EyePoint Pharmaceuticals, Inc. (EYPT) Q4 2022 Earnings Report, Transcript and Summary

Good day and welcome to the EyePoint Pharmaceuticals Fourth Quarter and Full Year 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. [Operator Instructions]. Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your speaker, Mr. George Elston, Chief Financial Officer. Please go ahead, sir.

Thank you and thank you all for joining us on today's conference call to discuss EyePoint Pharmaceuticals fourth quarter and full year 2022 financial results and recent corporate developments. With me today are Nancy Lurker, Chief Executive Officer; Dr. Jay Duker, President and Chief Operating Officer; and Scott Jones, Chief Commercial Officer. Nancy will begin with a review of recent corporate updates. Dr. Duker will then discuss pipeline developments and Scott will comment on our commercial activities. I will close with commentary on the fourth quarter and full year 2022 financial results. We will then open up the call for your questions. Earlier this morning, we issued a press release detailing our financial results and recent corporate developments. A copy of the release can be found on the Investor Relations tab on the company website www.eyepointpharma.com. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments, and regulatory matters and timelines, the potential success of our products and product candidates, financial projections, and other plans and prospects. 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 most recent Annual Report on Form 10-K, which is on file with the SEC, and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Nancy Lurker, Chief Executive Officer of EyePoint Pharmaceuticals.

Thank you, George. Good morning, everyone and thank you for joining us as 2022 was really an exceptional year for EyePoint Pharmaceuticals. We continue to execute on our goal of being the leader in innovative sustained ocular drug delivery using our best in class Durasert technology to achieve improved outcomes with more convenient dosing regimens. I'll begin by reviewing our lead development program EYP-1901 and why we believe this therapy’s six to nine months treatment interval, zero order kinetics, and new ocular mechanisms of action could be a game changer in retinal diseases like wet AMD that require lifelong treatment. EYP-1901 is a bioerodible Durasert insert that delivers Vorolanib, a selective and patented tyrosine kinase inhibitor delivered through a single intravitreal injection in the physician's office. We have advanced EYP-1901 into two Phase 2 clinical trials in wet AMD and non-proliferative diabetic retinopathy otherwise known as NPDR based on the positive DAVIO Phase 1 clinical trial results that we reported last year. EYP-1901 has emerged as a promising potential therapeutic for serious eye diseases, bringing key attributes to patients including delivery of the active drug Vorolanib consistently over six to nine months, with the majority of patients not requiring any supplemental therapy up to six months after a single treatment in wet AMD. A new mechanism of action to treating retinal eye diseases beyond the current anti-VEGF ligand blockers on the market today through potential for neuroprotective and anti-fibrotic benefits to the retina, a proven drug delivery technology with a very positive safety profile, and upon completion of our Phase 2 trials and importantly, the EYP-1901 will have the most robust clinical data for any ocular TKI program with over 180 patients having been dosed by the end of our Phase 2 programs in both wet AMD and NPDR. This is in addition to a strong ocular safety and efficacy data set from clinical trials of Vorolanib delivered orally in previous trials treating over 150 patients. EYP-1901 delivers the TKI Vorolanib, which potentially brings a new mechanism of action to retinal disease beyond what currently exists with the current anti-VEGF large molecule therapies on the market today. When you look at treatment regimens outside ophthalmology, it's often standard practice to address multiple mechanisms of action in parallel in order to improve efficacy. We believe these retinal eye diseases with serious consequences such as blindness should be treated using all resources at our disposal as well through a multi-pronged approach that targets multiple disease drivers. Additionally, EYP-1901 sets itself apart by using our proven best in class bioerodible Durasert technology for drug delivery, which delivers the drug at zero order kinetics which provides constant steady dosing over six months or longer. Dr. Jay Duker will review EYP-1901’s potential, unique clinical advantages for patients in more detail later on this call. But of note, we look forward to presenting preclinical neuroprotection data for Vorolanib from a gold standard mass model of retinal detachment at the 2023 ARVO annual meeting in April. Beginning with wet AMD the current standard of care requires monthly or bimonthly eye injections of ligand blocking anti VEGF biologics which can be cumbersome and unpleasant for patients as it's very difficult for patients to maintain this routine for the rest of their lives. Importantly, we know from robust databases that even one missed or skipped appointment could mean vision loss for the patient. The positive Phase 1 DAVIO clinical trial results support are treatment maintain therapeutic approach for this disease with the potential to transition a majority of patients through every six month treatment with EYP-1901. This can fundamentally change the way physicians treat this disease and manage patients by having drug consistently delivered providing treatment, treatment which we are confident will enhance patient compliance and improve clinical experience. We are actively enrolling patients in the Phase 2 DAVIO 2 clinical trial of EYP-1901 as a potential six-month maintenance treatment for wet AMD. This is a massive multibillion dollar market opportunity with millions of patients in need of new treatments for this blinding eye disease and we aim to bring a life changing treatment to these patients with EYP-1901. DAVIO 2 is a randomized aflibercept control also known as Eylea trials enrolling approximately 144 previously treated patients. To our knowledge, this is the largest Phase 2 trial being conducted in wet AMD amongst TKI treatments. We anticipate announcing top line six months results, late in the fourth quarter of this year. The Phase 2 Pavia clinical trial presents a compelling and proactive potential therapy for the treatment of non-proliferative diabetic retinopathy. The approved large molecule anti-VEGF follow-up biologics to treat NPDR require frequent injections just like wet AMD for this disease where patients may not feel symptoms and as a result may forego regular treatment. In fact, nearly 97% of NPDR patients receive no course of treatment apart from observation by their retinal specialist until their disease progresses to vision loss. Consequently, there's a great unmet need in NPDR patients for a safe, efficacious, and convenient treatment options that would maintain patient vision proactively through zero order constant dosing. With EYP-1901, we have the opportunity to potentially fulfill this need within every nine months. Sustained delivery treatment option for patients that aligns with their office visits and provides patients and physicians with the comfort of having sustained drug delivery during the period between office visits. The Pavia clinical trial remains on track to complete enrollment in fourth quarter of this year. Between our DAVIO 1 trial of 17 patients and our DAVIO 2 trial of approximately 144 patients, we will have the most robust data set of any other TKI product in development for wet AMD. We are confident that the strength of this data along with our proven drug delivery system and passive molecules will give EyePoint a significant optionality as we evaluate our pivotal Phase 3 clinical development program path to market and in discussions with strategic global partnerships. Further we look forward to enrolling our first patient in a third Phase 2 trial evaluating diabetic macular edema or DME in late 2023 or early 2024 timeframe. Importantly, EyePoint continues to in fact remain actively engaged in expanding our sustained ocular delivery pipeline beyond EYP-1901. We continue to evaluate molecules for potential use in our Durasert technology, which can be tailored to each drug and disease indication for future growth. We're very excited because this week we also announced a research collaboration with Rallybio to evaluate the C5 complement inhibitor using our proven Durasert technologies to develop a sustained delivery treatment option for geographic atrophy. We're very excited to update you on this evaluation over the coming quarters and Dr. Duker will talk further about that as well. Turning now to our commercial results, YUTIQ continues to demonstrate strong customer demand in the fourth quarter of 2022, which resulted in a very compelling 55% increase in YUTIQ net product revenue compared to Q4 2021. At the upcoming 2023 ARVO Annual Meeting, we will present three abstracts discussing our YUTIQ calm study, which is a Phase 4 multicenter registry study and a collaboration between EyePoint and the Cleveland Clinic. Scott Jones, our Chief Commercial Officer will provide additional detail on this topic later on, but I'd like to recognize our commercial team for delivering on yet again another strong quarter and a strong year of product revenue for YUTIQ and for EyePoint. Additionally, we're excited to share that in partnership with Ocumension Therapeutics, YUTIQ launched in China in the fourth quarter of 2022. This commercial launch marks an important milestone in furthering our mission of improving the lives of patients with serious eye disorders around the world and we're very pleased to partner with Ocumension to expand YUTIQ’s global reach in the emerging Chinese market. Finally, we completed a number of other significant corporate milestones in recent months. This February, we entered into a lease agreement for the construction of a commercial manufacturing facility to support global product supply of EYP-1901 and YUTIQ. The lease is for a 40,000 square foot standalone facility in Northbridge, Massachusetts that will be built to our specifications. EyePoint was awarded 1.9 million of state and local grants for this facility and of note lease payments not commencing until completion of construction, which is anticipated in the second-half of 2024. This investment reflects the confidence we have in EYP-1901’s potential for clinical and commercial success and this level of control over our supply chain will provide an important point of value differentiation for YUTIQ and we hope eventually EYP-1901 in the years to come. In January of this year, we were also delighted to promote J.S. Duker MD to the additional role of President. Dr. Duker has served as a Chief Operating Officer since November of 2021 and in this expanded role, he will continue his duties as Chief Operating Officer and now will also oversee regulatory affairs. Jay has been a tremendous asset to our team since he joined as COO and we look forward to continuing to benefit from his deep ophthalmic expertise as an expert in retinal surgery and strong leadership in his new role as President. I'll now turn the call over to Dr. Jay Duker, our President and Chief Operating Officer to provide an update on our lead program, EYP-1901, as well as other pipeline initiatives. Jay.

Thank you, Nancy and good morning, everyone. Before I begin, I'd like to reiterate what important point this is in EyePoint’s journey. Our team is positioned to execute on multiple catalysts this year as we advance our Phase 2 clinical programs and growing pipeline opportunities. I'm also incredibly grateful to Nancy and the Board of Directors to allow me to take on a new leadership role at EyePoint as President in addition to Chief Operating Officer. I will begin with reviewing why as a practicing retinal physician, I'm incredibly excited about the potential of treating patients with EYP-1901 and why it represents a potential huge leap forward in this space before reviewing our clinical data and our Phase 2 programs in progress. Turning to our lead product candidate, EYP-1901 is an investigational sustained release therapy that uses a bioerodible formulation of our Durasert technology, which we are now referring to as Durasert E for erodible with Vorolanib, a tyrosine kinase inhibitor that acts through intracellular binding of all vascular endothelial growth factor or VEGF receptors, thereby blocking all VEGF isoforms. The role in its differentiated MOA versus the standard of care ligand blockers may provide additional treatment benefits beyond anti-VEGF activity with extended longevity between treatments such as neuroprotection. And we planned to share preclinical data from a mouse model of retinal detachment that suggests this differentiated advantage at the 2023 ARVO Annual Meeting next month. Additionally, compared to other TKI’s Vorolanib features reduced off target binding, specifically minimal activity against Type 2 leading to a potentially improved safety and efficacy profile. Bioerodible Durasert E, a miniaturized injectable insert is the same technology used in the non-erodible products like YUTIQ. However, the non-erodible shell is removed. Durasert products have been delivered to over 80,000 eyes with a consistently strong safety profile. So to summarize, our program features a differentiated molecule, Vorolanib coupled with the best in class delivery system Durasert. In wet AMD, EYP-1901 is being studied as a maintenance therapy suggesting a new treatment paradigm which we call treat-to-maintain. Our goal is to maintain vision in anatomy in the majority of wet AMD patients with a single injection of EYP-1901 for an interval of six months or longer. By providing this sustained delivery therapy and a new mechanism of action, patients and practitioners can potentially have the flexibility to safely reduce the number of visits to the retina specialist. Last summer we reported positive 12 month safety and efficacy results at the American Academy of Ophthalmology Meeting in Chicago with the Phase 1 DAVIO trial evaluating EYP-1901 in previously treated wet AMD. The DAVIO trial enrolled 17 patients and each received a single in office intravitreal injection of the EYP-1901 at one of four different dose levels. All enrolled patients were previously treated with standard of care anti-VEGF therapy. No reinjection with the study drug was performed during the trial and typical criteria for supplementation with the standard of care anti-VEGF was employed. We were pleased that the 12-month data featured no reports of ocular SAE or drug related systemic SAEs, no reported events of vitreous floaters and ophthalmitis, retinal detachment, insert migration into the anterior chamber, retinal vasculitis, posterior segment inflammation, or retinal vascular occlusive events. In November 2021 we presented six-month data that confirmed stable best corrected visual acuity with a change from baseline of only minus 2.5 ETDRS letters coupled with a stable macular anatomy as the central subfield that this change on OCT was only minus 2.7 microns. After a single injection of EYP-1901 53% of eyes were supplement free up to six months and up to one year one third of eyes were supplemental anti-VEGF free. Additionally, there continued to be clinically significant treatment burden reduction of 73% at 12-months compared to 75% at the six-month visit. On the heels of these positive data, we initiated two separate Phase 2 clinical trials of EYP-1901, one for the treatment of wet age-related macular degeneration called DAVIO 2 and one studying the drug in non-proliferative diabetic retinopathy or NPDR, called the PAVIA study. The DAVIO 2 trial was expected to roll approximately 144 wet AMD patients previously treated with a standard of care anti-VEGF therapy and randomly assigned to one of two doses of EYP-1901, approximately 2 milligrams or approximately 3 milligrams. This is versus an on label aflibercept control. EYP-1901 is delivered with a single intravitreal injection in the physician's office similar to current FDA approved anti-VEGF treatments. The primary efficacy endpoint of the DAVIO 2 trial is non-inferiority of the change in visual acuity compared to the aflibercept control as measured at six months after the EYP-1901 injection. Secondary efficacy endpoints include change in CSD as measured by OCT, time to first supplemental into the job, production and treatment burden and safety. We look forward to progressing the DAVIO 2 trial and anticipate top line results in the fourth quarter of 2023. Turning to non-proliferative diabetic retinopathy or NPDR. It is a very common disease affecting almost one third of diabetic adults over the age of 40 and is projected to impact over 14 million Americans by 2050. In NPDR, blood vessels are weakened, potentially leading to swelling of the macula called diabetic macular edema or DME and in some cases, growth of abnormal retinal blood vessels or proliferative diabetic retinopathy, also called PDR. If left unchecked, NPDR can be the harbinger of severe visual loss. Because the currently approved therapies for NPDR require a significant visit and treatment burden, 97% of NPDR patients are currently observed. This provides a significant market opportunity for EYP-1901, which may be able to effectively be delivered at nine month intervals or longer in NPDR. As a practicing retina specialist, I would be excited to have a safe, effective and tolerable sustained release therapy to prevent the complications of NPDR. The first patient was dosed in the Phase 2 PAVIA trial of EYP-1901 for the treatment of NPDR in September of 2022. This trial is expected to enroll approximately 105 patients randomly assigned to one of two doses of EYP-1901, approximately 2 milligrams or approximately 3 milligrams or to the control group, which will receive a sham injection. In this trial as well, EYP-1901 is delivered with a single intravitreal injection in the physician's office. The primary efficacy endpoint of the trial is improvement of at least two diabetic retinopathy severity score levels at week 36. Secondary endpoints include the occurrence of DME and or PDR, retinal ischemia, and non-perfusion as well as safety. We remain on track to complete trial enrollments in the fourth quarter of 2023. Finally, we look forward to initiate a third Phase 2 clinical trial to evaluate EYP-1901 in DME later this year or early next year, and we continue to evaluate potential product candidates through internal discovery efforts, research collaborations, and in licensing arrangements to continue to build our pipeline. As Nancy noted, we announced an exciting collaboration with Rallybio to evaluate their C5 Complement Inhibitor in our Durasert technology. We have been actively evaluating Complement Inhibitor mock drills for use in our drug delivery technology, as we see a significant opportunity to provide a sustained delivery treatment for geographic atrophy and potentially earlier forms of dry MD. Similar to our approach with EYP-1901 by providing constant dosing of drugs over time, we hope to see improved outcomes and reduced treatment burden for patients. In summary, we are very proud of the clinically validated results we've seen from the Phase 1 trial of EYP-1901 and we are excited to write updates on the Phase 2 DAVIO and PAVIA trials as well as preclinical data on Vorolanib’s differentiated mechanism of action in the years to come. I will now turn the call over to Scott Jones, Chief Commercial Officer for the commercial update. Scott.

Thank you, Jay. We're excited to report a strong year for our commercial business with 39.9 million of net product revenue, a 13% increase compared to 2021. Our Q4 net product revenue for YUTIQ was 9 million compared to 5.8 million for the fourth quarter ended December 31, 2021, a 55% increase. YUTIQ customer demand was approximately 980 units compared to approximately 890 units for the third quarter of 2022, a 10% increase. We're pleased with the continued customer demand increase for YUTIQ based on continued utilization by retinal physicians and consistent messaging from a marketing and sales teams. We continue to collect real world data on the benefits of YUTIQ for the treatment of chronic non-infectious posterior segment uveitis in the Phase 4 CALM registry study, which is conducted in collaboration between EyePoint and the Cleveland Clinic. Data from the YUTIQ CALM registry study were presented in poster presentation by Dr. Pouya Dayani at the Retina Society's 55th Annual Scientific Meeting in November 2022. And we look forward to presenting an additional update from the Calm study and three abstracts at the 2023 ARVO Annual Meeting next month. As Nancy previously mentioned, in partnership with Ocumension Therapeutics, YUTIQ commercially launched in China at the end of last year. Since its approval in the U.S. over four years ago, EyePoint has been able to deliver this innovative ocular therapy to patients and provide an improved standard of care for patients with upto three years of continuous control in chronic non-infectious uveitis affecting the posterior segment of the eye. We look forward to continuing to partner with Ocumension and expand YUTIQ’s global reach in China as we work together to improve the lives of patients with serious items of disorders around the world. We're very pleased by the strong 2022 performance and expect a profitable YUTIQ franchise in 2023. I'd like to thank our commercial team for their dedication to bring YUTIQ to physicians and patients in need. We look forward to updating you on revenues and demand in the quarters to come. I would now like to turn the call over to George to review the financials. George.

Thank you Scott. As the financial results for the three months and full year ended December 31, 2022 were included in the press release issued this morning, my comments today will be focused on a high level review for the quarter. For the quarter ended December 31, 2022 total net revenue was 10.5 million compared to 11.5 million for the quarter ended December 31, 2021. Net product revenue for the quarter ended December 31, 2022 was 9.9 million compared to net product revenue for the quarter ended December 31, 2021 of 11.2 million. Despite strong year-over-year performance by YUTIQ, total net product revenues were impacted by the anticipated loss of pass through reimbursement for DEXYCU at the end of 2022. Net Revenue from royalties and collaborations for the quarter ended December 31, 2022, totaled 0.6 million compared 0.3 million in the corresponding period in 2021. Operating expenses for the quarter ended December 31, 2022 totaled 54.3 million compared to 29.6 million in the prior year period. This increase was primarily driven by a one-time $20.7 million non-cash impairment charge of the intangible assets associated with DEXYCU due to the loss of pass through reimbursement by the Centers for Medicare and Medicaid, effective January 1, 2023. Further, there was a $6.6 million increase in R&D expense and $0.4 million increase in the cost of sales. This was offset by a $1.9 million decrease in sales and marketing expense and $0.7 million decrease in G&A expense. Non-operating income net totaled 0.3 million and net loss was 43.5 million or $1.16 per share, compared to a net loss of 19.4 million or $0.59 per share for the prior year period. Turning to the full year ended December 31, 2022, total net revenue was 41.4 million compared to 36.9 million for the full year ended December 31, 2021. Net product revenue for the full year ended December 31, 2022 was 39.9 million compared to net product revenues for the full year ended December 31, 2021 of 35.3 million. Net revenue from royalties and collaborations for the full year ended December 31, 2022 totaled 1.5 million compared to 1.6 million in the corresponding period in 2021. Operating expenses for the full year ended December 31, 2022 totaled 141 million versus 92.2 million in the prior year period. This increase was primarily driven by a one-time $20.7 million non-cash impairment charge of an intangible asset associated with DEXYCU which due to the loss of pass through reimbursement by CMS, effective January 1, 2023. Further, there was a $21.1 million increase in R&D expense, a 9.2 million increase in G&A expense, and 8.1 million increase in cost of sales. This was offset by a $2 million decrease in sales and marketing expense. Non-operating expense net totaled 2.6 million and net loss was 102.3 million or $2.74 per share, compared to a net loss of 58.4 million or $2.03 per share for the prior year period. Cash, cash equivalents, and investments in marketable securities at December 31, 2022 totaled 144.6 million compared to 211.6 million at December 31, 2021. We expect the cash on hand at December 31, 2022 and expected net cash inflows from our product sales will enable us to fund our current and planned operations into the second half of 2024. In conclusion, we are pleased with EyePoint’s progress in 2022 and are well capitalized to advance our product pipeline to key value inflection points later this year. I will now turn the call back over to Nancy for closing remarks.

Thank you, George. We trust this review has given you a greater understanding of EyePoint’s progress over the past year and our potential moving forward. Over the past year, we've executed the plan and our achievements form the foundation for future growth. This is a highly experienced management team, one we are keenly focused on delivering results and executing well. Biotech is a rewarding but risky business and it requires well thought out and methodically executed plans. 2023 promises to be another productive and rewarding for EyePoint pharmaceuticals as we continue to execute on multiple clinical catalysts and strengthen our commercial business. Over the coming year, we expect to complete enrollment in the Phase 2 DAVIO 2 trial of EYP-1901 in wet AMD and in the Phase 2 PAVIA trial of EYP -1901 in non-proliferative diabetic retinopathy. We expect to dose the first patient in the Phase 1one clinical trial of EYP-1901 in DME later this year or early next year. We expect to report top line six months data for our Phase 2 DAVIO 2 clinical trials. We expect to publish neuroprotective preclinical data for EYP-1901, using Vorolanib and we continue to grow revenue for YUTIQ. We've had a great year and we have a terrific team and we're confident that EyePoint will continue to execute. We look forward to keeping you all updated as we advance these value creating milestones. Before opening the call to your questions, I do want to note how grateful I am for a fantastic team at EyePoint pharmaceuticals, who continue to drive our progress and are responsible for our company's clinical, operational, and financial success to date. We've made tremendous progress, as I've mentioned in the last year, and we're excited and motivated to advance the future of sustained ocular drug delivery to benefit, most importantly, the millions of patients who are at risk of serious vision loss. Thank you all very much for listening this morning. And I'll now turn it over to the operator for questions. Thank you.

Thank you. [Operator Instructions]. And our first question will come from the line of getting Yatin Suneja with Guggenheim. Your line is open.

Yeah, good morning. This is Eddie on for Yatin. Thank you so much for taking my questions and congrats on all the progress. How soon after the Phase 2 data and 4Q do you think you'd be able to initiate a pivotal program and is there any other non-clinical or device work you need to do? And then if you could give us a little bit more color on what we should be looking for in the ARVO neuro protection data and how it might correlate to human patients and what might add -- what added benefit that might have for 1901 in the future? Thank you so much.

Yeah, Jay why don't you take that question or those two questions?

Sure. Hi, Eddie, thanks for the questions. First, pending the outcome of the data at the end of this year, we would expect to be able to initiate the pivotal trials in the second half of 2024. The other questions were about injector I believe…

Any other device work or non-clinical work?

Theory is I think, as we've stated many times publicly, we're developing a new patented state of the art injector that we expect to be used in the pivotal trials and commercially. We anticipate using that injector in our DME trial was the first trial that it rolls out. That still has some work to be done. While we're pleased with the current injection system, it's working quite well. We do like to update it with a state of the art injector. And, if need be, we would not delay the pivotals if there's any issue with the development of the new injector. But so far, the development is going smoothly, and we're on target to use it in DME.

Yeah, can I just add to that, so let me just reiterate. Number one, we're on track to starting our Phase 3, as Jay said, second half of next year. The injector is a phenomenal, really exceptional, state of the art injector patent protected. And what Jay is trying to also let me just say is that we're on track with the development of that injector but because of the state of the art, we don't want to guarantee that we would actually start right away with that. So we're ready to go with the current injector that we're using on Phase 2 studies and that's working just fine. And we can easily do a bridging study should we need to. So we are well prepared to go forward with our Phase 3 pivotal regardless and we're on track. Also just want to say for listeners a couple of things; number one, getting ready for Phase 3 takes a lot of pre-planning. You have to have clinical supplies ready to go and well developed. not only the injectable but the actual implant itself. You have to have an Interface 2 meeting with the FDA, you have to have made sure that you've got your pivotals well designed, that all takes a lot of pre-planning and ensure that you get it right. You don't start these trials hastily because they are very large, and they do require substantial investment. We're going to go about this methodically, carefully, and ensure we also are as fast to market as possible given the guardrails that I just mentioned. The last thing you want to do is rush into Phase 3 trials hastily and end up with problems on your hands. And we're not going to do that. So we think we're going about the right way. We think it's the prudent, but a prudent, but also ensuring that we ensure fast to market, and we're confident that we're on the right track right now.

Great, thank you so much. And then on the ARVO data?

Jay, do you want to take that ARVO data?

Yes. So the model that was used was a retinal detachment model in animals. After retinal detachment is created, the photoreceptors will degenerate because they're no longer in contact with the retinal pigment epithelium. And what you'll see from our data is that eyes that were treated with Vorolanib had much less damage to their photoreceptors and their subsequent visual acuity than the control eyes that were not treated. This is a model for neuro protection. Retinal detachment technically is subretinal fluid and you may be aware that subretinal fluid is also a feature of wet macular degeneration, and diabetic macular edema. So, while this is a general model for neuro protection, we think they will possibly and likely be read through to the diseases that we're currently treating with EYP-1901.

Great, thank you so much.

Thank you. One moment for our next question. And that will come from the line of Georgi Yordanov with Cowen. Your line is open.

Hi, everyone and congratulations on all the progress. Thank you for taking our questions. So maybe starting with the Rallybio partnership, we didn't notice they have two C5 assets based on the antibody platform. Maybe can you talk about the requirements of putting a large protein into the Durasert, maybe talk about why some previous attempts to develop long acting [indiscernible] Eylea have not been successful and in general what gives you confidence that you'll be able to formulate it with one of Rallybio assets? And then we do have a follow-up on the DAVIO trial.

Yeah, let me just -- let me make one quick comment and I will let Jay take it from there. First of all, let me make a statement on this, the Rallybio C5 is alpha body, it's a smaller -- it's smaller than the large ligand blockers, like Eylea that are on the market today. So I want to make that clear, it is not as big as an antibody. So that's a key point. Second of all, I'm not going to claim this is going to be easy, it's not, but we do have a stellar scientific team. And they're already going to quickly begin working on this. So we're -- we'll see what happens. But I think this team is very, very well versed in how to deal with this and hopefully, we can be successful. Jay, you want to go ahead.

Yeah, so in order to get a drug to work in Durasert, there's a lot of different factors. The size of the molecule is really what helps to determine the payload. Obviously, bigger molecules, you're not going to be able to get as many into an insert. So that's one factor. Proteins in general tend to degrade at body temperature and that's why small molecules have been preferable. Our team is optimistic about our ability to deliver this alpha body in a sustained release fashion. But until we really have some data to share, I would say that, again, we are optimistic but as Nancy said, this is -- it has a difficult path, others have tried and with large molecules and they have not been able to achieve it. But we're optimistic.

And do we have any idea of -- have you disclosed when you could potentially hear an update on the progress of this program?

No, we're not going to get that right now. It's way too early for that.

Thank you. Thank you. Yeah, we're very excited about the asset. And then just finally, can you remind us of the powering assumptions for DAVIO 2 and specifically, if the trial is positive, and you hit [indiscernible] in terms of non-inferiority, could it potentially serve as one of the two pivotal studies?

Yeah, let me -- we've stated this before but I'm going to say it again, this is not powered for a P value of 0.5, I want to be very clear about that. And I've said that multiple times. We did not believe, first of all you also have to go out longer in time, as you saw the FDA just issued guidance on these Phase 3 pivotal trials, and wet AMD, and they were very clear. You have to go out nine months, you have to have two dose arms, and a number of other things. The good news is, because we've had our type teaming with the FDA, our planned Phase 3 pivotals, which takes time, I want again reiterate to plan for and develop the right doses and begin to produce the clinical supplies, so that you're ready to go. We followed what the FDA said and based on the guidance that was just issued, we feel we're in a great spot in terms of our pre-planning that’s occurred and we don't have to deviate at all. So that's the great news. But we do not expect that this will count as a pivotal and again, why did we do that? Because these are expensive, large global trials. I can point to any number of companies in this space, I shouldn't say any number, but a few that went from Phase 1 straight to pivotal and failed. You have to have a robust database, you've got to be confident in the data that you've got, and we look forward to the readout of our Phase 2. As I mentioned, we expect that to be 144 patients, coupled with our Phase 1, and what was done in the oral database, we think we'll have a robust database to make wise decisions going into pivotal studies. By the way, we do plan to run those both in parallel and as a result, we still believe that we are in a great spot competitively to get to market in a fast way.

Can I just add one more comment to that? It really -- it won't be a pivotal for reasons that Nancy stated. But I think if you look at our Phase 2 design and say how will the pivotal differ, basically, in just two ways. The major way that it's going to differ is we're going to do reinjection and the second is the time. The FDA asks for nine months after your study drug is injected at a minimum for efficacy and they want to your safety. So this we're having a readout in DAVIO 2 of six months after 1901 goes in. So that's the -- will be the at least in the planning stage right now, the major differences between the Phase 2 in the pivotals.

This is great. Thank you so much. It's super helpful. And congratulations again on the progress.

Thank you.

Thank you. One moment for our next question. And that will come from the line of Jennifer Kim with Cantor Fitzgerald. Your line is open.

Hey, everyone, thanks for taking my questions. I have a few here. Maybe to start off with timelines for 1901. I think you said that the data is coming by year-end of this year and I'm wondering, does that language reflect anything in terms of, I guess, like what you're seeing in terms of enrollment? And then same with PAVIA, that seems all on track, so how does enrollment look for that trial? And then DME, I think that timeline, you said later this year or early next year, is there anything that sort of like pushed that timing? Thanks.

So let me answer first, I'm going to let Jay take the DME. So first of all, we are happy with our current enrollment rate, we're on track, we still expect barring any unforeseen circumstances that we will have a readout later this year. Now, again, I just want to -- stuff happens so I'm always cautious in making any definitive statements. But right now, we're happy with where we sit. And Jay, why don't you take DME?

So, with respect to DME, we are looking at that trial in kind of a multi-pronged way. I mentioned already that we expect that to be the first trial that uses our state of the art injector. And so we would like to, from a timing perspective, have that injector ready to go with DME. That, again, may or may not be the rate limiting step here there are other factors that certainly go into decisions strategically about when to start a trial and how large, etc. So we're still kind of working through that. I think we'll be able to nail down the start time a little bit more later in this year. But right now, it looks like Q4 start and as I said, one of the things we'd like to do along with testing 1901 in DME is literally give it a shot with the new injector.

Okay, and then with PAVIA that -- like the timeline has been pretty consistent. Does that reflect anything in terms of what a sustained delivery treatment option could mean for this kind of patient population or I guess the unmet need, it is pretty clear that you need sustained delivery?

Yeah, I think the time of the reflection and time of getting patients in has much more to do with the type of patient that would enroll in an NPDR trial versus a wet AMD trial number one. And number two is, interestingly, if you've got a patient with wet AMD is getting injections, you ask them, do you have wet AMD that you're getting injections, the answer they're going to give is yes. If you ask a diabetic, what level of retinopathy do you have, they have no clue. And therefore, it's a little bit harder for the patients to get interested in the trial and even in some ways for the doctors to identify those patients, because in general even retinal physicians in their office aren't documenting the diabetic retinopathy scale of their patients. So it means casting a wider net of the patients to get the appropriate ones. And so, this isn't new. We said before, it's probably going to take about a year to enroll the PAVIA trial. And as Nancy said, so far, so good, our moment is going great in the times that we have been talking about for full enrollment and beta read out are still consistent.

Okay, and then my second question is, I think during your opening remarks, Nancy, you mentioned having like, significant optionality in terms of the global pivotal program. Can you go more into that in terms of how you're thinking about all that?

Yeah, so our goal is to potentially get a partnership with a strategic partner and we are in discussions with a number of them as we speak. So it obviously depends on the data, but really that's our goal. We want to minimize dilutive financing. And our goal is to be able to go into those pivotals with a partner. These again are large studies, and we can do it ourselves if we need to. But our preference is to partner this with a large pharma or mid to large pharma companies. So the main one, most of you know who those are. And again, it's going to be somewhat dependent. Obviously, it's going to be dependent on the readout of our Phase 2 data. So we do expect that anything announced, should we be able to strike a deal will happen in the first half of 2024, a data readout as we said is towards the end of 2023.

Okay, that's helpful. And then my last question, a smaller question, is there anything that drove the higher cost of sales for the quarter?

Yeah, we have a great team, we will see two. And I'm just going to say, and I've told our team this. First off we have a great product, YUTIQ is really a terrific product for patients with posterior segment uveitis, the team has done a fantastic job. And they've done a fantastic job as well reaching out to retinal specialists over and above just uveitis specialists because they treat posterior segment inflammation as well and uveitis. So they've done a fantastic job. I just want to say it's a tribute to having a high quality team, a sound marketing plan, and how you go about talking about the product that physicians start to realize where the opportunity is. And the product continues to deliver in terms of efficacy and safety. It just continued to do very well. Now again, I always put caveats because drugs are funny things. Generally, we've got a great track record, we continue to have a great track record, never can promise that something couldn't happen down the road. But right now, it just continues to look great. Scott, I'm going to ask if you want to add anything to that.

Thank you, Nancy. I would reiterate a lot of the comments that you had. I think, Jennifer, if I heard your question correctly you're asking about the change in the cost of sales. I think a lot of that is related to just investment, timing of investments that were made for various meetings and some of the ongoing trials that are going on, such as the CALM study, etc. So it was really that was more of a timing issue.

Okay. Alright. Thanks for taking my questions, guys.

Thank you. One moment for our next question.

This is George, just to clarify on cost of sales to Jennifer's question. The big driver, YUTIQ is a bigger mix because of the drop off in DEXYCU. And cost of sales in Q4 in particular, was impacted by a slight provision for remaining DEXYCU inventory because of that drop off. We don't expect that to continue 2023 forward. And the items that Scott talked about are below the cost of goods line, just to clarify for the callers.

Thank you. And our next question will come from the line of Yale Jen with Laidlaw. Your line is open.

Good morning and thanks for taking the questions. So my first question is in terms of the new injector you're developing. Could you provide a little more color in terms of the specifics so the benefit attributes could provide by this new device?

Oh, sure, Jay go ahead on that, but let me just say that it really is best in class. Well, it's a -- we believe a state, it's a state of the art for sure. And I would also say could be best in class. It's just a really, really nice injector. And we've obviously tested that with physicians who are using it. So Jay, you can take it from here.

Yeah, so the current injection system is based on the YUTIQ injector, which was developed well over a decade ago. It's essentially like a syringe with a plunger and the doctor presses the plunger to get the inserts into the eye. With a state of the art injector you have a trigger or button that you press and the mechanism within the injector delivers in a very controlled manner, the inserts. Now remember, we can inject up to three inserts with a single injection. And we want to do that in a safe and controlled manner. This new injector system allows that. What it also will feature is a visual guide to the doctor that lets him or her know that all the inserts have been delivered. So it's in a very ergonomic package. We're trying to minimize things like disposable items, minimize the size of the packaging, things that really physicians care about for stocking and the environment and things like that. So we're really looking at it kind of from a 360 perspective to provide retinal specialists and ophthalmologists something that they find to be easy, ergonomic, and very reliable, even when delivering up to three inserts.

Okay, great. That's very helpful. Maybe two quick ones. The first one is in terms of the -- you announced yesterday. My question is why choose C5 versus other sort of complements which are also in development, is there any specific sort of reason for that?

Let me take that. Look, Rallybio is a great company, and they've got a C5 that is validated in some of their other clinical trials. We like a lot of it also depends on making sure that you get the right terms and you've got a good partnership. C5 and C6 both are validated targets. Right now, I would say we're probably neutral between the two. So our goal was to work with a partner that we had a good collaboration with, has a validated target, and we are in sync. So I think it is just as simple as that. And look, it's certainly a well validated target. I think there's a lot yet to play out between the nuances between C3 and C5, but I want to state both of them are highly validated targets now.

And if I could add, check it out to that. We're still watching very carefully this space and looking at potentially other partnerships and other targets. Other companies are looking at membrane attack complex as a target, as well as Complement Vector B. And I think both of those are promising. They're clearly not as validated as either C3 or C5. But I don't think from a scientific perspective, you should view this partnership as we believe C5 is validated while C3 or the other ones are not, not at all. We think that there may be multiple ways to block Complement successfully here in what we can provide is that zero order kinetics sustained release fewer injections, and perhaps because of your order kinetics better results.

Okay, great. And then last question here is that the given YUTIQ has a pretty robust quarter sales and should we anticipate at least for a modeling perspective, that 2023 quarterly that will be -- the fourth quarter number will be a baseline moving forward for 2023?

Yeah, first of all, let me reiterate, yeah, we don't give guidance, we never have, and we're not going to start. Second of all, and by the way, just take the pandemic as a case in point so in terms of being able to project guidance. The other issue is that remember, in Medicare Part B drugs, and frankly probably a lot of Medicare Part D as well, you end up with quarterly to quarterly fluctuations. So first quarter, oftentimes is lower in all -- in most categories of drugs, it is lower than fourth quarter the prior year. And the reason is, because insurance resets, co-pays kick back in again, and so patients tend to -- and also you get holiday bills coming in. So what we find is first quarter patients tend to skimp on their drug utilization. That being said, we are looking great in first quarter and we do expect 2023 overall, will be higher than 2022. But I'm not going to sit here and project quarter by quarter by quarter because again, this is a category in Medicare Part B, where co pays kick in and first quarter can oftentimes be a little weaker than fourth quarter. But again, we want to look year-over-year, quarter-over-yearly quarter. And we expect to continue to have slightly higher highs each quarter over prior year’s quarter.

Okay, great. That's very, very helpful and congrats on all the progress.

Yeah, thank you.

Thank you. One moment for our next question. And that will come from the line of Yi Chen with H.C.W. Your line is open.

Thank you for taking my questions. Just to clarify, was there any sales product revenue from DEXYCU in the first quarter?

George, do you want to comment on that?

Yeah. There was Yi. We still had DEXYCU revenues in Q4, but it dropped off meaningfully from the -- and then we will file again next week.

Do you expect any further impairment charge?

No, so if you look at the results this morning, and you'll see that we've recorded a full impairment of the DEXYCU intangible. And there was -- and to the earlier question, there was a little bit of incremental inventory that was reserved for us as well. So from a financial perspective, we start 2023 with a clean slate as it relates to DEXYCU.

Okay, was there an increase in the price for YUTIQ?

Yeah, we always have very, very modest price increases. But again, we always take very modest ones. And George if you want to just comment what we took in 2022 but again, we typically stay way below inflation. They're very, very modest.

Yeah, I think you've just -- most are the vast majority of the revenue increase for YUTIQ is demand and you could see that in the details quarter-over-quarter. The team continues to do incredibly well with that product. And price is a very small piece of that.

Got it. And lastly, so shall we expect the gross margin for 2023 to return to the levels observed in the third quarter, second quarter of 2022?

So I would say that YUTIQ that carried a much higher margin than DEXYCU so I would expect margins to improve as it relates to just that. Because it will largely be just that product in 2023. Again, we're not giving full guidance on that but it is safe to say that we expect markets to improve because of the weighting higher to YUTIQ.

Okay, thank you.

Thank you. I'm showing no further questions in the queue at this time. I would like to turn the call back over to management for any further remarks.

Yeah, I want to thank everybody for your time. I again, want to reiterate I'm very proud of our progress. We are very keenly focused on executing methodically and we expect to have hopefully, a good year in 2023. So thank you very much. Look forward to keeping you all updated as we continue to make progress, especially on our Phase 2 clinical program. Thank you.

Thank you all for participating. This concludes today's program. You may now disconnect.