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Edited Transcript of CLSD.OQ earnings conference call or presentation 10-Nov-20 9:30pm GMT

·33 min read

Q3 2020 Clearside Biomedical Inc Earnings Call ALPHARETTA Nov 11, 2020 (Thomson StreetEvents) -- Edited Transcript of Clearside Biomedical Inc earnings conference call or presentation Tuesday, November 10, 2020 at 9:30:00pm GMT TEXT version of Transcript ================================================================================ Corporate Participants ================================================================================ * Charles A. Deignan Clearside Biomedical, Inc. - CFO * George M. Lasezkay Clearside Biomedical, Inc. - President, CEO & Director * Jenny R. Kobin Clearside Biomedical, Inc. - Head of IR * Thomas A. Ciulla Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer ================================================================================ Conference Call Participants ================================================================================ * Annabel Eva Samimy Stifel, Nicolaus & Company, Incorporated, Research Division - MD * Jonathan Patrick Wolleben JMP Securities LLC, Research Division - VP & Equity Research Analyst * Shveta Vilas Dighe Wedbush Securities Inc., Research Division - Associate * Zegbeh Claudel Jallah ROTH Capital Partners, LLC, Research Division - Director & Research Analyst ================================================================================ Presentation -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- Ladies and gentlemen, thank you for standing by, and welcome to the Clearside Biomedical Third Quarter 2020 Financial Results Conference Call. (Operator Instructions) I would now like to hand the conference over to Jenny Kobin, Clearside Investor Relations. Thank you, and please go ahead, madam. -------------------------------------------------------------------------------- Jenny R. Kobin, Clearside Biomedical, Inc. - Head of IR [2] -------------------------------------------------------------------------------- Good afternoon, everyone, and thank you for joining us on the call today. Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements. Various remarks that we make during this call about the company's future expectations, plans and prospects constitute forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed 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 Charlie Deignan, our Chief Financial Officer. After our formal remarks, we will open the call for your questions. I would now like to turn the call over to George. -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [3] -------------------------------------------------------------------------------- Thank you, Jenny. Good afternoon, and thank you for joining us on the call today. The third quarter of 2020 was very productive for Clearside, both operationally and clinically as we had numerous positive advances to our pipeline. As we announced on our last quarterly call, we secured acceptance of our investigational new drug application for our lead development asset, CLS-AX, our proprietary suspension of axitinib for suprachoroidal injection. With this IND, we plan to initiate our first clinical trial with CLS-AX in wet AMD patients. I'm extremely proud of the cross-functional team that's worked so diligently to take axitinib from just a concept a little over 1-year ago to our expected initiation of a Phase I/IIa clinical trial by the end of this year. As Tom will discuss in his remarks, we are eager to advance axitinib into the clinic as we believe its intrinsic tyrosine kinase inhibitor characteristics can be further leveraged through our SCS Microinjector. In preclinical studies, CLS-AX delivered suprachoroidally was observed to be well tolerated and showed significant tissue concentrations over time. These characteristics, if demonstrated clinically, may support suprachoroidal axitinib's potential to reduce the profound treatment burden for patients suffering from wet AMD. Our Phase I/IIa clinical trial for CLS-AX is expected to begin by the end of this year, and we anticipate reporting initial data from the first cohort in mid-2021. In addition, we continue to progress our internal preclinical work to expand our pipeline. One of our focus areas is on a nonviral vector gene therapy program that we refer to as our therapeutic biofactory. We are also working on a development program utilizing suprachoroidal administration of an integrin inhibitor small molecule suspension, initially focused on diabetic macular edema. Tom will elaborate on these early-stage programs shortly. For XIPERE, our new contract manufacturer is completing the technology transfer and working diligently to prepare to manufacture the XIPERE drug product GMP batches. Once these batches are made, we expect that we will be able to generate the required stability data for our new drug application resubmission to the FDA. The cooperation and productivity of our new CMO, working together with the Clearside team has been exceptional. And I'm very pleased to report that we remain on track with our expectation to resubmit our NDA in the first half of 2020 -- 2021, excuse me. And we expect the FDA will review the NDA within 6 months of the resubmission date. We are excited by the progress made this past quarter by our development partners using our SCS Microinjector to deliver their drug candidates into the suprachoroidal space. REGENXBIO has enrolled and dosed multiple patients in its Phase II clinical trial to evaluate the suprachoroidal delivery of RGX-314, an adeno-associated virus gene therapy using our SCS Microinjector for the treatment of wet AMD. Based on our licensing agreement with REGENXBIO, this progress triggered a milestone payment to us in the third quarter. REGENXBIO also announced that they received IND clearance by the FDA to evaluate the suprachoroidal delivery of RGX-314 in patients with diabetic retinopathy. This trial is now active, and REGENXBIO expects to begin enrolling patients with diabetic retinopathy by the end of this year. Our oncology licensing partner, Aura Biosciences, announced they have dosed the in their Phase II clinical trial, evaluating the safety and efficacy of suprachoroidal administration of AU-011 as a potential first-line treatment for patients with primary choroidal melanoma. The initiations of these clinical trials represent major milestones for us as they are the first partnered programs to utilize our SCS Microinjector as the mode of administration for the partner's therapeutic products. We believe we are the partner of choice for accessing the suprachoroidal space as our SCS Microinjector has been used in multiple clinical trials with consistent safety and reliability. As such, we continue to expand our intellectual property portfolio in the U.S. and in Europe. We now have 21 granted U.S. patents and 20 European patents, providing extensive coverage of our SCS Microinjector and its use, administration of any drug into the suprachoroidal space by injection as well as coverage for specific suprachoroidal product candidates. We are committed to extending our global patent estate as we continue to expand our internal product pipeline and increase patient access to innovative therapies through our suprachoroidal injection platform. With that, I will now ask Dr. Tom Ciulla, our Chief Medical Officer and Chief Development Officer, to elaborate on our research and clinical development programs. Tom? -------------------------------------------------------------------------------- Thomas A. Ciulla, Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer [4] -------------------------------------------------------------------------------- Thank you, George. We've made significant advances in our pipeline over the last several months, and I'm pleased to share these updates with you today. As George mentioned, our clinical development team is on track to initiate our CLS-AX Phase I/IIa clinical trial by the end of this year in patients with wet AMD. Our outside clinical research organization has been chosen, and we are working with them to prepare the trial sites for initiation. As a reminder, a Phase I/IIa trial will be an open-label dose escalation trial to assess the safety and tolerability of a single dose of CLS-AX administered through the suprachoroidal injection procedure. Eligible patients are those who demonstrate stable visual acuity following 2 or more previous injections with aflibercept, an anti-VEGF agent. As a tyrosine kinase inhibitor that inhibits VEGF receptors 1, 2 and 3, axitinib's and VEGF inhibition could be more effective than current focused anti-VEGF A inhibition, and there is already independent wetter demonstrating its potential efficacy in preclinical models of corneal, retinal and choroidal angiogenesis. Also, in preclinical models, it has been shown to be more potent and have better ocular biocompatibilities than other TKIs, suggesting the potential for efficacy and safety advantages. And we believe that delivery of the agent via suprachoroidal injection not only has the potential to leverage the attributes of axitinib, but may also allow for less frequent dosing and, therefore, a lower treatment burden for patients, which addresses a large unmet need. Because this is a first-in-human trial, our primary objective is to assess the safety and tolerability of CLS-AX in these wet AMD patients. We will also evaluate secondary metrics, including pharmacokinetics, visual function, culinarily anatomy and the need for additional treatment with intravitreal aflibercept. The trial of approximately 15 patients and 3 cohorts will include a total of 5 patient visits. With the timeline for each cohort at around 6 months, we expect initial safety data from the first cohort in mid-2021. In addition to CLS-AX, we remain dedicated to expanding our internal pipeline. As noted previously, we have been interested in suprachoroidal administration of gene therapy. Recently a published preclinical paper from the renowned ocular gene therapy group at the University of Iowa demonstrated that suprachoroidal delivery is a viable route for AAV mediated retinal transduction. And they concluded that further investigation for potential human gene therapy is warranted. We are pursuing a therapeutic biofactory approach to the delivery of gene therapy via DNA nanoparticles, and our preclinical research has demonstrated several promising characteristics. First, suprachoroidal administration of DNA nanoparticles has yielded similar marketing activity compared to subretinal administration. Second, we have observed that suprachoroidal administration of DNA nanoparticles containing therapeutic transgenes is better tolerated than when delivered intravitreally. Third, we have seen preliminary signs of protein expression for the duration of the preclinical studies. And finally, OCT imaging demonstrates opening of the suprachoroidal space posteriorly all the way to the optic nerve, which supports the potential to address macular disorders in addition to peripheral retinal disorders. We are excited about the potential of this platform using our SCS Microinjector for both a biofactory and native gene replacement approach. I'm also encouraged by our integrin inhibitor program as integrins represent a novel target with limited competition. Integrins are multifunctional cell adhesion molecules that regulate critical cell processes such as adhesion, migration, proliferation, invasion, survival and apoptosis. Additionally, they play a critical role in pathologic processes such as inflammation, angiogenesis and fibrosis. We believe that suprachoroidal delivery of an integrin inhibitor suspension may provide targeting, compartmentalization and durability advantages over topical or individual delivery, similar to what we've observed in other preclinical studies of small molecule suspensions like triamcinolone and axitinib. Therefore, we have been running a series of preclinical studies with our integrin inhibitor suspension to assess the ocular tolerability, distribution and pharmacokinetics. We expect our first set of data from these preclinical studies in the first half of next year. Ultimately, we hope to address the pathologic processes in diabetic macular edema and macular degeneration. As George mentioned, we are very pleased with the progress made by our development partners over the last several months. Last week, our partner, REGENXBIO, announced that it has enrolled and dosed multiple patients in its Phase II gene therapy clinical trial for the treatment of wet AMD utilizing RGX-314. This trial was evaluating the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using our SCS Microinjector. The study entitled AAVIATE is a multicenter open-label randomized active controlled dose escalation trial that's expected to enroll approximately 40 patients with severe wet AMD across 2 cohorts. The primary endpoint of the trial is mean change in vision in patients dosed with RGX-314 compared to patients receiving monthly injections of ranibizumab. Other endpoints include mean change in central retinal thickness and number of anti-VEGF individual injections received following administration of suprachoroidal RGX-314. This study is first in-human gene therapy trial utilizing our SCS Microinjector. I want to remind everyone that gene therapy has typically been delivered via subretinal injection, which involves pars plana vitrectomy in the operating room and creation of a retinotomy followed by a limited retinal attachment as therapies injected into the subretinal space. This subretinal injection procedure has been undergoing optimization for over a decade. We believe that suprachoroidal injection should expose more surface area to the gene therapy, providing the potential to treat large amounts of retina less invasively. Since we are in the early stages of this approach, there may still be more optimizing to do as the most appropriate dosing schedule is determined for each therapeutic. I'd like to note that in REGENXBIO's earnings conference call this -- last week and commenting on the AVA trial using Clearside's SCS Microinjector, they stated that RGX-314 has been well tolerated to date, including no evidence of inflammation. The tolerance of suprachoroidally administered gene therapy in humans, especially without prophylactic steroid therapy, would represent an important initial sign of progress. REGENXBIO expects to complete enrollment of the first cohort by the end of 2020 and report initial safety data from the first cohort in early 2021. We are excited about this groundbreaking approach and look forward to the important safety signals from this first in-man dose cohort of a suprachoroidally administered gene therapy. In addition, REGENXBIO has received acceptance of its IND application by the U.S. FDA to evaluate the suprachoroidal delivery of RGX-314 in patients with diabetic retinopathy. This Phase II trial, entitled ALTITUDE, is now active. REGENXBIO expects to begin dosing patients across 15 leading U.S. retina centers by the end of 2020 and plan to report interim data from this trial in 2021. We are very excited about the REGENXBIO clinical trials for 2 important reasons. First, office-based suprachoroidal administration potentially avoids the risks associated with pars plana vitrectomy, retinotomy and subretinal injection, especially in diabetic patients. And second, the ability for physicians to treat patients in their offices could substantially increase patient access to care compared to current models of referring patients to regional ocular gene therapy surgical treatment centers. We are also encouraged by the progress by our oncology partner, Aura Biosciences. In September, they announced the dosing of the first patient in their Phase II clinical trial evaluating a suprachoroidal administration of AU-011 in patients with choroidal melanoma. For this trial, Aura is utilizing Clearside SCS Microinjector to deliver AU-011 to the posterior segment of the eye where choroidal melanomas are located. The objectives of this study include assessment of safety and preliminary efficacy in the treatment of choroidal melanoma utilizing suprachoroidal administration of AU-011. Other objectives include determining the highest tolerable dosing regimen as well as assessing immunogenicity. Notably, the first cohort of this Phase II study demonstrated favorable safety data with no adverse events noted. These preliminary safety results with Aura's viral nanoparticle conjugates are important because they may further support the potential for viral vectors in the suprachoroidal space. Furthermore, choroidal melanoma is a rare and aggressive type of eye cancer and is the most common intraocular cancer in adults with a high potential of it becoming metastatic. This presents a critical treatment need and we are encouraged with the potential for AU-011 to treat this devastating disease and improve the lives of patients. Our medical (inaudible) authors team continues to proactively engage in scientific and medical communities. Several clinical data presentations were given at the Annual Scientific Meeting of the Retina Society. We also deliver a corporate and clinical overview at the Retinal Futures Forum. And we look forward to presenting data at the American Academy of Ophthalmology annual meeting later this week. Importantly, we also announced that data from our Phase II clinical trial in diabetic macular edema was published in ophthalmology retina to peer-review Medline Index Retina Journal of the American Academy of Ophthalmology. The trial entitled TYBEE is (inaudible) when used with individually administered aflibercept in patients with DME over a 6-month evaluation period. This early data suggests a potential role for XIPERE, if approved, in reducing treatment burden for DME patients. Finally, we have just published a clinical characterization of suprachoroidal injection procedure across 3 retinal disorders in the ARVO peer-reviewed Medline Index Journal Translational Visual Science & Technology. The study described in this paper demonstrated that suprachoroidal injection was well accepted by physician investigators. And that the device and procedure may accommodate a wide range of anatomic and demographic variables. These studies suggest that suprachoroidal injection could be readily adopted in clinical practice for targeted compartmentalized delivery of ocular therapies. Altogether, we've made tremendous progress both internally and with our development partners to broaden the scope of development activities for our suprachoroidal injection platform. And most importantly, we look forward to continuing this path and trajectory in 2021. I will now turn the call over to our CFO, Charlie Deignan, to review our financial results. -------------------------------------------------------------------------------- Charles A. Deignan, Clearside Biomedical, Inc. - CFO [5] -------------------------------------------------------------------------------- Thank you, Tom. Our financial results for the third quarter were published this afternoon in our press release and are available on our website. Therefore, I will summarize our current financial status. As we reported, our cash and cash equivalents at the end of September 2020 totaled approximately $15 million. Our quarterly cash burn remains consistent with spending focused primarily on resubmission of the NDA for XIPERE and our anticipated clinical trial initiation for CLS-AX. The planned investments in our preclinical work are also incorporated into our operating plans. As George and Tom discussed, our partner, REGENXBIO, initiated their Phase II clinical trial utilizing our SCS Microinjector, which triggered a milestone payment from them of $3 million. With this additional licensing revenue, we are able to extend our cash runway, and currently expect to have sufficient resources to fund planned operations into the third quarter of next year. We remain active participants in sell-side sponsored events and look forward to presenting at the Stifel Virtual Healthcare Conference next week. I will now turn the call back over to George for his closing remarks. -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [6] -------------------------------------------------------------------------------- Thank you, Charlie. In August of last year, we introduced a new strategic direction for Clearside. The two-pronged strategy included: first, building an internal research and development pipeline in areas such as novel small molecules and nonviral gene therapy; and second, establishing external collaborations with other companies to allow them to access the suprachoroidal space in specific therapeutic areas we could not or did not intend to pursue. As you've heard in our remarks today, this strategy has come to fruition through the hard work and dedication of our team over the last 15 months. We have built a diversified pipeline of clinical and preclinical programs. We have focused our spending on the growth of key assets. And we have secured nondilutive funding via upfront and milestone-based payments with a potential future royalty revenue stream. We expect this momentum to continue into 2021 with the potential approval of XIPERE, receipt of initial clinical data for CLS-AX in wet AMD patients and the advancement of our preclinical programs. I would now like to ask the operator to open the call up for questions. ================================================================================ Questions and Answers -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- (Operator Instructions) Our first question comes from the line of Liana Moussatos with Wedbush. -------------------------------------------------------------------------------- Shveta Vilas Dighe, Wedbush Securities Inc., Research Division - Associate [2] -------------------------------------------------------------------------------- This is Shveta for Liana. Congrats on all the progress. For XIPERE, how long would it take for the new CMO to produce the registration batches? And then from there, how long would it take to generate the stability data to submit -- to resubmit the NDA? And I have one question on CLS-AX. When you report the safety data mid-21 next year, do you also plan to report any secondary endpoints? -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [3] -------------------------------------------------------------------------------- Okay. Well, thank you for that question. I'll let Tom take the second question in a minute. I'll take the first one on XIPERE. We disclosed again today that our timing on the NDA resubmission would be no later than the first half of next year, 2021, where things are going very well with the new CMO. To be precise, once we make the registration batches, it will take us 3 months to produce the stability data. Once we resubmit, we expect that we will get action on our resubmission within 6 months of the resubmission date. Tom, you want to answer the question about CLS-AX? -------------------------------------------------------------------------------- Thomas A. Ciulla, Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer [4] -------------------------------------------------------------------------------- Sure. Just a quick review. So it's a Phase I/IIa study. It's an open-label dose escalation study. There's 3 cohorts of 5 patients each. We'll begin at the 0.03 milligram dose. And we have multiple endpoints that will include predominantly safety, but we'll also be assessing the tolerability, visual function, ocular anatomy and need for additional therapies. And we will be presenting all of those endpoints in mid-2021. -------------------------------------------------------------------------------- Operator [5] -------------------------------------------------------------------------------- Our next question comes from the line of Zegbeh Jallah with ROTH Capital Partners. -------------------------------------------------------------------------------- Zegbeh Claudel Jallah, ROTH Capital Partners, LLC, Research Division - Director & Research Analyst [6] -------------------------------------------------------------------------------- Just have a couple here. The first one, I think, relates to CLS-AX. Just kind of wondering for this study, if we're going to have data from all of the cohorts? Did I hear you, Tom, say that we'll just have data from cohort 1? And then do you expect that we will see efficacy data from just the lowest dose, for example, the 0.03 milligram or do you expect efficacy at higher doses? -------------------------------------------------------------------------------- Thomas A. Ciulla, Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer [7] -------------------------------------------------------------------------------- Well, thanks for the question, first of all. So as you know, there's 5 patients per cohort. And again, it's really key towards safety. It will be hard to make any efficacy conclusions with such a small sample size. But nevertheless, we'll have some signals of biologic effect, including visual acuity, OCT and angiographic parameters. We will, of course, be presenting data from each cohort as we accumulate that data and escalate the dose. -------------------------------------------------------------------------------- Zegbeh Claudel Jallah, ROTH Capital Partners, LLC, Research Division - Director & Research Analyst [8] -------------------------------------------------------------------------------- And another follow-up on here. With the data from REGENXBIO coming up early next year, I think a lot of people are also going to be interested in your efforts with nonviral gene delivery. So can you just talk about where you are with that progress in a little bit more detail? -------------------------------------------------------------------------------- Thomas A. Ciulla, Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer [9] -------------------------------------------------------------------------------- Sure. So as I mentioned in my prepared remarks, we have 2 programs that we're working on. And we've seen some interesting results so far. What we've already reported is that suprachoroidal delivery of a marker gene versus intravitreal delivery results in the same activity of that market team, which provided us some hope about going forward. So we're now working with therapeutic transgenes. What we've observed so far is that we can open the suprachoroidal space acutely in this rabbit model all the way to the posterior pole, which suggests that we can treat macular disorders as well as peripheral disorders. We've also seen expression of this therapeutic gene for the duration of the studies. And we've also observed that when we inject suprachoroidally versus intravitreally on clinical exam of these retinas, the suprachoroidal delivery seems to be better tolerated. We're in the process of further quantifying these results, and we hope to present this sometime in 2021. -------------------------------------------------------------------------------- Zegbeh Claudel Jallah, ROTH Capital Partners, LLC, Research Division - Director & Research Analyst [10] -------------------------------------------------------------------------------- And then the final one here from me. I think just a high-level one for George, maybe. And maybe I've already asked this in the past, but as you think about having different pipeline program, you also have the integrin stuff that you're working on. Are you thinking about partnerships at all or do you anticipate independently moving these programs into the clinic and beyond? -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [11] -------------------------------------------------------------------------------- Thanks, Zegbeh. I appreciate that question. I think the difference between now and 14, 15 months ago is that we have these choices to make when we didn't last -- this time last year, and that's a good thing. We're going to be actively evaluating how we go forward with our various programs. I wouldn't say that collaborations are out of the picture. But right now, what we're really focused on is getting the XIPERE NDA resubmitted in the most timely fashion to kick-off the CLS-AX clinical program. And to generate more data on those preclinical programs, so we can make the decision as to whether they're programs that we can afford to bring forward because they justify that or they should be programs that we might be able to do better with a partner. But our strategy is still to develop an internal pipeline as well as external collaborations. And that's not changing. -------------------------------------------------------------------------------- Operator [12] -------------------------------------------------------------------------------- And our next question is from the line of Annabel Samimy with Stifel. -------------------------------------------------------------------------------- Annabel Eva Samimy, Stifel, Nicolaus & Company, Incorporated, Research Division - MD [13] -------------------------------------------------------------------------------- High-grades, a lot of great progress and a big difference from last year. So -- and I want to get a sense. You made a comment earlier that the ophthalmology community is becoming much more comfortable with the SCS platform and its use. I guess my question is, how are they getting that comfort and that experience? There aren't any products on the market yet. Is it primarily through some of the clinical work that you're doing or is it just primarily through the published work? Are these physicians working with SCS platform at all and getting much more comfortable with the delivery into that area of the eye? I guess, the second question I have is with regard to some expectations around milestones and when we might see some, obviously, you've got a lot of clinical and regulatory events coming up that may trigger some. So, for example, with resubmission, of XIPERE, is that on resubmission? Is it only on approval? Are you going to get any milestones with some upcoming data? And then, I guess, finally, in this COVID environment, it's pretty clear that ophthalmology has been the worst hit -- one of the worst hit areas in terms of clinical development. So are you seeing any slowdown, not necessarily of your partners' activity, but in terms of additional partnership talks that -- or any additional requests that you're get -- inbound requests from partners to use your technology? -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [14] -------------------------------------------------------------------------------- That's a lot to digest, Annabel. -------------------------------------------------------------------------------- Annabel Eva Samimy, Stifel, Nicolaus & Company, Incorporated, Research Division - MD [15] -------------------------------------------------------------------------------- I can break it down, if you forget. -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [16] -------------------------------------------------------------------------------- I was trying to take notes while you were talking. On the suprachoroidal, there's maybe a couple of ways we can answer that. I'll let Tom speak in a moment. But the question was about people becoming more comfortable with suprachoroidal. I think there's a couple of reasons for that, and then I'll let Tom elaborate on that. And then he might talk about the COVID question as well. First of all, our team has done a tremendous job in getting the word out about how safe and how reliable and how easy to use the suprachoroidal administration has been. Okay. We've done a number of presentations both in person before COVID hit and virtually since COVID has made most of these conference -- all these conferences go virtual. So we've really gotten the news out. We've established a scientific advisory board with some key opinion leaders that really buy into the suprachoroidal approach. There's also been a fair number of preclinical works, specifically worked by Peter Campochiaro that's really just started to create some justification for people to be interested in the space, both for viral and nonviral gene therapy. He's done it both, and that's probably what led to our -- a leading reason why REGENXBIO wanted to partner with us last year. So there's the preclinical work that's going on. There's the information that's being spread by our medical affairs team. And just all the work we've done with Aura, with Bausch, with ReGenX in terms of training their people, and then turning around and training their investigators. The word is spreading that this is a fairly straightforward process to use and the data is starting to be accumulated that looks like the suprachoroidal space can make a difference in many conditions that are being treated with certain therapeutic agents. That delivery to the -- behind the visual field might be preferable to administration in front of the visual field. Tom, do you want to comment any further on that, what seems to be a growing acceptance and interest in the suprachoroidal space? -------------------------------------------------------------------------------- Thomas A. Ciulla, Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer [17] -------------------------------------------------------------------------------- Sure. I think you summarized it really well. I just wanted to sort of start from scratch and mentioned that we've done over 1,000 injections. We've run global trials: Phase I and -- Phase I, II, III global trials, and we trained hundreds of clinician investigators. We found that it was very well adopted. And then as George mentioned, there's been some preclinical gene therapy studies using suprachoroidal approach. He mentioned Johns Hopkins, but I also wanted to highlight the University of Iowa has also published a paper recently pursuing suprachoroidal injection preclinically of gene therapy. And then as George mentioned, there's a whole host of trials now, actually using our very micro inductor. So there'll be 4 clinical trials this year assessing 3 assets. And of course, we mentioned REGENXBIO, they'll have 2 trials for AMD and DME. Their investigators have all undergone training. Aura Biosciences similarly has their Phase II trial up and running with our SCS Microinjector. Their investigators are also -- have also received and are also undergoing training. We'll have our own Phase I/IIa trial with axitinib. We'll be training investigators for that. And I also had mentioned that even globally, Arctic plans to pursue clinical trials in China, and they'll have training programs. As Bausch medical affairs will also be very actively engaging the retina community as it plans for launch. And then finally, I just wanted to highlight or amplify what George mentioned, our medical affairs team has been incredibly active this year. We've had over 35 presentations at multiple retina congresses. And I did mention earlier that we just published, it's available a fully online download. We just published a clinical characterization of the suprachoroidal injection procedure using a microinjector. And that showed that the procedure is very well accepted by clinician investigators and that showed that the -- or suggests that the procedure could be a very rapidly adopted in clinical practice. -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [18] -------------------------------------------------------------------------------- Tom, do you want to just comment very briefly? And then we'll get to her final question on COVID impacting recruitment. -------------------------------------------------------------------------------- Thomas A. Ciulla, Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer [19] -------------------------------------------------------------------------------- Sure. So the American Society of Retina Specialists has put out guidelines for COVID. And basically, the guidelines essentially state that essential therapies like anti-VEGF therapies for AMD should not be halted because, obviously, patients require it. And by and large, the retina community has adopted quite well. They continue to treat patients with anti-VEGF therapies for AMD and DME and RVO. We think for our Phase I/IIa clinical trial, as I mentioned, the initial cohort will just be 5 patients. We have multiple sites that are initiating. Each of these sites has been up and running, treating wet AMD patients without interruption/they're all very experienced investigators with our suprachoroidal injection procedure as well as experience with our early phase wet AMD trial. So we're fully confident that we'll be able to recruit 5 patients for our initial cohort without any significant interruption. -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [20] -------------------------------------------------------------------------------- And I'll just make one final comment. I haven't seen COVID really affect anything in terms of potential partnership discussions or anything interesting collaborations, I haven't seen that impact to any noticeable degree. And that's all I can say. We've actually not really been impacted in any significant way by COVID in terms of our business, fortunately for us. -------------------------------------------------------------------------------- Annabel Eva Samimy, Stifel, Nicolaus & Company, Incorporated, Research Division - MD [21] -------------------------------------------------------------------------------- Okay. Great. And then the last question regarding any way that we can start thinking about how to frame some milestones that might be coming in from various catalysts or developments you have with partners? Or have those not been disclosed and they won't be disclosed at any point going forward until they come vocal? -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [22] -------------------------------------------------------------------------------- I think we'll let Charlie handle that one. -------------------------------------------------------------------------------- Charles A. Deignan, Clearside Biomedical, Inc. - CFO [23] -------------------------------------------------------------------------------- Annabel, yes, unfortunately, due to a confidentiality agreements and the license deals, we can't disclose those. But the most important, the majority of the big milestone comes on approval of XIPERE. As we've disclosed, Bausch, there's a $15 million payment there and Arctic also our Chinese licensee also, there's some money associated with that. But -- and we can't give the details until they come in on any others. -------------------------------------------------------------------------------- Annabel Eva Samimy, Stifel, Nicolaus & Company, Incorporated, Research Division - MD [24] -------------------------------------------------------------------------------- Okay. If I may just ask one more question with regard to, I guess, I hear with wet AMD. I know that you've been presenting -- I'm -- not AMD, sorry, with DME, you've been presenting your data or publishing your data, the TYBEE data. Is -- obviously, there's other programs in development in DME, whether it's gene therapy for your partners or in moving on with wet AMD with your own axitinib and possibly moving into another area. Is pushing forward triamcinolone in DME, I guess, thought of as an older technology that maybe you're more interested in moving on to some newer technologies nonsteroid-based technology that may have better impact in the marketplace? -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [25] -------------------------------------------------------------------------------- The answer to that, I think, is fairly straightforward that the further development of XIPERE is entirely up to a Bausch + Lomb. It's their decision whether they want to push that forward for DME. We've shared all our data that we've generated both in RVO and DME with them. We've had conversations with them to bring them up to speed, so they know. But the decision about XIPERE going into additional indications is entirely in their control. We're working on other things on our internal pipeline, and that's their product. They've licensed that product, and the development is up to them. -------------------------------------------------------------------------------- Operator [26] -------------------------------------------------------------------------------- And our next question comes from the line of Jon Wolleben with JMP Securities. -------------------------------------------------------------------------------- Jonathan Patrick Wolleben, JMP Securities LLC, Research Division - VP & Equity Research Analyst [27] -------------------------------------------------------------------------------- Just a couple for me. I'm wondering, can you comment on the design of the CLS-AX trial on why the requirement for the anti-VEGF treatment? And should you expect to see the same response in both VEGF naive and VEGF experienced patients. And then based on your preclinical data, is 3 months what you're expecting for the duration of effect or do you think it could have a longer impact? -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [28] -------------------------------------------------------------------------------- I think that's for Tom. Tom, do you want to address that? -------------------------------------------------------------------------------- Thomas A. Ciulla, Clearside Biomedical, Inc. - Chief Medical Officer & Chief Development Officer [29] -------------------------------------------------------------------------------- Sure. So let me start with the first question, the design. So as you know, as you alluded to, we're requiring patients who have been treatment experienced. And the reason is for patient safety. This is first in-man, first time -- actually, first time any tyrosine kinase inhibitor has been injected in the suprachoroidal space. So we want patients who've already been treated, and we want to maintain the efficacy obtained with initial anti-VEGF therapy. However, that doesn't preclude later studying axitinib as primary therapy, but we wanted to go with a more conservative route because this is the first time any tyrosine kinase inhibitor has been injected in the suprachoroidal space. And I think, your next question -- well, actually, before I finish that question, I also want to add that other companies looking at novel therapies have also adopted a similar approach for their initial Phase I studies that patients will have been treated as well. So it's a fairly common and quite typical trial design. And I think your next question about expected duration, we expect to see multiple month duration. We know that the levels in the suprachoroidal space in retina with some of the doses that we're anticipating using will be above the IC50 for many, many months. This could very well be a 6-month therapy. Obviously, it's too soon to tell without any clinical data, but we're expecting multiple month durability. And I think -- was there a third question? -------------------------------------------------------------------------------- Jonathan Patrick Wolleben, JMP Securities LLC, Research Division - VP & Equity Research Analyst [30] -------------------------------------------------------------------------------- No, you touched on it. Congrats on the progress. -------------------------------------------------------------------------------- Operator [31] -------------------------------------------------------------------------------- And I'm not showing any further questions. So I'll now turn the call back over to George Lasezkay for closing remarks. Please go ahead. -------------------------------------------------------------------------------- George M. Lasezkay, Clearside Biomedical, Inc. - President, CEO & Director [32] -------------------------------------------------------------------------------- Thank you, and 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 in the future. Operator, you may now disconnect. -------------------------------------------------------------------------------- Operator [33] -------------------------------------------------------------------------------- Ladies and gentlemen, this does conclude the program. Thank you for participating, and everyone, have a great day.