Omeros Corporation

Good afternoon and welcome to today's earnings call for Omeros Corporation. At this time, all participants are in listen-only mode. After the company's remarks, we will conduct a question and answer session. Please be advised that this call is being recorded at the company's request and a replay will be available on the company's website for one week from today. I'll turn over the call to Jennifer Williams, Investor Relations for Omeros.

Good afternoon, and thank you for joining the call today. I'd like to remind you that some of the statements that will be made on the call today will be forward-looking. These statements are based on management's beliefs and expectations as of today only and are subject to change. All forward-looking statements involve risks and uncertainties that could cause the company's actual results to differ materially. Please refer to the special notes and the risk factors section regarding forward-looking statements in the company's annual report on Form 10-K. which was filed today with the SEC. Now, I would like to turn the call over to Dr. Greg Dimopoulos, Chairman and CEO of O'Meara.

Thank you, Jennifer, and good afternoon, everyone. I'm joined on today's call by David Borges, our Chief Accounting Officer, Nadia Dock, our Chief Commercial Officer, Andreas Grauer, our Chief Medical Officer, Gatney Melfi, our Chief Regulatory Officer, and Steve Whitaker, our Vice President of Clinical. Today I'll start with an overview of our 2024 financial results and provide updates across our development programs. David will go through our financials in more detail and then we'll open the call for questions. Let's begin with the financials. Our net loss for the fourth quarter of 2024 was $31.4 million or $0.54 per share compared to a net loss of $32.2 million or $0.56 per share in the third quarter of 2024. For the full year 2024, our net loss was $156.8 million or $2.70 per share. As of December 31, we had over $90 million in cash and investments on hand. Now that we have resubmitted our BLA for narsoplimab in TATMA, which we'll discuss in just a bit, our focus is on restructuring the balance sheet. Having substantially reduced the amount of the 2026 convertible notes last June, we now are in preliminary discussions with certain remaining holders of the 26 notes to retire and or refinance them to extend their maturity. As part of this debt restructuring, we intend to add substantial capital for operations. In addition, discussions are underway regarding potential partnerships, primarily around our complement franchise, which includes Narsoplimab, Zoltanabart, and OMS 1029. with additional discussions directed to our deeper pipeline. Other possible options of course include royalty monetization or debt or equity transactions including through the use of our existing at the market offering facility which provides for the sale of up to $150 million of our common stock at prevailing market prices. We're confident in our ability to leverage these opportunities to strengthen our financial position while driving long-term growth and near-term shareholder value. We will provide an update on our progress at such time as a definitive announcement can be made. With that, let's move on to an update on our development programs, starting with our complement franchise and our supplement, our first-in-class inhibitor targeting MASP2, the effector enzyme of the lectin pathway of complement. As we announced today, there has been a tremendous amount of activity moving us toward approval of narsoplumab for hematopoietic stem cell transplant-associated thrombotic microangiopathy, or TATMA, both in the US and in Europe. We expect that our first approved indication for narsoplumab will be TATMA, a serious often rapidly fatal condition that occurs too frequently in children and adults who undergo stem cell transplantation. Earlier this month, we resubmitted to FDA our biologics license application or VLA for narsoplimab in the treatment of TATMA. Over the past year, we've been working closely with FDA to complete the resubmission. This includes our meeting with the agency last September to finalize the content to be included in the resubmission and the subsequent receipt in November of FDA's final comments on both the protocol and statistical analysis plan to compare survival in our supplement treated TATMA patients to that of an external control population. The independent statistics group then incorporated all of FDA's comments and ran the analyses. Results of these analyses, which we have shared publicly and are included in the BLA, demonstrate narsoplimab's significant and clinically meaningful survival benefit. Resubmissions have no filing period. with the six-month review clock starting on the date sent to FDA, setting in this case a PDUFA date in September of this year. We do not expect that recent or anticipated changes at FDA will affect the review of our resubmission. Let's spend a little more time on those results of the narsoplimab analyses, which I expect will be instructive. As previously reported, the primary and all primary related sensitivity analyses were agreed with FDA and include propensity matching, which further enhances the matching between the patients in the narsoplimab pivotal trial and the control patients. At FDA's request, the analyses were also adjusted for potential immortal time bias. The primary analysis shows a more than threefold improvement in survival associated with narsoplimab treatment with a p-value of less than 0.00001. The related sensitivity analyses recommended by FDA were also conducted with results strongly and consistently supporting that same survival benefit. FDA further requested that we conduct analyses to assess even the effect of unmeasured confounders on our results, recommending that we use a measure called an expectation value or e-value. The E-value for our primary analysis was 5.7, demonstrating that the possibility of our results being affected by unmeasured confounders is vanishingly small. In other words, the results of the statistical comparison of narsoplumab versus a well-matched and rigorous external control group are robust, consistent, statistically significant, and highly clinically meaningful, uniformly demonstrating compelling evidence of improved survival for narsoplimab in TATMA. The BLA resubmission also presents analysis of survival in our Global Expanded Access Program, or EAP, often referred to as compassionate use with 136 adult and pediatric TMA patients at time of database lock. This includes a comparison of survival in the EAP versus survival in the same external control group used for the primary analysis and the related sensitivity analyses. The results of these EAP comparisons were consistent with those of the pivotal trial primary analyses. Hazard ratios, p-values, and e-values, all consistent. The EAP data also assessed survival in adults and children with TATMA who had failed treatment with other complement inhibitors, namely eculizumab, ravulizumab, and pegcetocoplan. as well as defibrotide prior to receiving Narsoplimab. These refractory TATMA patients showed one-year survival in excess of 50%, more than two-and-a-half-fold higher than the historically referenced survival in these refractory patients of less than 20%. Two months prior to resubmitting our BLA, we had shared with FDA all data from the primary analysis and the primary related sensitivity analyses and, over the following several weeks, also sent in completed portions of the resubmission. These submissions were provided at the agency's request to allow FDA's reviewers to begin their review prior to receipt of the full resubmission, but FDA made clear that the review clock would not start until the full submission was received, which again occurred earlier this month. Concurrent with preparing and submitting the BLA, we've been compiling our marketing authorization application, or MAA, for submission to the European Medicines Agency, or EMA, planned for the coming quarter. In anticipation of our upcoming submission, the EMA has appointed rapporteurs to shepherd our application through EMA's Committee for Medicinal Products for Human Use, or CHMP. The narsoplimab rapporteur country is Germany, and the co-rapporteur is Austria. Omeros met previously with regulatory authorities in multiple EMA member countries, including Germany, regarding narsoplimab for TATMA, and scientific advice from these meetings has been incorporated into the upcoming MAA. Upcoming meetings are scheduled between OMEROS and representatives from both rapid tour countries at which we will orient the representatives to the AM, to the MAA included data. Rather than requiring separate national approvals across Europe, the Narsoplimab MAA is eligible for submission under EMA's centralized review procedure. This allows us to submit a single MAA that, if approved, authorizes marketing of the product in all 27 European Union member states, plus Iceland, Norway, and Liechtenstein. Narsoplimab has orphan drug designation from EMA for treatment in omatopoietic stem cell transplantation. In preparation with our efforts on BLA and MAA submissions, two manuscripts authored by groups of international transplant experts have been drafted and are under review. Once finalized, both manuscripts will be submitted for publication in premier peer reviewed journals. The first, consistent with our primary endpoint for regulatory approval, compares survival of patients in the narsoplimab pivotal TATMA trial with the same external control used for our submissions. The second manuscript details the survival data from our global expanded access program in the 50 narsoplimab-treated children. Last month, two presentations reporting real-world outcomes from TATMA patients treated under the narsoplimab EAP were featured at the 2025 tandem meetings in Honolulu. The first, a podium presentation reported on the impressive survival in both adult and pediatric high-risk TATMA patients, including those who had failed another TATMA-directed therapy prior to receiving narsoplimab. The second reported on high-risk TATMA patients who had failed eculizumab and were subsequently treated with narsoplimab, achieving an over three-fold increase in one-year survival compared to the reported less than 20% survival in eculizumab refractory patients. Preparations for the market launch of narsoplumab are going well, and our commercial team is well prepared and eager to launch the drug. Transplant experts continue to express their patient's need for narsoplumab, asking how quickly it will be approved, As an increasing volume of data are made public regarding the safety concerns surrounding the currently used off-label therapies for TATMA, the need becomes increasingly acute. There are 174 transplant centers in the US. 40 of those centers perform 60% of the transplants, and 80 sites perform 80%. We effectively have relationships across these centers, and anticipation for the launch of Narsoplimab is high. Recall also that we, in collaboration with leading U.S. transplant specialists, and professional associations were responsible for establishing an ICD-10 diagnostic code and a CPT procedural code essential for billing in the treatment of TATMA. Once approved, narsoplimab would be the only drug specifically linked to these codes, facilitating reimbursement for use of narsoplumab while creating reimbursement barriers for off-label treatments not approved for TATMA. Now let's turn to our Zoltenibart program. Zoltenibart, also known as OMS906, is our lead MASK3 inhibitor shown to block activation of the alternative pathway of complement, a pathway that is therapeutically validated and involved in a wide range of diseases. Zoltenibar treatment has several important characteristics that positively differentiate it from treatment with other complement inhibitors. These differentiators including enhanced efficacy, convenient and reliable dosing, and potential safety advantages are related both to the Zoltenibar molecule and its target, MASP3. We continue making good progress in developing data demonstrating Xeltenabart's potential to be the preferred choice for the treatment of alternative pathway-related diseases. Xeltenabart is now in phase three development for paroxysmal nocturnal hemoglobinuria, or PNH, a life-threatening hematologic disorder. Our PNH Phase III program is comprised of two studies, one in PNH patients who are not receiving treatment with a complement inhibitor, and the other following a switchover design in which Zoltenabart is administered to PNH patients who have a suboptimal response to treatment with a C5 inhibitor, either eculizumab or rabulizumab. These study designs and populations are very similar to those of our successful Phase II trials, substantially de-risking our ongoing Phase III program. Both of our Phase III clinical trials directly compare the efficacy and safety of Zoltenibart monotherapy to that of the C5 inhibitors Eculizumab and Ravulizumab. and both FDA and European regulators have agreed with the trial designs. This is the first time that both trials evaluating an alternative pathway inhibitor in a Phase III program are being run with an active comparator. So both of our trial designs provide head-to-head comparisons with eculizumab and Ravulizumab and should provide data demonstrating superiority of Zoltenibart over the therapeutic class of C5 inhibitors. These head-to-head comparisons are important for several reasons. First, these data could form the basis for comparative superiority claims for promotion. This would also allow our sales and marketing teams to discuss Zoltenabart's superiority over C5 inhibitors with treating physicians, greatly accelerating healthcare provider awareness of Zoltenabart's advantages. The comparative data can also enhance market access and support pricing appropriately reflective of Zoltenabart's advantages over other agents. Also, to support market access and pricing, we met with the German Federal Joint Committee. The committee determines availability of reimbursement from German statutory health insurance funds and has specialized expertise in patient-reported outcome measures. Their recommended measures were incorporated into these Altena Bar Phase III design and are expected to help further secure appropriate pricing. Looking at trial logistics and execution, we have completed all Zoltenabart manufacturing needed for our Phase III program. We've also identified and sourced active comparator drugs. The trials include a total of 120 clinical investigative sites across 30 countries, which were carefully evaluated and chosen for clinical trial participation based in large part on their respective abilities to conduct well-run clinical trials and to contribute substantial enrollment. Pools of PNH patients ready to participate in the two trials have been identified and efforts continue to locate additional patients. We anticipate all data needed for submission of the BLA and global approval dossiers for Zaltanibar in PNH to be available in the fourth quarter of next year. The market size for PNH is large and growing, reported to be $3.9 billion in 2023 and projected at over $10 billion in 2032. We believe that Zaltanabart clinical program will position OMEROS to capture a substantial portion of that market. In addition to the phase three clinical program, we have two other ongoing PNH clinical trials. One trial is an extension study to provide long-term safety and efficacy data. This trial enrolls patients who have completed other OMEROS PNH clinical trials. The other clinical trial is the previously reported evaluation of Zoltenibar in patients who are naive to complement inhibitor treatment. Data from this trial have previously been presented at the American Society of Hematology and European Hematology Association annual meetings. This study has been amended to treat patients with our phase three dose, eight milligrams per kilogram of intravenous Altanabar treatment once every eight weeks, further de-risking our phase three program. The study shows strong efficacy. At the last available time point, all patients achieved an increase in hemoglobin of at least two grams per deciliter from their study entry baseline, one component of our Phase III primary endpoint. Twelve of 13 patients without myelodysplastic syndrome, which is a disease that suppresses bone marrow function and the generation of blood cells on which you would not expect an alternative pathway inhibitor to be effective, have achieved an absolute hemoglobin of greater than 12 grams per deciliter, the other component of our primary endpoint. These data are very encouraging for our Phase III outcomes. No safety signal of concern has been observed with Zoltenibar. We've submitted two abstracts to the upcoming conference of the International PNH Interest Group. Both were accepted. and will be presented at the conference occurring in mid-May in Paris. We also have submitted abstracts to the 30th European Hematology Association Annual Congress. Acceptance notifications will be sent by the Congress organizers by April 24th. Given the strength of our PNH data and the established validation of the alternative pathway in PNH, our commercial team has already begun planning for market launch. We conducted an advisory board in parallel with the American Society of Hematology annual meeting in December. The advisors were PNH experts from academic and community settings, and we've learned that both are critical, meaning academic and community physicians in a PNH patient's diagnosis and treatment journey. The experts uniformly underscored the unmet treatment needs remaining in PNH, specifically the patient problems resulting from extravascular hemolysis caused by C5 inhibitors and compliance concerns with newer oral therapy. There was significant discussion about the experts' concerns regarding robust compliance mechanisms required with current oral therapies to prevent treatment gaps that could lead to breakthrough hemolysis and life-threatening thrombotic events. They characterized compliance as multifactorial, not just remembering to take a pill or a subcutaneous injection, both which physicians cannot monitor. But with pills, self-administered injections, and other primary pharmacy benefit products, a significant issue is whether the patient can even afford to pick up their next prescription or instead choose to delay the refill due to other bills that need to be paid. This type of delay could be quickly life-threatening. These experts are convinced that Zoltenibart offers unique benefits, improved hemolysis control with convenient dosing that healthcare providers administer only four to six times per year, giving both the physician and the patient confidence that effective treatment is on board. They also emphasized Zoltenabart's expected improvement in the patient's experience and life, limiting the time that the patients are required to think about treatment with Zoltenabart to only a few occasions each year, really giving the patients a sense of empowerment over their disease by reducing PNH visibility and enabling those patients to almost forget about their PNH between infrequent Zoltenibar treatments. We're also advancing Zoltenibar for C3 glomerulopathy or C3G, an ultra-rare kidney disease commonly affecting children. Dosing is ongoing in our phase two study in this indication. We recently amended the protocol to expand the study population. We've added a treatment cohort of patients with normal plasma C3 levels, a group that is a substantial portion of the total C3G population. The phase two C3G trial requires enrollment of a relatively small number of patients, and assuming strong evidence of efficacy, we look forward to initiating our phase three program in C3G. As a reminder, Altena-Bart received a pediatric disease designation from FDA for the treatment of C3G. This designation can allow us to request a priority review voucher that can be used for a different product, cutting its review time to six months. The vouchers can also be transferred or sold and have had a recent market value of over $100 million per voucher. We're very excited about the potential for MAS3 inhibition in PNHC3G and a number of other indications involving the alternative pathway. And we are confident that CELTENABART's anticipated advantages, specifically more consistent efficacy, better safety, and superior dosing compliance and convenience with significantly lower treatment burden can effectively differentiate Sultenibar from other alternative pathway targeting therapeutics on the market or in development. Let's now look quickly at OMS1029, our next generation long-acting MASP2 inhibitor. Phase one clinical trial data make clear that OMS1029 can readily be dosed subcutaneously once every three months. providing a very convenient dosing regimen for chronic indications administered either in healthcare centers or at home. While our recent focus has been on narsoplumab and zeltenibar and deciding on next indications for each, we are also honing in on the first indication for Phase II development of OMS 1029. The product has already been manufactured and the quantity stored should be more than sufficient to support a Phase II trial. In addition to our antibody inhibitors of MASK2 and MASK3, progress continues on the development of potential drug candidates in our small molecule orally available MASK2 and MASK3 inhibitor programs. conclude our discussion on our franchise of complement therapeutics. Our studies continue with MASK2 inhibition in acute respiratory distress syndrome, or ARDS. We've generated compelling data in established animal models across all forms of severe ARDS, bacterial, viral, and chemical ARDS, and are awaiting completion of one additional study ongoing in animals infected with H5N1, avian influenza, or bird flu, which many experts believe will become the next life-threatening global pandemic. Once the results from the H5N1 study are available, we'll submit the already drafted manuscript broadly directed to narsoplimab benefits in ARDS for publication in a high-level peer-reviewed journal. Another publication we expect will be coming soon from Weill Cornell, which is focused on MASK2 inhibition's effects in long COVID. I'll turn now briefly to OMS 527, our PD7 inhibitor program aimed at treating addictions, compulsions, and movement disorders. OMF 527 is being developed for the treatment of cocaine use disorder at the request of and with funding from the National Institute on Drug Abuse or NIDA. As recently announced, we successfully completed drug-drug interaction safety studies where OMS 527 showed no enhancement of cocaine's detrimental effects. Instead, OMS 527 was beneficial to cocaine-administered animals. In view of this success, NIDA committed to fund $4 million for the upcoming year, which will fund the planned randomized double-blind parallel group inpatient Phase 1B clinical trial comparing the safety and efficacy of OMS-5272 placebo in the treatment of adults with cocaine use disorder. The preclinical, clinical, and mechanistic data generated to date suggests that our PD-7 inhibitor program could be effective in treating not just cocaine use disorder, but a broad range of addictions and compulsions. Work on the Phase 1B program is underway, and a preliminary data readout is targeted for year-end. We'll conclude today's review with our first-in-class therapeutic platform of molecular and cellular programs targeting a wide range of therapeutic areas, including cancer. Building on our understanding of immunity both innate and complement-mediated, and adaptive, meaning B cells as well as CD4 and CD8 T cells. Our objective is to move beyond existing targeted biologics, such as antibody drug conjugates, which have small therapeutic indexes and limited tissue penetrance, and to advance engineered cellular therapies, such as CAR T cells, which are expensive and time-consuming, these, again, we are planning to move beyond. To achieve this, we're developing a portfolio of next-generation biologics to treat cancer. Consists of new modalities of targeted drug conjugates with better therapeutic indexes and better tissue penetrance. which we expect will eventually sideline the current ADC technology. Our portfolio includes, in addition, an adoptive T cell technology combined with an immunostimulator that is easier, faster, and cheaper than current cellular therapy approaches. Our technology also maintains an enhanced anti-cancer immune response through subsequent repeat and simple therapeutic administrations. We're rapidly advancing our oncology programs and stealth development while we continue to build our intellectual property position. Over the past several months, we've sought the input and guidance of therapeutic area experts and advisors under confidentiality and have received a uniformly positive response. Our oncology platform is not our only stealth program. We're also developing and have created broad intellectual property around the program targeting the increasingly life-threatening challenges in infectious disease. We expect to be able to share our success publicly across both our oncology and infectious disease programs in the very near future. So with that, I will turn the call over to David.