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spk09: Ladies and gentlemen, thank you for your patience. This conference will begin momentarily. Once again, thank you for your patience, and this conference will begin momentarily. Greetings. And welcome to the Clearside Biomedical Third Quarter 2023 Financial Results and Corporate Update call. At this time, all participants are on a listen-only mode and a question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note, this conference is being recorded. I will now turn the conference over to your host, Jenny Colbin of Clearsight Investor Relations. Ma, the floor is yours.
spk03: 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, 2022, our quarterly report on Form 10-Q for the quarter ended September 30, 2023 to be filed today, 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 Levesque, our Chief Executive Officer, and Charlie Dugnan, 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.
spk04: Thanks, Jenny, and good afternoon, everyone. Today, I'm excited to discuss several recent value-creating achievements related to our SuperCoroidal platform. We've had two weeks of really good news. We completed enrollment in Odyssey, our Phase 2b wet AMD clinical trial, with top-line data expected in the third quarter of 2024. We announced a new partnership with BioCrisp Pharmaceuticals to expand our external development pipeline with a plasma calocrine inhibitor for the treatment of diabetic macular edema. Both of our other superchoroidal collaboration partners, Regenexx Bio and Aura Biosciences, recently presented positive safety and efficacy data through Phase II with their respective compounds using our SES microinjector. As for our Zypyr partners, Bausch & Lomb announced that Zypyr has been granted a permanent Category 1 CPT code in the U.S. to help facilitate better access and adoption of the product. Arctic Vision completed enrollment in their phase three clinical trials, Arcadis, also known as Zypyr, in uveitic macular edema in China. So let me discuss, let me start with discussing our lead program, CLSA-X. Last month, we completed recruitment in our Odyssey Phase 2B clinical trial, evaluating the safety and efficacy of CLSA-X, our highly potent tyrosine kinase inhibitor delivered by our patented SCS microinjector. As a reminder, Odyssey is a randomized, double-masked, active-controlled, multi-center study in participants with wet AMD. One of the most encouraging aspects of our CLS-AX program is the feedback that we receive from the medical community. Multiple leading retinal physicians have presented data from our OASIS Phase 1-2A clinical trial of CLS-AX in wet AMD at top ophthalmic meetings, including the recent AAO, ASRS, and Retina Society meetings. These presentations highlighted the excellent safety profile, stable vision, and reduced frequency of injections observed for up to six months. These presentations also created significant interest in our program from clinical trial participants, investigators, and sites that helped drive strong recruitment for our Odyssey Phase 2b trial. The completion of recruitment is a critical accomplishment for us as the final participants in the study advanced to randomization, either to the CLSAx treatment arm or the on-label of Flibbercept comparator arm. We expect randomization to be completed by the middle of December 2023, and we remain on track to report top-line data from Odyssey in the third quarter of 2024. Our goals for the Odyssey trial are to demonstrate an excellent safety profile, stable visual acuity, and a lower treatment burden in the CLSAx arm. The efficacy and safety results from Odyssey will then guide our pivotal Phase III development program or CLSAX. We believe the differentiated mechanism of action and high potency of excitinib, combined with safe and reliable delivery into the suprachoroidal space, has the potential to be a best-in-class approach for long-term maintenance therapy for individuals with wet AMD. We were thrilled to start this month by announcing our new global licensing partnership with Biocrist Pharmaceuticals. This collaboration expands the reach and demonstrates the versatility of our superchoroidal injection platform by adding another compound to be delivered with our proprietary SCS microinjector. The agreement includes $5 million in an upfront license fee, plus the potential for future milestone payments and sales royalties. The partnership with Biochrist is focused on the development of their proprietary small molecule, a vorlistat, to be administered via the superchoroidal injection for the treatment of diabetic macular edema. DME is the most common cause of vision loss in individuals with diabetes, and we believe there's a significant market opportunity in this indication. Avorlistat has high potency and low solubility, which are characteristics that are well-suited for suprachoroidal administration and important to achieving potential efficacy with reduced dosing frequency. Delivering Avorlistat into the suprachoroidal space and behind the visual field could allow orlistat to inhibit plasma calocrine directly at the location where the edema forms with a desirable durability of effect. Biocrist expects to continue conducting formulation and nonclinical work into 2024 and begin clinical trials in 2025. The versatility of our supercoital injection platform was on display at this month's American Academy of Ophthalmology medical meeting, where two of our other partners, Regenexx Bio and Oral Biosciences, presented very promising data with their respective compounds utilizing our SCS microinjector. Regenexx Bio reported the results of their Phase II altitude trial evaluating their gene therapy ABBB-RGX314 in diabetic retinopathy. the leading cause of vision loss in adults between 24 and 75 years of age worldwide. 314 continues to be well tolerated in 50 patients from dose levels 1 and 2 with no drug-related serious adverse events. At the second dose level, 314 prevented disease progression and reduced vision-threatening events in nonproliferative diabetic retinopathy at one year. Regenexx Bio has indicated they believe that a one-time in-office suprachoroidal injection of 314 gene therapy has the potential to stabilize and improve diabetic retinopathy severity score and reduce the long-term risk of vision-threatening events. Ora Biosciences reported positive clinical efficacy updates from its ongoing Phase II clinical trial with suprachoroidal administration of BELSAR for the first-line treatment of early-stage choroidal melanoma. Their Phase II trial is assessing the safety and preliminary efficacy of single and multiple ascending doses of BELSAR for up to three cycles of treatment. The Phase II data, with 90% of their patients at 12 months of follow-up, demonstrated 80% tumor control and 90% visual acuity preservation for patients that have been treated with three cycles of BELSAR and that meet the Phase III enrollment criteria. Safety profile continues to be favorable, no significant or treatment-related serious adverse events. This is very encouraging as most of these patients had tumors close to the fovea or optic disc and would likely have experienced severe and irreversible vision loss with the current standard of care. ORAS also announced agreement with the FDA under a special protocol assessment for the design and planned analysis of their Phase III COMPASS trial. They plan to dose the first patient in this trial this quarter. In addition to the R&D progress over the last few months, our commercial partnership with Zypyr have also announced important achievements. Bausch & Lomb announced that the American Medical Association has granted a new current procedural terminology or CPT code for Zypyr with support from the American Academy of Ophthalmology and the American Society of Retina Specialists. Category 1 code for the suprachoroidal injection procedure will help facilitate better access and adoption of Zypyr in the United States. The new CPT Category 1 code will be effective on January 1, 2024, replacing the current miscellaneous Category 3 code. At AAO, Baushamam also presented survey data on positive physician experience using Zypyr in the treatment of uveitic macular edema, indicating that physicians found Zypyr superchoroidal injection easy to learn with patient outcomes consistent with clinical trial data. Our Asia Pacific partner, Arctic Vision, also accomplished a major milestone with completion of enrollment in China of its phase three randomized double-blind placebo-controlled clinical trial with Zypyr in uveitic macular edema. As a reminder, Zypyr is referred to as Arcadis in China. If positive, the data from the phase three trial will allow Arctic Vision to apply for marketing approval in China. In addition, Earlier this year, Arctic Vision applied for marketing approval of Arcadis in Australia. We appreciate the commitment of both Bausch & Lomb and Arctic Vision to expand the use of Zypere and look forward to further updates. I'll now turn over the call to our CFO, Charlie Degnan, to provide a financial update. Charlie?
spk01: Thank you, George, and good afternoon, everyone. Our financial results for the third quarter were published earlier in our press release and are available on our website, Therefore, I will just provide a summary of our financial status. As of September 30th, 2023, our cash and cash equivalents total approximately $29 million. Subsequent to the end of the third quarter, we entered into the licensing agreement with Biocrist. We will receive $5 million in non-dilutive capital in the form of an upfront license fee. With this combined cash balance, we believe we have sufficient resources to fund our planned operations into the fourth quarter of 2024, which moves us past the expected completion of our Odyssey trial and the related top-line data announcement. In terms of investor outreach, we look forward to participating in the Stiefel Healthcare Conference on Wednesday of this week and BTIG's third annual Ophthalmology Day later this month. We look forward to keeping the investment community updated on our progress, and I'll now turn the call back over to George for his closing remarks.
spk04: Thanks, Charlie. The level of awareness and usage of supracoroidal administration continues to grow with the progress from both our internal programs and our supracoroidal development and commercialization partners. When it comes to the adoption of new therapeutic treatments, we know that safety is the top priority for physicians and their patients. Our supracoroidal approach has already proven method of delivery with a very clean safety profile, both commercially and in clinical development. Including our new partnership with Biocryst, we now have five collaboration partners actively targeting the suprachoroidal space for treatment of multiple serious retinal diseases using our SCS microinjector. We believe this represents significant future value for Clearside and for our shareholders. I would now like to ask the operator to open up the call for questions.
spk09: Thank you. At this time we will be conducting our question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.
spk06: One moment please while we poll for questions. Thank you.
spk09: Our first question is coming from Serge Bellinger with Needham & Company. Your line is live.
spk10: Hi, good afternoon. Thanks for taking my questions and congrats on the recent developments. I guess first one on the Odyssey trial, you completed enrollment. I think your target was 60 patients. Just curious if you overshot that number and you're assuming some level of attrition to get through a 36-week trial. And then secondly, maybe just talk about potential inflection points for the Regenexx and ORA partnership. Thank you.
spk04: Sure. Thanks, Serge. Let me take the first one. We had a very healthy recruitment rate in Odyssey. We had 32 sites signed up. 30 sites recruited at least one subject. So we had really good participation across all our sites. We were very happy about that. We have Our target, as you know, was 60 patients, a two-to-one randomization, 40 into the CLSAX group, and 20 in the on-label aflibricep comparator group. And when we terminated our recruitment, we had exceeded that slightly. So we're a little over that goal. We may have some attrition, as you normally do during the conduct of the clinical trial, but right now we're very happy with where we are. We got more than 60 in the trial, and so we're very grateful and very thankful to the sites and the KOLs and the investigators that participated. Like I said, it was a really very robust screening and recruitment program, and we were glad for everybody's participation. Your other questions were,
spk10: Regarding potential inflection points for the Regenexx, Bio, and Ora. Yeah.
spk04: Well, you know, the most important one is, I'll start with Ora first, is, you know, already got the SBA for going into phase three. I think the FDA looked at their phase two data, felt very comfortable about that, and they're looking to recruit their first patient. So, the start of phase three is going to be very meaningful to them as well as to us. And that should happen sometime this quarter. We're very hopeful on that. And they are going to be not restricted to the United States. They're going outside the United States as well to do their recruitment. For Regenexx, you know, Regenexx bio comes in two stages. First, they're DR from their altitude trial, and then they'll have their wet AMD data, I think, early next year. But we were very, very happy with what they were reporting in terms of what they saw in phase two for diabetic retinopathy. So the next big inflection point is them making a decision as to exactly when and how they're going to go into phase three. But I think that data looks very encouraging to them. And you'd have to ask them a little bit more what, you know, they're the ones that really know their plans. But them declaring a start of phase three in one or both of those indications would be very meaningful, certainly for them and for AbbVie, but it would be very meaningful for ClearSight as well. But we'll see what they say when they take more questions on that and they put together their final clinical development plans. I think we were very encouraged by what we saw in their Phase II data in DR. Thank you.
spk06: Thank you.
spk09: Our next question is coming from John Wallaban with JMP Securities. Your line is live.
spk02: Hey, thanks for taking the question. A couple on the Biochrist partnership. Just wondering about your current responsibilities and the handoff to Biochrist. I think you said sometime next year. I'm wondering what kind of work has been done already, and then what else do you think needs to get done before getting this in the DME patients? And then I have a follow-up on CSAX.
spk04: Sure. And remind me of the follow-up, John. I'll tend to forget as I'm talking about this. But in terms of Biochrist, we have been working with Biochrist for some time on formulation work and some early preclinical work that encouraged them to move ahead and take the license. That kind of work will continue into next year, as I said in my prepared remarks. We will be collaborative with them probably through next year doing IND-enabling studies, but the real handoff will really probably be at IND and they will take it forward from there. So we're going to work with them on some more animal studies and some fine-tuning of formulation. But once that's done, the IND is filed, it's their molecule and their product to take forward. So that's it on Bioprist. So now remind me of the follow-up.
spk02: To your comments, it does seem like we're at, you know, getting to a critical mass on supercoroidal news flow and then also in the TKI space and what AMD with some readouts coming soon with expectations there. Can you remind us of what you want to see in Odyssey and what you think a competitive profile will be and how, you know, any competitive dynamics may change that before Odyssey reads out?
spk04: Well, I've said this before. I said this to you almost a year ago. I remember us sitting together and talking about this. I hope that iPoint has good readout on their data. I think Ocular, I hope the same thing for Ocular too. I think all three of the companies really are in a position that we're trying to prove that tyrosine kinase inhibitors have a place. We're all coming at it slightly differently. There's two tyrosine kinase inhibitors, three different ways of administering them. You know, our chief medical consultant, our retina consultant, Tom Shula, we still talk to on a regular basis, always said people knew that tyrosine kinase inhibitors would have a place. It was just a matter of how to deliver them properly. So I think all of us have that approach and we're looking forward to that. I think that we believe in talking to our KOLs and our medical consultants that if we have maintenance therapy that can guarantee patients four to six months, we think we have a very good product to be part of the overall treatment paradigm for wet AMD patients. And personally, in our trial, I'm looking, I'm hopeful and very encouraged. I just believe that we're going to get more than that. We're going to get at least five to six months. But, you know, the data will be the data. I think anything, any kind of data that supports that the dosing is four to six months, five to six months, when you look at where the anti-VEGF A's are right now, they can't really guarantee everybody gets to four months. They can't even guarantee everybody gets to three months if you look at the Vavizmo label and even the high-dose Ilea label. So we look at this as we believe we're going to have it this extended duration. We think it's going to have a place. And the other thing I would say to you is, you know, I keep telling people I look at the future of wet AMD in particular, as more like cancer chemotherapy in that there'll be different mechanisms of action, different places where the drugs work in the retina, and I think combination therapy is really gonna be very important for a number of the patients right now. We know that anti-VEGF only underserves a certain amount of patients. There's a certain number of patients that don't respond very well, don't respond at all, or over time become somewhat refractive to that single mechanism of action. So we think there's a very good place for a different mechanism of action. In our particular case, we think we have a very safe and reliable way to administer it. It doesn't cause any problems in the front of the eye in terms of impairment of vision or anterior chamber toxicity, and certainly no systemic problems. So we think we have a very good chance to become an important part of treating the wet AMD patient population as long as we're in that five, six-month duration.
spk02: That's helpful context. Thanks, George. Appreciate the call.
spk04: Sure.
spk09: Thank you. Our next question is coming from Jack Padovano with Stifel. Your line is live.
spk08: Hi, this is Jack calling on for Annabelle. Thanks for taking our question. Hi, Jack. So for Odyssey, have you powered the study to see non-inferiority at three months or six months? And how are you now accounting for rescue treatments? Because I know that in the OASIS study, there were some patients who were rescued per protocol, and there were some others who were rescued because the investigator got a little nervous. So how are you handling that?
spk04: Okay. First of all, let me make a clarifying remark about powering. This trial is not designed to be a non-inferiority trial. It is not designed to be a superiority trial. What we're doing is just comparing two groups. We have a single dose. What we're trying to determine is what is the optimal duration of effect that we would then go into establishing a phase three trial that would be powered appropriately either for non-inferiority or superiority compared to standard of care. And we're still not even really sure what the standard of care might be by the time we get there. We don't know whether Robizmo will be included in the standard of care like Lucentis and like ILEA are currently now. So we're just trying to, we're trying to do to see how well can, how far can we go, how much duration can we affect and not be substantially different than the kind of best corrected visual acuity in the comparative group. So it's not really powered. Statistically speaking, it's not powered for non-inferiority or superiority. What we try to do, and you're right about OASIS, and I was looking at the OASIS data again the other day, and in our two high-dose cohorts, the half milligram and the milligram, and we're using the one milligram in ODYSSEY, actually, most of the off-protocol or early rescues happen one month in to our highest dose, and it didn't happen in the lower dose, the 0.5. For some odd reason, I think that was just a matter of small numbers and randomization and what have you. But we were very concerned about that because we thought, well, in some cases, the doctors didn't have a lot of experience with this, and they pulled the trigger early, even though we had very strict criteria. It was the first time they were using CLSAX. They may not have known what to expect. A couple of things I would say about off-protocol treatments now. Our study design with the three loading doses giving CLSAX with the second loading dose we think will help prevent those off-protocol near-term supplemental treatments. Second, this time around we spent a lot of time in multiple meetings training the site investigators, going over the OASIS data, and really training them that You know, the CLSAX, they don't have to worry about it too much early on. They need to stick strictly to the criteria that we've given them in terms of rescue or supplemental therapy. And I think the increased familiarity with many of these physicians that were in the previous, a number of them were in the previous OASIS trial, now with that increased familiarity with the change in the study design with our loading doses, I think that we're going to do a very good job of minimizing off-protocol early retreat
spk06: Great. Thanks for the clarification. Okay.
spk09: Thank you. Once again, ladies and gentlemen, if you have any questions or comments, please press star 1 on your phone at this time. Our next question is coming from Yi Chen with HC Wainwright. Your line is live.
spk05: Thank you for taking my question. In view of the recent FDA draft guidance on wet AMD and the phase three trial design from your competitors. Can you comment on what parts of the ODC trial design need to be changed in the future pivotal trial? Thanks.
spk04: Well, thanks for the question. The answer is I don't know right now because we want to see what the data is that the data from the Odyssey trial will dictate a lot of how we go to the FDA and propose to do a phase three trial. I think the draft guidance, and we're waiting for the good guidance to be finalized, by the way, the draft guidance, the phase three trials are probably going to have to be at least nine months long. They're going to have to have multiple dosing and they're going to have to have some comparison to a standard care that we know where I think there needs to be some clarification is part of the draft guidelines and i know a number of companies have probably commented on this about the the dosing of the comparator to be the same dosing as the treatment and i think that that's been a question of how to deal with that when you're what you're trying to do is dose much less frequently than the standard of care and we've seen ocular go in a direction where they're saying well we're going to give one dose of a flibroceb and one dose of our accident A lot of questions about that trial design, what went into that trial design, what was the thinking and the conversations with the FDA. So it's a little early for us to do that. We're very committed to this current trial design of Odyssey as Phase 2B. The way we set it up, we have talked to the FDA about this trial. We did make a change, because you may remember one of the things we were going to do is use Bisno as a comparator. In view of the draft guidelines, we moved it back to doing a Flibbersev on-label. We think that makes sense. We think that's the thing that is the most relevant, to compare yourself to an on-label standard of care. And that's what we think makes the most sense. We'll see what the data comes out of Odyssey. As the data comes out, as we evaluate that data, that will really guide how we go to the FDA with a proposal for Phase III.
spk06: Thank you. Thank you.
spk09: As we have no further questions in queue at this time, I will hand back to Mr. Lozeski for any closing remarks he may have.
spk04: I want to thank everyone for joining us on the call this afternoon. We appreciate your continued interest in ClearSight and we look forward to updating you on our progress. Operator, you may not disconnect the call. Thank you again.
spk09: Thank you. This concludes today's conference and you may disconnect your lines at this time. We thank you for your participation.
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