Clearside Biomedical at Stifel Forum: Strategic Moves in Ophthalmology

On Tuesday, 27 May 2025, Clearside Biomedical (NASDAQ:CLSD) presented at the Stifel 2025 Virtual Ophthalmology Forum. The company’s leadership, including CEO George Liseski, outlined their innovative approach in ophthalmology, focusing on the suprachoroidal space delivery platform and the promising development of CLS-AX for wet AMD. While the company highlighted the potential advantages of their technology, they also acknowledged the need for strategic partnerships and funding to advance their Phase 3 trials.

Key Takeaways

• Clearside’s suprachoroidal injection method offers a less invasive alternative to traditional injections, potentially reducing complications.
• The Phase 2b ODYSSEY trial results for CLS-AX showed promise, with plans for a Phase 3 trial using a flexible dosing schedule.
• Strategic partnerships are crucial for funding future trials and commercialization efforts.
• The company emphasizes differentiation from competitors like Vabysmo and Eylea HD through flexible dosing and retreatment criteria.
• Clearside is actively pursuing potential investors and partners to support their ongoing projects.

Financial Results

• Existing partnerships include Bausch and Lomb and Arctic Vision for XIPERE commercialization in Asia.
• Arctic Vision has further partnered with Santen Pharmaceuticals for the Pan Asia region.
• Clearside is seeking strategic partners and investors to fund the Phase 3 trials for CLS-AX.

Operational Updates

• Over 15,000 injections have been performed using Clearside’s proprietary suprachoroidal injection device.
• CLS-AX, having completed its Phase 2b trial, is ready for Phase 3, with a focus on flexible dosing.
• XIPERE, an FDA-approved product for suprachoroidal delivery, is actively marketed through existing partnerships.
• The company maintains a robust intellectual property portfolio covering device use, manufacture, and design.

Future Outlook

• The upcoming Phase 3 trial for CLS-AX will span two years, with a primary endpoint at 52 weeks, utilizing a non-inferiority design compared to Eylea.
• Clearside aims for a 3-6 month dosing interval, with flexibility to redose patients as needed.
• The company continues outreach to potential investors and partners to secure funding for future initiatives.

Q&A Highlights

• Suprachoroidal injection is highlighted as less invasive, with a reduced risk of endophthalmitis.
• CLS-AX offers flexible dosing, allowing redosing for patients not reaching the 6-month mark, and emphasizes real-world retreatment criteria.
• The FDA guidelines stress the importance of adequate masking and a non-inferiority design to minimize regulatory risks.
• To reduce variability, the Phase 3 trial will exclude patients with characteristics linked to high variability in treatment response.

For a detailed understanding, readers are encouraged to refer to the full transcript below.

Full transcript - Stifel 2025 Virtual Ophthalmology Forum:

Operator: Great.

Annabel: Great. Hi. Good morning, everyone, and thanks for joining the Clearside Biomedical session. It’s our pleasure to have George Liseski, president and CEO, of Clearside. Charlie, I don’t see here, but Victor Chong, who is the chief medical officer and head of r and d, and it’s great to have you all here.

Clearside’s got a great platform and a great, strategy. So maybe, George, you can give us a quick overview of Clearside, the platform and the program, both proprietary and partnership strategies, and then we can launch into some q and a.

George Liseski, President and CEO, Clearside Biomedical: Sure. Thanks, Annabel, and thanks for inviting us to be part of the conference today. We really appreciate the time. Since its inception, you know, ClearSight’s focused on delivering, therapeutic agents to the suprachoroidal space. We are a pioneer in that space, and we’ve developed a proprietary injection procedure and device that we’re very proud of.

It’s worked, it’s safe, it’s reliable, and it’s effective to deliver a variety of different, entities into the suprachoroidal space. Early on in at least, I’ve been the CEO since 2019, Early in that, tenure, we established a few validating partnerships, one with Oral Biosciences, another with REGENXBIO, to develop a suprachoroidal delivery in areas where we did not have any expertise. One was for a viral like drug conjugate to treat a choroidal melanoma. The other was a gene based therapy, a REGENXBIO, that went after a variety of retinal diseases. Those were areas that we did not have any expertise other than we could help them deliver the drug to that space.

We also did a commercialization, partnership, strategy with Bausch and Lomb and Arctic Vision, in the Asia region for our first approved, product, FDA approved product for suprachoroidal delivery, and that was XIPERE, which is triamcinolone into the suprachoroidal space. We did not have the ability to do commercialization of that product, so we partnered that. And so we think all of these partnerships are really been validating that other companies found interest and utility in delivering drugs to the suprachoroidal space. And one of the final note on Arctic Vision, they’ve recently partnered with Santan Pharmaceuticals, the the major ophthalmology company out of Japan, to commercialize that product in the region, in the Pan Asia region. We as I mentioned the device itself is proprietary.

We have a very strong intellectual property portfolio in and around the device, the use of the device, the manufacture and design of the device, as well as the use of delivering drugs to the suprachoroidal space through that device for a variety of disorders. Finally, we’ve taken, and this will be the bulk of probably your questions for the rest of the time. For Victor, we’ve developed a CLS AX, which is axitinib for wet AMD, delivery into the suprachoroidal space. We successfully finished phase two b, our ODICEY trial. We think we have a phase three ready product with flexible dosing with the duration of a TKI, but the flexible dosing of a biologic.

And so we’re very proud of that, and we’re currently looking and having discussions with additional potential investors as well as potential strategic partners, for CLS AX so we can continue its development, through phase three and onto commercialization.

Annabel: Right. So, thanks for the overview. And and maybe, you know, before we get into the program, for those that are not as familiar, can you talk about the benefits of injecting into the suprachoroidal space of the eye, its advantages, its disadvantages, and whether with XIPURE being on the market, you’ve gotten greater acceptance of this. I know that there’s been some who are skittish about injecting into that area of the eye, but it seems that that, they’re getting more and more experience, and there’s you’re getting more and more partnerships related to that delivery mechanism. So maybe you can just go into that a little bit.

George Liseski, President and CEO, Clearside Biomedical: Sure. I’ll let Victor take most of that, but I will say that, as people use XIPERE, they’ve been very excited about the results that they’ve seen. It’s performed better in terms of duration and effect than was predicted by our pharmacokinetic models. And once the physicians become comfortable with the procedure, they found it to be very accessible, very easily used in their practice, and, very acceptable for them, from a practice point of view. But I’ll let Victor really address the bulk of your question.

Operator: Yeah. Thank you very much, George, and thank you, Anna, for having us. I think that, you know, the thing to think about it that for most people would probably familiar with intravitreal injection. Intravitreal injection, you get all the way inside the eyeball. And is instead instead of going all the way, you’re injecting a drug into the suprachoroidal space, which is kind of like in the coat of the eye, you know, in such in such a way.

I think it’s from that perspective, it’s less invasive because it didn’t go through all the way, but it’s as easy as intravitreal injection. And it’s an office office based procedure. It’s not a surgical procedure. And I think that, what you said that, you know, just like any new procedure, I I still remember when we were first doing intravertebral injection, people are skittish about it, as you said, using that term. And but now it’s really a routine thing.

And I think that is the same thing with suprachoroidal injection. When you have never done a procedure before, when you’re doing something slightly similar but slightly different, you take a little bit of time to learn. And we discovered that it’s only take two or three injection, then you’ll be be very good at it. Another two to three injection, then, you know, recent survey than more than 90, 3% of the people think the procedure is easy. So I think from our point of view that the acceptance are increasing.

We have more more than over a hundred peer reviewed publication in last few years and over more than 15,000 injection using our injector in patient. And I think we believe that without our partner, RB, moving to phase three in diabetic retinopathy and us into wet AMD, and it will become a mainstream procedure. And finally, one of the biggest re benefit probably is that because that, it doesn’t get all the way into the eye, there will be have no risk of endopharmitis, which is one of the major, potential complication of intravitreal injection.

Annabel: Great. That’s helpful. So just getting into CLS AX now, outside of this mode of delivery, can you tell us how your, TKI stands out stands out from others in development? Maybe how it compares to some of the new anti VEGF compounds that are out there, Revismo or Eylea. You have a wide range of durations right now that that came from your phase two.

So help us frame that in terms of what’s available today and what’s in development, as well with

Operator: competitors. Yeah. I think that, you know, we can you you’re absolutely right that we can separate two type of competition. I think one type of competition is the current TKI in development from our competitor. And but they are going for a six month duration only, and then you need rescue in between.

And, again, we do know what AMD patient have different, kind of, durability for the drug that we use, and not everyone can get to six months. And so that is kind of like something that we think that our, molecule is significantly better from that perspective, the flexibility to counter the variability of patient. And then comparing with the more recent approval now, then obviously recent approval also have that flexibility of one to four months, but we are going after three to six months. And again, that increasing the durability would also help us in the marketplace. So it’s just two different type of competition, but we believe that we are competing with the potential market leader of the future rabbisimo and RD high dose.

Annabel: Got it. And, maybe just on on that point, can you review your phase two data and tell us what you pulled out of your phase two that that sort of describes some of these differentiating features. I know a lot of people try to compare across trials. Maybe you can even talk about some of those features where you can’t really compare and get a good sense.

Operator: Yeah. I think a good trial is always difficult, but I think that we can look at the science point of view that, you know, well, which TKI have a better TKI in terms of, lower IC 50. So I think we believe that acitinib had a much lower IC, IC50, so we’d have a much better efficacy potentially. And then when you’re actually looking at our redosing or, comparing with a competitive rescuing criteria that we have not only we have more active patient, but we have the easiest criteria to redose. And despite that, we are very, very similar to ocular and but even slightly better to eye point in terms of that, dosing feed, need, you know, up to six months.

And I think it’s also important that we are the only company that did not have any ocular SAE at all, and some other company do have ocular SAE. And most importantly, I think that we have redosed at least once in almost every patient in our phase two. And I think that we know that how patient behave, after redosing with our own drug. And then our competitor went straight to phase three. I think there is a risk for going to phase three when you never redose, and but we have redose, and we learn from that.

Annabel: Okay. Maybe just on on that point, some of your competitors are looking for six month durations as long as nine months, as long as twelve months, and you’re it’s pretty clear that you’re looking for you’re you think the sweet spot is three to six months. So maybe help us understand those differences. Like, why why do you think that’s the right sweet spot? You know, the the view that maybe the superficial view is that, you know, the longer duration, the better.

Is that not the case? Maybe just help us frame that.

Unidentified speaker: Yeah. I think that,

Operator: you know, we have talked to a lot of KOLs that people don’t think that more than six months is needed. And, however, that, you know, from a label perspective, that you can always use less frequent than what your label said. So I think that is something that, you know, people thinking about that, oh, could you go for longer? And, you know, label say three to six months. And, yeah, of course, you can go longer, just like Eylea that is supposedly every two months, and but you can obviously do it less frequent.

So I think that is from a labeled perspective that we believe that that flexibility makes sense. And, again, when you’re talking about that some people say more than six months, but they are talking about, you know, superiority trial, which is something that we have never seen, since the first approval from Lucentis way back. So I think that is some is thing that in the regulatory world, there were anything which is not standard have increased, risk. So that’s why that we went for the gold standard on inferiority design and also very similar to the recent approval. And, again, you have brought to our notice by the agency that you you need rescue and especially when the rescue are near the primary endpoint, I.

E. Short about a year, and they will this will be considered as a treatment failure by the agency. And, again, that could increase the risk of regulatory failure. So we take the approach that, using a design that which was just been approved quite recently with, vibevisomol and highly high dose that allowing the flexibility of, different frequency, and then we were not expecting any rescue and similar to the phase three of the most recent approval. I think from a regulatory point of view that we are using a gold standard methodology.

George Liseski, President and CEO, Clearside Biomedical: And and, Annabel, let me just add one thing. I think that we have to make sure it’s clear that we think six months is the right sweet spot. It’s not that we’re trying to have three to six months, but we’re able to redose those patients that don’t make six months. We think the vast majority of patients will make six months on our therapy and the advantage of our drug as Victor’s has explained is for that minority of patients that don’t make six months. In our case, we can redose them.

For the minority of patients that don’t make six months on our TKI competitors, they need to be rescued with standard of care. And it’s not only a regulatory risk, but it’s shifting back and forth between drugs. So we look at ourselves more like a Bobismo, like high dose Eylea, that the goal really is six months, and we think the vast majority of patients should make six months based on our data so far. It’s just if for that small group that are that are difficult, if not impossible, to identify at the start of therapy, we get to redose them with our own drug rather than rescue.

Annabel: Okay. Got it. Got it. Maybe can you sorry. Can you, talk about that that criteria for the retreatment.

I know it differs the criteria for retreatment differs, I guess, from trial to trial. Can you just remind us what that is just so we can sort of be able to frame a little bit better, in terms of why you had some people, you know, retreating at some four months or at five months or at six months?

Unidentified speaker: Yeah. So I think that,

Operator: you know, there is criticism by, clinician that, even in mybisma and early high dose, the criteria are something that they probably wouldn’t use in the clinic, and they they certainly come, you know, once they complain, but talking about that what is design that which is artificial. I think that we have talked to a lot of people and we think that, you know, again, certainly there was a recent publication suggesting that, intraretinal fluid, which is fluid inside the retina, are more important. And, again, for me myself, I, in my clinic, I would take them more seriously as well. So I think that, you know, we would be separating intraretinal fluid and subretinal fluid rather than just a CST change or just any, OCT change. So I think that will be closer to what people are using in the clinic.

And, again, a lot of, our KOL supported that idea, and then so I’ll decide a much more real world from that perspective than what they would more traditionally use in a in that she didn’t extend on everyday, practice.

Annabel: Okay. Got it. And can you just remind us how long is your phase the the way you’ve designed the phase three trial, how long will the trial be, and how what how many points of readouts will you have, and what might you learn, from this trial that you’re not gonna learn from other trials?

Unidentified speaker: Yeah. So I think that,

Operator: just like most, just like basically all regulatory trial that you need to be two years, at least that in one of the two phase three study, we are aiming to do both studies to two years. And, we would have a short running loading phase period, you know, about four months, which is, again, you know, consistent with that we want to use an EYLEA to load the newly treated extremely naive patient. So overall, it’s about two years and three months from that perspective. The primary endpoint was set up with the agency at around 52 weeks from baseline, and fifty two weeks is partly because that we would like to have two cycle of our drug. So going for six months, two cycle is forty eight weeks.

So the key primary readout is at fifty two weeks from baseline, and then the study duration is two years.

Annabel: Okay. Got it. But there are going to there’s, I guess, there’s a after the twelve weeks, there’s gonna be a check on the on the patients, every four weeks thereafter. And at some point, if all these patients don’t last six months, you’re gonna start having a bifurcation of the different arms that get treated for four every four months or every six months. How should we think about all those different arms?

Are you gonna have different powering for the different arms? Does it get exceedingly complicated, or or or am I thinking about it incorrectly?

Operator: Yeah. So so that’s a really great question. I think that is a bit of a confusion to a lot of people. But, again, if we are going back to VIBISMO and, IDH dose for that matter, that they they had a two to four months label, but there’s still one group. I think IDH is slightly more confusing.

They had a so called q twelve arm and a q sixteen arm, but I think they’ll be going back to VIBISMO. It’s probably closer to our design. They they are really one group. So CLAX, is one group, but then have different via different dosing frequency for different patient, but it’s in from the original sample population. So we discussed with the agency the the it’s not a sample group.

It’s just one group of c l a x versus the comparator group, which is Eylea on label. So so that, statistical modeling is is almost exactly the same as what you will see in the Bismarck from that perspective. And our agency fully accepting that, and, again, that was approval from that perspective. So so it’s not different group, but it’s really that because we understanding what AMD patient have variability. And that variability or frequency, we then using our drug in different frequency and just like what we’re doing in real clinical practice from that point of view.

So so it’s not really a different group. However, that, you know, what you were talking about is that, slightly different from VIBISMO, we optimize our study. And because some people do say that, well, our plan to study seem to be a bit smaller than, say, VIBISMO. And I think that there’s two reasons for it. One is that we know that for non inferiority design, the variability would could potentially kill your study.

And we have talked to the agency that we know that from the previous, peer reviewed data that, you know, patient that who have poor vision, who have, thicker retina, they are more likely to have, variability in the study. So so we eliminate them, but these are very relatively small number of people that we eliminate. So so I think that we talk to the agency, and the agency understand our reasoning and accepting our proposal. And furthermore, that, we are using a four and a half letter margin, which is actually what the agency agreed with us on. And unlike that, we’re basically using a four letter margin, for instance.

Annabel: Okay. Got it. Got it. I’m just, and just on that point, can you just, I know we were talking about the variability there. This is a treatment naive population.

Can you just help us understand the inclusionexclusion criteria that might be different from the other trials? And you mentioned how you optimize this population with patients who have thicker CST. Is that because they are poor responders? Just trying to make sure that we understand how this might affect the trial outcomes.

Unidentified speaker: Yeah. So I think that

Operator: we are not necessarily talk about so called poor responder or nonresponder. I think that was a misconception from that perspective. We’re talking about patient that we knew that have high variability of results. So so I think that is, slightly different, and it so happened that from past, understanding of of record that, you know, when you got a very thick retina or when you got very poor vision, your result or your your number of letter gain have a much higher variability. So we, showed that to the agency and agency accept that, yep, you know, those variability, is not needed to to be allowed to be included in the study.

So I think that’s a kind of something that, we are not, selecting a population specifically other than reducing the variability for our study.

Annabel: Okay. Got it. Got it. Just wanted to make sure people understood that. So, now when you talk about retreatment, how do you define when a patient needs to be retreated?

Is it also similar to the other trials that incorporate rescue, or is there some variation there?

Operator: Yeah. So I think that, number one is that we are very different from the other TKI trial because they are rescuing, and rescue is really a rescue, because we solve our problem or the variability of patient in terms of frequency that, you know, to the different duration. And, again, we have also heard a lot of criticism that, anything from the agency as well that even in a high dose, the dosing frequency going up and down even before primary endpoint. And we understood from the agency then making their label, discussion much more complicated. And so on our type c discussion with the agency, we, you selected to think that, you know, well, we only test it once.

And then once you test it once, then we’re using that same dosing frequency for the rest of the year. And I think that is something the agency really like the idea and supporting our our decision on that. I think that’s also have good implication for the real world because I think that will also allow us to actually use that, you know, to be in clinical practice. I know that patient physician might not want to, which I understand, but if they have that flexibility is the term, I think that we have additional data at the same time that we allow the physician to go from extend it from three months to four months to five months to six months and so on. So I think that flexibility is what physician want and it’s what the physician like.

Annabel: Got it. Got it. So as we’re talking about this, can you, everyone’s got a different it seems like everyone has a different idea as to what the FDA treatment guidelines are or FDA guidelines are on the design. So how do these studies align with the guidelines? FDA has made a big deal about not wanting masking.

There’s been some problems with Eylea HD. So maybe you can talk about that the FDA guidelines a little bit and help us understand that.

Operator: Yeah. I think the FDA guideline is a guideline and also that one that people talk about is the draft guideline in particular, and there was some confusion on that guideline that we have clicked, clear with the agency. And the agency always maintained the discussion about that what is important is, adequate masking. So I think that was more important. I think that there was a confusion about, you know, so called sham injection or or on and so on.

But, again, you know, if you read the document, sham injection was never discussed at all. So I think there was a little bit of confusion about what people were talking about to actually people that actually have read the guideline. And also that there’s a confusion about the comparator. So, again, if you’re going for a non inferiority design, the guideline was very clear, you can only use Lucentis or Eidia. So there was no other, option per se.

So I think that, you know, I would, certainly encouraging people to go back and look at the guideline. And indeed that earlier this year that I gave a talk in one of the conference to explain the guideline indeed at which that presentation is in our in in our website. So so I think there is a lot of confusion, but the agency have been very clear to us, you know, that a non inferiority design with good masking is the way to go, and any other design have more regulatory risk. And, again, in particularly on treatment failure. And, again, they take it very seriously, rescue, even a small number can lead into non approval.

So we really pushing very hard to go for the solving the problem of variability of patient using variable dosing and variability to give us the label that we can use in clinic. And finally, that we would not expect rescue so we don’t have children failure.

Annabel: Right. And then one last question for you, George. Any, progress on how we’re gonna be funding these trials?

George Liseski, President and CEO, Clearside Biomedical: Well, we’re continuing our pro our outreach program to strategic partners as well as potential investors. We have engaged a number of people in discussions, and we’re hopeful that that we can soon have an idea of how we can have CLSAX advance into phase three and be paid for. But we’re we’re continuing. We’re looking at all different options, combination of investors and and potential, strategic partners, strategic partners alone, and we’re having those, those outreach and those discussions. As as we sit here and talk, we’re doing that.

Annabel: Excellent. Okay. Well, we’re out of time now, but thank you very much, for for giving us that overview and helping to clarify a few of those points. Appreciate the time.

George Liseski, President and CEO, Clearside Biomedical: Thank you again, Annabel. Appreciate it very much.

Annabel: Bye. Take care.

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