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spk06: future business prospects, or future events or plans are forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions, actual outcomes and results are subject to risk and uncertainties that could differ materially from those forecast due to the impact of many factors beyond the control of the collector. The company assumes no obligation to update or supplement any forward-looking statements, whether as a result of new information, future events, or otherwise. Participants are directed to the cautionary notes set forth in the press release, which is available on the investor relations portion of the company's website, as well as the risk factors set forth in selectors annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward-looking statements. At this time, I would like to turn the call over to Jim Caruso, President and Chief Executive Officer of Selector. Mr. Caruso, please go ahead.
spk12: Thank you, Operator, and good morning, everyone. It is my pleasure to be here with you provide a corporate update for our second quarter of 2024. With me today are Dr. Andrei Shustov, Senior Vice President, Medical, Jared Longcore, Chief Operating Officer, Shane Lee, Chief Commercial Officer, and Chad Colleen, Chief Financial Officer. I will begin today with a brief recap of our progress over the past quarter and discuss anticipated near-term milestones. I will then ask Chad to provide an update on our financials. Andre will follow with additional insights regarding our Clover Wham pivotal study, followed by Jared, who will provide an operations update on the regulatory front and manufacturing. Finally, Shane will review our commercial progress. We will then open the call for Q&A. As you are likely aware, on July 23rd, we announced our full data results from our pivotal trial in WM, which were truly impressive and maintained the potential to meaningfully improve upon the current standard of care in WM. Andre will talk to you the quality of the data in an extremely challenging patient population. However, I'd like to emphasize to everyone that the patients in the clinical trial were by far the most refractory ever studied in this indication, with iaprofessine I-131 representing the fifth median line treatment. It is therefore impressive to observe comparable results obtained in Clover Wham to those reported in first and second line with other treatments. Of course, our near-term organizational focus remains locked on Iopopacin's WM regulatory and commercial objectives. Iopopacin has also demonstrated utility in other hematologic indications, such as relapsed refractory multiple myeloma and DLBCL. And clinical development is ongoing in our Phase 1b for pediatric high-grade gliomas. As you may recall, we initiated and enrolled the first patient in this Phase 1b study earlier this year. With iapofasine's ability to cross the blood-brain barrier, we remain excited about the potential it may provide in this high unmet medical need treatment setting. We plan to provide a study update in the second half of this year. Beyond iaproposine, our PDC platform continues to serve as the backbone to our radiotherapeutic franchise. We have now successfully conjugated nearly all available isotopes with our platform, including beta, OG, and alpha emitters, and have completed extensive preclinical proof of concept work in each area. We are currently advancing one of our actinium-based conjugates through IND enabling studies in preparation for a phase one in solid tumors. We continue to focus on completing the work for our NDA filing with plans to submit our filing to the FDA in the fourth quarter. Assuming we are granted priority review associated with our fast track designation, we expect a six month review. Finally, prior to turning the call to Chad for greater detail, I would like to emphasize that the 8K filed this past Friday, indicating that we are in process of restating our recent historical financial statements, although unfortunate, does not impact cash or cash burn, and the changes to historical earnings will all be non-operating and non-cash. Chad?
spk03: Thank you, Jim. Our cash and cash equivalence balance as of June 30, 2024, $25.9 million compared to $9.6 million as of December 31, 2023. Note that at the end of the first quarter, we had a cash balance of $40 million, resulting in the net cash used in operating activities during the second quarter being approximately $14.1 million. In addition to the cash on hand at the end of June, in July, nearly all of the investors from the September 2023 financing exercised their tranche fee warrants at a reduced as converted common stock price of $2.52 per share. Those investors who exercised their tranche fee warrants also received new warrants as part of the transaction, which generated gross upfront proceeds of approximately $19.4 million before customary expenses and fees. The company believes its cash on hand, inclusive of the July warrant exercised proceeds, adequate to fund budgeted operations into the second quarter of 2025. The three warrant tranches issued last month provide potential additional funding based upon their respective expiration dates, which occur with a first tranche of approximately $17 million after we receive a PDUFA date from the FDA. a second tranche of approximately $32.9 million after we receive approval of Hypopathy in I-131 from the FDA, and a third tranche of approximately $23.5 million after the first quarter in which we generate $10 million in revenue from Hypopathy in I-131. Assuming our discussions with the FDA go as planned, this funding would get SelectR to the point where we will be cash flow positive. Turning back to the second quarter, R&D expense was approximately $8.2 million compared to $6.3 million in the second quarter of 2023. The increase is largely driven by the timing of expenditures for our WM pivotal trial to support patients' final visits and perform the extensive analytical work necessary to complete the NDA submission. We have also continued investing substantially in our product sourcing, manufacturing, and logistics infrastructure by developing multiple sources for each aspect of Hypopathy production. G&A expense for the second quarter of 2024 was $6.4 million compared to $2.0 million last year. This incremental spend is focused on the establishment of the necessary commercialization capabilities to support product sales upon our expected 2025 NDA approval. As Jim stated earlier, we filed an AK with the SEC indicating that we are in the process of restating our historical financial statements for fiscal years 2022 and 2023 in the first quarter of this year. This was precipitated by a reevaluation of the accounting for the warrants issued in October 2022. At the time they were issued, the warrants were classified as equity. This was based on our assessment, which was supported by third-party expert evaluation. We now believe they should be classified as liabilities, necessitating a revision in our historical reporting. While previously reported earnings will be modified, the restatement does not impact cash or cash burn, and the changes to historical earnings will all be non-operating and non-cash. The work required to restate the historical results is in process and must be completed before we can file Section 10Q. which delays the 10Q filing. We're performing this work as rapidly as possible, and while we do not have a definite target date for completion, we expect it will take approximately six weeks. With that, I will now turn the call over to Andre.
spk02: Thank you, Chad, and good morning, everyone. Recently, we provided an update on the top-line results from our pivotal global WEM study that is fully enrolled with all living patients who have completed study treatment remaining in long-term follow-up. There are 65 patients in the safety data set defined as all patients receiving at least one dose of ayurvedic in I-131, and there are 55 patients who met the criteria for inclusion in the efficacy evaluable set defined as all patients who have received at least 60 millikurie total administered dose and have undergone at least one response assessment. The response rates and safety data discussed today are as of May 31st, 2024 data cutoff date. As a reminder, CLOA-WAM is a global, single-arm, Phase IIb study examining hypoxin I131 in relapsed and refractory patients who have received at least two prior lines of therapy, including those patients who failed or had suboptimal response to BTKI, the only FDA-approved class of treatment for this cancer. Study patients received a total of four doses of apophysin I-131 over two cycles without maintenance or retreatment and were evaluated for response at regular protocol-defined intervals using standard IWWM criteria. As Jim stated, patients enrolled in ClovoVamp were the most heavily pretreated and the most refractory WM patient population ever reported in clinical trials. Please allow me to review a few key patient and disease characteristics. The median age was 70 years, with oldest enrolled patient aged 88 years. The median number of prior therapy was four, with a range from two to 14. 71% of patients were previously treated with BTKI, 91% were treated with rituximab, and 84% received prior multi-agent chemotherapy. Over 90% of patients were refractory to at least one class of drugs, with refractories to BTKI reported in 67%, to rituximab in 60%, and to chemotherapy in 56% of patients exposed to those treatments. 40% of all patients in efficacy set were considered dual-class refractory, including BTKI and rituximab, and 27% were triple-class refractory, including BTKI, rituximab, and chemotherapy. Further, more than half or 55% of global WEM patients in the efficacy-valuable set were considered median or high-risk based on ITSS WEM score, which is a recognized negative prognostic factor for progression-free survival and overall survival in WEM patients treated with available therapies. Finally, Approximately 30% were found to have wild-type mighty ADA gene, a known genomic factor confirmed resistance to BTKI therapy. Now, let me briefly review key efficacy results. Hypophycin I131 demonstrated an impressive and clinically relevant 80% overall response rate and 98.2% clinical benefit rate. This is highly meaningful for this elderly patient population with an incurable malignancy. For these patients, any reduction in tumor burden or even disease stability brings clinical benefit, improves symptoms, and extends progression-free survival and time-off treatment. The major response rate, defined as partial response or better, was 56.4%, significantly exceeding the protocol-defined primary endpoint statistical hurdle of 20%. We're also excited to report that in line with our previous observation and reported trends in late responses after apophysin therapy, an additional partial response was registered after the latest data cutoff, effectively bringing the MRR to 58.2%. As follow-up of study patient continues, we might expect further improvement in major response rate due to delayed responses. Further, the data show the 7.3% complete response or very good partial response rate in a patient population in which CRs have not been previously observed or reported. I would also like to highlight the observed high response rate to hypofysin in highly refractory and challenging to treat patient subpopulations. First, among patients with mighty 88 wild type tumors that are inherently resistant to BTKI therapy, the overall response rate was 81%. And among those previously treated with BTKI, the overall response rate was 72%. In patients with tumors refractory to both BTKI and rituximab or dual refractory, the overall response rate was 65%. And in those with tumors refractory to BTKI, rituximab, and multiple chemotherapy agents or triple refractory, which are the patients with no available treatment options, the overall response rate was 54%. Seeing these rate of responses in highly refractory patient population is very impressive, and we believe it positions ipophysin as the standard of care for relapsed refractory patients and for development in earlier lines of therapy. The duration of clinical benefit is critical for elderly patients with WM. The treatment-free survival enabled by ipophysin I-131 fixed course of therapy is in sharp contrast with continuous or maintenance therapy approaches currently utilized with FDA-approved agents and significantly improves patients' quality of life. Durability of responses in Cloverweb were assessed on 41 overall responders and 26 major responders at the data cutoff date on March 7, 2024, with a median follow-up of 8.8 months. that did not include four additional overall responses and five additional major responses recorded at the latest cutoff date of May 31st, 2024. The median duration of response and median progression-free survival were not reached, with an estimated 72% of patients with overall response and 78% of patients with major response remaining progression-free at 18 months. This is in sharp contrast with our findings using data extracted from community-based oncology providers indicating that among those approximately 10% responders in third-plus line of therapy, the duration of response is expected to be around six months. We anticipate that as our data matures, the durability enabled by both the 80% overall response and a 58% major response rate will continue to improve and position ayopophicin as an attractive option in WL treatment landscape, assuming FDA approval. To put Clover Wham efficacy results into clinical practice perspective, it is our belief that while MRR is an important endpoint that satisfies the study primary objective threshold and positions ayopophicin favorably for regulatory approval, and the VGPR-CR are important research endpoints that supports hypofascin as disease-modifying therapy. It is the overall response rate and clinical benefit rate combined with impressive durability and time of treatment that will drive treatment decisions in favor of hypofascin in the management of this challenging patient population. Hypophasin I-131 was well tolerated in this vulnerable elderly patient population possessing multiple age-related comorbidities with their bone marrow compromised by cancer and multiple prior toxic therapies. The observed safety profile remains consistent with previously reported data. Grade 3 or higher treatment emerged in adverse events occurring in more than 10% of patients in a safety population with an N of 65 were thrombocytopenia, 80%, neutropenia, 69.2%, anemia, 44.6%, lymphopenia, 13%, and all infection, 12.3%. There were no reported opportunistic or invasive fungal infections observed in the study patients. In the entirety of the study, there was only one AE-related death reported in a safety set, and it was from infection. Importantly, unlike other WM therapies, iapophysin demonstrated negligible off-target effect on solid organ systems. Patients did not experience cardiovascular, pulmonary, neurologic, renal, or liver toxicities, which lead to treatment discontinuation with other available therapies in a significant proportion of patients. To put ClovoGram safety results into clinical practice perspective, Observed cytopenias are consistent with the age-related physiologic loss of marrow function, cumulative amount of prior myosuppressive therapies, and the degree of pre-existing inflammatory marrow suppression due to high disease burden in ClovoM patients. Two mid-cycle cytopenia occurrences were transitory and well-managed. The cytopenias recovered with standard supportive care in all patients, within a median two to four weeks of the nadir. Further, despite the high rate and degree of thrombocytopenia, there are no clinically significant or life-threatening bleeding events in the study. Notably, the low rate of serious infections in Clover-Webb study patients with known immunosuppressive effect of underlying malignancy and from prior therapies is encouraging in the context of severely immunocompromised patients. Effective management of cytopenias and prophylaxis of infections attests to understanding and comfort of hematologic oncologists managing these patients both in an academic setting and in a community. It is also important to point out that with continuous treatment therapies, adverse events such as cardiotoxicity or peripheral neuropathies must be managed over the entire course of treatment or until therapy is discontinued for lack of effectiveness or intolerance with other agents. In summary, ClovoM was the largest study in relapsed refractory post-BTKI patients to date and the first WM study to evaluate dual refractory and all-class refractory patient populations. We believe that achieving an 80% overall response rate and 58.2% major response rate updated after the latest data cutoff with the previously noted durability is nothing short of remarkable, especially with a demonstrated favorable safety profile. The four-dose truly fixed duration course of treatment and prolonged treatment-free interval will provide clinically significant and meaningful benefit for elderly patients with an incurable lifelong malignancy. we also anticipate that the data will continue to mature favorably. To conclude, we believe that based on the demonstrated global WEM study results, hypofascin has the potential to become first-in-class and best-in-class radiotherapeutic agent to address the high clinical need for WEM patients. With that, I will turn the call to Jared.
spk10: Thank you, Andrei. As Andrei described, Our clinical data from the Clover-WAM study continues to be quite impressive and improves with time. We remain actively engaged in the review, quote-unquote, cleaning and prepping of the Clover-WAM pivotal study data for the near-term NDA submission. As you are aware, the NDA submission process requires relentless attention to detail and is a time-consuming project. For your background, the thousands of patient data points collected over the course of the study must be validated and verified. This is a process called data cleaning, which also includes identifying and correcting any data entry errors. Once this process is complete, the database is locked and the final study data sets can be produced for the NDA. This information is required for the completion of the clinical study report and the clinical sections of the NDA submissions. We are expediting this process by performing several of these activities in parallel. For example, as a subset of the data is cleaned and finalized, we use this data to complete required sections in both the clinical study report and the NDA, rather than waiting for the entirety of the data to be finalized. This allows us to shorten the traditional timelines of approximately six to eight months of final study results to a submission to a submission around four to six months to that submission timeline. In addition to these activities, we continue to work closely with the FDA to ensure our submission meets all requirements. Planned remaining FDA interactions prior to the final submission include the determination of the potential need for a confirmatory study, and should the FDA require one, agreement on the design of the confirmatory study and the pre-NDA meeting with submission plan for Q4 2024. Shifting now to the supply chain, our supply chain and logistics for radiopharmaceuticals have been a challenge for some organizations. There are essentially three main components to the manufacture and supply of radiopharmaceuticals. First, the isotope. Second, the carrier or targeting ligand. And third, the combined finished product. Due to the infrastructure and specialized facilities necessary to produce radioactive isotopes, both the sites of production and supply of these isotopes are limited. Whether it's iodine-131 or actinium-225, there are selected sources globally. At Selectar, we have adopted a strategy to contract with suppliers of the isotope directly and to establish these relationships early in our drug development process. As discussed previously for iapovacine I-131, which utilizes iodine-131, We have contracted with and validated three separate suppliers and continue to assess additional suppliers. Our current partners provide redundancy in the isotope supply to allow uninterrupted production of iaproxen I-131 either weekly or multiple times a week. The same model is being employed for our Actinium program. We are partnering with both existing and future suppliers of Actinium, which will provide sufficient supply of Actinium throughout the drug development process and into commercialization. This approach can be employed for a variety of radioisotopes, whether they are alpha, beta, or OG emitting. The second key component is our targeting ligand, or PLE, which is the basis of our NavVol platform. Similar to the isotope sourcing strategy, we validated and secured sourcing from multiple contractors. Currently, a single targeting ligand batch produces enough of the targeting ligand to allow for greater than a three-year supply of Iopopocene I-131 at maximum forecasted sales volumes and would support at least one other program with the capacity to increase supply as needed. Finally, we're also multi-sourcing Iopopocene I-131 as the fully finished, ready-to-use product. We currently have two production sites in North America that can supply approximately 200 patient doses per week at current capacity with the capability to scale to nearly 1,000 weekly doses. In addition to supplying our finished product requirements, our outsourcing model provides additional benefits. One, we have significantly reduced the capital expenditure and future maintenance costs associated with an internal manufacturing capability. Second, we have demonstrated the ability to complete the IFOC and I-131 technology transfer in timely and efficient process to multiple sites, which allows for the rapid transition into another organization's manufacturing facility as needed. In addition to addressing potential production constraints unique to radiopharmaceuticals, we have taken a similar approach to addressing potential issues with logistics. We have developed a novel formulation for IFOC and I-131 that provides a 17-day shelf life once produced, This unique advantage via Pocosin I-131 provides physicians and patients with greater treatment schedule flexibility and a likely reduction in drug wastage, resulting in a lower total cost of treatment to the healthcare system. Additionally, like our approach with sourcing of manufacturing materials, we have partnered with multiple logistics and shipping organizations to ensure global delivery to the treatment sites within 48 to 72 hours of production, ensuring a minimum of 14 days and a maximum of 16 days to dose a patient. As described, we have built a robust and redundant supply chain that allows us to meet the finished product requirements for IFOVC and I-131 today and into the future. Additionally, this modular outsourced model is being replicated for other radiotherapeutic programs, like our Actinian program, to ensure clinical research and commercialization supply as needed. I will now turn the call to Shane for the commercial update. Shane?
spk04: Thank you, Jared. Good morning, everyone. I'm excited to share our commercial planning progress regarding the product launch of iapofasine in Waterstones Macroglobulinemia, or WM. We continue to make significant advances in our commercial capabilities and understanding of the WM market dynamics, which, along with the highly scalable nature of the market, will allow our team to capture the WM opportunity with a focused and efficient commercialization model. As previously noted, WM is a rare type of non-Hodgkin's lymphoma with a prevalence of approximately 26,000 patients in the U.S. Of these, about 80% are currently receiving active treatment. The market is highly concentrated with 80% of the opportunity located in just 15 states. We plan to pursue a relapse or refractory indication, which has an estimated population of approximately 11,500 patients. We have also built conservative plans with a base case indication assumption for the third line plus setting, which represents an addressable population of 5,700 patients who could benefit from myoporphysine therapy. Of these, approximately 4,700 patients are currently receiving third line plus therapy, and approximately 1,000 patients have exhausted all treatment options, leaving them an acute need for new therapy. Additionally, there are approximately 2,200 new third-line plus patients each year, which means that 2,200 additional patients advance into the third-line plus treatment setting annually. Our base case assumption provides a significant iapophysine market opportunity in terms of the total addressable population and the likelihood of orphan drug pricing. Importantly, there is a significant unmet need in the third-line plus settings. with only approximately 10% of third-line plus patients achieving a major response, and the duration of response for these one in 10 patients is approximately six months. Moreover, 60% of the drugs utilized in this setting are non-FDA approved, which means limited competitive promotional activity and a low share of voice. It is also notable that as a result of limited treatment options, approximately 50% of patients are treated with a therapy they received in an earlier line. We recently completed additional third-party research evaluating the profile of ibuprofen in WM. The key findings from this research demonstrated that WM treaters acknowledged the urgent need for more effective treatments, new mechanisms of action. The WM treaters also emphasized the importance of achieving durable responses and maintaining a high quality of life for patients with the primary treatment goal of reducing IgM levels. We also observed an interesting finding that there was a lack of consistency in treatment goals amongst hematologists because of the heterogeneity of disease. In other words, most therapies are limited in clinical benefit based on patient characteristics. Therefore, this created lack of consistency with treatment approach and outcome based on the limitations of existing therapies. The same hematologist participants also reviewed the Iopovacine product profile and provided a highly positive rating, acknowledging that iapofasine addresses key treatment goals and existing unmet needs, while highlighting the fixed course of therapy. Hematologists were very encouraged by iapofasine's results in such a difficult patient population, noting its potential to treat the broad WM patient population, which contrasts with existing therapies. Iapofasine's efficacy and unique mechanism of action were highlighted as key differentiators for its use in WM. We were encouraged by this research supporting our belief that iapofasine will be highly differentiated to address the clear unmet need in WM, providing durable, meaningful responses regardless of patient characteristics with a fixed course of therapy, thereby simplifying the treatment process for providers and patients. In conclusion, our commercialization efforts are advancing steadily support the potential U.S. launch of iapofasine in WM. The research findings underscore significant unmet need and the potential impact of iapofasine for the treatment of WM. We are confident that iapofasine's unique profile and demonstrated efficacy will address the critical needs of WM patients and provide a much-needed new treatment option with a potential FDA approval. I will now turn the call back over to Jim Caruso for closing remarks.
spk12: Thank you, Shane. It certainly remains an exciting time for us at Selectar, with a potential approval for IOPOFA C9131 on the horizon, coupled with our unique delivery platform providing differentiated radioisotope offerings. We are confident in our market position and excited about our future. We look forward to our meaningful milestones in the second half of this year, positioning us for further advancements and real growth as a company. With that, I would now like to open the call for Q&A. Operator?
spk06: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the number one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the number two. If you are using a speakerphone, Please leave the handset before pressing any keys. One moment, please, for your first question. And your first question comes from Jonathan Ashkoff of Roth. Please go ahead. Your line is open.
spk08: Thank you. Good morning, guys. I think I might have missed a couple of numbers you were throwing out there. Do you have a new major response rate of 58 point something?
spk12: That is correct, Jonathan. With the latest data cut, it's now 58.2%. And I think Andre can talk to, you know, one of the reasons why, you know, we see consistent improvement over time with iapofasine for these patients.
spk08: And that's based on what?
spk12: Thank you, Jonathan.
spk08: Or you can say that. It's based on what? Yeah, the patient N.
spk02: So we have, Jonathan, good morning, under here. So we have 55 patients in the efficacy-available set, and as Jim pointed out, after the most recent data cutoff, we just registered another late response, effectively bringing the MRR rate to 58.2%. We also expect that we might see additional major responses based on our prior observation that we demonstrated or reported in January, that responses can occur as late as six months after receiving therapy. So we would not be surprised and we actually anticipate that we might have additional major responses as follow-up continues.
spk08: Okay, that's very helpful. Chad, can you help us out a little closer on even if it's just the bottom result for the quarter, meaning the net income, and can you help us out on a share count and whether that's a time point or a weighted average?
spk03: So I can't provide a net income at this point, Jonathan, because the restatement has to be brought all the way forward. The evaluation needs to be done on a quarter-by-quarter basis to do that. That's why we didn't provide it in the comments, unfortunately. We simply need to work through that before we can essentially publish that information. So my apologies there. We did obviously provide operating expenses, but the non-operating components need to be further sanitized.
spk08: And how about the share count?
spk11: So on the share front, yes.
spk03: I think the expectation is we're going to get an 8K published on that because I want to essentially publish the entire cap table, and so that is forthcoming. You should have that in the very near future.
spk08: Okay, that's helpful. This is also something I may have missed, but when will your HGG – data come out, your next data set for that, and how's about starting the timing for phase one for the alpha emitter actinium?
spk12: Sure. I'll have Andre talk to the pediatric high-grade glioma study, and then Jared can address our work with our actinium-based program.
spk02: Thanks again, Jonathan. We started enrollment in the HGG study at the very beginning of this year. with patients already enrolled in a study and a few patients being screened as we speak, we anticipate that we'll provide initial look, initial results from that study by the end of the year.
spk08: Okay. And starting phase one.
spk10: Yeah, great question, Jonathan. Real fast, what I'd say is, you know, we sit in a unique advantage in that our phospholipid ether delivery targeting mode is validated, you know, based on the iapovacine data as a validated targeting ligand. And we have a unique advantage in that that allows us to accelerate our timelines into clinical trials and completion of IND-enabling studies. I think, as we mentioned before, we expect to complete the IND-enabling studies here in the fourth quarter of this year and either late this year or early next year. initiate that phase one study with the actinian broker.
spk12: And Jarrett, we haven't talked about it very much, but could you share a little bit about the OG program?
spk10: Yeah, absolutely. So obviously, as Jim just alluded to, Jonathan, you know, we've gotten, you know, as we've talked about, we've validated with a number of different isotopes or different emitting isotopes. And as Jim just said, We also have the advantage of being able to use OG emitting isotopes quite readily, and we do have a program that has been in the background for a while that we're moving forward with that we would expect that we could quickly initiate a phase one study in that arena as well shortly on the heels of the actinium pending capital.
spk08: Okay, that answers my questions.
spk11: Thank you, guys. All right. Thank you, Jonathan.
spk05: And your next question comes from Jeff Chung of Oppenheimer. Please go ahead.
spk06: Your line is open.
spk09: Hi, guys, and thanks for taking the question. A couple from me. Andre, you gave a really long and really detailed update on the data, and obviously key up there was the increase in the MRRR. Were there any other changes that I might have missed from the prior data set that was described in July?
spk02: Thank you, Jeff. I don't think you missed anything. This is the single most impactful update, even though it's just one additional response. It brings us closer to our previously reported number within margin of error. So the current MRR effectively is 58.2%, and we expect that we might have in the next few months additional responses converting from minor to major responses as we model at the beginning of the year. But where we sit now is 58.2%, and that's the most impactful update from a month ago.
spk09: Great. Thank you. In terms of the NDA filing, one of the major reasons folks have been getting, you know, refusal to files or rejections have been on the CMC side. So you talked about a lot about the importance of supply chain and how you've built redundancy in your supply chain. But can you speak to the level of confidence in the NDA filing in the CMC section? perhaps what you've done in terms of quality audits and preparations for FDA inspections?
spk10: Yeah, absolutely. So that's a great question, Jeff. And there's a lot to unpack in that. So I'll try to unpack as much as I can in a little bit of time here. But so as it comes to our confidence, we are highly confident for a number of reasons, not least of which, you know, we've done, we've been producing ibuprofen at, at, these facilities for a while now, particularly one of those facilities we've been producing and have not missed a single batch in over three years. As I exemplified, we've replicated that process and the second facility have produced multiple batches now, a number of batches at that facility without any hitches as well. So we're very confident in the robustness of the ability to do the tech transfer and of both manufacturing facilities to to actually produce the material as defined and with inside the criteria as necessary for release. In addition to that, you know, again, we've done that from the beginning to the end of sort of things. And, you know, like anything, we use a, you know, design sort of approach with our manufacturing that allows us to get control by design sort of or quality by design sort of approach. So we're always looking to optimize and enhance that a little by little. So that's part of it. The other piece that I think we've done is, you know, when we started this process, we actually, and I'm going to get in a little bit too much detail probably, but we took this outside of our hands and we actually had an outside group come in and do a gap analysis on our entire manufacturing process from beginning to end to identify any potential gaps and any historical areas that we would need to backfill or questions we might want to answer to make sure our manufacturing submission was as robust as possible, and we did that. One of those folks was actually a gentleman who used to work at the FDA and had actually established a lot of their radiopharmaceutical manufacturing criteria. So we were taking a very robust look at that, and we've gone through that, and we continue to sort of reassess it. Now, as you enunciated, the last piece is, you know, the audits, as I'll call them, whether that be pre-FDA audits or regular audits. We do our own regular audits both by our team and by external teams every couple years with all of the sites. We've done that and right now we've done it with everybody leading into the FDA submission. To your point, we are with every one of our manufacturers right now. We do have on the books the plan to do pre-FDA, pre-NDA evaluations so that when they do get audited, we will have already gone through there again just to make sure and tighten the screws so that everything is above board and appropriate, so to speak.
spk09: Perfect. Thank you very much for that, Jarek. And then one very quick clarification. For the actinium-based program in solid tumors, the carrier there is the same as iopophosin, correct? Or is it a modification?
spk10: There is a modification, but what I would say is it's about 90-ish percent, 95 percent, depending on what chemist you ask, the same. There are slight tweaks.
spk09: Okay. So in essence, the targeting agent is the same.
spk11: Exactly. Got it.
spk09: Got it. Great.
spk12: Thanks, guys.
spk11: All right.
spk12: Thank you, Jeff. We appreciate your questions and obviously, you know, your continued interest and support of the company. Thank you.
spk06: Thank you. And your next question comes from Ahu Demir of Lidenberg Kalman. Please go ahead. Your line is open.
spk01: Good morning. This is Chong for Ahu Demir. Thank you for taking our questions. We also have a question regarding the NDA applications. So for the application, what population are you targeting? Will be three-line clients, patients treated with BTK inhibitor before, or it will be double or triple refractory patients? And are there any additional analysis that the company plan to do prior to the submission? Thank you.
spk11: Okay.
spk12: I think prior to handing it over to Jared and Andre for their perspective and optics here, you know, as we originally designed the study, it was for a third-liner grader, originally post-BTKI. Based on the patient population and role that supported that, it's essentially a relapsed refractory patient population. And so, you know, it is our belief that we have an opportunity as we continue to engage with the FDA that our data package would be supportive of a relapsed refractory indication or essentially second line and beyond. And so I can have Jared and or Andre provide both the regulatory and some of our clinical thinking around that.
spk10: Yeah, I think from a regulatory perspective, you know, if you look at the patient population, as Jim said, and as Andre defined, or described to you when you look at patient characteristics, you can clearly see that this is a highly relapsed refractory patient population, whether you want to cut it from post-BTKI, which essentially is, you know, BTKIs are predominantly being used in first line these days kind of element, to whether you just want to say, let's just look at the refractory. I think the key element there is, as Andre stated, The data shows that irrespective of the patient population, the drug works consistently and robustly in all of these patients. And because of that, when the agency or any agency evaluates the drug based off of that and they start to do sub-analyses, what you see is there's really no change in the patient population or the response rates. And that means that you're likely to get a broader label and a label like what Jim just described, the relapse refractory. I'll turn it over to Andre for any other defaults.
spk02: Thank you, Jared. I will thank you for this question. It's a very important question that we're discussing internally, and I'm completely aligned from clinical perspective with my colleagues that our data is supportive of broad applicability in clinics of hypofascin in WM patients. as described in our whole population in global WAM, contain patients post-chemo, post-BTKI, post-retux, exposed to couples of those classes, all of those classes, different genomic profiles. So the data is highly applicable clinically to entire WM population and clinically, again, supports the proposed label that Jared discussed, and more importantly, applicability once and if hypophysis is approved, applicability to a broad variety of patients with relapsed refractory WM.
spk05: That's very helpful. Thank you.
spk11: Of course. Thank you.
spk05: Thank you.
spk06: And your next question comes from Ted Tantoff of Piper Sandler. Please go ahead. Your line is open.
spk07: Great. Thank you very much, and thanks for the update. Following up on some of the questions with respect to the NDA, I'm curious, what are the major segments that still need to be done? You got into some good detail on the CMC portion. Is clinical and everything else all ready to go? just giving a sense for what still needs to be done. Thank you.
spk10: Absolutely, Ted. And this is, yes, essentially all modules are nearly complete. And when I say that, so CMC is complete, preclinical is complete. I think module two is essentially complete. Module one will be finished when we have the full sort of what sort of table contents completed based off of the clinical piece. So right now what we, where we sit is really wrapping up the final pieces of clinical. And when I say that, what I mean is all of the other clinical components have been, are essentially there and done. It's really just the addition of the final data reports and essentially the CSR out of the, out of the Clover Wham study. So as those, as that data comes in and gets put into the, into the NDA, that essentially will wrap it up. And that's exactly, you know, as I tried to describe in the conversation earlier, you know, that's where that detail comes in, that process of going from having the data to finalizing the data and having a locked database and all the analytics completed.
spk07: Sure. And then would you guys anticipate having a panel for this? I know it'll probably take some time, but what are your thoughts on that?
spk10: Thank you. Ted, just so that I understand, when you mean a panel, are you thinking of an ODAC?
spk07: Yes, advisory committee, correct.
spk10: Yeah. So, you know, obviously that's something... We will come to, eventually, I wouldn't be surprised if there is an ODAC request or a desire by the agency to have an ODAC. As you may be aware, many of the radiopharmaceuticals have not actually had an ODAC. They've gone through without that. However, you know, we're not, you know, we're flexible with that. I don't know, Andre, if there's anything else you'd like to add.
spk02: Yeah, thank you, Jared, and thank you, Tad. Great question, and we, again, keep discussing this continuously internally. Our efficacy data looks, from our perspective, really impressive and great. Tolerability and safety data is also impressive. Having said that, it depends on the composition of FDA panel that reviews it and how comfortable they are experienced with the disease they're looking at, whether they need additional advice from the panel. I think it's a toss-up at this point from clinical perspective. We will continue to prepare for it. We are putting groundwork, assuming that it might be necessary to go through.
spk11: We will be ready. Great. Sounds good. Thank you so much. All right. Thank you, Ted. Appreciate your questions.
spk06: Thank you. And at this time, there are no further questions in the queue. I will now turn the call over to Jim Caruso for closing remarks.
spk12: Thank you, Operator. I would like to thank certainly our analysts and everyone for joining us today. We look forward to speaking with you, hopefully in the near term. Thank you.
spk06: Thank you, everyone. This includes today's conference call. You may now disconnect.
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