinical trials.

As background on the treatment need preside here uveitis is a set of ocular inflammatory conditions approximately one third of uveitis patients will develop UBS macular edema, the build up of fluid in the macula, which causes rabbits filing and destroys vision.

Dr. Thomas Chula: Retina physicians love adopting new technologies and embracing new therapies to add to the treatment R-Syp. And as many of our meeting presentations and publications have shown, there is strong interest in our supercordial delivery platform within the retina community. In fact, our published study, evaluating use of our SCS microinjector, highlighted that supercordial injection was well accepted by physician investigators with potential for rapid adoption into clinical practice. Importantly, our microinjector has been clinically tested in multiple disorders with over 1,200 supercordal injections with a favorable safety profile in clinical trials.

Macular edema is a leading cause of vision loss and blindness in uveitis patients you can occur for uveitis affecting any anatomic location anterior intermediate posterior or pan uveitis.

We are pleased with the FDA approved label for <unk>, which includes all of the anatomic locations could potentially treat a broad patient population with macular edema associated with uveitis.

Approval of XI per supports our supercritical delivering platform as our preclinical work is now translated to proven clinical results. The core advantages of trading via the supercritical space include targeted delivery to our second quarter retinal tissues of potential efficacy benefit.

Compartmentalize Asian away from unaffected tissues from potential safety benefits and bioavailability as acquired retinal tissues are essentially be with there.

Furthermore, for small molecule suspensions, there are prolonged pharmacokinetics, which facilitate durable therapies.

This target delivering compartmentalization was associated with our successful phase III Peachtree clinical trial supporting the efficacy and safety insights here.

Dr. Thomas Chula: As background on the treatment need for Zypire, UVI is a set of ocular inflammatory conditions. Approximately one-third of uveitis patients will develop uveitic macular edema, which causes rapid swelling and distorted vision. Maculidema is a leading cause of vision loss and blindness in UVitis patients and can occur if UVitis affects any anatomic location, anterior, intermediate, posterior, or pan uveitis.

Durability was demonstrated in our Magnolia extension study and is driven by the relative intelligibility and particle size of the formulation and the Super Gorilla space.

We have seen similar preclinical durability with other small molecule suspensions, including a complement inhibitor plasma, California inhibitor and the tyrosine kinase inhibitor at citizens, which is the active ingredient in our CLS ax proprietary formulation.

I'll next discuss our CLSA X program in more detail I'm very excited about combining the potential benefits of Panther. Jeff. In addition, with the targeting compartmentalization and durability and potential benefits of supercritical delivery.

Of note current AMD therapies buying purge ethane. However in addition to the HSA has been shown to Upregulation other forms of there, Jeff which may contribute to limited outcomes.

Dr. Thomas Chula: We are pleased with the FDA-approved label for Zypire, which includes all of these anatomic locations, to potentially treat a broad patient population with macularedema associated with UVIIS. Approval of Zypair supports our supercarital delivery platform, as our preclinical work has now translated to proven clinical results. The core advantages of treating via the supercoral space include targeted delivery to affected core retinal tissues for potential efficacy benefits, compartmentalization away from unaffected tissues for potential safety benefits, and bioavailability as the core retinal tissues are essentially bathed with therapy.

Sitting at a highly potent tyrosine kinase inhibitor may improve these outcomes with its broad VEGF blockade and it's already been shown to effectively inhibit corneal retinal and choroidal angiogenesis in numerous animal models.

In addition, supercritical administration may further leverage these potential benefits of equipment by more directly targeting the affected retinal in Korea Korea Coralloid tissues.

We recently published a preclinical study demonstrating the targeted delivery with supercritical administration, along with favorable ocular distribution and durability compared to encode vitriol delivering these.

These preclinical studies helped provide the rationale for our first in man Supercoil CLSA X clinical program and support our belief that supercritical CLSA ex could represent a very competitive therapy in the future.

As we reported last quarter, we are pleased with the promising safety and Tolerability results from cohort one of wafers.

Ongoing phase <unk> clinical trial with CLS Ax.

Dr. Thomas Chula: Furthermore, for small molecule suspensions, there are prolonged pharmacokinetics which facilitate durable bare, This targeted delivery and compartmentalization was associated with our successful phase 3 peach-free clinical trial, supporting the efficacy and safety of Zypher. Durability was demonstrated in our Magnolia Extension study and is driven by the relative insoluability in particle size of the formulation in the supercortal space.

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

We have all three cohorts of approximately five patients each.

Every endpoint for the trial will assess the safety and Tolerability for three months following Supercoil administration of CLS Ax.

To recap, our Super <unk> safety and Tolerability data from cohort one no study suspension of stopping rules were met and there were no serious adverse events importantly, there were no signs of inflammation vitreous haze intraocular pressure safety signals vasculitis or integrate till dispersion of CLSA X.

Dr. Thomas Chula: We have seen similar preclinical durability with other small molecule suspensions, including a complement inhibitor, a plasma calicron inhibitor, and the Tyres and Kinase inhibitor, Exitinth, which is the active ingredient in our CLSAX proprietary formula. I will next discuss our CLSAX program in more detail. I'm very excited about combining the potential benefits of panvegett addition with the potential benefits of targeting compartmentalization and durability of supercurdial delivery. Of note, current AMD therapy is buying VEGFA.

They were two treatment emergent adverse events that were assessed as unrelated to CLS ax.

Durability is an important component of our treatment plan and we are encouraged by the preliminary signs of potential durability that we saw in cohort one, especially given the very low initial dose of 0.03 milligrams at CLSA X and these highly anti VEGF treatment experienced patients that were enrolled.

With these results from cohort one we had advanced to cohort two at a dose of 0.1 milligram. While this is still a low dose of CLSA X. It's a three three fold increase compared to the cohort one dose.

In September we reported that we completed enrollment in cohort two whereby all patients that receive a quicker step out their first visit and a single dose of CLSA eggs at their second visit one month later patients are monitored monthly by their physicians for the next three months of their treatment and we expect to report safety and Tolerability results from cohort.

Two by the end of this year.

For cohort two we're also adding a three month extension study to follow patients over a longer period of time.

We believe that by combining the Pan Digest attribute of citizen with a proprietary CLSA X formulation and delivery via our SCS Microinject here, we may facilitate an effective treatment option for patients suffering from wet AMD.

Dr. Thomas Chula: However, in addition to VEGFA, it has been shown to upregulate other forms of VEGF, which may contribute to limited outcomes. Exitinib, a highly potent tyrosine and kinase inhibitor, may improve these outcomes with its broad VEGF blockade, and it's already been shown to effectively inhibit corneal, retinal, and corotal angiogenesis in numerous animal models.

Furthermore, a well characterized small molecule like sitting in may have less potential for immune response compare to a biologic agent.

The recent well documented safety challenges associated with other approved and investigational wet AMD therapies, we cannot emphasize enough the importance and pine focus of the safety component in our Oasis trial, if our cohort two data readout continues to demonstrate supportive safety results, we will dose escalate in cohort three.

And have potential to escalate even further if we believe it's appropriate.

Dr. Thomas Chula: In addition, supercoral administration may further leverage these potential benefits of excitement by more directly targeting the affected retinal and corroidal tissues. We recently published a preclinical study demonstrating this targeted delivery with Super Quirlo administration, along with savable ocular distribution and durability compared to intratumoral delivery. These preclinical studies help provide the rationale for our first in man supercroyal CLSAX clinical program and support our belief that supercloidal CLSAX could represent a very competitive therapy in the future.

With respect to our partner programs. The last few weeks have been a very exciting time for clear sight in our supercritical delivery platform and our development partners have reported promising results from several trial using our SCS microinjection to deliver their product candidates into the supercritical space.

I'll start with orogenic style as they're running two multicenter open label randomized control dose escalating studies evaluating the efficacy safety and Tolerability of Super colloidal delivery of RG <unk> in 2014.

Excitingly data presented by <unk> bio is the first data ever presented utilizing gene therapy delivered in the supercritical states.

The first trial and trial entitled Aviate is targeting the treatment of patients with severe wet AMD, who are responsive to anti VEGF treatment importantly patients in the trial do not receive prophylactic immune suppressive corticosteroid therapy.

Dr. Thomas Chula: As we reported last quarter, we are pleased with the promising safety and intolerability results from cohort 1 of Oasis, our ongoing phase 1 clinical trial with CLSAS. OETS is a multi-center open-label study to establish the safety and tolerability of escalating doses of CLSAX, administered by supercordial injection, in patients suffering from wet AMD. The study involves three cohorts of approximately five patients each. The primary endpoint for the trial will assess the safety and tolerability for three months following supercoil administration of CLSA.

In September we can expire reported the filing.

And cohorts, one two and three super quite a deliberate rdx three 2014 was well tolerated in 50 patients with no drug related serious adverse events and <unk>.

Cohort one positive initial efficacy data at six months after a onetime treatment with <unk> hundred 14 show the treatment effect observed with stable visual acuity in retinal thickness and <unk> hundred 14 demonstrated meaningful reduction in anti VEGF treatment burden.

For cohort two we can expire plans to report interim results at six months of follow up at the upcoming AAN meeting later this week.

Cohort three has completed dosing in patients positive for neutralizing antibodies.

And <unk> expanded the trial to enroll cohorts four and five at a higher dose.

Dr. Thomas Chula: To recap our supercoyal safety and tolerability data from cohort one, no study suspension of stopping rules were met, and there were no serious adverse events. Importantly, there were no signs of inflammation, vitreous haze, intraocular pressure safety signals, vasculitis, or intubital dispersion of CLSA.

The second RPX clinical architecture 14 clinical trial is a phase II trial for the treatment of diabetic retinopathy entitled altitude similar to 88 patients in this trial did not receive prophylactic immune suppressive corticosteroid therapy before or after administration of RPX screens 2014.

In October at pretax by a reported the following cohort one had positive initial data that demonstrated supercritical delivering RPX three of 2014 was well tolerated and 15 patients with no drug related serious adverse events.

Intraocular inflammation observed and 33% of patients demonstrated a to a more step improvement from baseline on a standardized diabetic retinopathy severity scale compared to zero percent of patients in the observational control.

Dr. Thomas Chula: There were two treatment emergent adverse events that were assessed as unrelated to CLSA. Durability is an important component of our treatment plan, and we are encouraged by the preliminary signs of potential durability that we saw in cohort one, especially given the very low initial dose of 0.03 milligrams of CLSAX and these highly anti-vegeff treatment experience patients that were enrolled. With these results in cohort one, we advanced to cohort two at a dose of 0.1 milligram. While this is still a low dose of CLSAX, it's a 3.3fold increase compared to the cohort one dose.

Part two is currently enrolling.

And cohort three is currently enrolling patients positive for neutralizing antibodies.

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

Or a reported that supercoil administrations, Dear SCS microinjection may improve the therapeutic index and optimized treatment parameters for <unk> 011.

It is currently running a phase II trial comprised of an open label dose escalating phase and a randomized masked dose expansion phase that is assessing the safety and efficacy of eight ascending single and repeat doses of <unk> one one.

SCS micro injector administration.

In October order, a part of the phone.

Interim safety data showed no treatment related serious adverse events dose limiting toxicities or grade three adverse events cohorts. One through five are fully enrolled with a total of 13 patients.

Dr. Thomas Chula: In September, we reported that we completed enrollment in cohort two, whereby all patients received a flibber step at their first visit and a single dose of CLSAX at their second visit one month later. Patients were monitored monthly by their physicians for the next three months of their treatment, and we expect to report safety and tolerability results from cohort two by the end of this year. For cohort two, we're also adding a three-month extension study to follow patients over a longer period of time.

And cohort six is enrolling the.

The randomized phase of the trial is planned to begin in the second half of 2022 and patients with documented growth to establish the safety and efficacy of <unk> 011, and serve as the first phase of pivotal pivotal trial for the treatment of indeterminate lesions and quite a melanoma the.

The continued progress that we can expire in aura Biosciences is very encouraging and we look forward to their ongoing clinical trial results.

Before I conclude my discussion I would like to touch on our integrated gene therapy programs.

We're working on integrating formulation studies that will continue into 2022 and our research team is currently running preclinical studies, including pharmacokinetic work assessing ocular distributions.

Dr. Thomas Chula: We believe that by combining the pan-deghs attributes of exitinitin with our proprietary CLSAX formulation and delivery via our SDS microinjector, we may facilitate an effective treatment option for patients suffering from wet AMD. Furthermore, a well-characterized small molecule like exitinine may have less potential for immune responses compared to a biologic agent.

Our gene therapy program. This year, we presented and published data, including preclinical studies and Super quarterly delivered non viral DNA nanoparticles.

Containing a mile 17, which causes usher syndrome, and it's too large to fit in AAV vectors outside of our existing gene therapy licensing relationship with photonics vinyl, we have the opportunity to partner with other companies working on gene therapy, using non viral vectors or viral vectors targeting diseases that are.

Not primarily treated with current standard of care anti VEGF therapies, such as geographic atrophy in inherited retinal diseases, including Usher syndrome <unk> disease.

Dr. Thomas Chula: With the recent, well-documented safety challenges associated with other approved and investigational wet MD therapies, we cannot emphasize enough the importance and prime focus of the safety component in our OASIS trial. If our cohort 2 data readout continues to demonstrate supportive safety results, we will dose escalate in cohort 3 and have the potential to escalate even further if we believe it's appropriate. With respect to our partner programs, the last few weeks have been a very exciting time for ClearSide in our Super Quirital delivery platform, as our development partners have reported promising results from several trials using our SDS microinjector to deliver their product candidates into the supercordial space.

In closing we continue to remain active within the retina physician community with 10 presentations recently, given at the Retina Society and American Society of retina specialists medical meetings.

We will also have three type hear presentations at the American Academy of Ophthalmology meeting this weekend.

These presentations and other ongoing interactions with leaders in the field continue to generate interest in our supercoil space and the potential to adopt this procedure in their practices I will now turn the call over to our CFO, Charlie Deignan to review our financial results Charlie.

Thanks, Tom.

Actual results for the third quarter were published this afternoon in our press release and are available on our website. Therefore, I will summarize our current financial status.

Cash and cash equivalents as of September 32021 totaled approximately $25 2 million, which included the $3 million in payments from Arctic vision for the expansion of their license territory scores up here, our quarterly cash burn is primarily due to the activities related to our CLSA X program and obtaining approval.

For Zip here.

<unk> and our broader research pipeline are also incorporate it into their operating areas.

Dr. Thomas Chula: I will start with Agenics Bio as they are running two multi-center, open label, randomized control, dose escalating studies evaluating the efficacy, safety, and intolerability of supercroyal delivery of RGX314. Excitingly, data presented by Regenics Bio is the first data ever presented utilizing gene therapy delivered in the superchoral space. The first trial, entitled Aviate, is targeting the treatment of patients with severe wet AMD who are responsive to anti-vege-F treatment. Importantly, patients in the trial do not receive prophylactic immune-suppressive cortical steroid therapy.

The a pool of ZIP here, we anticipate receiving a total of $19 million and non dilutive funding for approval and prelaunch milestones from our commercialization partners. We expect these funds along with a $5 million of deferred revenue from the upfront payment will be recorded in the fourth quarter of 2021.

Since revenue on the income statement.

Additional capital will be utilized to advance our clinical development pipeline led by CLSA X.

Based on our current funding of planned spend we now expect to have sufficient resources to fund our operations into 2023.

We appreciate the interest and support from our shareholders and the broader investment community and we look forward to participating in several virtual investor events over the next few weeks.

Dr. Thomas Chula: In September, Regenix bio reported the following: In cohorts 1-2 and 3, supercordial delivery of RGX-314 was well tolerated in 50 patients with no drug-related serious adverse events. In cohort 1, positive initial efficacy data at six months after one-time treatment of RGX-314 showed a treatment effect, observed with stable visual acuity and retinal thickness, and RGX-314 demonstrated a meaningful reduction in anti-vege-f treatment burden. For cohort 2, Regenics Bile plans to report interim results at six months of follow-up at the upcoming AAO meeting later this week.

Health Care conference the Piper Sandler Health care conference and the UBS ophthalmology today.

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

Thank you Charlie.

In closing I'd like to take a moment to recognize the accomplishments of our team here at clear side.

Their hard work and dedication for the past several years has taken XI peer through discovery research clinical development and ultimately to FDA approval.

I'm extremely proud of their efforts to get site appear to the finish line.

I'd also like to thank our shareholders clinical investigators and board of directors.

Who have supported us through this multi year process.

Our recent success only inspires us to continue to move forward as we focus on advancing CLS ax through its clinical program and exploring future opportunities to make a difference in the lives of patients suffering from short sight threatening diseases.

Dr. Thomas Chula: Covart 3 has completed dosing, and patients are positive for neutralizing antibodies, and Regenix Bio is expanding the trial to enroll cohorts four and five at a higher rate. The second RGX314 clinical trial is a phase two trial for the treatment of diabetic retinopathy entitled Alps. Similar to Aviate, patients in this trial do not receive prophylactic immune-suppressive cortical steroid therapy before or after Cohert One had positive initial data that demonstrated supercordial delivery of RGX314 was well tolerated in 15 patients with no drug-related serious adverse events. No interocular inflammation was observed, and 33% of patients demonstrated a two or more step improvement from baseline on a standardized diabetic retinopathy severity scale compared to 0% of patients in the observational control.

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

As a reminder to ask a question you will need to press star one on your telephone keypad.

Again that is star one on your telephone keypad.

You have your first question coming from the line of Annabel <unk> from Stifel. Your line is now open.

Hi, Thanks for taking my question.

I have a few so first for sure less.

Acts in cohort two.

I just want to verify whether this would be the same heavily pretreated population.

You saw in cohort one.

And.

See you at it on a three month extension that was not part of cohort one as well.

Alright, I think that was just a one month. So just can you go through those details one more time in for cohort three youre going to be adding or sorry, you're going to be increasing dose again to 10 times of what it was cohort. One are you also adding extension studies for that one.

I think I missed that.

And.

And then you know all of us.

Dr. Thomas Chula: Cohort 2 is currently enrolled. And cohort three is currently enrolling patients with positive and neutralizing antibodies. In addition, our partner, Orobioscience, has presented the first set of data utilizing supercoital delivery to treat coerdle melanoma, the most common primary ocular cancer in adults, or reported that Supercoral Administration, a SCS microinjector, may improve the therapeutic index and optimize treatment parameters for AU011, or is currently running a phase two trial comprised of an open-label dose escalating In October, the order reported the following.

So again on CLS Ax.

Obviously, the treatment landscape is evolving to go longer and longer some are already pushing out to six months.

Anything for a year.

I know that you're also aiming for that six to 12 months.

If you don't reach that durability, where is it that you have.

M to modify is it primarily in the dose or is there something in the formulation.

Okay.

Yes.

For SCS delivery.

And I've got a couple more follow ups. Thanks.

Tom you want to take the first several of those questions.

Yes, thanks, everyone.

So I asked.

Sorry.

So let me take I think the first one was about the extension study. So so if you call cohort one was with a very low dose.

0.03 milligrams.

And we did not include an extension study for that.

For cohort two and beyond we are adding a three month extension study. The primary study includes three months of follow up.

In all cases, including cohort one.

And then the extension study include another three months of follow up after the initial dose it will be six months of follow up. So I think that was your first question. The second question was I think you were asking what the cohort three dose is we've already announced that we.

Dr. Thomas Chula: Interim Safety data showed no treatments related serious adverse events, dose limiting toxicities, or grade three adverse events. Cohorts 1 through 5 are fully enrolled with a total of 13 patients, and cohort six is enrolling. The randomized phase of the trials planned to begin in the second half of 2022 in patients with documented growth to establish the safety and efficacy of AU011 and serve as the first pivotal trial for the treatment of indeterminate lesions and corto melanoma.

We intend to use the <unk> three milligram dose and yes. It is a tenfold increase.

And the dosing versus cohort one.

And I should add that.

The primary focus of this study is safety because it has to be this is a first in man study.

Study using a tyrosine kinase inhibitor in a supercritical space. So we're purposely starting low and we're purposely escalating gradually.

Safety is a primary concern as I mentioned in my prepared remarks.

Ben.

Some well publicized safety issues with with other companies in this space using biologics and although we're confident in our safety profile, we feel that a small molecule may have less intrinsic risk of an inflammatory response, we're still very much focused on safety.

Dr. Thomas Chula: The continued progress by Rogenics Bio and OroBioscience is very encouraging, and we look forward to their ongoing clinical trial results. Before I conclude my discussion, I would like to touch on an Integrate and Gene Therapy program. We're working on intricate formulation studies that will continue into 2022, as our research team is currently running preclinical studies, including pharmacokinetic work assessing ocular distribution. In our gene therapy program, this year, we presented and published data, including preclinical studies and supracutally delivered non-viral DNA nanoparticles containing the Myo 7 gene, which causes Usher syndrome, and is too large to fit in an AV vaccine.

Dr. Thomas Chula: Outside of our existing gene therapy licensing relationship with genic Spinal, we have the opportunity to partner with other companies working on gene therapy using non-viral vectors or viral vectors targeting diseases that are not primarily treated with current standard of care anti-vege-f therapies, such as geographic atrophy and inherited retinal diseases, including Usher syndrome or start-art disease. In closing, we continue to remain active within the retina physician community, with 10 presentations recently given We'll also have three Zipair presentations at the American Academy of Ophthalmology meeting this week. These presentations and other ongoing interactions with leaders in the field continue to generate interest in the supercoral space and the potential for physicians to adopt this procedure in their practice. I will now turn the call over to our CFO, Charlie Degman, to review our financial results. Thanks, Tom.

Better efficacy and we've seen that with another company using blockade of a veg F. C. N D in conjunction with VEGF a inhibition in their phase two trial.

They showed.

Superior results over VEGF, a only blockage of course, there were two injections every month, but nevertheless, conceptually it suggests that blocking.

Charles A. Deignan: Thanks, Tom. Our financial results for the third quarter were published this afternoon in our press release and are available on our website. Therefore, I will summarize our current financial status. Our cash and cash equivalence as of September 30th, 2021 totals approximately $25.2 million, which includes the $3 million in payments from Arctic Vision for the expansion of their licensed territory scores atypier. Our quarterly cash burn is primarily due to the activities related to our CLSA program and obtaining approval for Zypier.

[noise] multiple forms of that Jeff could lead to better efficacy outcome. So.

We think our approach.

Multiple potential benefits, including durability and <unk>.

<unk>, Jeff blockade, which has potential for their efficacy.

And you're gonna be enrolling the same treatment experienced population correct.

Yeah. So all patients how to have had prior treatment in this study and.

It's a great question because in.

In a way we're choosing the most difficult patients to treat initially user patients who've been very treatment experienced in our cohort one the average of 26 prior injections and.

And they had to have persistent activity confirmed by mask Reading Center assessment of imaging, but these are patients who are.

Charles A. Deignan: Investments in our broader research pipeline are also incorporated into their operating area. With the approval of Zypier, we anticipate receiving a total of $19 million in non-dilutive funding for approval and pre-launch milestones from our commercialization partners. We expect these funds, along with the $5 million of deferred revenue from the Bowsup Front Payment, will be recorded in the fourth quarter of 2021 as licensed revenue on the income statement. This additional capital will be utilized to advance our clinical development pipeline led by CLSA.

Highly VEGF anti VEGF treatment dependent with the persistent dizzy so so it's.

It's a very high bar and we simply our King our initial studies on safety, but but yes, very highly treatment experienced and it sets a high bar.

Okay. If I could just squeeze in one more question about the partnership programs and noticed that I have a signed agreement with <unk>. Thanks for their subretinal formulation for three one for.

To what extent could this involves S. Yes delivery in the future do you have any options for them to to sort of expand into the US yes delivery of it I'm just curious if there are any behind his discussions there. Thanks.

Charles A. Deignan: Based on our current funding and planned spend, we now expect to have sufficient resources to fund our operations into 2020. We appreciate the interest and support from our shareholders and the broader investment community, and we look forward to participating in several virtual investor events over the next few weeks. The Defoe Health Care Conference, the Piper Sandler Healthcare Conference, and the UBS Optomology Conference. I will now turn the call back over to George for his closing remarks.

Let me take that one.

We have not seen the the details of the F B rejects deal.

Guess it close today I'm resigned some time ago, but then it obviously close today, but our understanding is that the deal is not limited to Subretinal. It's.

It's it's all as any form of administration of our G X 314.

Okay. That's all right then.

Yep.

Your next question comes from the line I'll see Chen from each feel lean right. Please go ahead.

George Luzeske: In closing, I'd like to take a moment to recognize the accomplishments of our team here at Clearside. Their hard work and dedication for the past several years have taken Zypier through discovery, research, clinical development, and ultimately to FDA approval. I'm extremely proud of their efforts to get Zipur to the finish line. I'd also like to thank our shareholders, clinical investigators, and board of directors, who have supported us through this multi-year process

Hi, Thank you for taking my question can you remind us who are the which drugs are the major competitors on the market today was ikea.

Do you want to pick up.

Sure.

You know I think the the the obvious competitor Arizona's. Your next it's also a steroid just delivered individually.

Ours is a steroid deliver super quarterly so I think that's probably the most analogous of course, there's others as you take an <unk> and then there's a whole host of other therapies given systemically anti metabolite.

George Luzeske: Our recent success only inspires us to continue to move forward as we focus on advancing CLSAX through its clinical program and exploring future opportunities to make a difference in the lives of patients suffering from sight-threatening diseases.

But you know there's positions like to to use local therapy.

And so the field of competition for local therapy.

You know is still somewhat limited and we think are a purchase <unk> quite a delivery is very much differentiating feature as I mentioned in my prepared remarks.

We target the effective quarterback tissues, but we're essentially injecting the therapy directly into the affected tissues.

The therapy is compartmentalize away from the front of the I, which is potentially very important for a corticosteroid as you know corticosteroids.

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone keypad. Again, that is star 1 on your telephone keypad. You have your first question coming from the line of Annabelle Samimi from SPFEL. Your line is now open.

Can increase the risk of ocular hypertension, glaucoma and cataracts, we have pharmacokinetic data showing that.

We do indeed, compartmentalize, a steroid away from the front of the eye and we have a really robust safety profile in in our various you'll be attic macular edema studies, especially the Peachtree Azalea studies, we've also shown durability and our Magnolia studies. So so there is competition, but we think that.

Annabel Eva Samimy: Hi, thanks for taking my question. I have a few.

Our approach is very differentiated and has.

Annabel Eva Samimy: So first, for CLS AX and cohort 2, I just want to verify whether this would be the same heavily pre-treated population that you saw in cohort 1. And, you know, you added on the three-month extension that was not part of cohort one as well, right? I think that was just one month. So just can you go through those details one more time?

Potential benefits over other therapies.

Got it second question do you believe C. O S X has to be has to show superiority over a flu shot to be commercially successful in the future.

That's really great question. That's important question, but it's it's we're just at the very beginning innings of this with a ballgame.

This is just a.

Very simple straightforward single dose escalating study and it would it would have to be you know.

Everything stayed independent and as we go on.

Annabel Eva Samimy: And for cohort three, you're going to be adding, sorry, you're going to be increasing the dose again to 10 times what it was. For cohort 1, are you also adding extension studies to that one? I think I missed that.

So we.

We have potential to show better durability.

Then existing therapies, we are potentially showed better efficacy than existing therapies, and because we compartmentalize the drug and the space and we use a small molecule instead of a biologic with potential the show maybe better safety, but again all this is all speculative I think that's everything.

Annabel Eva Samimy: And then, you know, also again on CLSAX, obviously, the treatment landscape is evolving to go longer and longer. Some are already pushing out to six months, aiming for a year. I know that you're also aiming for that six to 12 months. If you don't reach that durability, where is it that you have room to modify? Is it primarily in the dose, or is there something in a formulation?

[noise] is data dependent.

Got it thank you.

Next question is from Andrea I, you're right on a red Bush. Please go ahead.

Alright, Thank you and good evening.

Congrats on the progress during the quarter.

So just some thoughts I've used those questions for Tom on the the Regina expiry data that was recently.

Annabel Eva Samimy: that you can adjust for SCS delivery. And I've got a couple more follow-ups. Thanks.

Presented to get your thoughts on.

<unk> get your thoughts on the data, but also how you see them either as.

Dr. Thomas Chula: Tom, you want to take the first several of those questions? Yes, thank you. A few of the 20 questions I asked.

Ah Ah Ah leave through to the CLS X program.

Yeah, just just talk on those that'd be great. Thanks.

Dr. Thomas Chula: Sorry. So let me take you. I think the first one was about the extension study. So, if you recall, cohort one was a very low dose, 0.03 milligrams, and we did not include an extension study for that. For cohorts two and beyond, we are adding a three-month extension study. The primary study includes three months of follow-up in all cases, including cohort one. And then the extension study includes another thing. three months of follow-up after the initial dose. So it'll be six months of follow-up.

Let me take your second question first I think there is very little read through Uhm two two R. C O S X program.

They're they're utilizing the gene therapy, it's a viral vector we're using a small molecule it's not a biologic uhm.

If I didn't know any of their data uhm I would predict that.

A small molecule have some potentials safety benefits because.

It doesn't have potential for an immune response like a viral vector does.

But.

The second half of your.

Question. The first half to your first question now I'm very excited about their data I actually I think their data is very very compelling. So far it's early they're diabetic retinopathy data in particular.

We had a really clean safety profile.

Dr. Thomas Chula: So I think that was your first question. The second question was, I think you're asking what the cohort three dose is. We've already announced that we intend to use the 0.3 milligram dose, and yes, it is a tenfold increase in the dose compared to cohort one. I should add that, you know, the primary focus of the study is safety, because it has to be, this is a first in man study using a tyrosine kinase inhibitor in a supercordial space. So we're purposely starting low, and we're purposely escalating gradually because safety is our primary concern.

I think this paved the way for Super Cordle gene therapy delivery, which of course is an office procedure as opposed to Subretinal surgery I was at spark previously and helped launch <unk> help train occuring.

After gene therapy treatment centers and as you know.

Administration of luck Stern, most other gene therapies and involve subretinal delivery in which the trip to the operating room with Vitrectomy Ah.

A hole in the written out of a call in Vietnam, even check the therapy under the retina you create a limited retinal detachment all of which has potential to cause problems. So in in office gene therapy, a delivery would be.

Really fantastic not just for <unk> bio and clear side, but really for the entire field. So I think that rejects file is doing some really important work.

Dr. Thomas Chula: As I mentioned in my prepared remarks, you know, there have been some well-publicized safety issues with other companies in the space using biologics. And although we're confident in our safety profile and we feel that a small molecule may have less intrinsic risk of an inflammatory response, we're still very much focused on safety. So we are escalating.

And advancing the entire field and I think they're diabetic retinopathy study data is very exciting.

Oh, just a quick follow up again your thoughts as a retinal specialist any.

Possible explanations for the difference in the information or a T and both studies uniform as you mentioned cleaning diabetic retinopathy, but there was something speakers and the wedding in the study.

It's hard for me to comment on other companies a trial. Although we are we are partners with them and work with them closely I don't have access all the data they do but but from from a fire I can say that just just reflect what they've said is that if.

Dr. Thomas Chula: I think your third question was about durability, and this is a conversation we have a lot with other KOLs and investors. And, you know, everybody talks about prolonged durability, six months, one year, one and done. But the truth of the matter is that we don't have anything right now that's beyond three or four months. And even if, you know, if you look at some of the therapies that are about to be approved, when they talk about three and four months of durability, it's only a fraction of the patients that go that long.

[noise] formation they've seen.

In their A&D patients was in a minority occasions it was subclinical.

It was treated with topical therapy. It was it was.

It was limited it really didn't have any.

Meaningful safety effect and also.

Again, it's very early and.

And I think time will tell but I do think.

Their actions speak to their confidence in the approach because their dose escalating an additional cohorts so to meaningfully higher dose.

Dr. Thomas Chula: You know, there's an aspirational bar of durability that's quite high, but the reality is far lower. So we think that, you know, durability somewhere in the sweet spot of three months. Retina physicians are going to evaluate their patients at least once a quarter, regardless of the durability of the therapy. And anything beyond that, obviously, is great. But I think the reality is that it's set much lower.

They are assessing this in patients who are neutralizing antibody positive for the vector and they're not using corticosteroid I mean immune suppressive regimen. So I think.

To me that shows that they are very very.

Very meaningful confidence in their approach and and the safety of their approach.

Okay, great. Thanks, I'll jump back into to appreciate the economy.

Your next question is from John <unk> from G. N P security. Your line is now open.

Hey, Congrats on all the progress and thanks for taking my questions. A couple quick ones for me I know you are targeting five patients in each code orange at six and Kolar, one I don't think I've seen.

Dr. Thomas Chula: And then I think your fourth question was, you know, what else does this approach offer besides durability. And as I mentioned in my prepared remarks, Exitinidin is a very, very highly potent hyrigenin inhibitor. Because it's a pan-VGF inhibitor, there's potential for it to not only be durable because of its formulation in the supercordal space, but there's also potential for it to have better efficacy. And we've seen that with another company using a blockade of VEGF, C, and D, in conjunction with VEGFA inhibition.

You say, how many patients have been dosing quarters. So I was hoping you could let us know that and then also you started dosing of core three and if not why not that might kick off.

Uhm.

We are available publicly that we've completed dosing and cohort too and.

As you might recall from the study design.

Patients are followed three months after they received CLSA ask we have a safety monitoring Committee meeting review all the data and then.

A side on dose escalation. So we have not started cohort three yet.

Okay, and how many patients did your dose of color too.

I think.

All we all we've really talked about is the total number of patients the approximate number of total patients and the three cohorts.

Dr. Thomas Chula: In their phase two trial, they showed superior results over VEGFA-only blockage. Of course, there were two injections every month, but nevertheless, conceptually, it suggests that blocking multiple forms of VEGF could lead to better efficacy outcomes. So we think our approach, you know, has multiple potential benefits, including durability and pan-VGF blockade, which has the potential for better efficacy.

That's right. So we come out and said that we were targeting.

Five patients per cohort.

And I think that's all we've disclosed publicly.

Okay and back to an earlier question you mentioned that these patients are pretreated. So my guess is we're not going to see much wiggle and <unk>.

Thickness, but you did see nice improvements in D. C. VA in cohort one is the expectation to see dose dependent increases in B C. Game. These patients or is there a ceiling, perhaps given the stage of the disease or is it more of the durability that we want to see in terms of retreat and I'm. Just wondering what you were expecting when we get to these.

Dr. Thomas Chula: And you're going to be enrolling the same treatment experience population, correct?

Dr. Thomas Chula: Yeah, so all patients have to have had prior treatment in this study. And, you know, it's a great question because, in a way, we're choosing the most difficult patients to treat initially.

[noise] doses.

Oh, that's a great question.

With small numbers of patients uhm.

It's hard to hard to spot with small number of very treatment experienced patients. It's hard to speculate what we're going to see I think what we saw was a pleasant surprise, because we weren't expecting these patients to improve and again with small numbers of treatment experienced patients.

Dr. Thomas Chula: These are patients who've had a lot of treatment experience in our, in Covert 1, the average of 26 prior injections, and they had to have persistent activity confirmed by Mask Reading Center assessment of imaging. So these are patients who are highly VEGF or anti-VGF treatment dependent with persistent disease, so it's you know it's a very high bar, and you know we simply are keying our initial studies on safety, but yes, very highly treatment experience, and it sets a high bar.

There could be.

Ceiling.

Effects with visual acuity improvement in for effects with CST improvement, we did see some for effects and CST improvement and cohort one so it's hard to predict and really this study as a safety study and.

But we didn't want to do is continue the dose escalation.

Until we find.

Find a dose that is both safe and shows.

Meaningful signs of biologic activity.

Got a fair enough. Thanks again for taking my questions.

Yeah last question is from is that last summer I forgot that I'm finding please go ahead.

Dr. Thomas Chula: Okay, and if I could just squeeze in one more question about partnership programs, notice that Abby signed an agreement with Regenics Bio, I think, for their subretinal formulation for 314. To what extent could this involve SCS delivery in the future? Do you know if there are any options for them to sort of expand into the SCS delivery of it? I'm just curious if there were any behind-the-scenes discussions there. Thanks. Let me take that one.

Hi, guys. Thanks for taking my customer congrats on the Apple.

Sure I can.

Yeah, just have three quick questions. The first one was just about your thoughts on the <unk> <unk> <unk> <unk> <unk> <unk> <unk> <unk> <unk> pieces, but ours just went with it Tom perhaps we can talk about how you see it the hurdle unlucky cheated person so naive.

<unk> and you're not the timeline, perhaps they're purple, which could be faster and then the second one is just because both coming up a little differently gentle filled out in terms of the coffee I'd like debating Jack table for the zipper collateral space can you talk a little bit about the propriety proprietary suspension that's <unk> that's <unk>.

Dr. Thomas Chula: Let me take that one. We have not seen the details of the Avv Regenics deal. I guess it closed today. It was signed some time ago, but then it obviously closed today. But our understanding is that the deal is not limited to subruth. It's all, it has some form of administration of RGX 314. That's our understanding.

Is that the same suspension for all Sir I say ask them, what kind of books coffee you guys look for and what are you trying to optimize what with that that poverty and then the last bit yeah is Ah Ah comment on inherited retinal disease that time, I think you mentioned it and I never focused <unk>, but I was just wondering if you guys.

Operator: Your next question comes from the line of Yi Chan from H.C. Wainwright. Please go ahead. Hi, thank you for taking my question, King.

Yi Chen: Hi, thank you for taking my question. Can you remind us who are the, which drugs are the major competitors on the market today for Zypia? Tom, do you want to take that? Sure.

Can comment on how you're thinking about that opportunity and if that could be a partnership all you could do it independently.

Dr. Thomas Chula: You know, I think the obvious competitor is Andrejave. It's also a steroid, delivered individually. Ours is a steroid, delivered super quarterly. So I think that's probably the most analogous. Of course, there are others. There's Utique and Redisert.

Sure. So you have to have a competitive landscape initially as I mentioned earlier.

I think there's a little bit of a disconnect between the the sort of aspirational uhm.

Durability, and what we see in reality.

Dr. Thomas Chula: And then there's a whole host of other therapies, you know, given systemically anti-metabolize. But, you know, physicians like to use local therapy. And so the field of competition for local therapy is still somewhat limited.

Right now patients are are dependent on very frequent fixed uhm dosing, we know if most patients in.

In the United States or Undertreated, because they simply can't come in often enough to receive their therapy and ultimately they're they're they're they're real world outcomes are pretty poor and I published on this extensively in the past.

Dr. Thomas Chula: And we think our approach of supercoidal delivery is very much a differentiating feature. As I mentioned in my prepared remarks, we target the affected coronetinal tissues, but we're essentially injecting the therapy directly into the affected tissues. The therapy is compartmentalized away from the front of the eye, which is potentially very important for a cortical steroid. As you know, cortical steroids can increase the risk of ocular hypertension, glaucoma, and cataract. We have pharmacokinetic data showing that we do indeed compartmentalize a steroid away from the front of the eye.

And then.

So if you use on label they can do okay and.

Don't have therapy to prove that.

And.

Meaningful fraction of patients they could potentially go three to four months.

And so I I also think most of the therapies out there are anti VEGF, a so I think I think.

CLSA acts as well position potentially with respect that your ability and the fact that the pan VEGF inhibitor that we we've leveraged yet further by by targeting the affected tissue to really get high levels were and burnt them and keeping it away from unaffected tissues.

As I mentioned earlier I also think we have potential safety benefits with Ah well characterized small molecule like except nib over a complex biologic.

Dr. Thomas Chula: And we have a really robust safety profile in our various uveitic macular deema studies, especially the peach tree azalea studies. We've also shown durability in our magnolia studies. So, you know, there is competition, but we think that our approach is very differentiated and has, you know, potential benefits over other treatments.

So like I think I think C O S X could fit very well into the competitive landscape and then and I also think that.

Again, it's data dependent but.

We don't know if it will be used for maintenance.

Operator: Got it. And second question, do you believe CLS-A-X has to show superiority over Flitha-Sep to be commercially successful in the future?

Of efficacy because of its potential durability wherever you use is potentially the primary mile therapy or used even in refractory cases, so I think it will fit well into the competitive landscape for your second question about formulations I'm not sure how much of this we've disclosed publicly on the George if you want to take that one.

Dr. Thomas Chula: You know, that's a really great idea.

Dr. Thomas Chula: You know, that's a really great question, it's an important question, but we're just at the very beginning innings of this ball game. This is just, you know, a very simple, straightforward, single-dust escalating study, and it would have to be, you know, everything is data-dependent and as we go along. So, you know, we have the potential to show better durability than existing therapies. And we have the potential to show better efficacy than existing therapies.

Formulations of <unk> of us.

<unk> hear an accent and then.

George.

Anyway.

I can just say that I don't think we discuss the formulation in detail.

But basically you know these are small molecule suspensions I mentioned that the durability is driven by the relative install your ability of the of the suspension as well as the particle size and so that that's what drives the durability and we've seen this with.

A multitude of small molecule suspensions pretty clinically.

Dr. Thomas Chula: And, you know, because we compartmentalize the drug in space and we use a small molecule instead of a biologic, we have the potential to show maybe better safety. But, again, all this is speculative. I think everything is data-dependent.

Seen it with with.

<unk>, we've seen it with except nib we.

We've seen it with a compliment inhibitor as well as a plasma account can inhibitor.

And what's.

What's really encouraging now.

With respect to XI peers that it's been approved and so we were seeing read through of what we saw pre clinically known to the clinic.

Operator: The next question is from Andreas. Are you right from a red bush? Please go ahead.

Andreas Argyrides: Thank you and good evening. Congratulations on the progress during the quarter. So just some thoughts. I guess this question is for Tom on the Regenics bio data that was recently presented and to get your thoughts on, well, one, the data, but also how you see them either as a read-through to the CLS-A-X program. Yeah, just your thoughts on those. That would be great. Okay.

Especially with respect to our Magnolia study, which suggested durability.

And then finally as I thought you asked about uhm inherited retinal diseases.

We think that that rejects by was paving the way for supercritical delivery of gene therapies.

And obviously that would.

Include gene therapies for inherited retinal disease, we also believe that supercoil delivery.

Covers a large surface area potentially of the poster of hole cut.

Covers it peripherally in post earliest circumstantially and so in theory supercoil deliver it could provide an in office means to expose a large surface area periphery of the retina, which may line itself really well to the treatment of inherited retinal disease, which start and then that will periphery.

Dr. Thomas Chula: Let me take your second question first. I think there is very little read-through to our CLSAX program. You know, they're utilizing a gene therapy, it's a viral vector, we're using a small molecule. You know, it's not a biologic. You know, if I didn't know any of their data, I would predict that, A small molecule has some potential safety benefits because It doesn't have potential for an immune response, like a viral vector does, but, to the second half of your question the first half to your first question now I'm very excited about their data I actually think their data is is very very compelling so far it's early their diabetic retinopathy data in particular you know we had a really clean safety profile I think this paves the way for supercordial gene therapy delivery which of course is an in-office procedure as opposed to subretinal surgery I was at Spark previously and helped launch lexstrandall help train the ocular gene therapy treatment centers and as you know administration of luxurna and most other gene therapies involve subretinal delivery which is a trip to the operating room of the Trectomy a hole in the retina that we call retinony and eject the therapy under the retina you create a limited retinal attachment all of which you know has potential to cause problems so an in-office gene therapy delivery would be really fantastic not just for regentics bio and clear side but really for the entire field. So I think that Regenics Bio is doing some really important work on in advancing the entire field. And I think the diabetic retinopathy study on data is very

So as I mentioned earlier that field is still open for collaboration we've also looked at that a preclinical with DNA nanoparticles and published and presented that that at Argonne. This year.

Thanks.

That concludes the these conference call. Thank you all for participating you mean now disconnect.

Thank you.

[music].

Andreas Argyrides: Just a quick follow-up, again, your thoughts as a retina specialist. Any possible explanation for the difference in the inflammation rates in those studies, you know, from, as you mentioned, clean and diabetic retinopathy, but there were some instances in the wet A&D study?

Dr. Thomas Chula: You know, it's hard for me to comment on another company's trial, although we are partners with them and work with them closely. I don't have access to all the data they do, but, from afar, I can say that just reflect what they've said is that the inflammation they've seen in their AMD patients was in a minority of patients. It was subclinical. It was treated with tropical therapy.

Dr. Thomas Chula: It was limited. It really didn't have enough. any meaningful safety effect. And also, you know, again, it's very early, and I think time will tell. But I do think, you know, their actions speak to their confidence in the approach because they're dose escalating an additional cohort, so to a, you know, a meaningfully higher dose. They're assessing this in patients who are neutralizing antibody positive for their vector, and they're not using cortical steroid immune suppressive regimen. So I think, To me, that shows that they have very, see, very meaningful confidence in their approach and in the safety of their approach.

[music].

Andreas Argyrides: Okay, great, thanks. I'll jump back in the queue. Appreciate the comment.

Operator: Your next question is from John Walden, from JMP Securities. Your line is now open.

Jonathan Patrick Wolleben: Hey, congrats on all the progress and thanks for taking the questions. A couple quick ones for me. I know you're targeting

Jonathan Patrick Wolleben: I know you're targeting five patients in each cohort. You had six in cohort one. But I don't think I've seen you say how many patients have been dosed in cohort two, so I was hoping you could let us know that. And then also, if you started dosing in cohort three, and if not, when that might kick off.

Dr. Thomas Chula: We've announced publicly that we've completed dosing in cohort 2. And as you might recall from the study design, patients are followed for three months after they receive CLSAX. We have a safety monitoring committee meeting, review all the data, and then, you know, decide on dose escalation. So we have not started cohort three years ago.

Jonathan Patrick Wolleben: Okay, and how many patients did you dose in cohort two?

Dr. Thomas Chula: I think Tom, all we've really talked about is the total number of patients, the approximate number of total patients in the three cohorts.

Dr. Thomas Chula: That's right. So we come out and say that we're targeting five patients per cohort, and I think that's all we've disclosed publicly.

Jonathan Patrick Wolleben: that these patients are pre-treated, so my guess is we're not going to see much wiggle in retinal thickness, but you did see nice improvements in BCVA in cohort one. That is the expectation to see

Dr. Thomas Chula: Well, that's a great question. You know, with small numbers of patients, You know, it's hard to, a small number of very treatment experienced patients. It's hard to speculate what we're going to see. I think what we saw was a pleasant surprise because we weren't expecting these patients to improve. And again, with small numbers of treatment experienced patients, there could be, you know, sealing effects with visual acuity improvement and four effects with CST improvement. We did see some four effects and CST improvement in cohort. one.

Jonathan Patrick Wolleben: So it's hard to predict. And really, the study is a safety study. And, you know, what we really want to do is continue the dose escalation until we find a dose that is both safe and shows, you know, meaningful signs of biological activity.

Operator: Got it. Fair enough. Thanks again for taking the question. Your last question is from Zegh de Jala, from Ross Capital Partners.

Zegh de Jala: Your last question is from Zegh de Jala, from Ross Capital Partners. Please go ahead.

Zegh de Jala: based studies in pre-treated or treatment naive patients, but I was just wondering if, Tom, perhaps you could talk about how you see the hurdle in the pre-treated versus the naive setting and, you know, the timeline for their approval, which could be faster. And then the second one is just because this came up a little bit from the regentic data in terms of the viscosity of what's being injected into the supercarotidyl space, can you talk a little bit about the proprietary suspension that dipyriorizant uses?

Zegh de Jala: And is that the same suspension for CLSAX? And what kind of viscosity do you guys look for? And what are you trying to optimize for with that viscosity? And then the last bit here is a comment on inherited retinal diseases. Tom, I think you mentioned it.

Dr. Thomas Chula: And I know the focus still remains on CLSAX, but I was just wondering if you guys can comment on how you're thinking about that opportunity and if that could be a partnership or you could do it independently.

Dr. Thomas Chula: Sure. So you initially asked about the competitive landscape. You know, as I mentioned earlier, I think there's a little bit of a disconnect between the sort of aspirational durability and what we see in reality. You know, right now, patients are dependent on very frequent, fixed doses. We know that most patients in the United States are under-treated because they simply can't come in often enough to receive their therapy. And ultimately, their real-world outcomes are pretty poor.

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Dr. Thomas Chula: And I've published extensively on this in the past. And then, you know, so if you use them on label, they can do okay. And, you know, we'll soon have therapies approved that, you know, in a meaningful fraction of patients, they can potentially go three to four months. And so I also think most of the therapies out there are anti-vegetarian FAA. So I think CLSAX is well positioned potentially with respect to durability and the fact that it's a Pan Vegg F inhibitor that we leverage that further by targeting the affected tissues to really get high levels where we want them and keeping it away from unaffected tissues.

Dr. Thomas Chula: As I mentioned earlier, I also think we have potential safety benefits with a well-characterized small molecule like exitinib over a complex biologic. So I think COX could fit very well into the competitive landscape. And I also think that, you know, again, it's data dependent, but we don't know if it will be used for maintenance of efficacy because of its potential durability, or it would be used as, you know, potentially as a primary mile therapy or used even in refractory cases. So I think it will fit well into the competitive landscape.

Dr. Thomas Chula: For your second question about formulations, I'm not sure how much of this we've disclosed publicly. I don't know, George, if you want to take that one, formulations of xipier and excitinib, George? Anyway, I can just say that I don't think we've discussed the formulation in detail. But basically, you know, these are small molecule suspensions. I mentioned that the durability is driven by the relative insoluability of the suspension as well as the particle size. And so that's what drives the durability.

Dr. Thomas Chula: We've seen this with a multitude of small molecule suspensions preclinically. We've seen it with the Trinamillin or Zypyr, we've seen it with Exitinib, we've seen it with a complement inhibitor, as well as a plasma calico inhibitor. And, you know, what's really encouraging now with respect to Zypure is that it has been approved. And so we're seeing read-through of what we saw preclinically now into the clinic, especially with respect to our Magnolia study, which is just the durability.

Dr. Thomas Chula: And then finally, Zegva, you asked about inherited retinal diseases. You know, we think that Regenics Bio is paving the way for the supercordal delivery of gene therapies. And obviously, that would include gene therapies for inherited retinal disease. We also believe that supercordial delivery, you know, covers a large surface area, potentially, of the poster of the hole. It covers it peripherally, and posterally, and circumferentially. And so, in theory, supercordial delivery could provide an in-office means to expose a large surface area of the periphery of the retina, which may lend itself really well to the treatment of inherited retinal diseases, which start in the retinal periphery. So, as I mentioned earlier, you know, that field is still open for collaboration. We've also looked at that preclinically with DNA nanoparticles and published and presented that at our vote this year. Thanks, Tom.

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Operator: That concludes this conference call. Thank you all for participating. You may now disconnect.

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