Clearside Biomedical Inc (CLSD) 2023 Q3 法說會逐字稿

Greetings, and welcome to the Clearside Biomedical third quarter 2023 financial results and corporate update call. (Operator Instructions) Please note this conference is being recorded.

I will now turn the conference over to your host, Jenny Corbin of Clearside Investor Relations. Ma'am, the floor is yours.

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, 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; 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.

Thanks, Jenny and good afternoon, everyone. Today, I'm excited to discuss several recent value-creating achievements related to our suprachoroidal platform. We had two weeks of really good news. We completed enrolment 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 BioCryst Pharmaceuticals to expand our external development pipeline with a plasma kallikrein inhibitor for the treatment of diabetic macular edema. Both of our other suprachoroidal collaboration partners, Regenxbio and Aura Biosciences recently presented positive safety and efficacy data through Phase2 with their respective compounds using our SCS Microinjector.

As for our XIPERE partners, Bausch + Lomb announced that XIPERE has been granted a permanent category, 1 CPT code in the US to help facilitate better access and adoption of the product. Arctic Vision completed enrolment in their Phase 3 clinical trial ARCATUS also known as XIPERE in uveitic edema in China.

So let me discuss -- let me start with discussing our lead program, CLS-AX. Last month, we completed recruitment in our ODYSSEY Phase 2b clinical trial evaluating the safety and efficacy of CLS-AX, 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 received from the medical team. 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 AOASRS and Retina Society meeting.

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 help 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 advance to randomization, either to the CLS-AX treatment arm for the on-label aflibercept comparator. 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 demonstrated excellent safety profile stable visual acuity and a lower treatment burden in the CLS-AX arm. The efficacy and safety results from ODYSSEY will then guide our pivotal Phase 3 development program for CLS-AX. We believe the differentiated mechanism of action and high potency of [edema], 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 BioCryst Pharmaceuticals. This collaboration expands the reach and demonstrates the versatility of our suprachoroidal 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 BioCryst is focused on the development of their proprietary small molecule of Orlistat to be administered via the suprachoroidal 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.

Avoralstat that 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 of Avoralstat into the suprachoroidal space and behind the visual field could allow Avoralstat to inhibit plasma kallikrein directly at the location where the edema forms with a desirable durability of effect.

BioCryst expects to continue conducting formulation and nonclinical work into 2024 and begin clinical trials in 2025.

The versatility of our suprachoroidal injection platform was on display at this month's American Academy of Ophthalmology medical meeting, where two of our other partners from Regenxbio and Aura Biosciences presented very promising data with their respective compounds utilizing our SCS Microinjector. Regenxbio reported the results of their Phase 2 ALTITUDE trial evaluating their gene therapy, ABBV-RGX-314 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 one and two with no drug-related serious adverse events. At the second dose, 314 prevented disease progression and reduced vision threatening events and non-proliferative diabetic retinopathy at one year. Regenxbio has indicated they believe that a onetime 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.

Aura Biosciences reported positive clinical efficacy updates from its ongoing Phase 2 clinical trial of suprachoroidal administration of bel-sar for the first-line treatment of early-stage choroidal melanoma. Their Phase 2 trial is assessing the safety and preliminary efficacy of single and multiple ascending doses of bel-sar for up to three cycles of treatment.

Phase 2 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 bel-sar and that meet the Phase 3 enrolment criteria. Safety profile continues to be favorable with no significant treatment-related serious adverse events.

This is very encouraging as most of these patients had tumors close to the phobia optic disc and would likely have experienced severe and irreversible vision loss with the current standard of care, Aura's also announced agreement with the FDA under a special protocol assessment for the design and planned analysis of their Phase 3 CoMpass trial. We 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, XIPERE have also announced important achievements. Bausch + Lomb announced that the American Medical Association has granted a new current procedural terminology or CPT code for XIPERE 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 XIPERE in the United States. The new CPT Category 1 code will be effective on January 1, 2024, for replacing the current miscellaneous Category 3 code. At AAO, Bausch + Lomb also presented survey data on positive physician experience using XIPERE in the treatment of uveitic macular edema, indicating that physicians found XIPERE suprachoroidal 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 enrolment in China of its Phase 3 randomized double-blind, placebo-controlled clinical trial with XIPERE in uveitic macular edema. As a reminder, XIPERE is referred to as ARCATUS in China. If positive data from the Phase 3 trial will allow Arctic Vision to apply for marketing approval in China. In addition, earlier this year, Arctic Vision applied for marketing approval of ARCATUS in Australia. We appreciate the commitment of both Bausch + Lomb and Arctic Vision to expand the use of XIPERE and look forward to further updates.

I'll now turn over the call to our CFO, Charlie Deignan, to provide a financial update. Charlie?

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 30, 2023, our cash and cash equivalents totalled approximately $29 million. Subsequent to the end of the third quarter, we entered into the licensing agreement with BioCryst, we will receive a $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 Stifel Healthcare Conference on Wednesday of this week at BTIG 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.

Thanks, Charlie. The level of awareness and usage of suprachoroidal administration continues to grow with the progress from both our internal programs and our suprachoroidal development and commercialization partners. When it comes to the adoption of new therapeutic treatments, we know that safety is a top priority for physicians and their patients. Our suprachoroidal approach is 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.

(Operator Instructions) Serge Belanger, Needham & Company.

Good afternoon. Thanks for taking my questions, and congrats on the recent developments. I guess first one on the ODYSSEY trial, you completed enrolment, 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 Regenx, and Aura Bio, or partnership? Thank you.

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 are very happy about that. We have by target, as you know, was 60 patients and two to one randomization, 40 into the CLS-AX group, and 20 in the on label of aflibercept 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've got more than 60 in the trial end. So we're very grateful and very thankful to the to the sites and the KOLs and investigators that participated we had, like I said, it was a really a very, very robust screening and recruitment program. And we were glad for everybody's participation.

Your other questions were --

Regarding a potential inflection points for the Regenxbio and Aura Biosciences.

Well, you know, the most important one is I'll start with Aura first is always already got the SPA for going into Phase 3. I think the FDA looked at their Phase 2 data felt very comfortable about that and they're looking to recruit their first patients. So, the start of Phase 3 is going to be very meaningful to them as well as to us. And that should happen sometime this quarter or very hopeful on that and they are going to be not restricted in the United States. They are going outside the United States as well to do their recruitment.

For Regenxbio, Regenxbio comes in two stages first, their wet AMD 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 2 for diabetic retinopathy.

So, the next big inflection point is then making a decision as to exactly when and how they're going to go into Phase 3. But I think that data looks very encouraging to them, and you'd have to ask them a little bit more what they're the ones that really know their plan. But then declaring a start of Phase 3 in one or both of those indications would be a very meaningful, certainly for them and for AbbVie but would be very meaningful for Clearside as well.

But we'll see what they say when they when they take more questions on that and they put together their final clinical development plans. And I think we were very encouraged by what we saw in the Phase 2 data in DR.

Thank you.

Jon Wolleben, JMP Securities.

Hey, thanks for taking the question. A couple on the BioCryst partnership, just wondering about your current responsibilities and the handoff to BioCryst, I think you said sometime mid next year. Wondering what kind of work's 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 CLS-AX.

Sure. And remind me of the follow-up, Jon, I can't help them to forget as I'm talking to this. But in terms of BioCryst, we have been working with BioCryst with some Pepco for some time on formulation work and some early preclinical work that encourage 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 are we're going to work with them on some more animal studies and some fine tuning the formulation. But once that's done the INDs filed, it's their molecule and their product to take forward.

So I got a message on BioCryst. So now remind me of the follow up. If you comment, it does seem like we're at, getting to a critical mass on suprachoroidal news flow and then also in the TKI space in wet 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 the competitive dynamics may change that before ODYSSEY results?

Well, I've said this before, I said this to you almost a year ago, I remember us sitting together and talking about this, and I said I hope that High Point has good readout on their data. I think Ocular is -- I hope the same thing for Ocular, too. I think all three of the companies really are in a position and we're trying to prove that tyrosine kinase inhibitors have a place for all coming at it slightly differently. There's two tyrosine kinase inhibitors, three different ways of administering them.

Our Chief Medical consultant or retina consultant, Tom Shuler, we still talk to on a regular basis, always that people knew that tyrosine kinase inhibitors would have a place, and it's 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 some patients four to six months, we think we have a very good product to be able to be part of the overall treatment paradigm for wet AMD patients.

Personally in our trial, I'm looking, I'm hopeful, and I'm 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 the data will be the data, but I think any kind of data that supports the dosing period for the six months, five to six months, when you look at with the [anti-VEGF] are right now, they can't really guarantee everybody gets to four months. They can't even guarantee everybody just three months. If you look at the revised label and even the high dose IV label.

So, we look at this is we believe we're going to have with this extended duration. We think it's going to have a place. And the other thing I would say to you is I keep telling people I look at the future of wet AMD, in particular as more like cancer chemotherapy. In that there will be different mechanisms of action different places where the drugs work in the retina and I think combination therapy is really going to be very important for a number of the patients right now.

We know that anti-VEGF only underserved certain among our 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 because this that single mechanism of action.

So we think there's a very good place for a different mechanism 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 wet AMD patient population as long as we're in that five, six month duration.

Very helpful contacts. Thanks, George. Appreciate the color.

Sure.

Jack Padovano, Stifel.

Hi, this is Jack calling on for Annabel. Thanks for taking our question. 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 treatment? 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 on. So how are you handling that?

Okay. First of all, let me make a clarifying remark about powering. This is not -- 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 where we have 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 3 trial that would be powered appropriately and see, but 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 the revised model will be included in standard of care like incentives and like I said, we are currently now. So, we're trying to do is see how well, 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 comparator group.

So it's not really powered, statistically speaking, it's not powered for non-inferiority or superiority. What we tried to do you're right about our waste this week, and I was looking at the OASIS data again, the other day and in our two high dose cohorts of 0.5 milligram and 1 milligram, and we're using the 1 milligram at ODYSSEY.

Actually, most of the off protocol or early rescues happened one month in to our highest dose and it didn't happen in the lower dose, the 0.5 milligram. And for some odd reason, I think that was just a matter of small numbers and randomization and what have you, so 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. This the first time they were using CLS-AX, they may not have known what to expect.

Couple of things I would say about our drug protocol treatments, now our study design with the three loading doses giving CLS-AX with the second loading dose -- we think we'll help prevent those off protocol near term supplemental treatment.

Second, this time around we've spent a lot of time in multiple meetings, training the site investigators, going over the OASIS data, and really training them there the CLSAX and 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 increase from America familiarity with many of these physicians that were in the previous away, a number of them were in the previous OASIS trial. Now with the 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 cost protocol early retreat.

Great. Thanks for the clarification.

Okay.

Thank you.

Yi Chen, H.C. Wainwright.

Thank you for taking my question. In view of the recent FDA draft guidance on wet AMD and the Phase 3 trial design from your competitors, can you comment on what parts of the ODYSSEY trial design need to be changed in the future pivotal trial? Thanks.

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 3 trial. I think the draft guidance and we're waiting for the guidance to be finalized by the way, the draft guidance.

The Phase 3 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 in comparison to a standard of care that we know where I think there needs to be some clarification years, part of the draft guidelines. And I know a number of companies have probably commented on this about 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 that direction with them saying, well, we're going to give one dose of aflibercept and one dose of our vaccine. 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've set it up, but we have talked with 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 InfoBase, though as a comparator in view of the draft guidelines, we moved it back to doing aflibercept on label. We think that makes sense. And we think that's the thing that is the most relevant to compare yourself two 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. And as we evaluate that data, that will really guide how we go to the FDA proposal for Phase 3.

Thank you.

Thank you.

As we have no further questions, in queue. At this time, I will hand back to Mr. Lasezkay for any closing remarks you may have.

I want to thank everyone 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. Thank you again.

Thank you. This concludes today's conference, and you may disconnect your lines at this time. We thank you for your participation.