Greetings, and welcome to the Clearside Biomedical Fourth Quarter and Year-End Financial Results and Corporate Update Conference Call. As a reminder, this conference call is being recorded. I would now like to introduce your host, Jenny Kobin, Clearside, Investor Relations. Please go ahead..

Good afternoon, everyone, and thank you for joining us on the call today. Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements.

Various remarks that we make during this call and about the company's future expectations, plans and prospects constitute forward-looking statements for purposes of the private securities Litigation Reform Act of 1995.

The 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, 2019, our quarterly report on Form 10-Q for the quarter ended September 30, 2020, and our other SEC filings available on our website.

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

On today's call, we have George Lasezkay, our Chief Executive Officer; Dr. Thomas Ciulla, our Chief Medical Officer and Chief Development Officer; and Charles 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..

vitreous haze, anterior chamber cells and interior chamber flare. Based on these data, we believe XIPERE administered suprachoroidally, has the potential to be a novel treatment that improves the lives of patients suffering from macular edema associated with uveitis. Also for XIPERE, we have two strong partners in Bausch & Lomb and Arctic Vision.

Bausch & Lomb has the exclusive license for the commercialization and development of XIPERE in the United States and Canada, and an exclusive license for Europe and the United Kingdom, Australia and New Zealand, South America and Mexico.

Arctic Vision has the exclusive license for the commercialization and development of XIPERE in Greater China and South Korea and has announced the approval of their investigational new drug application for a Phase III clinical trial in China. We appreciate the continued support and input from our partners as we look forward to the potential U.S.

marketing approval for XIPERE and the initiation of a Phase III trial in China before the end of this year. As we announced last week, we have completed patient dosing in the first cohort of OASIS, our Phase I/IIA clinical trial for CLS-AX in patients with wet AMD.

CLS-AX is our proprietary suspension of the tyrosine kinase inhibitor, axitinib, for suprachoroidal injection. We believe CLS-AX can improve the treatment of wet AMD in three important ways.

First, that may offer safety benefits by compartmentalizing drug away from the vitreous and the anterior segment; second, it may improve efficacy by directly targeting affected chorioretinal tissues with high drug levels; and third, it may reduce patient treatment burden due to prolonged durability of the small molecule suspensions in the suprachoroidal space, thereby reducing the frequency of injections.

Our differentiated approach with CLS-AX combines with the high potency and pan-VEGF attributes of axitinib, a suprachoroidal delivery by our SCS Microinjector to potentially deliver these benefits. OASIS is a U.S.-based open-label single dose escalation trial to assess the safety and tolerability of CLS-AX in wet AMD patients.

Our continued progress on OASIS is important as we continue to expand our pipeline with new assets and indications, and we look forward to reporting initial safety data from cohort 1 by midyear.

With our CLS-AX OASIS clinical trial and the programs run by our strategic partners, there are currently four ongoing U.S.-based clinical trials with three different novel candidates administered into the suprachoroidal space using our proprietary SCS Microinjector. I will now turn over the call to Dr.

Tom Ciulla, our Chief Medical Officer and Chief Development Officer. Tom will elaborate on our internal development pipeline featuring CLS-AX and our integrant inhibitor program. He will also provide an update of our partners program with REGENXBIO and Aura Biosciences.

Tom?.

active sub focal corneal vascularization secondary to AMD, two or more anti-VEGF treatments with a meaningful response in the four months preceding the screening visit; and specifics related to patients' best corrected visual acuity to ensure patient stability after anti-VEGF treatment. Patients are being assessed at weeks 4, 8 and 12.

If needed, patients would be retreated with aflibercept based on a loss from best measurement of 10 or more letters and best corrected visual acuity with associated excitation or an increase in central subfield retinal thickness greater than 75 microns or the presence of a vision-threatening hemorrhage due to their AMD.

All of these are criteria typical for corneal trials. The primary endpoint for the trial will set the safety and tolerability of CLS-AX for three months, following its administration. Last week, we announced that our first cohort of patients is fully enrolled.

Based on the trial design, each patient has received aflibercept at their first visit and a single dose of a CLS-AX at their second visit one month later. Overall, we are very pleased with the rapid progress we made enrolling patients.

Compared to other individually delivered therapies, we believe SCS administration of CLS-AX is attractively differentiated, potentially providing synergistic safety, efficacy and durability benefits.

We look forward to reporting initial safety data from cohort 1 of OASIS midyear and continuing with cohort 2 at a higher dose in the second half of the year. With respect to our other research efforts, we continue to explore opportunities to expand our internal development pipeline through new molecules and disease applications.

Over the course of last year, we advanced our integrate inhibitor program with a focus in the area of diabetic macular edema and macular generation where specific integrins have been implicated in these diseases.

Integrins are multifunctional cell adhesion molecules that regulate cell processes and play a clinical role in pathologic processes such as inflammation, angiogenesis and fibrosis.

Integrins also represent a novel target with limited competition, and we believe that given their unique mechanism of action, our proprietary suspension could serve as a primary therapy, adjunctive therapy to anti-VEGF treatments or as a secondary therapy in refractory cases.

Similar to what we have demonstrated with our other small molecule suspensions, axitinib and triamcinolone acetonide, we believe our suprachoroidal delivery approach of an integrin inhibitor could provide targeting, compartmentalization and durability advantages over other delivery approaches.

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

Gene therapy remains an extremely promising approach to treat retinal diseases, particularly those that are inherited, and we believe that our SCS technology can enhance the benefits of this approach. We are excited about the advancements made by our partner, REGENXBIO and their gene therapy program utilizing our SCS Microinjector.

REGENXBIO is currently conducting two Phase II clinical trials evaluating the efficacy, safety and tolerability of suprachoroidal delivery of their agent, RGX-314. We are very encouraged by the REGENXBIO clinical trials for two important reasons.

First, office-based suprachoroidal administration potentially avoids the risks associated with pars plana vitrectomy, retinotomy and subretinal injection, especially in AMD and diabetic retinopathy patients.

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

The first trial entitled AAVIATE is targeting the treatment of patients with severe wet AMD who are responsive to anti VEGF treatment. They have completed enrollment in the first cohort and expect interim efficacy data in Q3 2021. REGENXBIO has reported that RGX-314 has been well tolerated to date in the AAVIATE trial.

This is quite encouraging as they are not only using - as they are not using prophylactic steroid treatment in the trial and the tolerance of suprachoroidally administered gene therapy in humans would represent, like, an important sign of progress.

REGENXBIO has also begun enrollment in cohort 2 and expects enrollment completion for that cohort in the second quarter of this year. The second RGX-314 clinical trial is for the treatment of diabetic retinopathy. This trial entitled ALTITUDE is ongoing and initial data is expected in 2021.

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

Our oncology partner, Aura Biosciences, continues to enroll their Phase II clinical trial evaluating their proprietary virus-like drug conjugate, AU-011, delivered via our SCS Microinjector into the suprachoroidal space.

The trial is assessing the safety and primary efficacy of AU-011 in patients with choroidal melanoma, a rare and aggressive form of eye cancer that is the most common intraocular cancer in adults.

We look forward to continued progress in Aura, and we are encouraged by the potential for AU-011 to treat this devastating disease and improve the lives of cancer patients. I will close today with a brief overview of our recent interactions with the retina physician community.

Despite all of the meetings being held virtually over the last year, our medical affairs team continues to make meaningful connections at congresses and through numerous publications. Most recently, we presented at the Annual Macular Society Meeting as well as the Angiogenesis, Exudation and Degeneration 2021 Program.

At Macular Society, leading retina physicians presented a wide variety of information on our programs, including presentations on CLS-AX, XIPERE and suprachoroidal administration of small molecule and nanoparticle suspensions.

Importantly, data was also presented on the safety of the suprachoroidal injection procedure utilizing our SCS Microinjector across three retinal disorders, demonstrating the broad applicability of our injection platform.

The androgenesis presentation highlighted several of the key attributes of axitinib and Clearside suprachoroidal delivery of the agent, including the ease of administration and as demonstrated in the video of a clinical trial patient undergoing the office-based suprachoroidal delivery procedure.

In addition to these medical meetings, we have also had multiple papers accepted for publication. In February of this year, the peer-reviewed British Journal of Ophthalmology published a paper on our AZALEA clinical trial.

Which is an open-label, prospective multicenter study evaluating the local and systemic safety of XIPERE in subjects with noninfectious uveitis with and without macular edema. AZALEA corroborates and augments a successful Phase III PEACHTREE trial in which XIPERE was observed to be well tolerated over the 24-week period.

And our XIPERE Phase III extension study in Magnolia was also recently accepted for publication in the British Journal of Ophthalmology. In January of this year, in the online publication expert opinion on drug delivery, there was an in-depth analysis of the biomechanics of suprachoroidal drug delivery.

This focused on how compartmentalizing therapies away from the unaffected tissues along with fluid transport properties in forming our customization for pharmacologic agents may allow for a more tailored treatment of diseases affecting choroidal tissues.

And finally, in December of 2020, there was a paper in Translational Vision Science and Technology regarding how suprachoroidally delivered DNA nanoparticles transfected retina and retinal pigment epithelium and choroid in rabbits. Link to these publications and presentations are available on our website in the Science section.

In closing, given our extensive experience with over 1,200 patient injections performed to-date and a robust training program, we believe our SCS Microinjector could be readily adopted in clinical practice. We look forward to continued progress in 2021 and updating you as the year unfolds.

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

Charles?.

Thank you, Tom. Our financial results for the fourth quarter and full year 2020 were published this afternoon in our press release and are available on our website. Therefore, I will summarize our current financial status. Our cash and cash equivalents as of December 31, 2020 totaled approximately $17 million.

This includes $6.9 million of funds raised in the fourth quarter through our aftermarket or ATM facility. In January 2021, we raised aggregate net proceeds of $14.4 million from a registered direct offering and our ATM facility.

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

Our current quarterly cash burn is primarily related to work on XIPERE manufacturing, NDA resubmission and the CLS-AX clinical trial. The planned investments in our preclinical work are also incorporated into our operating plans.

In summary, we expect that our current financial resources will enable us to potentially reach multiple value-creating events over the next 12 months. We appreciate the interest and support of the investment community, and look forward to participating in the upcoming ROTH and Needham conferences.

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

Thanks, Charlie. I'd like to wrap up our formal comments today with a few final points. First, as the pioneers in treating back of the eye diseases through the suprachoroidal space, we continue to demonstrate that our injection technology platform can be utilized for a range of potential ophthalmic conditions and with multiple therapeutic entities.

Second, we have considerably expanded the clinical use of our first-in-class proprietary SCS Microinjector. In just the last six months, four clinical programs using our SCS Microinjector have been initiated, both from our internal pipeline and from partner-led efforts.

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

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

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

[Operator Instructions] First question comes from the line of Andreas Argyrides from Wedbush Securities. You are now live..

This is Andreas on for Liana Moussatos.

Our first question is with initial data from other pan-VEGF inhibitors now becoming available, what would you like to see as far as rescue free rates at three months in the upcoming readout of OASIS?.

Tom, I think that's your question..

Thank you for the question. So the question has to do with potential or projected rescue rates in the upcoming OASIS study. And I just want to back pedal a bit and remind everybody that this study is really - at least the first cohort is really geared towards safety.

This is the first time a tyrosine kinase inhibitor has been injected in man suprachoroidally. And so really, the first cohort is geared towards safety. We want to make sure it's well tolerated before we escalate.

So with that in mind, we have absolutely no prior data on what we can expect with this mode of delivery, and it's very difficult to do cross-trial comparisons from other TKI studies where the TKI is packaging the sustained delivery device and injecting individually. So it's really hard at this point without any data for me to speculate.

And that's really the whole goal of the study is to collect that initial data, again, geared towards safety with the first cohort and dose escalate thereafter..

Understood. And I'll just ask one follow-up and then jump back in the queue.

How are the - thinking about the higher doses in the second and third cohorts, how are those doses being determined? Are they predetermined or on a result basis?.

That's a great question. The question was doses for the upcoming cohort. So as we've noted on clinicaltrials.gov, the initial dose will be 0.03 milligrams. Cohort 2 will be 0.06 milligrams and cohort 3 will be 0.1 milligrams. But your point is well taken. So these are prespecified.

But obviously, we have the ability to amend a protocol and adjust accordingly..

Next one on the queue is Annabel Samimy from Stifel. You are now live..

Congratulations on the progress. A lot going on with your proprietary and your partner programs. I had a couple here. So I guess, first with CLS-AX. I guess I'm not going to ask you to comment on the grade but data. But there are a number of pan-VEGF trials that are ongoing or starting - about to start.

And I'm just wondering, from a competitive perspective, would you envision SCS delivery might speed up or possibly slow down the development relative to competitors? For example, if you have a longer duration, could this be a problem competitively? I guess it won't matter if you had better data.

But how do you think about the development pathway? Is it a race and how do you expect to sort of manage that?.

I guess I'll take that to start. That's a great question. And I think you mentioned other programs. So as I mentioned in my prepared remarks, suprachoroidal delivery of a tyrosine kinase inhibitor is well differentiated from other modes of delivery.

We believe there are synergies between the intrinsic properties of axitinib and the attractive features of suprachoroidal delivery. So first, for axitinib, as you may know, it's a pan-VEGF inhibitor. It's one of the most highly potent tyrosine kinase inhibitors.

And it's been shown in preclinical studies to have better compatibility with ocular cells and other TKI. So there may be not only an efficacy benefit intrinsically with axitinib due to its potency, but potentially a safety benefit. And then we think we can leverage that further with suprachoroidal delivery.

So we know that when we inject small molecule suspensions suprachoroidally, we can compartmentalize them in the suprachoroidal space. We get very high levels in that space and very, very low levels in the vitreous and basically undetectable or rather limited in the aqueous.

So we think by compartmentalizing the drug in the suprachoroidal space, we're going to minimize the risk of any snow globe effects or any off-target effects. And then in terms of efficacy, by achieving very high levels in that space, we can further potentially enhance the efficacy of axitinib.

And finally, we know from the work we've done with several small molecule suspensions, we have multi-month durability. So we think that suprachoroidal delivery of a TKI, a potent TKI, like axitinib, is very well differentiated and, clearly, potentially separates us from other TKIs.

And I might add that, as you know, TKIs have been assessed topically, systemically and intravitreally. And in many of these cases, there's been a biologic effect. So we think that TKIs probably work, and it's not a matter of mechanism of action, but really one of delivery. And we think we solved that problem..

Okay. Great. And then if I could ask a second question, I guess, regarding REGENXBIO, their program, 314. So we saw the long-term results from the subretinally administered RGX-314 and the durability seems really good. And I guess, that was measured partly by the - also by the reduction of the anti-VEGF - by the reduction of anti-VEGF injections.

I guess, maybe - and it's something not quite long. And I guess maybe you can help us understand what expectations would be for suprachoroidally delivered 314 based on what you saw from the subretinal durability? And what is the possibility of that higher protein expression repeated in humans? I think you saw it preclinically already.

So maybe you can talk a little bit about that..

Sure. So it's a great question. And as you know, REGENXBIO is in Phase II for wet AMD and diabetic retinopathy. They've announced that they completed an enrollment of patients in cohort 1, their initial dose. They expect interim efficacy data from cohort 1 in the third quarter of this year, and they've already begun enrollment in cohort 2.

But I want to, again, back up little bit and just remind everybody that, once again, this is first-in-man a viral vector gene therapy has been injected suprachoroidally.

And I think that their announcement, that has been well tolerated to date, is really a huge step forward because, as you know, viral vectors can be associated with inflammation when delivered individually. And the fact that they've already announced that it's been well tolerated, again, is a step in the right direction.

So I think just like our first cohort of our CLS-AX study, their first cohort of suprachoroidal delivery of their vector, RGX-314, is - I would speculate is really geared towards safety.

And the fact that it's been well tolerated to-date, I think it's a huge step forward, not just for REGENXBIO and RGX-314, but really the entire field of viral vector gene therapy, particularly for biofactory. And obviously, they're going to dose escalate as they've already done in cohort 2.

And I think just as they've done with their subretinal program with five cohorts, they'll escalate until they find a dose that's not only safe but also efficacious. So I think we're in the early innings, but I think it looks very promising so far..

Okay. And one last question, if I may.

Is there any work that's being done, I know that Bausch is controlling the commercialization of XIPERE, but have you established - or have they established some kind of training program for physicians, given that SCS - I mean, I imagine that the SCS delivery would be something that you would - or XIPERE would be something that you would want to use the launch pad in training for all the other programs that are coming down the pipe? So can you talk about the training program that's being established for that?.

Yes, I think, Tom, you can speak to what med affairs has done with Bausch training of at least the Bausch employees..

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

We actually are looking at this with surveys and we'll be presenting this at ARVO as a means of physician training virtually. We also have a very robust in-person training program. And I can tell you that it's been extraordinarily well received by physicians.

We recently published, what I call, our procedure performance paper, which is available on our website, which indicates that the procedure itself is very well accepted by physicians, and our interactions with Bausch as well as REGENXBIO and Aura in terms of training has been really stellar. We've had great experiences with these companies.

And finally, I want to mention that we have some injection videos on our website. And I think if you have a chance to view those, I would encourage you to do so, because they demonstrate how relatively facile physicians can become with injecting. We actually have an injection video of CLS-AX.

And you can see from the video that it seems to be well tolerated. It seems to be fairly quick and efficient. So we're really confident that this procedure could be readily adopted in clinical practice when it's approved, especially in the retina community where these physicians love gadgets and love procedures..

[Operator Instructions] Next on the queue is Jon Wolleben from GMP Securities. You are now live..

Congrats on all the progress. Just a couple from me as well on CLS-AX. Tom, you mentioned a few times that the focus for this first readout midyear is going to be on safety, but you are collecting a few different efficacy end points.

So I was hoping you could let us know specifically what data to look forward to midyear on the efficacy front?.

Sure. We hate to even call these endpoints efficacy endpoints with only five patients. But your point is well taken. They tend to be traditional efficacy endpoints. And again, they're all listed on clinicaltrials.gov. But it will be the usual endpoints that most companies report. So, of course, we'll have best corrected visual acuity.

We'll be looking at the need for rescue, we'll be looking at anatomic features on OCT and geography, and OCT and geography, particularly central subfield thickness. And of course, again, because it's mostly geared towards safety, we'll be looking at adverse events - treatment-emergent adverse events and serious adverse events..

That's helpful. And I think you mentioned that the plan is to start the second cohort in the second half of this year.

So I'm wondering how much safety follow-up have you designated that's necessary before dose escalating? And is that the same between cohorts 2 and 3 as well?.

Great question. So as you know, patients will be followed for three months after their CLS-AX injection. Then we'll essentially tabulate their results, present it to the safety monitoring committee, and they'll help us decide whether it's safe to move on or not.

We plan to start recruitment just at the beginning of the second half of this year and potentially have results from cohort 2 by the end of the year..

Terrific. And just shifting gears, one last one from me. On the preclinical Integrin platform, you mentioned wrapping up the preclinical work this year is the goal.

Will we be seeing any of that data this year? And is the expectation to have a lead candidate or a multiple? How are you thinking about next steps for the Integrin platform?.

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

We're currently formulating this as a small molecule suspension. It's currently undergoing preclinical testing to assess the ocular tolerability, the ocular distribution and pharmacokinetics.

As you know, we've done a significant amount of work with small molecule suspensions, and we expect it to be well tolerated to show favorable distribution, that is to be high levels in the targeted core retinal tissue layers and low levels anteriorly, and to have multi-month durability.

So we will hopefully be wrapping those studies up this year and sharing some of those results with the retina community and the investment community..

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

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

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