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spk12: 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.
spk00: 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 note regarding forward-looking statements in the company's quarterly report on Form 10-Q, which was filed today with the SEC, and the risk factors section of the company's annual report on Form 10-K for a discussion of these risks and uncertainties. Now, I would like to turn the call over to Dr. Greg Dimopoulos, Chairman and CEO of Omero.
spk04: Thank you, Jennifer, and good afternoon, everyone. We appreciate you joining us for today's call. We'll start with a corporate update and an overview of our third quarter 2022 financial results, followed by a more detailed financial summary. Joining me on the call today are Mike Jacobson, Nadia Dock, Kathy Melfi, and Steve Whitaker, our respective heads of finance, commercial, regulatory, and clinical. Let's start with narsoplumab and transplant-associated thrombotic microangiopathy, or TATMA. We now have the decision from FDA's Office of New Drugs on our appeal of the Complete Response Letter, or CRL, that we earlier received from the Office of Cardiology, Nonmalignant Hematology, Endocrinology, and Nephrology. It proposes a path forward based on historical survival data. Specifically, the designer proposed a resubmission. That includes comparing response from our completed pivotal trial to a threshold derived from an independent literature analysis and evidence of increased survival from patients in our completed trial compared to an appropriate historical control group. It also notes that persuasive evidence of superior survival versus a well-matched historical control group could be sufficient, even in the absence of the independent literature analysis. Given its very recent receipt, we're working through the details of the decision with our team of regulatory and legal advisors. We will update our shareholders once we have completed our analysis and have determined our preferred path forward. Elsewhere in our narsoplimab development program, our Phase III Artemis IGAN trial evaluating narsoplimab for the treatment of IgA nephropathy remains on track to read out nine-month proteinuria data in mid-2023. For narsoplumab and acute and long COVID-19, discussions continue with the U.S. government regarding the preparedness strategy for current and potential future pandemics and upcoming funding pathways and programs. These represent multiple opportunities for both the COVID-related assays that we are developing, as well as for narsoplumab as a therapeutic for COVID-19 and potentially other severe infective diseases. In addition to our two recent peer-reviewed articles in Frontiers in Immunology and in the Journal of Clinical and Translational Medicine, we are preparing several manuscripts for publication further detailing the role of MASP2 in the lectin pathway across COVID-19 and a range of pulmonary diseases. Turning now to OMS 1029, This is our longer-acting next-generation antibody against MASP2. We're advancing through our single ascending dose phase one clinical trial, evaluating OMS1029 in healthy subjects, having now completed three of our six planned cohorts. The pharmacokinetic and pharmacodynamic data are right in line with our predictions. and the drug has been well tolerated with no safety concerns. Planned CMC toxicology and regulatory activities are also on track to enable initiation in mid-2023 of a phase one multiple ascending dose study of OMS 1029, which will then allow rapid progression into a variety of phase two indications currently under evaluation. We're planning for once monthly to once quarterly subcutaneous or intravenous administration for OMS 1029, which we expect will make it well-suited for chronic indications. Completing our MASP2 portfolio, we believe that we're closing in. on a lead development candidate for our small molecule MASP2 inhibitor. Data indicating whether we have been successful in our goal to identify a lead orally available compound is expected by year end. So let's now discuss the other major component of our complement portfolio, that being OMS906, our lead antibody targeting MASP3. As we have discussed previously, MAS3 is the key activator of the alternative pathway of complement. A phase 1B program is underway evaluating OMS906 in both raviolizumab-treated and treatment-naive TNH patients. Enrollment is on track to begin in December, and initial patient data are expected in the first quarter of 2023. Another OMS906 Phase 1B program is initiating in patients with C3 glomerulopathy. And data here are expected shortly after PNH data. The commercial opportunity for alternative pathway inhibitors is well established. We expect that OMS906 has a good likelihood of demonstrating significant advantages over other alternative pathway inhibitors on the market or in development. These advantages include decreased infection risk and a more convenient dosing profile with subcutaneous or intravenous administration as infrequent as once every several months. Another important advantage is that MAST3 does not appear to be an acute phase reactant. meaning that unlike other alternative pathway targets, the concentration of MASP3 does not increase in the setting of inflammation. This could prove to be a major advantage of OMS906 over other alternative pathway inhibitors whose targets are acute phase reactants. Those agents carry the risk of inadequate dosing during intercurrent inflammatory diseases or conditions such as infections or surgery, which can lead to the underlying disease breaking through the treatment. Because MAS3 is thought to be the only alternative pathway target that is not an acute phase reactant, OMS906 dosing can be stable, can remain stable, and is expected not to carry the risk of breakthrough of the underlying disease. The likely effectiveness of OMS906 was recently underscored by publicly reported results of a Phase III trial using either rabulizumab or eculizumab, each a C5 inhibitor, combined with iptacopan, a factor B inhibitor. Iptacopan has also been reported to successfully treat PNH in patients not receiving other complement inhibitors. The results in each population showed marked reduction of both intra- and extravascular hemolysis in PNH, overcoming the extravascular hemolysis caused by C5 inhibition alone. Remember that OMS 906 blocks the conversion of Profactor D to Factor D, which activates Factor B. So 906 alone would be expected to achieve results very similar to that reported by a cacopam for use either with a C5 inhibitor or alone. We look forward to sharing OMS 906 data in both PNH and C3 glomerulopathy soon. Let's turn now to financial results for the third quarter. To understand fully those results, I'll provide some important context by revisiting a bit of recent history. Last December, OMEROS completed the sale of its commercial ophthalmic product Omidria to Raynor Surgical. The transaction with Raynor required us to reclassify all historical Omidria revenue and expenses as discontinued operations, to record the present value of future estimated Omidria royalties as a contract royalty asset on our balance sheet, and to record the royalties earned as a reduction from the OMIDRIA contract royalty asset. Our royalty rate for U.S. net sales of OMIDRIA is currently 50%, which equates to nearly 80% of the total operating profit. Our loss for the current quarter was $17.5 million, or 28 cents per share. compared to $22.7 million or $0.36 per share in the third quarter of last year. Our non-cash expenses were $4.6 million or $0.07 per share for the current quarter and $6.4 million or $0.10 per share for the prior year quarter. Our total cash burn for the reporting quarter was $26.6 million, approximately $5 million of which were manufacturing costs. For the third quarter, our 50% royalty on RainerNet sales was $16.5 million. This is down slightly, approximately $700,000 from the second quarter due to the timing of wholesaler purchases leading into the July 4th holiday weekend. Rainer's gross to net discounts were consistent with those of the second quarter. And Rainer's third quarter unit sell-through to the ASCs and hospitals were in fact up 4% over the second quarter. Fourth quarter OMIDRIA sales are expected to show continued growth. As of September 30, 2022, we had $221 million of cash and investments on hand available to support ongoing operations. This includes the $125 million that we received from DRI Healthcare Trust in exchange for a relatively small portion of our expected future Omidria royalties. This royalty asset sale closed on September 30th. Under the terms of the agreement, DRI is paid solely out of the amidria royalties we receive from Raynor. The structure of the transaction is very favorable to Omeros. The potential maximum total royalties payable by Omeros to DRI through the full term 2030 of the agreement are $188 million. OMEROS's royalty payments to DRI are back-loaded. For example, the maximum royalty payment that could be received by DRI in 2022 is $1.7 million, rising to only $13 million in 2023. In fact, DRI does not have the potential to receive, in aggregate, $125 million, which is the amount equal to DRI's upfront payment to us until August of 2028. Further, the royalty amount to be paid by OMEROS to DRI in any given year is capped. If royalties paid by Raynor to OMEROS for any given year are less than that capped royalty amount to which DRI is entitled for that year, DRI absorbs the shortfall. OMEROS is not responsible for nor is DRI able to recoup or carry forward that shortfall amount to a subsequent year. So effectively, when we look at this, one can think of the agreement as resetting at the start of every year through the term of 2030. with the royalties to be paid by Omeros to DRI for that year limited to the capped amount originally specified in the DRI agreement, and any shortfall in Omeros' payments to DRI during the previous year being forgiven. In this way, the transaction shifts risk from Omeros to DRI. specifically shifting risk associated with Rainer's ability to generate the OMIDRIA royalty stream. For example, while unlikely to occur, the risk of lost royalties due to a product recall or the loss of separate payment for OMIDRIA is no longer solely borne by OMEROS. Rather, DRI would absorb the loss of any shortfall from the capped royalties to which they were otherwise entitled. Concurrent with offloading these risks, OMEROS received the upfront payment of $125 million and will continue to receive all royalties from Raynor in excess of OMEROS' annual capped payment to DRI. Those excess royalties that are nearer to OMEROS are expected to be substantial. Also, to be clear, this is an asset sale, not a loan. DRI has no recourse and no security interest in any of OMEROS's assets other than the annual capped royalties through 2030 as specified in the agreement. Because DRI receives only capped royalties and will not share in any upside in Omidria sales growth nor in any milestone payment by Rainer to Omeros triggered by achievement of long-term separate payment for Omidria, our accountants at Ernst & Young have advised that we record the already received $125 million upfront payment as a liability. This is consistent. with the accounting of nearly all other companies' recent asset sales. And Mike will provide additional details on this a little later in our call. The proceeds of the DRI transaction and our continued participation in the substantial OMIDRIA royalty stream provide us with financial flexibility. to address the late 2023 maturity of $95 million of our outstanding convertible notes in the manner best suited to market conditions and our business priorities as they evolve. We also have a $150 million at the market sales agreement, which for purposes of good housekeeping, we have just filed to keep effective. The ATM, of course, has not been used. Here are a couple of additional pieces of good news on Omidrea. Last week, CMS, or the Center for Medicare and Medicaid Services, released its 2023 final rule for the outpatient prospective payment system. In that rule, CMS reaffirmed Omidrea's qualification for separate payment when used as part of cataract or lens replacement surgery. in ambulatory surgery centers, or ASCs, under CMS's non-opioid surgical pain management policy. CMS reaffirmed this qualification for Omidria at least through 2023. Also, the Non-Opioids Prevents Addiction in the Nation Act, or the No Pain Act, is making good progress. with strong bipartisan and bicameral support that includes chairpersons and key members of relevant congressional committees. The bill now has half the Senate and 118 representatives as sponsors and cosponsors. The sponsors are optimistic that a vehicle for the bill will be available in the near future. The No Pain Act would provide separate payment for non-opioid pain management drugs like Omidria in both the ASC and hospital outpatient department settings for a renewable five-year period. Passage of the No Pain Act would trigger a $200 million milestone payment to Omeros from Raynor Surgical. The entirety of this milestone payment would belong to Omeros. because, as I mentioned earlier, this milestone is excluded from the DRI transaction. Let's now wrap up our program update with some of our other pipeline programs. Our PD7 inhibitor program, OMS 527, is the focus of discussions regarding third-party funding for continued development in the treatment of addictive disorders. OMF527 is also being evaluated at Emory University in primate models known to be clinically predictive for the treatment of L-DOPA induced dyskinesias. L-DOPA is the most widely used drug in the treatment of the roughly 10 million patients worldwide with Parkinson's disease. L-DOPA induced dyskinesias are the often severely severely disabling involuntary movements caused by L-DOPA, and more than 50% of Parkinson's patients develop these dyskinesias following extended treatment with L-DOPA. Preliminary data from Emory are encouraging, and we expect final data by year end. If these final findings hold, we're considering moving OMS 527 which already has successfully completed a Phase I clinical program into a Phase II trial in patients with L-DOPA-induced dyskinesias. That is a disorder with really no good treatment and one that represents a substantial unmet need. We'll close the update today on our programs with our immuno-oncology. efforts in which we are evaluating a number of novel approaches to treat cancers. These programs have grown out of our work from our GPCR program, specifically GPR174. In our immuno-oncology programs, we're advancing research on potential cellular and molecular therapies for cancers. On the cellular front, we're evaluating novel approaches for both CAR T and adoptive T cell therapies. We've identified pathways in T cells that limit their ability to kill specifically tumor cells. By using inhibitors of these pathways, we've significantly and preferentially enhanced the expansion of T cells that specifically recognize and efficiently kill tumor cells. An important problem that limits the efficacy of current adoptive T cell therapies is a lack of central memory phenotype, a phenotype specifically that sustains a robust immune response against the cancer and is crucial to prevent relapses. To overcome this issue, we've identified inhibitors that work by skewing T cells towards a memory T cell phenotype, endowing T cells with better fitness and sustained tumor killing functions. We continue to develop and validate our novel approach, and we believe that it could improve response rates for patients receiving either engineered or native T cell therapies for liquid or solid tumors. On the molecular front, we've developed novel biologics that could specifically target cancer cells and kill them directly or indirectly through potentiation of the immune system. Preliminary data on this front are also encouraging and will keep you updated as developments arise. Again, we expect to have updates later this year. I'll turn the call over now to Mike Jacobson, our Chief Accounting Officer, who will go through a more detailed discussion of our third quarter financial results, as well as more details on the DRI deal. Mike?
spk02: Yeah, thanks, Greg. As Greg briefly discussed, in December of last year, Raina required a mid-rate and associated business operations. The sale required us to restate our financial statements for all the prior periods, into continuing operations and discontinued operations. This means that for all of 2021, immediate revenue and operating expenses are shown in a single line on our income statement as discontinued operations. In addition, for 2022, any immediate related activities are also included in discontinued operations. All of our other activities are included in continuing operations. We receive royalties of 50% of the net sales of Amidria in the U.S. until the earlier of either January 1st, 2025, or the payment of the $200 million milestone. The milestone to be paid by Rainer in the event that a separate payment is secured for Amidria for a continuous period of at least four years. Thereafter, we'll receive a 30% royalty on U.S. net sales for the duration of the relevant patent terms, which extends to at least 2033. We will also receive a 50% royalty on any non-U.S. net sales of Omidria over the life of the relevant patents. From an overall standpoint, considering U.S. royalties and the reduction in our operating expenses, We received nearly 80% of the US operating profit when royalties are 50%, and then over 40% when the royalty is 30%. Looking or turning to our actual results, our net loss for the third quarter was $17.5 million, or $0.28 per share. This compares to a $30.8 million loss, or $0.49 per share, for the second quarter of this year. Our non-cash expenses for this quarter were $4.6 million, or $0.07 per share. As of September 30, 2022, we had $221 million of cash, cash equivalents, and short-term investments available for our general operations. This is a $98 million increase from June 30 of this year. Excluding the $125 million received from DRI, our decrease in cash and investments from the end of the second quarter was $26.6 million. We also have an at-the-market sales agreement that allows us to sell from time to time up to $150 million for common stock. As Greg discussed earlier, on September 30th, we entered into an agreement with DRI whereby we received $125 million upon closing. and are obligated to pay DRI up to $188 million out of the monthly royalties under MEDRIA net sales between September 1, 2022, and December 31, 2030. Monthly, as Rainer makes the royalty payments, DRI receives their predefined portion of the royalty payment, which is a prorated monthly portion of the annual royalty cap for the applicable year. we are entitled to any remaining royalties received. DRI is not entitled under the agreement to carry forward and later recoup any shortfall in the royalties received on our MEDRIA for any annual period or if or less than the cap amount applicable to that calendar year. In addition, DRI has no recourse to our assets other than our mid-year royalty receipts. As required under GAAP, we have recorded the $125 million received from DRI as a liability on our balance sheet rather than as a reduction in our mid-year contract royalty asset. As Greg mentioned, despite this being an asset sale without any recourse or securitization other than the predefined royalties owed, we are required to book the $125 million payment as a liability, the direct result of DRI's royalty payments being capped. We will record implied interest expense at 9.4% on the outstanding liability, and the implied interest expense will be recorded as a component of continuing operations in our income statement. The annual amounts that DRI is entitled to receive and additional details on the transaction are included in Note 8 in our quarterly TNQ filed earlier today. Cost and expenses from continual operations for the third quarter were $50.8 million, which is an increase of $13.3 million from the second quarter. The increase is primarily due to commercial narsopalmab drug substance manufactured in the third quarter, which we expensed as a research and development cost, given that we do not yet have FDA approval for narsopalmab. As we finalize our path forward for TA TMA, we continue to gauge our narsopalmab cells and marketing spend until the timing of FDA approval is clear. Interest expense for the third quarter was $5 million and consistent with the previous quarter. Now let's look at Omidria royalties. As I mentioned previously, royalties earned are recorded as a reduction in the Omidria contract royalty asset on our balance sheet. In the third quarter, actual royalties earned from Omidria sales was $16.5 million, which was a decrease of $700,000 from the second quarter. The decrease is due to the timing of the wholesaler purchases at the end of the second quarter, due to just when the 4th of July holiday hit. For the third quarter, actual mid-year unit sales purchased by the ASD and the hospitals increased 4% over second quarter purchases, while Rainer's gross to net discounts remained consistent. Discontinued operations include two key components, royalty interest income and periodic re-measurements to the immediate contract royalty asset. We recorded $37 million of income in discontinued operations in our third quarter income statement, recognizing for accounting purposes the $8 million of interest earned on the immediate contract royalty asset and $29 million in the re-measurement adjustments to the Amidria contract royalty asset, based primarily on the increase in Amidria sales that we're seeing. Now let's take a look at our expected quarter results. We expect overall operating costs from continual operations in the fourth quarter to decrease from the third quarter of 2022. As the supplement drug substance manufacturing for the year was completed, and expensed in the third quarter. Interest expense for the fourth quarter should be approximately $8 million. This is an increase of $3 million due to the transaction with DRI being accounted for as a liability. Income for discontinued operations should be in the $8 to $9 million range. With that, I'll turn the call back over to Greg.
spk12: all right thanks mike uh operator let's open uh the call to questions thank you at this time we will conduct the question and answer session as a reminder to ask a question you will need to press star 1 1 on your telephone and wait for your name to be announced please hold one moment for the first question Our first question comes from Colin Bristow with UBS.
spk07: Hey, good afternoon, and thanks for taking my question. So on the HSCT TMA indication, just curious, is there an outcome here where you would ultimately sort of abandon taking this forward? And then in terms of the comparable historic data set FDA wants us compared to, It seems likely that FDA presumably already performed some sort of similar internal literature review versus what they're asking you to do. I'm just curious, has FDA given any indication of this or the efficacy bar that it believes is the appropriate benchmark? Thanks.
spk04: Hi, Colin, and thanks for the questions. In answer to your first question, you know, look, we believe, as we have believed, since we've seen the data on this drug that this should be approved and warrants approval so with respect to abandoning that I mean that's really not not on the option table at this point I mean so I think that that answers that pretty clearly as of now with respect to your second question did FDA conduct research with an historic control group and may have some idea of the threshold that they're expecting. We have no indication of that, but can't speak for what FDA has done to that regard. I'll ask Steve or Kathy if they have any other views on that.
spk13: Excuse me, Greg, no, I don't know if FDA did anything, but it would surprise me if they had actually done an independent review. Okay, thank you. Thanks, Colin.
spk12: One moment for our next question. And our next question comes from Steve Brozak with WBB Securities.
spk03: Hey, good afternoon, Greg. Two questions. The first one, I'm not sure if you're aware, but it looks like there's been some negative voting on Beirut and how they were looking at their therapeutic on COVID. But one of the questions that popped up specifically around it was, a failure to understand mechanism of action. I'm not going to compare them to you because obviously it's completely different, but can you go and give us some, as much detail as possible on how comfortable you are with mechanism of action and specifically how that brought you into developing the diagnostic approach to understand what the markers, what the signals were and as much detail as you can give on that. And then I've got a follow-up question, please.
spk04: I'm sorry, Steve. You're asking about mechanism of action in TATMA or mechanism of action in COVID. I'm trying to make sure I answer your question.
spk03: Sorry, absolutely. Mechanism of action, as you understand, in COVID, and also how the companion diagnostic system you've set up plays into this information. not just what you've done, but what other people have written about it. And I've got one follow-up afterwards, please.
spk04: Sure. And I heard you say you would like that in as much detail as possible. I think, you know, the details are well published on this, not only in our publication, so in the publication in Frontiers in Immunology, also the publication that the – the manuscript published in Clinical and Translational Medicine, I think, lays out the mechanism pretty clearly, as does the first publication that covered the response to narsoplimab in severe COVID patients treated in Bergamo. Yeah, I will hit this, I think, at a very high level since that's all been well documented. But the bottom line is that COVID-19 is an endothelial injury. And that is the same as what we're seeing in TATMA. We have data. We have clinical data. You have published data from Bergamot. You have a standard of care controlled double-blind study out of I-SPI where narsoplumab showed the greatest benefit to survival reported by the I-SPI group despite the challenges sort of aligned against narsoplumab in that study. You also have in vivo, so models of animal models of COVID-19. You have data showing very clearly when you're getting into the assays that it is lectin pathway hyperactivation. that is the driver in COVID-19. That lectin pathway hyperactivation results in a consumptive hypo complementemia. And that hypo complementemia then renders the adaptive immune response dysfunctional or non-functional. And that is likely the cause of secondary infection in COVID. And we know very clearly, looking clinically, that treatment with narsoplimab within one to two doses reverses that hypo-complementemia. So normalizes the complement profile and restores the adaptive immune response. All of that's been well-published, well-documented. The extension to long COVID is there as well in that the same hyperactivation of the lectin pathway is seen based on our data now looking at close to 1,000 patients. We see the same thing. in about 25 to 30% of patients with long COVID. So I don't know if, I mean, you know, that's a lot of detail, maybe more than you wanted, or maybe it's less than you were actually looking for. But I think in the interest of time, let me hold there and, you know, again, point you to the publication. Got it. All right.
spk03: Look, that actually is a great segue. And the secret in life is not doing too much, not doing too little, doing it just right, which is what you just did. But all kidding aside, FDA obviously came back and said that they wanted to have a literature, a review on the literature side. Now, one of the things that we look at is that, candidly, literature doesn't spring up all by itself. It is influenced, it is directed, it is created by the KOLs who take the time and are familiar with the subject matter. How would you position narseplumab with the KOLs that have worked with you, the hematological oncologists that are specific? And now I'm talking about stem cell TMA-related narseplumab use. How would you position them in terms of uh advocacy and an explanation of the the value of narsupplamab in terms of what the fda would be looking at into the future and i'll i'll hop back in the queue on that after that thank you hi i'm i think i understand the question i mean look uh we have strong advocacy
spk04: within the expert community, so within the community of stem cell transplanters who treat, well, number one, who perform this very rare procedure, and then as part of that management of the procedure and the post-procedural complications, treat TATMA. We have, as I said, very strong advocacy. You just need to look at the publication in the Journal of Clinical Oncology, which is really, I believe, the highest-ranked journal in oncology. I think the index factor on that one is about 55. You look at the author list, and I think that answers a lot about the advocacy. How we would, how they would help us going forward with FDA? You know, look, haven't thought through that part. We've just received this decision from FDA. We really need to digest it. We wanted to make it available for shareholders right away, but we've got a lot of work still to do as we digest it, work with our advisors to figure out how to most effectively and most expeditiously get narsoplumab approved for this indication. So, again, let me hold there and see if that answered your question.
spk03: Yes. Yes, it did. Thanks. Let me hop back in the queue. Thank you.
spk12: Okay. Thanks. One moment for our next question. And our next question comes from Eric Joseph with JP Morgan.
spk09: Hi, thanks for taking the question. If FDA, on TMA with Nersoplimab, if FDA wants to see survival benefit in a matched historical patient population, do you have a sense of the minimum benefit in survival you would have the power to detect, given sort of the conservative sizing of your study population? And then on IGAN with Phase 3 Artemis, You noted that enrollment's ongoing and you have a nine-month readout expected mid-year. Can you just clarify how close you are to full study enrollment? And do you expect the study to maintain adequate powering to detect a difference in protein area when you read out next year? Thanks.
spk04: Yeah, with respect to what would be the minimum threshold that FDA would want to see with respect to narsoplimab survival benefit relative to historical control. We haven't had a chance to discuss that with FDA. We know that what we've seen with narsoplimab clearly exceeds, particularly given the severity of the patients that we treated with narsoplimab, clearly exceeds what's in the literature, and we think that likely the literature is reflective and frankly likely over reflective of what is happening in the real world just given publication bias, which would usually don't publish negative data as you know. So if anything, it's an overstatement. But the mortality benefit or the survival benefit that we have seen with narsoplimab we think is quite substantial. With respect to your second question on the IGAN trial study enrollment powering, we've powered that at 90%. And our enrollment is wrapping up, and we believe, as I said, we're on track for mid-2023 top-line data. I mean, Steve, do you have any other comments or more color you can give to that?
spk13: I don't think so, Greg. We powered at 90%, and we did it conservatively, and we will have data in
spk04: mid 2023 with our nine point I'm sorry our nine million point right to be clear those are the longer term EGFR data as we've been very clear the data that we are looking for in mid 2023 are our 36 month 36 week protein area data
spk09: So just to clarify that, if I could, you're not necessarily going to have enrolled the full 450 patients per the clinical trials entry to be sufficiently powered for proteinuria.
spk04: No, the sufficient proteinuria powering is not based on the 450 patients, Eric. It's based at 90%. percent confidence is based at effectively about 60 percent of that. Is that correct, Steve? And the 450 is the power needed for all patients with the EGFR endpoint. So I think you may be conflating those two numbers.
spk09: That's very helpful. Appreciate it.
spk04: Yeah. Okay, great. Thank you.
spk12: One moment for our next question. And our next question comes from Greg Harrison with Bank of America.
spk06: Hi there. This is Mary Kate. I'm for Greg. Thanks for taking our questions. Regarding the updates expected at ASH, including the trial designs of the phase two study in pediatrics, maybe what differences should we keep in mind as you evaluate narsopimab in pediatric patients? And do you expect a similar impact in this population? Thank you.
spk04: Yeah, let me turn that over to Steve Whitaker. Steve, can you address that?
spk13: Sure. We would expect a similar treatment effect in the pediatric population. Pediatric studies tend to be smaller than the adult studies. And The study will be similar to that, which we ran a single-arm study. There will be a chart review historical control associated with it for the MAA, which we do not have to finish this prior to the MAA. Let me just make that clear. But we did have agreement with the pediatric committee of the EMA.
spk04: Does that help, Mary?
spk06: Yeah, that's great. Thank you.
spk04: Okay.
spk12: Want to look for our next question?
spk04: I might add one point on the pediatric, which is that pediatric patients tend to do better with TMA following transplant than do adults. It's almost as if they're two different populations. One is the resiliency, I think, of children as a cause. The other is the diseases in the children for which they undergo transplant are often not as lethal as are those in the adult population.
spk12: And our next question comes from Brandon Foulkes with Kantor.
spk01: Hi, thanks for taking my question. Greg, maybe just a point of, not clarification, but in terms of when you say you're considering your options to address the path that the FDA put out there with this historical control and independent literature analysis, are you considering options to address that in particular, or may you be considering broader options as well on NOSOP and the TATMS?
spk04: Yeah. Hi, Brandon. Thanks for the question. With respect to the options that we're considering, you know, certainly we're looking, we're considering a broad range of options. With respect to historical control, we think that that is a very doable option, one that can be addressed. We need to sort through how best to do that. But I think in answer to your question, if I caught it, some of it was dropping away on our end. I think we had a little bit of a breakup electronically here. But I think if I'm answering your question, we're also looking at what we can do more broadly. And let me turn to Kathy, our head of regulatory, and see if anything you want to add there, Kathy.
spk10: Sure, Greg. And as Greg mentioned before, we will be going back to FDA to discuss the outcomes, and as we always do, to reach agreement with them on what is expected and what we need to do. So, again, as Greg also mentioned, we're still sorting through this and our options, but we'll plan to put together what we think is a very robust proposal, whatever that may look like, and go to the FDA with it.
spk04: Yeah, you know, obviously, Brandon, the objective is get the drug approved as quickly as possible. There's no approved treatment. Patients need it. We're hearing that from the physicians. We're hearing that from the physicians who have used it. You know, even those who were initially sort of non-believers who have now used it and are believers as the result of compassionate use, you know, I think there's a clear need And this is why we're committed to getting this approved as quickly as possible.
spk12: One moment for our next question. And our next question comes from Serge Ballinger with Needham.
spk11: Hi, good afternoon. Hi. Just a couple questions on the recent OND decision and their proposed path to resubmit the BLA. If I recall, up to early 2019, the pivotal study for nisipumab and HFCT-TNA had a primary endpoint of a mortality comparison to historically matched controls. Just curious. If the data the FDA is looking for is similar to what you were already doing as part of the trial, and I guess in hindsight, why was that endpoint modified back then?
spk04: Thanks. Thanks. Appreciate the question, Serge. Yes, you're correct. We had initially proposed just what you identified. which was an historical control. And using survival as the primary endpoint with an historical control. The division rejected that proposal and instead asked for a response-based endpoint with a threshold to exceed. And I think you're probably correct around the dates as well. I'd have to go back and specifically look. But yeah, I think you sound like you're up to speed on that. So I'll take your word on the dates. But yes, you are correct. So we had initially proposed sort of just what we're seeing now as the option going forward or as an option going forward. And yes, FDA had requested that we instead pursue a response-based endpoint with a threshold to exceed. And together with FDA, we developed that response-based endpoint. Does that answer your question?
spk11: Well, I guess the proposed path that was elucidated in their denial a couple days ago, how close is it to what you were already doing as a secondary endpoint in that pivotal study?
spk04: I think it is, I think it is, I think it's very close. I mean, it's, I think, as we read it it's effectively the uh the same thing uh okay with with the historical control so uh which is what initially was uh proposed by america so yes uh i think you know again uh we were very willing to do it at that time i think we're we're you know obviously able uh to to undertake that uh that right now and in the same with the same approach that uh that we were proposing as you said uh several years ago got it thank you okay i would now like it to turn it back to dr demopolis for closing comments All right. Thank you, operator. And then thanks to all of the folks with the questions. They were on point and we appreciate them. Again, want to thank everyone for joining the call today. We'll continue to keep you updated on our progress. I know that everyone's very focused on on this route forward with narsoplimab and tatma we can assure you we're we're working very hard on that and we'll have updates as we have more information for you i think the the coming year frankly the rest of 2022 and the and the coming year holds some really we think exciting milestones for the company. And we'll let you know how all of those go. As always, we appreciate your continued support. And all please have a good evening. Thanks again.
spk12: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
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