Greetings, welcome to the Clearside Biomedical Second Quarter 2023 Financial Results and Corporate Update Call. At this time, all participants are in a listen-only mode, and a question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press Star Zero on your telephone keypad. Please note, this conference is being recorded. I will now turn the conference over to your host, Jenny Kobin of Investor Relations. You may begin.
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 31st, 2022, our quarterly report on Form 10-Q for the quarter ended June 30th, 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. The last 6 months have demonstrated that Clearside is the clear leader in delivering agents to the suprachoroidal space. We have a proprietary suprachoroidal space injection technology that utilizes our patented SCS Microinjector. We're able to deliver small molecules and gene therapy behind the visual field, targeting multiple retinal diseases. We have the first and only FDA-approved SCS product with XIPERE, and we have four external validating SCS delivery collaborations, as well as an early-stage internal research and development pipeline. Importantly, as we expand our development opportunities, both internally and with our partners, our versatile therapeutic platform continues to grow. Together with our licensing partners, there are now six ongoing SCS trials in five different indications, utilizing four potential therapies. Clearside's lead internal clinical development program is CLS-AX, our proprietary suspension of axitinib, delivered into the suprachoroidal space.
CLS-AX is targeting the multi-billion dollar market for wet AMD. Let me take a moment to talk about the market opportunity and why we believe we can truly make a difference in the lives of the millions of patients suffering from this disorder. Wet AMD is a crowded arena for the development of new products, mainly due to the large and growing market as a result of the aging population, particularly in the US. With the higher demand, there's room for new treatments that provide significant improvement over current therapies, including reducing the treatment burden for patients and their caregivers. Based on the label for existing marketed products for wet AMD, Lucentis is recommended to be dosed 12 times a year, Eylea, 2 mg, 6 times a year, and recently approved Vabysmo, up to 6 times per year.
In contrast, we believe that CLS-AX may be up to a twice-a-year treatment for wet AMD. This matters because it has been well documented that patient compliance is a challenge, and therefore, a treatment option where patients maintain their vision with less frequent dosing may achieve improved patient outcomes. CLS-AX could reduce the onerous treatment burden for patients who currently require frequent dosing and numerous office visits with existing approved drugs. CLS-AX has the potential to be a better maintenance treatment option based on three main differentiating factors. First, CLS-AX utilizes axitinib, which is the most highly potent tyrosine kinase inhibitor, delivering 10 times more potency than other TKIs in preclinical studies. Second, CLS-AX is administered suprachoroidally using our proprietary SCS Microinjector. This delivery mechanism does not require surgery and does not require an implant inserted into the eye.
It's delivered by physicians in their office and has proven to be safe and reliable, both commercially and in multiple clinical trials. Thirdly, in our OASIS phase 1, 2A clinical trial, we showed that a single administration of CLS-AX demonstrated a favorable safety profile with no signs of inflammation. In terms of duration, in the extension study of OASIS, in higher dose cohorts with a single dose of CLS-AX, two-thirds of the participants did not need supplemental treatment for 6 months or more. Also, these participants experienced a 77%-85% reduction in treatment burden, as measured by the number of anti-VEGF treatments they received during the 6 months compared to the 6-month period prior to entering the OASIS trial. Importantly, we also observed signs of biological effect with stable mean best-corrected visual acuity, or BCVA, and stable mean central subfield thickness, or CST.
Encouraged by the promising OASIS results and following the FDA draft guidance for drug development of treatments for wet AMD, last quarter, we initiated ODYSSEY, our randomized, double-masked, multicenter phase 2b clinical trial in participants with wet AMD. The overall objective for the trial is to evaluate the safety, efficacy, and duration of CLS-AX treatment in participants with wet AMD. The other arm in the trial is a current standard of care, Eylea or aflibercept. Our goals for the ODYSSEY trial are to demonstrate similar visual acuity outcomes with a lower treatment burden for the CLS-AX arm and to obtain the necessary clinical data to determine a desired CLS-AX fixed dosing regimen for a phase 3 wet AMD clinical development program. We are pleased that the trial is off to a solid start and is progressing as planned. Multiple participants have been randomized to receive either CLS-AX or aflibercept.
Clinical trial sites have been eager to be part of the trial. We have nearly all of our planned 30 sites currently open to enroll participants in the trial. As a reminder, ODYSSEY is expected to enroll a total of 60 participants, randomized to either CLS-AX 1 milligram or Aflibercept 2 milligrams, with a 2-to-1 randomization schedule. This means that there is expected to be 40 participants in the CLS-AX arm and 20 participants in the Aflibercept arm. The treatment period is a total of 36 weeks. In the trial, CLS-AX will be administered by suprachoroidal injection using Clearside's SCS Microinjectors, and Aflibercept will be administered by intravitreal injection. The primary outcome measures for the trial are the mean change in BCVA over the 36-week period, as well as the assessment of safety and tolerability of CLS-AX.
The secondary outcome measurements are treatment burden, as measured by total injections, including the need for supplemental therapy over the trial duration, and other changes in visual function, visual function, and ocular anatomy, such as CST. One important component of ODYSSEY is the eligibility require criteria. Our inclusion criteria is designed to ensure that participants in our trial have active disease at screening. Eligible participants will be treatment-experienced and will undergo diagnostic imaging at their screening visit, followed by masked reading center confirmation of persistent active disease. This level of specificity is to ensure that participants are in need of treatment, will likely respond to and benefit from treatment with anti-VEGF therapy. We believe this will allow the proper assessment of the potential advantages of CLS-AX in patients with wet AMD.
We further believe CLS-AX will demonstrate the ability to maintain visual acuity with a longer duration of action in order to reduce the treatment burden for patients with wet AMD. We are confident in our overall trial design and the potential success in ODYSSEY. We look forward to reporting top-line data in the third quarter of 2024. Moving on to XIPERE, we continue to receive positive feedback from clinicians regarding the use of XIPERE with patients. Our North American commercial partner for XIPERE, Bausch + Lomb, continues to conduct product education and training sessions for healthcare providers, with more than 1,200 retinal specialists trained to date. These sessions have been well attended and well received. Physicians report that the suprachoroidal injection procedure utilizing the SCS Microinjector is easy to learn and that XIPERE is highly effective in treating their patients with macular edema associated with uveitis.
Looking forward, Bausch + Lomb is focused on increasing engagement with uveitis specialists across the country and working on reimbursement parameters that will make it simpler for physicians to use XIPERE for their patients. Our Asia Pacific partner, Arctic Vision, continues to move forward in two indications with their development of XIPERE, which they refer to as ARCATUS. For the first indication of uveitic macular edema, Arctic Vision is currently enrolling a confirmatory phase 3 trial in China. If positive, the data will allow Arctic to apply for marketing approval in China. In addition, Arctic recently announced that the Therapeutic Goods Administration of Australia has formally accepted its new drug application for suprachoroidal use of ARCATUS for the treatment of uveitic macular edema.
The acceptance of the NDA in Australia is an additional validation of the suprachoroidal administration being an innovative, recognized form of ophthalmic drug delivery and another step towards the global commercialization of XIPERE. The second indication of Arctic is diabetic macular edema. Arctic has completed a phase 1 clinical trial, and we expect them to report the data from the trial later this year. This data could provide helpful insight into potential for broadening the use of XIPERE in other indications. We're excited about the progress Arctic Vision has made to expand the use of XIPERE, and we look forward to further updates from them. We also continue to work closely with our partners, developing breakthrough technologies to deliver gene therapy and ocular oncology treatment utilizing suprachoroidal delivery with our SCS Microinjector.
Earlier this month, REGENXBIO announced updates on its ABBV-RGX-314 program for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie. In July, REGENXBIO presented interim data from the phase 2 AAVIATE and ALTITUDE trials, demonstrating suprachoroidal delivery of 314, administered to patients with prophylactic steroid eye drops, resulted in zero cases of intraocular inflammation. Additional data from REGENXBIO on both trials is expected over the next 6 months. Interim efficacy data from the ALTITUDE trial in diabetic retinopathy is planned for the American Academy of Ophthalmology meeting in November of 2023, and the interim efficacy data from the AAVIATE trial in wet AMD is expected to be presented at the Hawaiian Eye and Retina Meeting in January 2023. Our oncology partner, Aura Biosciences, announced their progress last week with their drug candidate, bel-sar, for the treatment of choroidal melanoma.
Their global phase 3 clinical trial is expected to dose the first patient in the second half of 2023, and is designed as a superiority trial comparing bel-sar versus sham, with the primary endpoint as time to tumor progression. Aura has qualified trial sites globally, with multiple sites ready to enroll patients in the US. In addition, Aura expects to present updated efficacy data in the second half of 2023. The Phase 2 data will include 12 months median follow-up of patients treated with the therapeutic regimen intended to be used in the global Phase 3 trial. With that summary of our programs, I'll now turn the call over to our CFO, Charlie Deignan, for a financial update.
Thank you, George. Good afternoon, everyone. Our financial results for the second quarter were published earlier in our press release and are available on our website. I would just provide a summary of our financial status. As of June 30th, 2023, our cash and cash equivalents totaled approximately $35 million. We continue to prudently manage our cash as we move forward with our programs. We have worked to fine-tune our budget over the next year. Based on our current outlook, we now expect to have sufficient resources to fund our planned operations into the third quarter of 2024. Over the next few months, we look forward to participating in several investor conferences, including the H.C. Wainwright Ophthalmology Conference this Wednesday, the Cantor Fitzgerald Global Healthcare Conference in September, and the JonesTrading Healthcare Summit in October.
We look forward to keeping you updated on our progress. I will now turn the call back over to George for his closing remarks.
Thanks, Charlie. In closing, our state-of-the-art suprachoroidal injection technology continues to advance globally. CLS-AX is targeting a large market opportunity in wet AMD, with a new mechanism, new mechanism of action utilizing pan-VEGF inhibition and a unique suprachoroidal delivery using our SCS Microinjector. We are confident in our Phase 2b ODYSSEY trial design and the potential for CLS-AX to offer patients a therapy that will maintain their vision while reducing the burden of frequent injections. Our current partners are making meaningful progress as well and reporting encouraging clinical data across their respective programs. We continue to receive positive feedback on our SCS Microinjector and the potential advantages of drug delivery to the suprachoroidal space. We remain very active within the medical community, at scientific meetings, and in ongoing discussions with key opinion leaders in the treatment of back-of-the-eye diseases.
Clearside has pioneered drug delivery behind the visual field to treat retinal disorders. We will continue to explore opportunities to expand the use of our suprachoroidal injection technology platform. I'd now like the operator to open the call for questions.
Thank you. At this time, we will be conducting a question-and-answer session. If you'd 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 poll for questions. Thank you. Our first question is coming from Jon Wolleben with JMP Securities. Your line is live.
Hey, thanks for taking the questions and the updates. A couple from me, George.
Thanks, John.
Almost 30 sites are open now. Wondering if you still feel good about that number, if you think you'll add more or you have enough. Then also, I think you commented that patients are being dosed. Can you tell us how many have been dosed so far in the study?
Okay, John. Our goal was 30, and we're very close to 30. We feel comfortable with 30. We have a lot of interest. We may enroll a few extra over 30. That's possible. Right now, our goal is 30, and we're just about there, so we're feeling very good with that. In terms of updates, we have reported that we've begun the randomization process, so we've had multiple patients be randomized between the CLS-AX arm and the aflibercept arm. At this point in time, we're not giving updates on the actual number of patients in the trial.
Okay. Interesting nuance in the design for ODYSSEY is the ability to redose CLS-AX, depending on when, you know, someone hits rescue criteria. Wondering about your modeling about, you know, how many patients do you think will be redosed with CLS-AX or rescued with EYLEA, based on the OASIS data? I think this, you know, could give us a lot of interesting information we're not going to get from other TKI studies.
Yeah, we... Listen, we've designed this trial in a way that we think we're going to have a lot of success in getting this to be a 4-6-month treatment. I'm very hopeful, and I expect a high degree of success of getting the vast majority of the patients towards 6 months. I don't believe, unless there's some deviations from protocol, I would be very surprised if we have any rescues that are less than 12 weeks in the CLS-AX arm. There, you know, that would— Our expectation is there's be very few, if any, early, early-stage rescues in less than 12 weeks after the first CLS-AX dose. Which, if you remember, we've got the 3 loading doses, and we're dosing CLS-AX at the second loading dose of aflibercept.
We're doing aflibercept on label for both groups, in terms of loading, and then we're going switching to, in the aflibercept arm, they're being dosed every 2 months on label. In the CLS-AX arm, we're going to dose at least every 6 months with CLS-AX, unless supplemental therapy is required earlier. I, I really don't anticipate any significant number of patients being rescued before 12 weeks after the initial dose.
Okay.
I think OASIS is really, the OASIS data really gives us that kind of encouragement. Again, we have to run the trial. We have to do, you know, carry out the trial according to the protocol. If we run according to the protocol and based on what we saw in OASIS, I think there'll be very few.
Can you talk about the opportunity for treat and extend with CLS-AX versus potentially looking at a treatment-naive population in a subsequent study? I'll hop back in the queue. Thanks again.
Okay. John, just real quick, could you repeat that again? I just missed the last part of that.
How, how you think about the treat and extend opportunity like you're studying now, or potentially looking at a treatment-naive population in a subsequent study?
Well, you know, like I said, that we're going to make sure that everybody in the CLS-AX arm gets a dose at 6 months if they didn't require one earlier. I think our real hope is that there'll be people that are being treated at 6 months, that by virtue of looking at BCVA changes and CST changes, really don't require it, you know? What we're trying to do here is we're really trying to determine what the proper fixed dose is to go into phase 3, because I believe that we need to go into phase 3 with a fixed dosing regimen.
You know, aflibercept has a fixed dosing regimen, but physicians quite often use the treat and extend. I think patients are going to be coming into the office, they're not going to come into the office twice a year or once a year. They're going to be coming back every couple of months, every other month. You know, if they come in at 6 months after getting their CLS-AX dose, in practice, if it was approved and their BCVA is stable and the CST is stable, I think it'll be just like any other therapy that people feel comfortable doing treat and extend. I, I'm not sure if that's completely responsive to your question, but I really look forward to seeing a fixed dosing regimen where we can clearly...
As I mentioned in the, the opening remarks, I mean, if you look at on label now, and even, even with Vabysmo, which was just recently approved, that dose is every 4 months at a maximum, you know, and there's a number of people that have to be dosed after 4 loading doses at every 2 months or 3 months. I think if we're in the 4-5 month, 5-6 month category, that's a major improvement for patients, and I, I think even at that point, doctors will still look to treat and extend, past that. We may be going past 5, 6, 7 months in, in number of patients.
That is helpful.
We have to see the data, and we have to... We really have to go into phase 3, I believe, with fixed dosing regimen, rather than the way it was done in the past, where there was a, a kind of a treat and extend, and we'll see how far we go. Our, our goal is to really set up that, the fixed dosing regimen.
Got it. All right. Thanks again.
Sure.
Thank you. Our next question is coming from Andreas Argyrides with Wedbush Securities. Your line is live.
Hi, Andreas.
Good afternoon. This is Caroline, actually, on for Andreas.
Hi, Caroline.
Hi.
Sorry, I can't see anything. It's been so-
It's okay.
Okay.
No worries. Thank you for taking our questions.
Sure.
Just 2 from us. Can you discuss your targeted timeline for enrollment in Odyssey and how enrollment is progressing? Are you seeing any impact from the availability of Vabysmo? Then second, can you just discuss the powering assumptions for Odyssey?
Okay, sure. The, the powering assumption, we're not conducting a non-inferiority trial. We're not conducting a superiority trial. There really isn't a powering assumption in here. What we're looking at is aflibercept on label to see what over the 36 week, yeah, 36 weeks, how those patients in the aflibercept arm do in terms of keeping a stable BCVA and CST. Then we're going to look at the CLS-AX arm, and what we're trying to do is to see whether the BCVAs and the CSTs are similar between the two groups and what our ideal dosing regimen would be on a fixed basis going into phase 3. Should it be every four months? Should it be every five months? Should it be every six months? Maybe, can we go longer than that?
Okay, there's not. This is not set up as a trial that has sufficient patients to have a powered outcome, as you would think of in a non-inferiority trial in particular. We, we think that the phase 2 design here, in terms of total patients that are in, in the, in the treatment arm, is very consistent with the way a number of the recent phase 2 trials have been run. We're not looking to convert this into a phase 3. We're looking to run a standard phase 2b trial here, trying to compare, again, in an estimation, on an estimation basis, how well we're doing and where we should go into phase 3 on a fixed dosing.
In terms of the enrollment, the, as I mentioned in the press release and in the opening remarks, we're, we're nearly at the 30 targeted sites that we want. We have all of, of our previous sites from OASIS are included in ODYSSEY, so we have very ex- people that are very experienced with CLS-AX already in. We'll be closing that out soon. On enrollment, we're not going to give enrollment updates per se, but what we are not changing is our, our, our disclosure regarding when we think top-line data is going to be available. We're still looking at third quarter of next year, and the way we've been able to enroll sites and as we see enrollment of participants going on, we're still very comfortable with Q3 of 2024 in terms of top-line data.
Okay, great. Thank you so much. Congrats on the progress.
Thank you.
Thank you. Our next question is coming from Sean Kim with JonesTrading. Your line is live.
Yeah, hi. Thank you for taking my questions. I guess first question for me.
Hi, Sean.
Hi. My first question is that in light of recent safety issues reported with an FDA-approved therapy in geographic atrophy, would you please remind us if there has been any retinal vasculitis reported with any of the suprachoroidal injections given thus far? A related question is, in comparison to intravitreal injections, whether the suprachoroidal drug delivery approach might be intrinsically more likely or less prone to causing retinal vasculitis and related adverse events.
Well, I think the, the first part of the question first, as far as I know, certainly with CLS-AX, we've had no, no events, no indication of any kind of inflammation, including retinal vasculitis. That is covering both the product itself, CLS-AX, the, the, tyrosine kinase inhibitor, as well as the injection technique and the injection procedure. We've not seen any of that. As far as I'm aware, we don't have any significant reports or any reports at all of retinal vasculitis. I'd have to double-check that to be sure, but there's nothing that comes to mind in the, our, in our partner's trials or in our previous, trials getting XIPERE approved, that that was a significant problem. Certainly, if you look at the injection procedure itself, using our SCS Microinjector, it's been very reliable, safe, very repeatable.
The physicians that are trained on it find it once they're trained on it, and the training doesn't take all that long, it's not that complicated, but it is important. Once they're trained, they find it an easy procedure, a very acceptable procedure, and, and very comparable in a sense to, from a patient experience and a physician experience to intravitreal injections. Retinal vasculitis has just not come up as a, as a problem that I can recall in any of our clinical trials or our partners' clinical trials.
Now, to be fair, REGENXBIO had, did have some inflammation in some of their earlier trials, but they've recently reported that, with the topical steroids in, in their phase 2 trial, I believe was in wet AMD, they've seen no signs of inflammation, and I've certainly not heard of any reports of retinal vasculitis.
Okay, that's helpful. Thank you. Related to the ODYSSEY trial, if I understand correctly, that, one of the goals for the ODYSSEY trial is to define the fixed dosing schedule, for potential- phase 3. My question is, what endpoint would it dictate that in dosing interval for phase 3? Would it be the BCVA liter change, or would it be more of a totality of data across different efficacy points?
I think the most important, and certainly from the FDA's point, perspective, the most important, endpoint would be the BCVA. They certainly want it. You know, Dr. Chambers at the FDA is very focused, first and foremost, on vision, vision preservation or vision improvement. I think the real most important factor would be the BCVA stability for the duration. How long can we keep that BCVA stable without requiring any kind of supplemental intervention? I think that's the most important thing. Other things like CST are important, I think BCVA is the most important factor there.
Okay, gotcha. Just as a quick follow-up on that is, just curious what your expectations might be for the aflibercept control arm in terms of that BCVA change through 6 months, specifically in the target population, for the ODYSSEY trial?
I'm not sure what to expect, you know, with BCVA. Regarding BCVA, I would hope that I would expect, not so much I would hope, but I would expect if the patients are the typical patients that go into that and they get and they get dosed appropriately on label with aflibercept, they'll have a similar outcome. There'll be a similar overall outcome to what you've seen with aflibercept dosed on label before in the hands of other people. I don't know why it would be any different in our hands than other people. We looked at how bevacizumab did versus aflibercept, using aflibercept as their control in phase 3. We saw how Vabysmo did against that.
We think that we can do as well against, as, as well against Aflibercept as Vabysmo did against Aflibercept, but we believe that our dosing interval is going to be longer than Vabysmo's turned out to be in their phase 3. I don't expect any difference in, in the way Aflibercept, the Aflibercept patients respond to Aflibercept, other than what you've seen in other trials in wet AMD, that, that enrolled a similar population.
It really does come down to the enrollment. What kind of patients are you putting in? Are you- if you're putting in patients that really don't have strong signs of active disease, you know, those patients are going to do really, really well because they may not have required any real intervention to begin with. There's lots of literature that will talk about patients that are relatively dry, but diagnosed with the disease, but no active signs of- no signs of active disease, might go for a long period of time between injections. We're trying to make sure that the two groups have people that are responsive to anti-VEGFs and have active disease when they're enrolled. Then I think the outcome in the aflibercept group will be pretty consistent with history.
Okay, great. Thank you.
Sure.
Thank you. Our next question is coming from Rohit Bhasin with Needham & Company. Your line is live.
Hi, this is Rohit on for Serge. Thanks for taking our questions.
Hey, how are you?
Hi, how's it going? Are you still evaluating new, potential new collaborations for the SCS Microinjector platform? Is the current cash balance sufficient to get us to a top-line readout of ODYSSEY? Thanks.
All right, I'll take the first part of that question, and I'll let Charlie take the second. Yes, we are in discussions with the other companies about potentially partnering in various disease states or with various therapeutic agents that we think might be useful, delivered suprachoroidally. We conduct those kind of business development activities on a regular ongoing basis. We don't jump into them lightly. We want to make sure they're very strategic and very positive for us and would be a positive for the company. We need to make sure that we have the right terms, the right partner, and it fits our strategy for partnering. We typically try to partner in areas where the collaborator has technologies that we cannot access, that we don't have any expertise in.
For example, gene therapy, that is not a core competency of us, of Clearside. That's why we partner in the area, look to partner in the area of gene therapies in particular. But there could be other small molecules that are proprietary to other companies that want to be put into our suprachoroidal delivery system, and we're certainly open to that. We have a constant set of conversations with people trying to put together the right deal that makes sense for us as well as for them. Charlie, I'll let you take the cash runway call.
Thanks. Yeah. Hey, Rohit. Yeah, our, as we said, our data's coming, planned to come Q3 next year, and our cash can get us into Q3 of next year. That's, you know, obviously, we'd want a cushion, you know, we can't, until we finish enrollment, know exactly within the quarter the data will come. You know, we will, you know, continue to look to extend our runway, you know, much past our. When the data comes in, you know, that's what we're doing now is looking at all, you know, dilutive and non-dilutive ways to extend our runway.
Great. Thank you.
Thank you. Our next question is coming from Jack Padovano with Stifel. Your line is live.
Hi, this is Jack calling in for Annabel.
Hi, Jack.
Hi, just a quick question from me. Could you briefly go over again, some of the economics with your partners, and if there's any chance that you might be able to see some additional near-term expected catalysts or milestones from them?
Charlie, is that something you would want to address?
Yeah. Sure. You know, you know, we haven't announced or we're not allowed to announce particular milestones, but, you know, as, as some of these, our collaborators are getting into phase 3, you know, typically there's phase 3 development milestones that go with them. You know, that would affect our EPS and revenues. You know, just don't forget that when we monetized our royalties with HCRx, Healthcare Royalty, those milestones will get wrapped up and go towards the cap we have to pay. If you remember, we took $32.5 million from them, and we'll have to pay 2.5 times that back, so approximately $81 million. Those, any milestones that come in will go directly to HCRx on our partnered programs.
Thanks.
Does that answer your question? Yeah.
Thank you. Our next question is coming from Yi Chen with H.C. Wainwright. Your line is live.
Thank you for taking my questions. Your partner, REGENXBIO, recently reported some progress with their candidate for wet AMD. I don't know if you can comment on whether their candidate in the future could potentially become be competitive to CLS-AX?
I'll take that question, Yi. I suppose it, it could. It depends, I think, you know, as I understand their therapy, their therapy is a gene therapy that generates a Lucentis-type molecule. Again, what CLS-AX does is a different mechanism of action than what REGENXBIO, the REGENXBIO/AbbVie product, would have. All right? It's pretty much standard anti-VEGF therapy, just like Eylea, Avastin, et cetera, Lucentis. Their, their, I think their potential claim to fame is they're going to last a long time in binding the circulating VEGF. From our perspective, we're taking a different mechanism, mechanistic approach, and that is we're blocking the VEGF receptors 1, 2, and 3. Any circulating VEGF, including, you know, if it's not completely bound, there's still circulating VEGF, and they're binding again, VEGF-A.
In many cases, there's an overexpression of patients once you start to bind the VEGF-A, especially on a longer term treatment, after a couple of years getting VEGF-A, anti-VEGF-A therapy, that there's an overexpression of C and E in particular, which can cause potential neovascularization. I think there, while it's potentially competitive in that they're going after wet AMD, as are we with CLS-AX, I think they could be complementary, if you want to put a positive spin on it. I think they'd be complementary because the mechanisms are different. Theirs would unlikely, based mechanistically, unlikely to address any of those patients that become resistant to VEGF, anti-VEGF-A therapy. Because in many cases, overexpression of C and E, while our mechanism, through using a tyrosine kinase inhibitor, would block all three VEGF receptors.
Even if there was overexpression of VEGF-C and VEGF-E, we would be blocking the interaction of, of VEGF-C and VEGF-E at the receptor sites. I think there's room for multiple products. I often refer to this area as starting to develop the characteristics of cancer therapy, where there's multiple approaches, multiple products used to treat particular cancer. I think it could be that the two products end up being able to be used together rather than just competing straight up for all wet AMD patients. I think there's room for both, and we'll see. The, the, the proof will be in the clinical data for both products.
Thanks. My next question is, I don't know if you can comment on the prescription volume of XIPERE and whether your quarterly license revenue is correlated to the prescription volume?
Okay, I'll let Charlie handle that. That's his.
Yeah. We don't, we don't have pre-prescription information. I think, you know, those of you that track retina drugs, difficult to get, so we can't give any guidance or trends on sales. We're contractually obligated to Bausch, not, not to discuss unless they do so. Until they start reporting out publicly the sales, I can't help you with that.
Got it. Lastly, could you comment on the potential timeline to, for your partner to obtain the approval of XIPERE in Australia?
Well, our understanding of the filing in Australia is that it's typically, it's very similar to the United States, in that your expectation should be about a 12-month review to approval cycle. They filed, 1 month or so ago, and so I would think it'd be, they'll have news by this time next year. That, that's kind of an educated guess on my part. We do, we do understand the Australian process for approval runs about, in a similar timeline to the United States, which is about 12 months.
Got it. Thank you.
Mm-hmm. Okay, sure.
Thank you. We have reached the end of our question and answer session, so I'll now turn the call back over to Dr. Lasezkay for any closing comments he may have.
Thank you. Thank you all for joining us on the call this afternoon. We really appreciate your continued interest in Clearside. We look forward to updating you on our progress throughout the year. At that, operator, you can now disconnect the call. Thank you again, all.
Thank you, sir. This concludes today's conference. You may disconnect your lines at this time. We thank you for your participation.