Q4 2019 Earnings Call

Operator: Ladies and gentlemen, please stand by. Your conference call will begin momentarily. Once again, please stand by. Your conference call will begin momentarily. Thank you for your patience and please continue to hold... [inaudible] BF-WATCH TV 2021 BF-WATCH TV 2021 (inaudible) Ladies and gentlemen, thank you for standing by and welcome to the Clearside Biomedical 4th Quarter 2019 Financial Results and Corporate Update Call. At this time, all participants are in a listen-only mode.

Ladies and gentlemen, please standby your conference call will begin momentarily once again. Please standby your conference call will begin momentarily. Thank you for your patience and leased continue to hold.

[music].

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. As a reminder, today's program may be recorded. I would now like to introduce your host for today's program, Jenny Kobin, from Investor Relations. Please go ahead.

Ladies and gentlemen, thank you for standing by welcome to the Clearsight Biomedical fourth quarter 2019 financial results in corporate update call. At this time all participants are in listen only mode. After the speakers presentation. There will be a question and answer session to ask a question during the session you'll need to press star one on your telephone.

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 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, 2018, our quarterly report on Form 10-Q for the quarter ended 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.

As a reminder, taste program may be recorded I would now like to introduce your host for today's program Jenny Kobin Investor Relations. Please go ahead.

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

The private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factor section of our inner report on form 10-K for the year ended December 31st 2018 are.

Quarterly report on form 10-Q for the quarter ended September Thirtyth 29 team and our other SBC filings available on our website.

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

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

George M. Lasezkay: On today's call, George Lasezkay, our President and Chief Executive Officer, will provide a strategic update. Dr. Thomas Chula, our Chief Medical Officer, will provide R&D highlights. And Charlie Deignan, our Chief Financial Officer, will provide a financial summary. We will then open the call for your questions.

On today's call George was ASCII, our president and Chief Executive Officer will provide strategic update.

Dr. Thomas Ciulla, our Chief Medical Officer will provide R&D highlight.

And Charlie Bracken, our Chief Financial Officer will provide a financial summary, we we'll then open the call for your question.

I would now like turn call over to George.

George M. Lasezkay: Thank you, Jenny. Good afternoon, and thank you for joining us on the call today. During 2019, the management team and I worked closely with our board of directors to re-evaluate the company's overall strategy. In August, we announced our plans to out-license rights to our lead asset, Zypion, in order to dedicate our resources to further developing our proprietary supercoroidal space, or SDS, injection platform. Our two-pronged strategy includes building an internal research and development pipeline in areas such as novel small molecules and gene therapy, as well as creating strategic collaborations with other companies to enable access to the SES to deliver their proprietary product candidates. I'm tremendously proud of the entire Clearside organization. They embraced this plan and worked tirelessly to accomplish these strategic objectives.

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

During 2019, the management team and I worked closely with our board of directors to reevaluate the company's overall strategy.

In August we announced our plans to out license rights to our lead asset type here in order to dedicate our resources to further develop our proprietary suprachoroidal space risks, yes injection platform.

Our two prong strategy includes building, an internal research and development pipeline in areas such as novel small molecule and gene therapy.

As well as creating strategic collaborations with other companies to enable accessed the S. Yes to deliver their proprietary product candidates.

I'm tremendously proud of the entire Clearside organization.

They embrace this plan and worked tirelessly to accomplish these strategic objectives.

George M. Lasezkay: In less than one year, we've added two validating R&D collaborations that will begin using our SCS microinjector in clinical trials in 2020. We've concluded preclinical studies for asset CLS-AAC and plan to begin a clinical trial later this year. We've also secured two key partnerships to further develop and commercialize DIPIR in the U.S., Canada, and Greater China.

In less than one year, we've added to validating R&D collaborations that will begin using our SCS micro injector in clinical trials in 2020.

We've concluded preclinical studies.

I said CLS, a acts and plan to begin a clinical trial later this year.

We've also secured two key partnerships to further develop and commercialize type here in the U.S., Canada in greater China.

George M. Lasezkay: Importantly, under these collaborations... We have received non-dilutive funding through upfront payments, and we are eligible to receive over $200 million in potential future development and sales milestone payments, as well as royalties on net sales that can be used to further support our internal R&D efforts. I will now provide an overview of the internal research and development work our team has accomplished as we look to address unmet needs in back-of-the-eye diseases. Our internal initiatives are focused on utilizing the SES injection platform to deliver small molecules that may show prolonged duration, as well as gene therapy using non-viral DNA nanoparticles. As we announced on our last earnings call, we are advancing our proprietary suspension of Excedinib for supracaroidal injection, which we refer to as CLSAX. We completed our preclinical work in 2019 and are targeting submission of an IND application in mid-2020. We have also completed preclinical proof-of-concept studies utilizing supercoroidal delivery of marker genes using DNA nanoparticles.

Importantly, these under these collaborations we have received non dilutive funding through upfront payments.

We are eligible to receive over $200 million in potential future development sales mile milestone payments as well as royalties on net sales that can be used to further support our internal R&D efforts.

I will now provide an overview of the internal research and development work. Our team has accomplished as we look to address unmet needs in the back of the eye diseases.

Our internal initiatives are focused on utilizing the yes, yes injection platform to deliver small molecules that may show prolong duration as well as gene therapy, using non viral DNA nanoparticles.

As we announced on her last earnings call. We are advancing our proprietary suspension of accident. It for Super Choroidal injection, which we referred to as C.L.S.A. acts.

We completed our preclinical work in 2019 and are targeting submission about 90 application in mid 2020.

We have also completed preclinical proof of concept studies utilizing supercritical delivery of marker jeans using DNA nanoparticles.

George M. Lasezkay: These studies demonstrate the potential for SCS administration to deliver genes, so we are now conducting further preclinical work with SCS delivery of therapeutics. Finally, we continue to assess a variety of additional small molecules to discover future potential assets and maximize the value of our versatile platform. Our collaboration partners are also making tremendous progress. Our decision to begin partnering our proprietary technology has validated our investment in suprachoroidal delivery using our SES microinjector. It has also expanded our overall development pipeline to include both gene therapy and small molecules and new indications including choroidal melanoma, wet AMD, and diabetic retinopathy. Last year, we initiated our collaboration with Regenexx Bio, one of the industry leaders in gene therapy fields, to evaluate the potential use of our SES microinjector to deliver adeno-associated virus, or AAV, gene therapy for ophthalmic indication We believe that delivery of gene therapy through the supracarotid space can potentially provide a targeted, in-office, non-surgical approach to treat patients with challenging retinal conditions.

These studies demonstrate the potential for SCS administration to deliver jeans. So we are now conducting further preclinical work with SCS delivery of therapeutic trans genes.

Finally, we continue to assess a variety of additional small molecules to discover future potential assets and maximize the value of our versatile platform.

Our collaboration partners are all thing also making tremendous progress.

Our decision to begin partnering our proprietary technology has validated our investment in Supercom Royal delivery using our SCS micro injector.

It has also expanded our overall development pipeline to include both gene therapy, and small molecules and new indications, including Royal melanoma, wet AMD D and diabetic retinopathy.

Last year, we initiated our collaboration with rejects bio one of the industry leaders in gene therapy field.

Well evaluate potential use of our STS micro injector to deliver Ed no associated virus or a b ophthalmic gene therapy.

We believe that delivery of gene therapy through the supercritical space can potentially provide a targeted in office nonsurgical approach to treat patients with challenging retinal conditions.

George M. Lasezkay: As Tom will discuss shortly, Regenexx Bio plans to initiate clinical trials this year in both wet AMD and diabetic retinopathy using our SES microinjectors. In 2019, we also entered into a collaboration with Aura Biosciences to use our SES microinjector to deliver their proprietary drug candidates for the potential treatment of ocular cancer. This is an area where there is a significant unmet medical need.

As Tom will discuss shortly rejects bio plans to initiate clinical trials. This year in both what Andy in diabetic retinopathy, using our SCS micro injector.

In 2019, we also entered into a collaboration with or a bio sciences.

Use our SCS micro injected to deliver their proprietary drug candidates for the potential treatment of ocular cancers.

This is an area, where there is a significant unmet medical need.

George M. Lasezkay: ORA plans to submit an IND amendment and initiate a clinical trial using our SDS microinjector in the second half of this year. Now, let's move to an update on Xypyr, our proprietary suspension of primed sinulone intended for suprachoroidal delivery via our SES microinjector for the treatment of macular edema associated with uveitis. From a partnering standpoint, we are very pleased to have completed two licensing deals for the commercialization and further development of Xypyr. This afternoon, we announced a new partnership with Arctic Vision for an exclusive license to commercialize and develop Xypyr in Greater China, which includes mainland China, Hong Kong, Macau, and Taiwan, and, in addition, South Korea. Arctic Vision is a specialty pharma ophthalmology company in China, led by industry veterans who have substantial global experience at leading eye care companies, including Allergan, and experience in launching eye care products in China, such as Ajudex.

Or plans to submit 90 amendment and initiate a clinical trial using our SCS micro injector in the second half of this year.

Now, let's move to an update on site here, our proprietary suspension of crime Standalone intended for supercritical delivery by or SCS micro injector for the treatment of macular edema associated with uveitis.

From a partnering standpoint, we're very pleased to have completed two licensing deals for the commercialization and further development of Xavier.

This afternoon, we announced a new partnership with Arctic vision for an exclusive license for the commercialization and development of zipper here in greater China, which includes mainland China, Hong Kong, Macau, and Taiwan and in addition, South Korea.

Arctic vision as a specialty pharma ophthalmology company in China led by an led by industry veterans, who have substantial global experience at leading eye care companies, including our again.

And experience in launching eye care products in China, such as ours you ducts.

George M. Lasezkay: Arctic also has strong resources and backing by top-tier global biotech venture capital investor Pivotal BioVenture Partners, which has a broad network in China, the U.S., and the European ophthalmic market. With this deal, Arctic may receive up to $35.5 million in development and sales milestones. This amount includes a $4 million upfront payment plus additional milestone payments for the achievement of specified events prior to and including U.S. approval. We are also eligible to receive tiered royalties of 10 to 12 percent based on annual net sales of Xypyr in Greater China and South Korea.

Arctic also has strong resources and backing by top tier global biotech.

Venture capital Investor.

Pivotal bio venture partners, which has a broad network in China, the U.S. and European Ophthalmic markets.

With this deal we may receive up to 35, and a half a million dollars in development and sales milestones.

This amount includes a 4 million dollar upfront payment plus additional milestone payments for the achievement of specified events prior to and including U.S. approval.

We're also eligible to receive tiered royalties of 10% to 12% based on annual net sales UBS IP or in greater China and South Korea.

George M. Lasezkay: We look forward to working with the ArcticVision team to help bring Xypyr to the greater China region. In October 2019, we announced that Bausch & Lomb, the ophthalmic division of Bausch Healthcare Company, acquired an exclusive license for the commercialization and development of Zyper in the United States and Canada. Bausch also has the right to pursue development and commercialization of Xipir for additional ophthalmic indications and the right to develop and commercialize our proprietary FCS microinjector in combination with certain other specified corticosteroids and nonsteroidal anti-inflammatory drugs in the field of ophthalmology. Bausch is a well-established and well-regarded ophthalmology company, and they have been an ideal partner for Clearside.

We look forward to working with Arctic vision team to help brings I appeared to the greater China region.

In October 2019, we announced that Bausch and Lomb, the ophthalmic division of Bausch Health care Company acquired an exclusive license for the commercialization and development of Sipe here in the United States in Canada.

Bausch also has the right to pursue development and commercialization UBS I fear for additional ophthalmic indications and the right to develop and commercialize our proprietary SCS micro injector in combination with certain other specified corticosteroids and nonsteroidal anti inflammatory drugs in the field of ophthalmology.

Bounce she is a well established and well regarded ophthalmology company and they have been an ideal partner for Clearsight.

George M. Lasezkay: We are working collaboratively with them across multiple disciplines in order to enhance the medical community's understanding of Zyper through publications and presentations, and appropriately prepare for the ultimate commercialization in the United States and Canada, in terms of the regulatory path forward in the U.S., as we have discussed before. The FDA has previously requested additional manufacturing stability data on the commercial product. The agency has provided clear guidance on the CMC data that it needs, and we have been working closely with Bausch and our contract manufacturer to formulate plans to produce the required final drug product material and obtain the requested stability data from new registration batches of Zypex. Furthermore, over the past few months, our manufacturer has been working with the FDA to complete certain manufacturing activities within its facility not specifically related to Zypyr production. This work is still ongoing and has contributed to an additional delay in the production of new Xipyr registration batches and the related stability data.

We are working collaboratively with them across multiple disciplines in order to enhance the medical communities understanding of XY peer through publications presentations and appropriately prepare for the ultimate commercialization in the United States in Canada.

In terms of the regulatory path forward in the U.S. as we've discussed before.

The FDA has previously requested additional manufacturing stability data on the commercial product.

The agency as provided clear guidance on the CMC data that it needs and we had been working closely with bausch and our contract manufacturer to formulate plans to produce the required final drug product material and obtain the requested stability data from new registration batches of zipper here.

Over the past few months or manufacturer has been working with the FDA to complete certain manufacturing activities within its facility not specifically related to zipper production.

This work still ongoing has contributed to an additional delay for production of news I pure registration batches and the related stability data.

George M. Lasezkay: We are working with our manufacturer to finalize the steps necessary to produce the Zyper drug product batches and the data we need in order to resubmit our NDA. We have also compiled the additional data requested by the FDA on the clinical use of the final to-be-marketed SES microinjector delivery system, including data from 160 patients in our TOPAS study for the treatment of macular edema associated with retinal vein occlusion.

We're working with our manufacturer to finalize the steps necessary to produce the zipper your drug product batches and the data we need in order to resubmit R. and D.A.

We have also compiled the additional data requested by the FDA on the clinical use of the final to be marketed SCS, Mike Road micro injector delivery system.

This includes a dataset from 160 patients in our Topaz study for the treatment of vascular DEMA associated with retinal vein occlusion.

Tom Chula: As previously reported, the FDA agreed in meeting correspondence that it would be acceptable for the company to submit such data, and we believe this will satisfy their request. We expect to resubmit our complete Xipir NDA by the end of this August, and we believe the FDA will review the resubmission within six months of the receipt date. And with that, I will now turn over the call to Tom Chula, our Chief Medical Officer. Thank you, George.

As previously reported the FDA agreed in meeting correspondence that it would be acceptable for the company to submit such data and we believe this will satisfy their request.

We expect to resubmit are complete site peer and D.A. by the end of this August and we believe the FDA will review the NDA resubmission within six months of the receipt date.

With that I will now turn over the call to Tom Shula, Our Chief Medical Officer.

Thank you George this afternoon, I will provide a summary of clinical and scientific information related to our internal research and development pipeline and touch on the clinical plans of our partners.

Tom Chula: This afternoon, I will provide a summary of clinical and scientific information related to our internal research and development pipeline and touch on the clinical plans of our partners. Last month, we had numerous presentations delivered on our pipeline and supracortial injection platform at both the Angiogenesis and the Macular Society Annual Meetings. These presentations mark a new chapter for Clearside, one in which we both publicly embrace what we've learned from Xipir and initiate our efforts to advance our pipeline.

Last month, we had numerous presentations delivered on our pipeline is super Cradle injection platform at both Andrew Genesis and at MCE Society annual meetings. These presentations Mark a new chapter for Clearsight, one in which we both publicly embrace what we've learned from site here and initiate our efforts to enhance our pipeline.

Tom Chula: At these meetings, we had top retina specialists presenting exciting material on our SES platform, gene therapy, and exsitin. The presentations presented strong scientific rationales to address real unmet needs, and we received very positive feedback from the medical community. Furthermore, these particular meetings represent key retina congresses. Angiogenesis only selects the most innovative therapies and technologies for presentation, and it has become a top meeting globally. And Macula Society is perhaps the most selective U.S.-based retina society attended by top U.S. and international retina surgeons.

At these meetings, we had top retina specialists presenting exciting material on our SCS platform gene therapy and exit.

The presentations for trains portray strong scientific rationale to address real unmet needs and we have received very positive feedback from the medical community.

Furthermore, these particular meetings represent key retina Congresses, Andrew Genesis only selects the most innovative therapies and technology, so presentation and has become a top meeting globally.

And Magnegas Society is perhaps the most selective U.S. based retina society attended by top U.S. and international retina specialists.

Tom Chula: Importantly, at the Macular Society, the first public data were presented on CLS-AX. In this presentation, Dr. Sri Krupp, director of the retina service at Case Western University, provided evidence for the use of CLS-AX as a potential long-acting therapy for neodascular age-related macular degeneration. supracaroidal Exsitinib, or CLSAX, has the potential to address primary needs for neovascular AMD patients, as its durability may reduce treatment burden while maintaining vision. Furthermore, its pan-VEGF-inefficient and wet-AMT has the potential to be more efficacious than current focused VEGF-inefficient approaches. Information from Dr. Krupp's literature review shows that there is strong preclinical evidence for the potential efficacy of exitinib as a tyrosine kinase inhibitor, or TKI. First, in humans, anti-VEGF-A upregulates VEGF-C and VEGF-D, suggesting a mechanism for anti-VEGF-A resistance and a potential therapeutic role for more broad VEGF inhibition with a TKI-like exsitin.

Importantly, macular society. The first public data was presented on CLS apex in this presentation Dr. Sri crew director of the retina service that case Western University provided evidence for the use a CLS acts as a potential long acting therapy for Neovascular age related macular degeneration.

So the accrual axitinib.

CLS X has the potential to address primary needs for Neovascular AMD patients as its durability may reduce treatment burden, while maintaining vision.

Furthermore, it's pan JAK inhibition and wet empty has the potential to be more efficacious than current focus that Jeff inefficient approaches.

Information Doctor groups Literature review show that there was strong preclinical evidence on the potential efficacy of accident as a tyrosine kinase inhibitor or Teekay hi.

First in human ended that you have a upregulates digest see embedded de suggesting a mechanism for anti VEGF, a resistance and a potential therapeutic role for more broad that Jeff inhibition with the Teekay <unk> like exit.

Tom Chula: Second, in multiple animal models, excitinib inhibited experimental neovascularization in the cornea, retina, and choroid. And third, in-vitro excitinib has better biocompatibility with ocular cells relative to other TKIs. In addition, some of the preclinical studies involve comparative efficacy and show that exsitinib more potently inhibited neovascularization than either anti-VEGF-A inhibition or other TKI. Substratotal CLSAX was also tested in multiple animal models, demonstrating high drug concentration in the retina and choroid, RPE sclera, and lower concentration in the vitreous, as well as Across animal models, suprachoridal CLSA-X was observed to be well-tolerated with no signs of toxicity at the intended clinical dose, with sparing of the anterior chamber of the eye and systemic circulation.

Second and multiple animal models exiting of inhibited experimental neovascularization in the corneal retina inquiry.

And third in vitro looks it never has better biocompatibility with occupy ourselves relative to other teekay odds.

In addition, some of the preclinical studies involve comparative efficacy and show that makes it more potently inhibited neovascularization than either anti VEGF, a inhibition or other Teekay OS.

Typical rental CLS Alex.

Was also tested a multiple animal models demonstrating high drug concentration in the retina inquiry R&D East Clara and lower concentration in the vitreous as well as reduction of fluorescein leakage and vessel growth versus control.

Cross animal models Super Choroidal, CLS Eightx was observed be well tolerated with no signs of toxicity at the intended clinical dose with sparing of the anterior chamber of the high end systemic circulation.

Tom Chula: This positive data supports continued advancement of this asset that has the potential to reduce both the treatment burden on patients as well as improve longer-term visual outcomes. As we have stated, we expect to submit an IED application for CLSAx in mid-2020 and to initiate a Phase I-IIa clinical trial later this year. As George mentioned, in preclinical studies, we continue to assess other small molecules targeting important pathways, as well as gene therapy opportunities, including DNA nanoparticles carrying transgenes.

This positive data supports continued advancement of this asset.

It has potential to reduce both treatment burden on patients as well as improve longer term visual outcomes. As we have stated we expect to submit an I'd applications. The CLS a acts in mid 2020 and to initiate a phase one two a clinical trial later this year.

As George mentioned in preclinical studies, we continue to assess other small molecule.

Targeting important pathways as well as gene therapy opportunities, including DNA nanoparticles carrying transactions.

Tom Chula: We plan to present some of this work, along with CLSAx preclinical work, at the annual meeting of ARVO, the Association for Research in Vision and Ophthalmology, which has accepted 15 presentations from our team of biomedical engineers, scientists, and external key opinion leaders. We also continue to present data on Zypyr in anticipation of its potential FDA approval. In January, we're pleased to announce that the peer-reviewed journal of the American Academy of Ophthalmology, entitled Ophthalmology, presented the results from the Phase III Peachtree trial of Xipir for the treatment of macular edema associated with uveitis. The journal publication of our positive phase 3 zyperic clinical trial results is an important milestone for us and further expands the understanding of our supracaroti In the trial, patients with non-infectious uveitis in the Xipir treatment arm experienced clinically significant improvement in vision relative to the control arm at six months, and no serious adverse events considered by the investigators to be related to treatment were reported.

We plan to present some of this work along with CLS CX preclinical work at the annual meeting of ARVO. The Association for research and vision in Ophthalmology, which has accepted 15 presentations from our team of buying medical engineers scientists and external key opinion leaders.

We also continue to present data and zipper here in anticipation of.

Okay and participation of its potential FDA approved.

In January we are pleased to announce at the peer reviewed journal of the American Academy of Ophthalmology entitled Ophthalmology presented the results published the results from the phase three Peachtree trial aside here for the treatment of macular edema associated with uveitis.

Journal publication of our positive phase threes I paired clinical trial results as an important milestone for us.

Further expands the understanding of our Super Choroidal treatment approach.

In the trial patients with non infectious uveitis and design pair treatment arm experienced clinically significant improvement in vision relative to the control arm at six months and no serious adverse events considered by the investigators to be related to treatment we reported.

Tom Chula: This data was the basis for our NDA submission, and we are encouraged by the results, as they demonstrate clinically meaningful improvement in nearly half of the patients treated. Moving now to an overview of the plans for our developmental partners, Regenexx Bio is testing the use of our proprietary SCS microinjector to deliver its AAV gene therapy agent, RGX314, to two different patient populations with the hope of offering non-surgical, in-office access to their one-time gene therapy treatment. For WET-AMD, Regenexx Bio plans to initiate a Phase II trial using our SDS microinjector in the first half of 2020. This trial is expected to evaluate patients in two-dose cohorts of RGX314 versus a control one. Interim data is expected from Cohort 1 by the end of this year.

This data was the basis for it for our end da submission and we are encouraged by the results as they demonstrate clinically meaningful improvement envisioned for nearly half the patients treated.

Moving now to the overview of the plans might developmental partners, which nx pilot testing the use of our proprietary SCS micro injector to deliver there a gene therapy agent, our Gxp 14 to two different patient populations with the hope of offering nonsurgical in office access.

To their onetime gene therapy treatment.

For wet AOMT, which nx bio plans to initiate a phase two trial using our SCS micro injector and the first half 2020.

This trial is expected to evaluate patients into dose cohorts of Archie XP 14 versus a controller.

Interim data is expected from cohort one by the end of this year.

Tom Chula: For the treatment of diabetic retinopathy, Regenexx Bio expects to submit an IND in the first half of 2020 and to initiate a Phase II trial using our SDS microinjector in the second half of this year. This trial is expected to evaluate patients in up to three dose cohorts of RGX314 versus a control line. Enrollment of Cohort 1 is expected to be completed by the end of this year, with interim data expected in 2021. Our partner, OroBioScientists, has also licensed our SCS microinjector as a potential non-surgical alternative to individual delivery of their proprietary anti-cancer drug candidates, which may enable the delivery of higher concentrations to the choroid and potentially enable treatment of larger tumors.

For the treatment of diabetic retinopathy, which annex buyout expects to submit an eye Andy and the first half 2020 into initiate a phase two trial using our SCS micro injector in the second half of this year.

This trial is expected to evaluate patients nothing three dose cohorts of RG ex the 14 versus a control arm.

Enrollment of cohort one is expected to be completed by the end of this year with interim data expected in 2021.

Our partner or Abaga scientists has also license our SCS, Michael injector as a potential nonsurgical alternative to individual delivery of their proprietary anticancer drug candidates, which may enable the delivery of higher concentrations to the quarterly potentially enable treatment of larger tumors.

Tom Chula: CORE is developing a novel class of therapy, viral nanoparticle conjugates designed to selectively bind and eliminate cancer cells without damaging surrounding normal tissue. CORE expects to initiate clinical testing during the second half of 2020 using supercoital delivery for AU011 for the potential treatment of certain ocular cancers, including coital melanoma. We remain excited about this partnership as it extends our exposure into the oncology setting. This month's Retina Congress has very effectively demonstrated the versatility of our platform, and we look forward to expanding this further in 2020. In addition to preparing an IND and initiating a Phase I-IIa trial for CLSA-X, our development team continues research around other compounds to advance into the clinic. I will now turn the call over to our CFO, Charlie Degnan, to review our financial results. Thank you, Tom. Our specific financial numbers for the quarter and the full year 2019 were published this afternoon in our earnings press release and are available on our website.

Or is developing a novel class a therapy.

Viral nanoparticle conjugates designed to selectively buying and eliminate cancer cells without damaging surrounding normal tissues.

Or expects to initiate clinical testing during the second half of 2020 using Super credit deliberate for eight you 011 for the potential treatment of certain onto a cancers, including choroidal melanoma.

We remain excited about this partnership as it extends our exposure into the oncology setting.

This month's written the Congress is very effectively demonstrated the versatility of our platform and we look forward to expanding this further in 2020.

In addition to preparing a 90 and initiating a phase one two age for Alpha CLS eggs are development team continues research around other compound to advance into the clinic.

I'll now turn the call over to our CFO Charlie segment to review our financial results. Thank you Tom.

Our specific financial numbers for the quarter and the full year 2019 were published this afternoon in our earnings press release and are available on our website. Therefore, I would like to spend this time, providing an overview of our financial plans for 2020.

Charles A. Deignan: Therefore, I would like to spend this time providing an overview of our financial plans for 2020. As we reported, our cash and cash equivalents at the end of December 2019 totaled $22.6 million, which included partner licensing revenue and private placement funding received in the fourth quarter of 2019. Please note that in the fourth quarter, R&D expenses were positively impacted by vendor credits of $2 million upon reconciliation of the final retinal vein inclusion trial costs. However, we do expect that R&D expenses will increase over the next several quarters as we complete the work to resubmit our NDA for Xipyr and submit an IND for CLSAX. Based on our current outlook, we expect to have sufficient resources to fund planned operations into the first quarter of 2021. We continue to carefully monitor our cash position to maintain expenses while advancing our programs. With that, I will turn the call back over to George for his final remarks. Thank you, Charlie.

As we reported our cash and cash equivalents at the end of December 2019 totaled 22.6 million.

Which included a partner partner licensing revenue and private placement funding received in the fourth quarter of 2019.

Please note that in the fourth quarter R&D expenses were positively impacted by vendor credits of $2 million. Upon Reg reconciliation of the final retinal vein retinal vein occlusion trial costs. However, we do expect that R&D expenses will increase over the next several quarters as we complete the work to resubmit R&D.

Presented here and submitted 94 CLS acts.

Based on our current outlook, we expect to have sufficient resources to fund to planned operations into the first quarter of 2021.

We continue to carefully monitor our cash position to maintain expenses, while advancing our programs with that I will turn to turn the call back over to George for his final remarks.

Thank you Charlie.

George M. Lasezkay: I truly believe in the potential advantages of delivering drugs into the SES, the versatility of our SES injection platform, and our ability to develop and deliver treatments that restore and preserve vision for people with serious back-of-the-eye disease. I also believe in the commitment of our team to improve the lives of these patients. I am honored to have been asked by the board to serve as Clearside's President and CEO, and I've entered into an employment agreement with the company reflecting that new position.

Truly believe in the potential advantages of delivering drugs into the FCS the versatility of our SCS injection platform and our ability to develop and deliver treatments that restore and preserve vision for people with serious back of the eye diseases.

Also believed in the commitment of our team to improve the lives of these patients.

I'm honored to have been asked by the board to serve as clear sides President and CEO.

And I've entered into an employment agreement with the company, reflecting that new position.

Operator: I look forward to continuing to work closely with the entire Clearside team and the medical and investment community. In summary, in 2020, we are laser-focused on getting our first product to the regulatory finish line and our next development product into the clinic, while also advancing our early-stage research and development pipeline and working with our partners to broaden the reach of our supercorroidal injection technology. I would now like to ask the operator to open the call up for questions. Certainly, once again, ladies and gentlemen, if you have a question at this time, please press star, then one on your touchtone telephone. If your question has been answered and you'd like to remove yourself from the queue, please press the pound key.

I look forward to can do continuing to work closely with the entire Clearside team.

And the medical and investment communities.

In summary in 2020, we are laser focused on getting our first product to the regulatory finish line and our next development product into the clinic, while also advancing our early stage research and development pipeline and working with our partners to broaden the reach of our supercritical injection technology.

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

Certainly once again, ladies and gentlemen, if you have a question at this time. Please press Star then one and you touched on telephone. If your question has been answered and you'd like to move yourself from the Q. Please press the pound key our first question comes from the line of Liliana.

Operator: Our first question comes from the line of Liliana Masatos from Web Bush Securities. Your question, please. Thank you for taking my questions and congratulations on your progress and to George for becoming a part of this. I have two questions.

Yes, It does from Wedbush Securities. Your question. Please.

Thank you for taking my questions and congratulations on your progress ended George for becoming official I have two questions. One is well the design of the phase one two way CLS extra wet AMD de have any efficacy endpoints are biomarkers and the second is will 2020 opex.

George M. Lasezkay: One is, will the design of the Phase I, IIA, CLS, AX, or WET-AMD studies have any efficacy endpoints or biomarkers? And the second is, will 2020 OPEX be a lot higher than 2019? Thanks, Liana, for the questions, and thank you for your kind remarks. I'm glad to be here, so thank you.

A lot higher than 2019.

Thanks, Liana for the questions and thank you for your kind remarks.

I'm glad to be here. So thank you.

Tom Chula: I'll turn, and I'll ask Tom to answer the first question about the trial. Thank you for the question. I can't comment on the specifics right now since we're still in the planning stages, but what I can generally tell you is that this is going to be a very straightforward, standard, phase 1, 2A study for neovascular AMD. It'll be a single-dose escalation study with several cohorts, and as you know, in these studies, these early studies, especially this first in man, super-carotidly injected excitinib study, the primary endpoint has to be safety, but of course, we'll look at visual acuity and OCT, and we'll have some efficacy signals, but again, these early single-dose And Liana, it's Charlie.

I'll turn I'll ask Tom to answer the first question about trial design.

Yes. Thank you for the question I can't comment on the specifics right now so it's a still in the planning stages. What I can generally tell you is that this is going to be a very straightforward standard phase one two a study for Neovascular AMD D. It'll be a single dose escalation study with several cohorts and.

As you know in these.

Studies. These early studies, especially this first in man Super currently injected Ics sit nib.

Study.

The primary endpoint has to be safety, but of course will look at visual acuity and he will have some efficacy signals, but again these early.

Single dose escalation study is a really geared more towards safety. Since this will be the first time executives injected into the Suprachoroidal space.

And the honest Charlie.

Charles A. Deignan: So our OPEC, so I would, for you, I would look at Q4 and how we're trending there. You know, earlier in the year, we had a commercial organization that we no longer have. So, you know, costs have trended down.

Our opex so lucky.

Are you I would look at.

Q4, and how we're trending there.

We had earlier in the year, we had our commercial organization that.

We know on behalf so cost trended down.

Charles A. Deignan: You need to add back, you'll see in our press release, the $2 million credit we received. So if you take that filing, we have to, we'll have our costs go up quarterly as we get closer to resubmitting our IND and kicking off the clinical trial, but not a dramatic increase from our current spending. Thank you very much.

Do you need to add back you'll see in our press release.

$2 million credit receive self you take that filing we will have our costs go up.

Quarterly as we get closer to filing resubmitting, our I'd and kicking off clinical trial, but not a dramatic increase from our current spending.

Thank you very much.

Your next question comes on line of Annabel Samimy from Stifel. Your question. Please.

Operator: But your next question comes in line with Annabel Saminy from Stifel. Your question, please. Hi guys.

Hi, guys congratulations on the deals today and.

George M. Lasezkay: Congratulations on the deal today and also for the official appointment, George. Now, I have a few questions. The first is, can you tell us a little bit about the ideal excision profile that you're seeking, given that it's a pan-VEGF inhibitor? Would you be seeking just extended durability or increased efficacy, you know, especially in light of what could be an increasingly competitive market? The second is whether, you know, for the Bausch resubmission, I'm sorry, for the NDA resubmission and the deal with Bau I couldn't help notice that you mentioned you're still in the planning phases of getting stability data. So the manufacturing issues are those are manufacturing issues of your particular manufacturer that have nothing to do with Xipear right now, or does it have to do something specific with the manufacturing of Xipear?

Also for the official appointment George.

So I have a few questions.

The first is can you talk a little bit about the ideal.

Profile that you're seeking given that it's a pan JAK inhibitor would you be seeking just for extended durability or increase efficacy.

Okay.

Actually in light of what could be an increasingly competitive market.

The second is weather.

For the the Bausch Resubmission I'm, sorry for the Indian Resubmission and the deal with Bausch I guess.

One.

I noticed you mentioned, you're still in the planning phases of getting stability data so manufacturing issues is that.

Those are manufacturing issues of your particular manufacturer.

That have nothing to do with with.

With sector right now.

Or does it have to do something specific.

George M. Lasezkay: And then once you figure that out, you can plan the Stability Batches. So I just want to clarify that. And once you get that in place, has BAUS shared any of their commercialization plans? I know you're at a lot of medical meetings and presentations, but it seems to be taking a little bit of a pause right now. Is that going to mess up any of their commercialization plans? And then, finally, can you help us with the structure of your licensing revenue? You had a nice bump this quarter, obviously.

With the manufacturing sites here and then once you figure that you can plan.

The stability batch so I just want to clarify that and once you get that in place has.

Shared any.

Our solution plans I know you're at a lot of medical meetings and presentations.

Seems to be taking a little bit of a pause right now is that going on that's up any of their commercialization plan.

And then finally.

Can you help us with the structure of your licensing revenue, we had a nice bump this quarter, obviously, you're getting some milestones.

Charles A. Deignan: You know, you're getting some milestones and some revenue, and how should we be thinking about licensing revenue rates going forward? You know, the upfront payment from the Arctic deal, should we recognize that right away? Should we put it on the balance sheet? How should we be modeling these out?

Revenues in how should we be thinking about licensing revenue rates going forward.

Yes, the upfront payment from the articulate should we recognize that right away should we put on the balance sheet, how should we be modeling we thought thanks.

George M. Lasezkay: Thanks. Okay. Thanks for three questions, Annabel, which is so kind. I had a few. I said a few, not a lot.

Okay. Thanks for three questions, Annabel, [laughter], which as I.

Got a couple [laughter].

Tom Chula: I was writing like a maniac here to try to keep track of it all. Let me have Tom answer the first question about the ideal exsitinib profile because it's a very good question, and I think Tom can answer that, and then I will take the question about the manufacturing issues that you raised. Again, that's an excellent question. So I think... In terms of unmet need, one of the biggest unmet needs is the treatment burden.

I I was writing like a maniac here to try to keep track of at all.

Let me, let me have Tom answer the first question about the ideal accident profile.

Because that's a very good question and I think Tom can answer that and then I will take the the question about the manufacturing.

Issues that you raised.

Again excellent question, so I think.

In terms of unmet need one of the biggest unmet need is treatment burden, we know in the real world patients only received six to seven into that Jeff They injection and yield only a one to three letter improvement in vision at one year. So so the real unmet need with respect to treatment burden haven't longer acting therapies, and then second unmet need is that there seems.

Tom Chula: We know in the real world, patients only receive six to seven anti-VEGFA injections and yield only a one to three letter improvement in vision at one year. So the real unmet need with respect to treatment burden is longer acting therapies. And then the second unmet need is that there seems to be a ceiling of efficacy. In some of the trials, in the Harbor trial, for example, if you went up on doses, you didn't have a better efficacy outcome.

To be a ceiling of efficacy in some of the trials.

In Harbor trial for example, if you went up on doses you Didnt have a better efficacy outcome. So there seems to be a ceiling of efficacy. So I think that's the on those are the two unmet needs we want to address with with.

Tom Chula: So there seems to be a ceiling on efficacy. So I think those are the two unmet needs we want to address with CLSA-X. And then in terms of delving into this a little bit more, I think, number one, excitinib itself, as you know, is a pan-VEGF inhibitor, not just the receptor. There's evidence now that when you use an anti-VEGF-A, you up-regulate other factors, including VEGF-C and D, and this may contribute to resistance or that ceiling of efficacy.

Yes, Alex and then in terms of delving into its little bit more I think number one.

Except in of itself as you know is a pan that Jeff inhibitor and hibbett is not the receptor.

There's evidence now that when you use an anti VEGF day Upregulate other factors, including Digest C and D and this may contribute to resistance or that ceiling of efficacy. So we think pan JAK inhibition has potential to be more efficacious and then number two.

Tom Chula: So we think pan-VEGF inhibition has the potential to be more efficacious. And then, number two, we think there are particular benefits to injecting in the supercorridor space. Small molecule suspensions like transimolone and excitinib have very long durability. We know from the studies we've done that they will last many months in the supracortal space, and that gives us the potential to address that treatment burden issue. And the other potential benefits of injecting into the supracortal space include targeting the layer of the eye where cortal neovascularization starts.

Do we think there's particular benefits with injecting in the Suprachoroidal space.

Small molecule suspensions like trying similar loan and accident.

Very long durability, we know from the studies, we've done that it will last many months.

In the Super core it'll space and that gives us a potential to address.

That treatment burden issue and the other potential benefits of injecting the Super Krill space include targeting.

The layer of the Iwear the quarterly amounts creation start so we can get very high levels there.

Tom Chula: So we can get very high levels there and potentially enhance efficacy through its administration in the supracortal space. And then another advantage, the final advantage I think of supracortal injection is that we're compartmentalizing the drug in that space, and that gives us potential safety advantages. We're going to limit off-target effects by compartmentalizing it there. So, a long-winded answer to your question, but we think that we can address very important unmet needs with supracortal excitinib. Okay. Thanks, Tom.

And potentially enhance ethic efficacy through its administration of the Suprachoroidal space and then the another advantage. The final advantage I think of Suprachoroidal injection is now we're compartmentalizing the drug in that space and that gives us.

Potential safety advantages, we're going to limit off target effects like by Compartmentalizing. It there. So long winded answer to your question, but we think that we can address very important unmet needs.

With supercritical accident.

Okay.

Thanks, Tom.

George M. Lasezkay: Let me try to address the issues that you raised regarding the NDA resubmission and vouch for product on the manufacturing issues. Here's what I can tell you. We've been working with our contract manufacturer and also in consultation with Bioshield to produce the registration batches and the stability data that we need for the NDA resubmission. The specific question you asked about is whether the contract manufacturer is still working to finalize certain manufacturing activities that aren't specifically related to Xipyr. They apply to multiple clients inside their facility. We happen to be one. That work is still ongoing, which has contributed to the delay that we've just announced, but those activities are coming close to completion. And with that, the contract manufacturer should be able to focus on the steps necessary to produce the registration batches that we need. And, therefore, we can submit that for stability data in order to resubmit our NDA. So we believe that, taking all of this into account, we're now on track for the NDA resubmission to be by the end of August, as we've announced.

Let me try to address the the issues that you raised regarding the NDA resubmission and Bausch and.

Product on the manufacturing issues, here's what I can tell you we've been working with our contract manufacturer and in and also when consult a consultation with bausch.

To produce the registration batches and stability data that we need for the NDA resubmission.

The specific question you asked about is the contract manufacturer is still working to finalize certain manufacturing activities that aren't specifically related to zipper, they apply to multiple clients inside their facility.

We happened to be one.

That work is still ongoing which has contributed to the delay that we've just announced.

But those activities are coming close to completion and with that the contract manufacturer should be able to focus on the steps necessary to produce the registration batches that we need and therefore, we can submit that for stability data in order to resubmit, our India. So we think we believe that taking.

All of this into account we're now on track to for the NDA resubmission to be by the end of August.

As we as we've announced regarding the commercialization plans, we know that Bausch is working to produce those commercial or are putting together commercialization plans. We are not intimately involved in their development of commercialization plans, but we have been our medical affairs team.

George M. Lasezkay: Regarding the commercialization plans, we know that Bausch is working to produce those commercials or is putting together commercialization plans. We are not intimately involved in their development of commercialization plans, but we have been, our medical affairs team is working with their team to help them prepare for launch. So part of what we're doing is probably working into their commercialization plans, but we don't have an intimate knowledge of exactly their thoughts on where and when and how they'll commercialize the product, at least at this time. Charlie, do you want to take that last question Annabel had? Yeah, sure, Annabel. So yeah, we just announced today the $4 million ARCTIC. I can't give you a definitive number.

Is working with their teams to help them prepare for launch so part of what we're doing is probably working into their commercialization plans, but we don't have an intimate knowledge of exactly their thoughts on where and when and how though they'll commercialized product at least at this time.

Charlie you want to take that last question Annabel have yes, sure antibody how to.

So, yes, we just announced today the 4 million Arctic.

I wouldn't I can't give you had definitive never we sold our analyzing about Mike I'm, suspecting, we won't be able to take that money.

Charles A. Deignan: We are still analyzing it, but I'm suspecting we will be able to take that money up front. So no deferred on that.

Upfront.

So no no deferred on that.

Charles A. Deignan: As we've announced, we'll have a number of milestones, potential milestones hit this year from other partners. Unfortunately, we have confidential agreements that we can't discuss those. But what we did announce is BOSH will, you know, we have a $15 million milestone payment related to our approval, U.S. approval. So I would imagine an approval will hit there. But I can't, unfortunately; there are other milestones.

As we've now so we'll have a number of milestones potential milestones hit this year from our other partners. Unfortunately, we have confidential agreements that we can discuss those.

Well, we did have announced is.

Bausch well, we have a $15 million.

Bob milestone payments related.

Up to our proven us approval, so I would imagine on accrual that that will head there, but I can't Unfortunately, there are other milestones at this point, we can't discuss the timing farm out to those.

Charles A. Deignan: At this point, we can't discuss the timing or amounts of those. Okay, so just to clarify on the milestones, the cash that takes you to the first quarter of 2021, does that include only the milestones that you've realized to date, or what you expect this year as well? Yeah, so the guidance is what our year-end cash can get us into 2021.

Okay. So just to clarify on the milestones the cash that takes you to the first quarter 21 does that include only the milestones that you realized to date or what you expect this year as well.

No. The guidance is what are you our yearend cash is can get us into 2021.

Charles A. Deignan: Okay, great. Thanks. I've got questions for all of you today. Yeah, good job.

Okay, great. Thanks, I got questions for all of you today.

Yeah Yeah.

George M. Lasezkay: Thank you. Our next question comes in the line from Esther Hong, from Jamie. Your question, please. Thanks for taking my questions. So with your platform and potential for partnerships, what can we expect in the near term in terms of future areas of partnership? Are you looking at would you be focused on additional XUS or additional indications where the platform could be used? And second, are you planning to partner with CLS-AX, or will this remain an internal program? Thanks. Let me take the last part first. We intend to keep CLS-AX internal.

Thank you. Our next question comes the line of Esther home from Janney. Your question. Please.

Thanks for taking my questions, so with your platform and potential for partnership.

On what can we expect in the near term in terms of future areas of partnerships are you looking at would you be focused and additional acts U.S. or additional indications where that's not from could be used and then second are you planning to partner CLS.

Hey acts or will this remain an internal program. Thanks.

Let me take the latter part last part first.

We intend to keep CLS adx internal we have no plans to partner that at this time.

George M. Lasezkay: We have no plans to partner with that at this time. In terms of additional collaborations, we're going to be very, very picky about what we do in terms of any additional collaborations. We are very happy with Regenexx Bio, and we're very happy with Aura.

In terms of the additional collaborations.

We're going to be very very picky about what we do in terms of any additional collaborations we are very happy with rejects bio we're very happy with aura believed they were validating for our injection system.

George M. Lasezkay: We believe they were validating for our injection system. We are being very careful about keeping a good portion of the ophthalmic space for us and our internal pipeline. And so I would not expect right now anything on the near horizon in terms of collaborations that we would announce similar to Regenexx Bio or Aura. That's not in our current thinking, but we're opportunistic where there's a collaboration that makes sense and we think it fits us strategically and doesn't compromise our internal strategic plan for our pipeline. We're always open to doing that.

We are being very careful about keeping a good portion of the ophthalmic space for us and our internal pipeline.

And so I would not expect right now anything on the near Horizon in terms of collaborations that we would announce similar to reject expire or that's that's not in our current thinking, but we're opportunistic where there's a.

Collaboration that makes sense, and we think it fits us strategically and doesn't compromise our internal strategic plan for.

Our pipeline.

We're always open to doing that but right now our focus is building the internal pipeline.

George M. Lasezkay: But right now, our focus is building the internal pipeline and maintaining good relations with our current collaboration partners. Great, thank you. Thank you. Our next question comes from Boris Piker from Cowen. Your question, please. Good afternoon. I guess the first question I have to ask in this environment is whether the Arvo meeting is canceled, as of now, on their website, it still says it's on, but if it's canceled, when would you be presenting these results? Tom, do you want to handle that?

And maintaining good relations with our current collaboration partners.

Great. Thank you.

Thank you. Our next question comes the line up for Speaker from Cowen Your question. Please.

Hi, Good afternoon, I guess, the first question I have to ask in this environment. If the ARVR meeting is canceled as of now and then on their website. It's still says its don but if it's cancelled but when would you be presenting these results.

Uh Huh, Tom you want to Im sure. So we actually had a 15 abstracts accepted this year and.

Tom Chula: Sure. So we actually had 15 abstracts accepted this year, and as you might know, they were actually published in the IOVS journal, the official journal of ARVO, so they did become publicly available. We've also submitted abstracts to the Retina Society, the American Society of Retina Specialists, and we're planning to submit to the American Academy of Ophthalmology.

As you might know they actually are published in the I O vs Journal the official journal of ARVO.

So they do become publicly available.

We've also.

Submitted abstracts too.

Retina Society to the American Society retina specialists, and we're planning to submit to the American Academy of Ophthalmology, So we'll be sure to have.

Tom Chula: So we'll be sure to have some version of these abstracts or presentations at these other meetings, should ARVO be canceled or postponed. And my second question, in terms of your Chinese partnership today, is just curious about the timeline for bringing Zypyr to China, and are there clinical studies that need to be done, or is Arctic Vision just planning to file based on existing clinical data? Thanks for that question. I'll take that.

Some version of of these abstracts are presentations at ash at these other meetings should I will be cancelled or postponed.

Gotcha, Okay and my second question.

In terms of your Chinese partnership announced today, just curious whats the timeline for bringing that appeared to China and our their clinical studies that need to be done or well is artificially just planning to file on existing clinical data.

Oh, Thanks for that question I'll take that.

George M. Lasezkay: I can't give you any specifics about when Arctic is planning to initiate their clinical trials or whether they see the product being approved in China. That's something that's confidential to them. There is the possibility that they could file with existing U.S. data, but right now, as far as we can tell, they're planning to initiate at least one clinical trial, but that's still for them to decide. There are one or two ways they could go.

I can't give you any specifics about when Arctic.

Is planning to initiate their clinical trials or they see the product being approved in China. That's something that's confidential to them. There is the possibility that they could file with existing U.S. data.

But right now as far as we can tell there they're planning to initiate at least one clinical trial, but that.

That's still up for them to decide there's there's there's one or two ways. They could go I believe at this point in time, they're planning on a clinical trial.

George M. Lasezkay: I believe at this point in time they're planning on a clinical trial, so that would be questions better addressed to them at this time.

That would be questions better drove them at this time.

Operator: Thank you very much for taking my questions. Thank you. Our next question comes from the line of Serge Belanger from Needham and Company. Your question, please.

Right. Thank you very much for taking my questions yes.

Thank you. Our next question comes from the line of search blown away from Needham and company. Your question. Please.

Hi, Good afternoon, just a couple of questions for me.

George M. Lasezkay: First, on Zype here, you've now completed two outlicensings for major geographies. I think Europe is the last remaining one that remains unpartnered. Can you give us details on what the European opportunity looks like for a product like Zype here, I guess, relative to the U.S. opportunity? Thanks, Serge. This is George.

First on the on site here, you've now completed.

Two outlicensing floor for major geographies.

I think Europe is the last remaining one that remains on partners can you give us details on.

The Europeans opportunity looks like for products like they appear I guess relative to the U.S. opportunity.

Thanks surge this is George.

George M. Lasezkay: We have looked at the European opportunity. I think there are some unique challenges in Europe, but that remains open to partnering and potential partnering. We think the opportunity there is probably smaller than the U.S., but...

We have looked at the European opportunity.

You think theres some unique challenges in Europe, but that remains open for partnering input potential partnering.

We think the we think probably the opportunity there is smaller than the U.S., but.

George M. Lasezkay: I think that really requires a lot more analysis on our part or potential partners' part. So right now, the EU is not our focus. We're focusing on making sure that the U.S.-Canadian collaboration with Bausch goes very well, the launch is successful, and as well now working very closely with our new Chinese partner to make sure that it gets off on the right foot in mainland China and the greater China area. That's really our focus now, and we'll consider things about the EU at another time.

I think that we really requires a lot more analysis.

On our part or potential partners part so right now the EU is not our focus we're focusing on making sure that the U.S. Canadian collaboration with Bausch goes very well the launches successful.

And as well now working very closely with our new Chinese partner to make sure that it gets off on the right foot in.

In mainland, China, and the greater China area, that's really our focus now and.

Will we will consider things about you at another time, but that.

George M. Lasezkay: We really want to make sure that, especially in the United States, this gets off to the right start, and that's really where our focus is at this time. And he talked about a new preclinical program for therapeutic transgenes. Let me just provide a little more details on what potential indications this program could address. Sure, I'll let Tom take that. Thanks for the question, Serge. It's an interesting question.

We really want to make sure that especially in the United States. This gets off to the right start and that's really where our focus is at this time.

Okay.

And you talked about it you.

Clinical program for therapeutic strategies.

Can you just provide a little more details on what the potential indications this program could address.

Oh sure I'll, let let Tom is that.

Thanks for the question surge, it's an interesting question.

Tom Chula: We haven't disclosed exactly what therapeutic transgenes we are looking into, but what I can tell you is that DNA nanoparticles are not viral capsids with antigens in an immune response, so there's much less of an immune response. That allows us to increase the dose and potentially even repeat dosing. The other key attribute is that they can carry much larger genes than AAV. So, for example, Stargardt and Usher both have genes that are too large to fit into current AAV vectors. So obviously, we're exploring a variety of transgenes. We have already presented some data suggesting that, at least in rabbits, when we deliver these DNA nanoparticles using a marker gene, we have equivalent activity, whether it's delivered suprachoroidally or subretinally.

You Havent disclose exactly what therapeutic transitions were going to or we are looking into.

But what I can tell you is that DNA nano particles.

I am not viral capsids with antigens in an immune response, so theres much less of an immune response that allows us to increase the dose and potentially even repeat dosing. The other key attribute is now they can carry much larger genes in a D.

So for example, stark art and Archer both have genes that are two large that fit into current a the doctors.

So so obviously, we're exploring a variety of transitions.

We have presented already that some data, suggesting that at least in rabbits, when we deliver.

These DNA nanoparticles using a marker gene we have equivalent activity, whether it's delivered supercross, Italy or sub retinal early so there's potential to have an office based.

Tom Chula: So there's potential to have an office-based gene therapy with large genes that's potentially repeatable. And, you know, obviously, I was at SPARC previously and have experience with Luxterna, an inherited retinal disease, so that's an area that we're currently exploring. Thank you. For the question and answer session of today's program, I'd like to hand the program back. For any further questions, Thank you once again 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.

Gene therapy with large genes, that's potentially repeatable and obviously.

I was at spar previously have experience with external inherited retinal disease.

So that's an area that we're currently exploring.

Thank you.

Thank you. This does conclude be question and answer session of today's program I'd like to hand, the program back to Dr. Sq for any further remarks.

Thank you once again 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.

Operator: Operator, you may not disconnect. Thank you. Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.

Operator, you may not disconnect.

Thank you. Thank you ladies and gentlemen for your participation in todays conference. This does conclude the program you may now disconnect good day.

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