Greetings, and welcome to the Clearside Biomedical ODYSSEY top-line data results conference call. At this time, all participants are on a listen-only mode. 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 Coben of Clearside Investor Relations. Ma'am, you may begin.
Good morning, and thank you for joining us on the call today to summarize the top-line results from Clearside's ODYSSEY phase IIb clinical trial in wet AMD. Before we begin, I would like to remind you that today, during the 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 nineteen ninety-five. 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 thirty-first, 2023 , our quarterly report on Form 10-Q for the quarter ended June thirtieth, 2024 , and 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. Victor Chong, our Chief Medical Officer, Charlie Deignan, our Chief Financial Officer, and Dr. Roger Goldberg, who is a practicing retinal specialist with Bay Area Retina Associates. The remarks on today's call will be accompanied by a slide presentation, which is available in the Events section of Clearside's Investor Relations website at clearsidebio.com. I would now like to turn the call over to George.
Thank you, Jenny, and thank you all for joining us this morning. For today's call, I will make some opening remarks about our data and our CLS-AX program, and then I'll turn the call over to Dr. Victor Chong, our Chief Medical Officer, who will walk through the positive results from our ODYSSEY phase IIb clinical trial and our plans going forward for CLS-AX. As Jenny mentioned, we are also joined by Dr. Roger Goldberg, a well-respected retinal specialist with extensive experience treating multiple back-of-the-eye diseases. After our formal remarks, we'll take your questions. We at Clearside are very excited and encouraged by our top-line results from the ODYSSEY trial. We believe the data demonstrated that CLS-AX is now a phase III-ready asset.
It's noteworthy that we achieved these positive results in a difficult-to-treat patient population, as we enrolled only participants with active disease, as confirmed by an independent reading center. The ODYSSEY trial results met three key objectives. First, we achieved the primary outcome by maintaining stable visual acuity to weeks 24 and 36, including repeat dosing with CLS-AX. Second, CLS-AX demonstrated compelling intervention-free rates with 100% of participants going three months, 90% going four months, 81% going five months, and 67% of participants going six months after their initial CLS-AX dose. Also, we reduced the injection frequency burden for the participants by 84%. And third, CLS-AX had a positive safety profile, including in participants who received redosing with CLS-AX, with no ocular or treatment-related severe adverse events.
Before we get into the details of the ODYSSEY trial, I'd like to provide a summary of the company and our mission. At Clearside, our singular focus is delivering on the potential of suprachoroidal drug administration. Our SCS injection platform has been validated with XIPERE, the first and only FDA-approved product for suprachoroidal delivery. We have multiple strategic collaborations and a comprehensive intellectual property portfolio on the design, manufacture, and use of the SCS microinjector in various retinal diseases and in multiple drug categories. As a result of our efforts and those of our collaborators, our SCS microinjector has been successfully used in thousands of clinical procedures, which clearly establishes Clearside as the proven leader in suprachoroidal drug administration. Based on our differentiated SCS platform, we are developing a pipeline of small-molecule product candidates for administration using our SCS microinjector.
Our lead program, CLS-AX, is targeting the multibillion-dollar wet AMD market. Our SCS injection platform utilizes a drug-device combination with proven versatility. Our product, XIPERE, is FDA-approved to treat uveitic macular edema and is commercialized by Bausch + Lomb in North America. Our Asia Pacific partner, Arctic Vision, recently completed a successful phase III trial in China, where XIPERE is known as ARCATUS. We also have established additional strategic collaborations, all demonstrating great success with our SCS Microinjector, delivering a wide variety of therapeutic agents. REGENXBIO and AbbVie have a suprachoroidal gene therapy to treat wet AMD and diabetic retinopathy, with their DR program headed into phase III. Aura Biosciences has a novel viral-like drug conjugate delivered suprachoroidally that is currently in a phase III trial to treat choroidal melanoma.
Combined, there are multiple clinical trials with four potential therapies in five different indications.
The safety profile of our SCS Microinjector is comparable to intravitreal injections and has been well accepted by retinal physicians. Importantly, the SCS Microinjector uses a 30-gauge needle, the same size as the most commonly used needle for intravitreal injections. Briefly, I want to review our lead product, CLS-AX, and how we are positioning it for real-world success. CLS-AX combines our expertise in developing small molecule suspensions with what we believe is a best-in-class tyrosine kinase inhibitor, axitinib. CLS-AX is delivered with the same SCS Microinjector utilized in our FDA-approved product, XIPERE, and by our strategic partners. Within the anti-VEGF market, wet AMD is by far the largest. Currently, it is a $12 billion market that continues to grow with the aging population.
One of the recent new treatments targeting wet AMD, faricimab, has generated over $4 billion since its launch, a notable indicator of the broad uptake and potential of this market. Wet AMD is a chronic disease requiring ongoing treatment. The most common reason for treatment failure is poor adherence to current regimens that include frequent injections and office visits that are often burdensome for elderly patients and their caregivers. We are looking to maintain visual acuity while reducing the injection frequency and thus reducing office visits. Extending the duration of maintenance therapy may improve adherence to treatment and improve real-world outcomes for patients and caregivers. We are positioning CLS-AX for real-world success.
This means we are focused on a clinical program that could produce data supportive of a prescribing label that enables effective and flexible maintenance dosing for patients with extended duration compared to current standard of care intravitreal wet AMD products. This would also allow seamless adoption into physician practices. With that background, I am now going to review a summary of our top-line data, then hand the call over to Victor to provide further detail. ODYSSEY enrolled sixty participants who were randomized in a two-to-one ratio, with forty participants in the CLS-AX group and twenty in the aflibercept comparator group. Unlike other recent TKI trials, participants in ODYSSEY required persistent active disease, either with fluid in the OCT or leakage on the angiography, in order to be enrolled.
Eligibility was confirmed by an independent reading center, which allowed for uniformity in entry to the trial.
The primary outcome was the mean change in BCVA from baseline to week thirty-six. A thirty-six-week endpoint is important, as this timeline is similar to recommendations by the FDA for phase III wet AMD clinical trials. Most importantly, the protocol called for patients to be redosed with CLS-AX at least once, with a mandatory CLS-AX redose at week 24. This allowed us to study CLS-AX redosing in preparation for phase III trials. No other TKI in development has any phase I or phase II redosing data. As shown in this trial diagram, both groups started with three aflibercept loading doses. In the CLS-AX group, participants received an initial dose of CLS-AX at the same time as the second dose of aflibercept, referred to as the baseline visit.
In the aflibercept group, participants received an aflibercept injection every eight weeks per the product label, with additional treatment allowed if needed.
For the CLS-AX group, there was a mandatory redosing with CLS-AX at week 24 , but if a participant needed treatment based on a disease activity assessment, or DAA, between week twelve and week 24 , they were redosed with CLS-AX. Our primary outcome was at week thirty-six. As we have previously stated, our goals at the start of this trial were to demonstrate that participants on CLS-AX could maintain stable BCVA throughout the trial, that CLS-AX is well tolerated initially and after redosing, and almost all participants would get to three months, and a majority of the CLS-AX participants get to six months without need for additional treatment, as determined by our DAA criteria. We are very excited and encouraged by our top-line results from ODYSSEY, and we believe we've met and exceeded our initial goals for the phase IIb trial.
Further, we believe this data strongly supports moving CLS-AX into phase III. We achieved the primary outcome in participants with active disease based on confirmation from the independent reading center. BCVA remained stable throughout the trial, measured as mean change in BCVA from baseline to week thirty-six. Anatomical control was also achieved as CST remained stable throughout the trial, measured as mean change from baseline to week thirty-six. CLS-AX also had a durable effect at all time points, with two-thirds of the participants going six months without the need for any additional treatment.
These compelling intervention-free rates reduced the frequency of injection by 84% up to week 24. As you can see on this graph, after receiving the baseline CLS-AX dose, 100% of the participants went 3 months, 90% went 4 months, 81% went 5 months, and 67% went 6 months without receiving any other treatment. It's important to point out that all of the 26 participants in the CLS-AX group who went 6 months without additional treatment did not meet the specified DAA retreatment criteria at week 24. But per the trial protocol, they all received the mandatory redose with CLS-AX at that time point. CLS-AX also demonstrated an excellent safety profile throughout the trial to week 36, including after the mandatory redosing at week 24.
There were no ocular or treatment-related SAEs. All of the ocular adverse events were considered clinically mild in both groups.
In addition, out of 84 CLS-AX suprachoroidal injections in the treatment group, there was only one incident where a patient noted some pain on injection, which compares favorably with intravitreal injections. We also observed similar discontinuation rates between the treatment and comparator groups. With that summary, I would now like to provide a brief introduction of our Chief Medical Officer, Dr. Victor Chong, and then turn the presentation over to him to provide further details on the ODYSSEY trial. Dr. Chong has strong expertise and an extensive background as a retinal surgeon and researcher with almost 10 years in large pharma, where he led ophthalmic development programs.
He joined Clearside in March 2024 from Johnson & Johnson, where he was the VP, Global Head of Retina at J&J Innovative Medicine. Prior to J&J, he was Global Head of Medicine, Retinal Health at Boehringer Ingelheim. Previously, Dr.
Chong served as head of department and consultant ophthalmic surgeon at Oxford Eye Hospital in the UK. Victor?
Thank you, George. In ODYSSEY, we aimed it for participants who were treatment experienced and also more difficult to treat with a high number of prior injections and reading center confirmed active disease. In this study, the participants were randomized to CLS-AX or aflibercept at the baseline visit. Between week 12 to week 24, a flexible treatment regimen was allowed on an as-needed basis, based on the disease activity criteria listed at the bottom of the slide. As a reminder, we were able to redose with our own drug if the DAA criteria was met, instead of using aflibercept for rescue, which distinguish our protocol from other TKI in development. If the DAA criteria was never met before week 24, participants received a mandatory redose of CLS-AX at week 24.
We were pleased to receive positive feedback and interest from investigators that translate to rapid enrollment for the trial.
ODYSSEY only took five months to fully enroll, despite our strict inclusion criteria, requiring the independent reading center confirmation of active disease. As you can see, we had 32 sites and 158 participants screened, with 60 ultimately enrolled. We had a strong completion rate, with approximately 97% of participants staying on the trial through week 24, and over 88% stayed to the end of the study at week 36. This low discontinuation rate is excellent for a 9-month trial. Here we show the demographic and baseline characteristics, which are typical in this type of trial. The key noted difference for ODYSSEY was that the median duration of wet AMD diagnosis was relatively short at 9.9 months, so these participants were fairly early in the treatment journey.
Now, I want to walk you through some additional data and several graphs that support the summary result George described it earlier. We are very pleased that ODYSSEY confirmed the ability to administer multi-dose of CLS-AX while maintaining a well-tolerated safety profile. Of the 40 participants in the trial, 32 received two doses of CLS-AX and six received the three doses. As you can see on slide 22, the BCVA was stable throughout the study and mostly within two letters of baseline in both CLS-AX and aflibercept groups. In addition, at the week 24 and week 36 time points, as targeted, CLS-AX was similar to the aflibercept control group, with no statistically significant difference in the separation between the two groups.
This data is also within the bounds of FDA guidance for an effective therapy for wet AMD and is a potential indicator for success if we can replicate this result in phase III. Similar to BCVA graph, slide 23 shows the central subfield retinal thickness between the groups. All CSRTs were measured and reported by independent reading center. The CSRT changes in the aflibercept group depicted the typical seesaw pattern of patients with active disease. However, CLS-AX reduced this fluctuation at week 36. There was only an eight-micron difference from baseline. Again, as targeted, CLS-AX was similar to the aflibercept control group, with no statistically significant differences between the two groups at week 36. Earlier,
George showed you the actual intervention-free rate, with 67% of the participants in the CLS-AX group reaching six months without additional treatment. Those numbers are depicted here on the blue line.
During the study, some participants were treated by an investigator, but did not actually match the disease activity criteria according to the independent reading center. If this criteria was rigidly applied, we would have an even better result, with close to 80% of the participants going six months without treatment, as depicted on the orange dotted line. In fact, none of the participants who make it to week 24 matched the DAA criteria per reading center confirmation, but they received mandatory redosing per protocol. What I'm also pleased to see here on the blue line is how well the drug performed up to week 12, 16, and 20. This very high rate, all over 80%, gives me confidence that we have a drug candidate that has the potential to compete on the market with currently approved therapies.
When I was a practicing retinal physician, I could see firsthand how challenging the treatment burden was for patients and their caregivers, who were required to come to my office frequently for the injections. Often, these visits were missed due to scheduling or other challenges. We know that if we can reduce that treatment burden with fewer office visits, it will have a meaningful impact for all involved. In our trial analysis, we look at the average number of treatments administered 24 weeks prior to screening visit and comparing it to the 24 weeks after the baseline visit, and we calculated the number of injections during this period. We were able to reduce the frequency of injection by 84%.
This is a really terrific outcome. CLS-AX maintained a positive safety profile throughout the trial, with no ocular SAEs and no treatment-related SAEs.
There were no drug or procedure-related ocular SAEs. There was no reported drug or procedure-related systemic SAEs, no endophthalmitis and no retinal vasculitis. There were four cases of intraocular inflammation that were all deemed clinically mild by the Safety Review Committee. Of these, two cases had minimal clinical signs that resolved. Two cases were potentially related to drug administration, and in all four cases, the inflammation was no longer detected at or before week 36. With this excellent result, we are now moving forward with our phase III planning. Our goal for the phase III program is to produce a flexible prescribing label that will allow dosing between every three to six months. It would potentially be more convenient and effective for patients, supporting adoption in the current physician practice and the position CLS-AX for a real-world usage.
We are continuing the analysis of all the saved results and plan to consult with our scientific advisory board as well as physician experts. We expect to conduct an end-of-phase II meeting with the FDA in early 2025 to align on the essential component of our phase III program. We expect to run two phase III study with aflibercept two milligram as the comparator, which is based on the draft guidance by the FDA. Our current thinking is a study design similar to the recently approved drug in this space, with treatment-naive participants in a non-inferiority and flexible dosing design. We have seen how easily this new therapy enter into the market as a replacement for the first-generation anti-VEGF products.
We believe that CLS-AX would follow this same pattern by replacing this newer therapy, since we have the flexible dosing of a biologic combined with the longer duration of a TKI. I will now turn the call back to George for the closing remarks.
Thank you, Victor. Again, let me say that we're excited by the trial results, as we believe that ODYSSEY successfully met or exceeded all of our targeted outcome goals and is ready to advance to phase III. We were able to maintain BCVA in a difficult-to-treat patient population while reducing the frequency of injections up to six months. All CLS-AX participants made three months, and 67% of CLS-AX participants reached six months without receiving any additional therapy. We observed a positive and acceptable safety profile with no ocular or treatment-related SAEs, which included redosing. 95% of participants in the CLS-AX group received at least two doses of CLS-AX.
To date, only Clearside has conducted a phase II trial in wet AMD with repeat TKI dosing data. The information gained from this repeat dosing will better inform the final design of our phase III CLS-AX program.
Based on this top-line data, we believe CLS-AX has the potential to provide patients and physicians with a well-tolerated drug for wet AMD maintenance therapy with reduced injection frequency and a flexible dosing regimen between three to six months. We're extremely encouraged by these results from the ODYSSEY trial, and we believe that CLS-AX is ready to move forward into a pivotal phase III program. At this time, I'd like to ask Victor to introduce our guest speaker and key opinion leader, Dr. Roger Goldberg. Victor, please go ahead.
Thank you, George. We are very pleased to have Dr. Roger Goldberg with us on the call. Dr. Goldberg is a key opinion leader with a very busy private practice in the San Francisco Bay Area. He did his educational training for undergrad and medical school at Yale University, and completed his residency in Miami at the Bascom Palmer Eye Institute. Dr. Goldberg also served as a member of our Safety Review Committee for the ODYSSEY study. Roger, thank you so much for joining us today. Let's address some opening background information, and then we will open the call for questions. Can you briefly provide our listener with a brief background of your practice?
Sure, Victor. Thanks for having me here today. I'm Roger Goldberg. I'm a retina specialist at Bay Area Retina in the San Francisco area. In addition to you know every day taking care of patients with a whole spectrum of retinal diseases, including of course lots of patients with wet macular degeneration, I also help to run a kind of a mid-size clinical research practice. For the last decade or so, I've been very involved in clinical research and was pleased to serve on the data safety board here for the ODYSSEY trial.
Great. Can you provide us with your overall impression on the ODYSSEY data with respect to safety, durability, and the biological effects?
Sure. So very exciting data, just kind of at a high level, and obviously, we'll continue to learn lots more as we unpack the data from what I think is a pretty good-sized Phase II trial here in wet AMD, and I think the results are exciting. Obviously, the durability is the key kind of driver in terms of the unmet need, because as you mentioned, there's this huge treatment burden. And ultimately, in the real world, we have clinical results that underperform what you might expect from the clinical trial data. And lots of us, myself included, believe in part that's driven by that very high injection burden, even with some of these next-generation agents like faricimab or high dose of aflibercept.
The durability, I think, is what makes this exciting, and then what makes it kind of practical or feasible is the fact that, you know, the clinical results support the durability, and we see that in terms of the kind of stability and best-corrected visual acuity. BCVA, of course, the functional endpoint, what's required by the FDA for approval. But we know that BCVA is a little more just noisy, especially as the smaller the trial is, the noisier BCVA can be. But we saw a very smooth curve for CLS-AX. I think retina specialists ourselves tend to look more at the central retinal thickness and the anatomic changes. As you mentioned earlier, with EYLEA, with aflibercept, we saw that typical seesaw pattern.
With CLS-AX, we see very steady control of the fluid over time. And even at kind of like the maximum fluid buildup, it looked to me very similar to what we see eight weeks after a two-milligram Aflibercept injection. So to me, that represents kind of great control. And frankly, I love... You know, it's really kind of like almost an adaptive clinical trial design, because it allowed for the redosing anywhere between 12 and 24 weeks with CLS-AX. So in that respect, I think it's almost more akin to the faricimab and eight milligram Aflibercept trials, because you redose with the IP, with the active agent. And then finally, as you mentioned, there were four cases of inflammation.
As you know, Victor, retina specialists are all hyper-aware of inflammation as an adverse event in any of the drugs that we inject into the eye, including those for wet AMD. As someone who was on the Safety Review C ommittee during the brolucizumab issues that came to light with retinal vasculitis, let me just kind of state here, we reviewed all four of the inflammation cases from ODYSSEY. They were nothing like what we saw with brolucizumab. There were no cases of vasculitis, no cases of retinitis or optic neuritis, swelling of the optic nerve. Two of the cases were quite mild, like on the order of point five plus cells in the anterior chamber, just resolved with a tapering of topical drops.
Two of the cases had some posterior involvement. One may be related to the injection technique, I think, which you hinted at. The DSMB reviewed angiograms for these cases, and again, no posterior involvement. What I think is really kind of compelling to me to say this is not some sort of hypersensitivity reaction, like with brolucizumab, and probably with pegcetacoplan as well, is the fact that all four of these patients were rechallenged with CLS-AX and didn't have some sort of more robust inflammatory response. To me, that's a good sign that this is not some sort of immunologic kind of challenge with the drug. I think as you mentioned, the inflammation had resolved in all four patients by study end.
Thank you. So you have a lot of experience in treating wet AMD patients. Can you discuss your thoughts on the patient population that we selected to enroll in ODYSSEY?
Yeah. So this was, I think, kind of, this was previously treated patients, but it was previously treated with kind of third-party confirmed active disease. And what that means is there has to be fluid present either on the OCT or leakage present on the angiogram. And so I think that, you know, certainly could be reflective of the fact that these are, you know, high VEGF needy patients. And we see that to some extent when we look at the seesaw pattern of the control arm, which is to say, hey, these are patients where even if you wait eight weeks, the fluid starts to build back up, and we see that in terms of central retinal thickness. So, so it in some respects can be a more difficult population to treat.
I think we'll continue to unpack this, as we dig into the data from ODYSSEY.
How do you think that TKI and suprachoroidal, what do you see, how that will be getting into the market?
Yeah. So I think this is, you know, I think these data here from ODYSSEY are probably good news for the entire class, because now we have kind of a third approach and a third example where TKIs are providing long-term, durable control of wet macular degeneration. So I think this helps, in some respects, de-risk all of the TKI programs. And then kind of specific to Clearside, as you mentioned, although there have now been thousands of suprachoroidal injections administered across many different clinical development programs, I think there's still been a little bit of, you know, uncertainty around the suprachoroidal approach.
And I think this is, again, kind of very reassuring that the suprachoroidal approach, not only is it feasible, I mean, we knew that with XIPERE, but we now have kind of confirmed it in another disease, with another agent, that you can kind of control back-of-the-eye diseases and take advantage of the suprachoroidal space, almost like as a reservoir for extended durability, drug delivery.
Thank you very much for that overview, Roger. At this time, we will ask the operator to open the line for questioning from the listener.
Thank you, sir. At this time, we will be conducting our question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue, and you may press star two 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. One moment, please, while we pull for questions. Thank you. Our first question is coming from Annabel Samimy with Stifel. Your line is live. Sorry, Annabel, I'm afraid we can't hear you.
Hello. Sorry about that. I was on mute. I apologize, so congratulations on this data, and this is very encouraging, and I have several questions, actually. Maybe the first one for Dr. Goldberg. As we think about the number of TKIs now that are demonstrating a clear activity and essentially de-risking all of the TKIs that show, you know, because they're showing obvious, you know, clear efficacy here. How do you think about maybe the ease and the benefit of injecting into the suprachoroidal space as opposed to intravitreal? How much does this change your treatment practice? And, you know, when you think about ideal treatment durations, you know, do you feel that three to six months is the ideal timeframe that you want to see?
Some of them go out potentially to nine months. You know, how do you think about in your treatment practice? How often you want to see the patient, and what these ideal treatment durations are, and how comfortable you are incorporating a micro injector into your practice? So that's a lot of questions for you, Dr. Goldberg. I apologize.
Yeah. It's okay. Dr. Goldberg, please feel free. Go ahead and answer.
Yeah. All great questions. My general perspective on the TKIs is that even if they can last for the vast majority of patients, six months, we, as retina specialists, probably will want to see those patients every three, maybe every four months, just to kind of check in and make sure, hey, for that specific patient, is there any evidence of disease activity that we want to treat? And I think with the ODYSSEY results here, what that's suggesting is you could actually redose with CLS-AX, rather than redose with a you know, bolus anti-VEGF kind of antibody approach, like with Aflibercept or Aflibercept. So, it kind of offers the promise of kind of essentially monotherapy, rather than combo therapy if patients need to be dosed less frequently than every six months.
And again, I think kind of there, there's the injection burden, but there is the office visit burden. My general sense is that, like, for a wet AMD patient, we're gonna wanna see those patients about three to four times per year, even in the setting of these kind of ultra-long-acting agents. In terms of suprachoroidal delivery, obviously it is, you know, kind of an order or two of magnitude less frequently performed right now. And I think the suprachoroidal space, you know, truthfully represents both, you know, an opportunity and a challenge for Clearside. But it's an opportunity because it's this untapped space where you can deliver, you know, small molecules in an extended-release format without anything kind of floating around in their vision.
But it probably will require some more, you know, training to kind of, you know, frontline mom-and-pop retina specialists out there, who's maybe not involved in clinical research, so hasn't had the kind of experience in clinical research using the suprachoroidal injector. So I think that will be, you know, again, kind of there'll be some training required to get people comfortable with it. But the truth is, once you've done, you know, a couple of suprachoroidal injections, it actually fits very smoothly into your workflow, because, you know, we're again, we're injecting it with a 30-gauge needle. It's in clinic. It doesn't require, you know, kind of advanced training.
This is not kind of anywhere akin to, let's say, Port Delivery System or even the, you know, what I would think of as the refill exchange procedure, which is required with Suvimo, the Port Delivery System from Genentech. So, it's pretty simple. It has its own CPT code. It will require, you know, kind of a little bit of boots-on-the-ground training, you know, with like, a model eye and the suprachoroidal injector, just to get people kind of comfortable with it, at first.
Okay, and-
I don't know if I answered all your questions. Sorry, because you had a bunch, but.
Yeah. No, thank you. That was helpful. And then for Victor and George, maybe we can just clarify, you know, some of the results that you saw. There were participants that were retreated. It was not if they were retreated based on actual disease activity. So it seems like some of these patients were retreated, and they didn't meet the criteria for disease activity. Can you, I guess, help us understand why they would have been retreated? And, you know, because, obviously if it was based on the criteria established, it would have been a little bit higher, better results. So I'm just trying to understand why some of those patients had been retreated. You know, what was it that that sort of indicated that they should get the retreatment?
Um,
Well, Annabel-
I guess that was-
You know that it-
I-
Yeah, you-
Yeah.
You know, in our first study in OASIS, we went through some of these issues, too, and we set out very strict criteria for the physicians to retreat, very strict criteria. But every once in a while, The reading center doesn't confirm what the physician believed they saw in the office, and so the retreatment occurred, even though reading center would have said it should not have occurred. And sometimes the physicians have the discretion to treat outside the criteria. So it happens from time to time. But I'll let Victor expound on that. Victor, you want to add to that? About-
Yeah, I think the main-
Okay.
Yeah, the main reason we saw is the how the investigator interpret the OCT findings. Because some of our recruitment criteria is based on the number, and then, you know, that the reading center, when they read the images, and then they got the number, and that's actually how we try to verify that.
Okay. And when you think about that patient population, the treatment-experienced patient population, would you say it was more akin to the population that you saw in OASIS, that was very high treatment burden? Or, it was just it could have been-
... you know, pre-mixed patients who would have been a responder. So essentially, did you see any difference, you know, what type of patient would have been, you know, would have lasted longer, you know, on just one injection versus needing to retreat?
Victor, you can go ahead, and you can try to answer that. I mean, the one thing I'd say, Annabel, is we have more analysis to do when we get down to the individual patient level. But, I'll let Victor comment on that.
Yeah. So I think that comparing OASIS is difficult because I think that, you know, OASIS is really a phase I study, so we have patients there who not necessarily yet, you know, respond quite well and also much further in the treatment journey. Our current ODYSSEY patient is mostly on year one, as we showed earlier, and that suggested that that was still in the active phase, you know, of the treatment. And then also that not only that they're in year one, they have a lot of injections to get to that point. So we believe that if we open up to a more general population, so all AMD patients, our results could even be significantly better.
Thank you. Our next question is coming from Andreas Argyrides with Oppenheimer. Your line is live.
Good morning, and congrats also on these very unique results.
Thank you, Andreas.
It's been a long journey for you guys, so I'm very excited to see it get to this point. One question, I guess, for Dr. Goldberg first. Mostly, just basically looking at these results, how do you see the type of patient based on disease severity that would fit the profile? I guess it's kind of a similar question that was asked before, but just a little bit more pointed. And then I have a couple of technical questions for the company.
Dr. Goldberg?
Sure. So, my general sense, and I think it applies here, to CLS-AX, is that TKIs will be excellent for maintenance therapy, but probably we'll still use kind of a bolus anti-VEGF for a kind of a treatment-naive patient to kind of quickly get the disease under control and then maintain it, maintain the control with a, with a long-acting TKI. And in this case, they were, you know, active disease, but the patients got three Aflibercept injections to kind of get the disease under control, and a TKI was put on the same day as injection number two.
And so I think kind of in the real world, we'll end up taking that type of approach, which is kind of get it under control with a bolus anti-VEGF, and then add a TKI for long-term control.
Andreas, you had some technical questions?
Yep. Yeah, and I think these are some questions that, you know, investors are gonna be asking. But I know it's early, but when you're thinking about the phase III, and you're looking at kind of the delta at thirty-six weeks, and how you're thinking about powering a non-inferiority study, do you have a number in mind as to how many patients you think you're gonna need for both studies?
Yeah, I think that at the moment, we are still discussing all different kind of options. I think that, you know, what I was referring in the presentation, that we are looking towards something similar to the more recent approval. So I would argue that our number would be somewhat similar to those trial, but we are opening all discussion and all options right now.
Okay, and then last one. Just regarding what you're seeing in terms of the standard deviation and the change in the BCVA, it goes from 7 at week 24 to about 10.5 at week 36. Any thoughts around the increase there? Yeah, that'd be helpful.
Yeah, I think in a small study that there could be what we have seen. There might be just one or two patients would change the dynamic a little bit. But I would expect that in a phase III study, those will level out.
All right. Fantastic. Congrats again, guys. Very happy for you.
Thank you.
Thank you. Our next question is coming from Yi Chen with HC Wainwright. Your line is live.
Thank you for taking my questions. My first questions, there seems to be some conflicting messages from the FDA, from the design of phase III trials from two of the potential competitors. So, what's your current view on the use of sham injections in phase III trials? And what's your view on whether two non-inferiority trials versus one superiority plus one non-inferiority trial in terms of phase III trials? And lastly, do you intend to seek special protocol assessment agreement with the FDA? Thank you.
Victor, you can answer that.
Yeah, so I think that is something that we are working towards. And as I mentioned, that this is our current thinking, and the two non-inferiority trial, as well as using sham, was quite recently approved. So I think that is in the direction of travel. And, we are expecting to have our end of phase II meeting early next year, and those are the discussions that we would want to discuss with the agency. And whether that, two very different trial is the best approach, then obviously, that different company have a different opinion on that.
Got it.
Thank you. Our next question is coming from Serge Belanger with Needham & Company. Your line is live.
Hi, good morning, and I'd like to also offer my congratulations on this data.
Thanks, Serge.
A couple of questions, couple questions from us. Results seem very similar to what we saw, at least in terms of the intervention-free intervals, with what we saw in the OASIS trial. So just curious if you agree with that statement, and if you were surprised at the consistency of the results between ODYSSEY and OASIS, and how that kind of shapes your expectations for phase III in treatment-naive patients?
Victor, that's yours to address.
Yeah. So I think that, you know, I think what we felt that treatment-naive is easier to compare. We have a lot of data, how a comparator EYLEA two milligram, how patient will behave. And again, we believe that, OASIS is even more difficult, and then, obviously, it's still quite difficult. And then I think, if anything, that when we move to treatment-naive, that-
Apologies, ladies and gentlemen, we appear to have lost Victor's line for a moment.
I can address a little bit of that. As Victor was saying, we went from ODYSSEY, which was a very difficult patient population. We referred to them as anti-VEGF addicts. Then we went to still a difficult but, less difficult to treat patient population in ODYSSEY. Then going to treatment-naive, I know Victor feels that as we go to treatment-naive patients, we expect our results will be, it could be, as good, if not better, in the treatment-naive patients.
Yeah.
So, you know, we've been steadily progressing through difficult-to-treat patient populations. I'll let you pick it up, Victor, now that you're back on.
Yeah, I'm very sorry for the line finding.
No, no problem.
Yeah. So, as I think, George, I heard George saying already that, you know, we felt that, you know, comparing with a comparator, a treatment-naive population is easy to understand and easy to calculate and more uniform, but they will be a general population. So we felt that, you know, and we would expect our results will be even better than what we see in ODYSSEY. But like what Roger said, that, you know, we would probably quite likely to be doing a loading dose, you know, from that perspective. So I think this is where we are thinking about.
But I think that, you know, as I mentioned earlier, that there was still that it is early days, and we are still analyzing the data, taking our learnings and go to the agency, and then, we will talk more about that, you know, in the future.
Okay. And then going back to the two cases of intraocular inflammation, just a little more color there. Did they occur after the first dose or the second dose, and did they require any steroid treatment?
Yeah, so, they vary, to be fair, and the two cases were very mild, that we mentioned earlier, was just a very short duration of topical steroid eye drops, and it went away. And it's debatable whether they are true inflammation or not. And then the two cases are procedure related, and one of the cases, both of the cases are after the first injection, and then they went and had the second injection, and then really no problem to a certain extent. But again, at this point, that is what we are disclosing. But they all seem to give me a great learning for a phase II program, whether how we improve our training on injection.
I think Roger mentioned that injection is still foreign to some of the doctor, but I think that is not too difficult to learn, but we can continue to improve upon that.
Thank you. We have time for one last question from Debunjana Chatterjee with JonesTrading. Apologies. Your line is live.
Hi. Thanks for taking my question. Maybe just a quick follow-up on the question about the inflammation. So, the two minimal cases were treated with topical steroid drops, and you mentioned the other two cases that were potentially related to the drug administration. So, the question is that what intervention was deployed to treat these ones, and was there any evidence of chorioretinitis or any FA findings for these?
Yeah, so Roger has already mentioned earlier that for those two cases that we have a lot more detail. And there was no sign of any inflammation in the posterior pole. And that was what Roger mentioned earlier. And I'm sorry. I missed the second part of your question, so there was no vasculitis, no choroiditis, no posterior pole involvement.
Okay, so no posterior involvement, no chorioretinitis, or any FA findings, right? And, maybe if you have time, what was the reasons for, like, the dropouts in the CLS-AX and, like, the control arms, the three and four dropouts that you saw?
Yeah, I think that, you know, it's not unusual for people to drop out. In fact, as you mentioned, there are four out of 40 in the CLS-AX arm, and actually three out of 20 in the EYLEA arm, and bearing in mind that this is quite elderly population.
Mm-hmm.
And the majority of the dropout is this, what we call, withdraw consent. It's basically that the patient doesn't want to stay in, and it's understandable. Our study are monthly visits, so I think that is the most common reason for dropout.
Okay, thanks for the granularity. And, thank-
Thank you. As we have reached the end of our question and answer session, I would now like to turn the call back over to Mr. Lasezkay for closing remarks.
Thank you. Thank you for your time and attention this morning. I'd especially like to thank Dr. Goldberg for joining us and providing his comments on the call today. We're excited about these obviously results, and we look forward to updating you on our progress as we advance CLS-AX into phase III. Operator, you may now disconnect the call.
Thank you. Ladies and gentlemen, this does conclude today's conference, and you may disconnect your lines at this time, and we thank you for your participation.