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spk16: Good morning and welcome to the YMAB Therapeutics, Inc. earnings conference call for the second quarter 2022. Today's conference is being recorded. Let me quickly remind you that the following discussion contains certain forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. Because forward-looking statements involve risks and uncertainties, they are not guarantees of future performance and actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of factors, including those risk factors discussed in the company's quarterly report on Form 10-Q for the fiscal second quarter ended June 30, 2022, as filed with the SEC on August 8, 2022. At this time, I would like to turn the conference over to Thomas Gadd, the company founder, interim CEO, and president. Please go ahead, sir.
spk17: Thank you. Good morning, everybody, and thank you for joining us today. And with me today, we have our CFO, Bo Kruse, our chief commercial officer, Sue Smith, and our chief medical officer, Vinesh Raja. I'm very pleased to briefly review with you our compliments throughout the second quarter of 2022. First and foremost, the resubmission of the BLA form Bertramab in the first quarter was accepted for priority review by the FDA, and we anticipate a decision after the upcoming PDUFA date in November 2022. We treated the first patient in pediatric AML with our CD33 bispecific antibody and continued the progress with our GD2 SADA construct, for which we obtained IND clearance, and secured clinical supply for our 177 lutetium non-cariated isotope from ITM Isotope Technologies in Munich. We have secured supply for phase one through phase three clinical development of our DD2 SADA, and we expect to treat the first patient with DD2 SADA in the fourth quarter of 2022. Our partnership with Cyclone Pharmaceuticals continues to advance well. In the past quarter, we have worked diligently on Danielsa's expansion to Greater China with an expected decision on approval later this year. We firmly believe that YMAPS is well-positioned to deliver multiple milestones, generate meaningful data, and further unlock the potential of our platform to provide benefit to patients while creating value for our shareholders. Now turning to our commercial franchise. Let me begin with our first commercial product, Danielsa, which was launched 18 months ago following the FDA's accelerated approval for the treatment of patients with relapsed and refractory high-risk neuroblastoma in the bone and bone marrow, who have demonstrated a partial response, minor response, or stable disease to prior therapies. All of us here at YMAPS are truly proud of the launch to date. and being able to offer Danielsa to children nationwide, and we look forward to Danielsa's potential expansion outside of the U.S. While Danielsa's product revenue have increased quarter to quarter since we launched, they came in at $9.8 million in the second quarter of 2022, which corresponds to a 7% decrease from the previous quarter. However, the decline included a slightly decrease in new patients early in the second quarter, which was partially offset by a rebound in June, and we are encouraged to see the rebound continuing through July. Q2 analyst consensus was 11.1 million, meaning that our Danielsa revenues came in 1.3 million below consensus, corresponding to approximately two patients. Our international revenue benefited from increased royalty income from partner sales, offset by a decrease in volume due to timing of partner orders. With the recent management changes, including a new chief commercial officer, we are confident that we are now on the right track. Sue Smith has been leveraging her prior experience in leading global launches and delivering operational efficiencies and successful development campaigns to highlight and differentiate Danielsa in the U.S. and potentially other markets. She has implemented several positive changes, and we are actually starting to see trends implemented by Sue. And I'm very pleased to have her on our call today. So over to you, Sue. Thank you.
spk14: Okay. Thank you very much, Thomas, and good morning, everyone. I'm pleased to be with you all today and happy to have the opportunity to talk about the progress we've made. In the first quarter, the company's commercial leadership team created and gained approval on a new rare disease strategic roadmap. In the second quarter, we focused on operationalizing it to focus our efforts to support company goals, empower our commercial team with new resources, and align appropriate customer support along the rare disease patient journey. The team is now using a variety of new patient finding strategies put into place in the first half of the year to identify clinicians and centers with active patients and to understand where they are in their journey. This allows us to improve our targeting and provide our account managers with real-time leads. This also helps our marketing efforts to target the right stakeholders when they need the information. We anticipate this will catalyze Danielza's adoption and drive the appropriate use of Danielza earlier in the patient's journey over time. In an effort to support caregivers and parents, we also launched a caregiver Facebook community initiative called the Danielza Caregiver Connection, or DCC. That helps connect caregivers with the knowledge they need from others who've been through the treatment process. DCC is supported by a strategic and hyper-targeted paid media plan to reach caregivers in the neuroblastoma community. This way, they can receive firsthand real-life experiences from Danielza families to educate parents and families on what they can expect with their child's relapsed or refractory high-risk neuroblastoma, and also how Danielza might benefit their child. At this point, we would like to thank the families who joined the DCC community for sharing their experiences, supporting others in the Danielza journey, and also entrusting us with their care. Our refined approach appeared to be effective in the first quarter of 2022 as we recorded Danielza product revenues of $10.5 million for the first quarter. We continued to leverage experiences from the first quarter of 2022 and used them to continue delivering Danielza to patients. However, our Danielza revenues came in at $9.8 million in the second quarter, of 2022, a 7% decrease, as Thomas mentioned, from the previous quarter, caused by a slight decrease in new U.S. patients earlier in the second quarter, but again, partially offset by the rebound in June that continued through July. Our soft April and May was due to the team's over-focus on implementing new rare disease strategies initiated in the spring. Second quarter was about building our rare disease roadmap. which was not measured in patients but provides the solid foundation of rare disease best practices upon which steady future growth can occur. And with this groundwork laid, these foundational programs are showing signs of gaining traction, with July featuring the most patients ever in our hub since launch. These things take time, but we are convinced that we're on the right track. And we're encouraged by the increase in the number of treatment centers that have gained experience with Danielza, with 36 treatment centers having administered Danielza across the US at the end of second quarter, up 6% compared to 34 centers at the end of the prior quarter. And two new centers added Danielza to the formulary in the second quarter. We're now also starting to see the addition of notable higher potential accounts using Danielza. We're seeing geographic expansion based on our new rare leads, and we're seeing patients being re-challenged with Danielza for the first time since launch, which is great to see. With more than half of our accounts having experience with multiple patients, we're growing our network of key opinion leaders to help with peer-to-peer education across the community. We're comfortable with our commercial plan and will stay the course. We reiterate our revenue guidance of 45 to 50 million for 2022, which includes an incremental benefit from international revenues. A year and a half into the launch, the team continues to drive Daniela's adoption and expand its physical footprint across the US. We're very encouraged by its benefits over other currently available options, including the rapid infusion, fewer hospitalization days, and the flexibility to be administered in the outpatient setting. To summarize, we remain confident about the long-term prospects for Danielsa as underscored by clinicians' feedback, formulary inclusions, and the evolved commercial foundation. Our core focus remains on continued accelerated market expansion, and we look ahead to conducting additional educational engagement to further broaden site activation.
spk13: Thank you, Sue.
spk17: As you can hear, everybody, we're very excited about the possibilities going forward. potentially expanding the commercial opportunity of danielza and growing top-line revenue while capturing additional pediatric unmet medical needs. This is further supported by the recent ASCO presentations of results from the Phase II trial that evaluated the combination of danielza with irinotecan, semisolemide, and sagamustin, GM-CSF, in 90 patients with chemoresistant high-risk neuroblastoma. The combination reached its primary endpoint with a 64% overall response rate and a 26% of patients achieving a complete response. The treatment was safe with no greater than grade two toxicities. This is the first time any anti-TD2 antibody has been studied in such a heavily pretreated patient population, and we are very pleased with the response rates achieved. This further demonstrates the potential of Danyelza in high-risk neuroblastoma, and we look forward to continuing our work towards label expansion. YMAPS is also committed to introducing Danyelza into larger adult indications, and we have ongoing partner discussions to address this potential opportunity. I'm moving over to UmbertoMAP. We are thrilled to report that the FDA has accepted our recent submission of UmbertoMAP's brand name on Blasters. the BLA for priority review, and a guided advisory committee meeting date to take place in October 2022, and a PDUVA date for November 30, 2022. We are optimistic about the potential approval based on meaningful improvement in overall survival rates and unparalleled efficacy in patients with CNS metastases from neuroblastoma. Currently, there are no FDA-approved therapies for this indication, and we hope that, if approved, Ombudsman will address the significant unmet medical need here. Ombudsman would fit very well into our commercial portfolio as a line extension to Danielsa, enable us to further leverage our commercial infrastructure without any major additional investments. Additionally, we believe that Ombudsman, if approved, would mature into an important drug with significant label expansion opportunities over several medical, unmet medical needs within pediatric rare diseases and would present larger indication opportunities targeting B7H3. Given that on birth map has been granted a rare pediatric disease designation by the FDA, we are eligible to receive a priority review voucher from the agency upon its potential approval. MSK is entitled to receive 33% of the net proceeds generated from a sale of such on birth to my POV, potentially securing a non-dilutive cash contribution to the company that would further extend our cash run rate. Turning now to our SADA technology. SADA is a key innovative platform in the YMAP's development portfolio that continues to show great promise in targeted delivery of radiopharmaceuticals to tumor sites with minimal off-target effects, proving opportunities to significantly increase the therapeutic indices. As we continue to optimize the technology, we become even more encouraged about the potential scientific advancement it represents for the company and the medical community. The IND for our first shard construct the GD2 shard for GD2-positive solid tumors, was filed last year, late last year, and after the IND clearance in July, we expect to treat the first patients during the fourth quarter of this year. We are focused on a two-pronged strategy here with efforts to treat adults in small cell lung cancer to validate the GD2 SADA while working on potential pediatric GD2 indications. Our strategy here is to out-license larger indications over time while we focus on unmet medical pediatric indications. We expect to treat the first patients in the fourth quarter, and we'll look forward to potentially being able to share tumor binding data in 2023, as our SADA development is based on a therapeutic approach where we plan to use imaging to demonstrate tumor binding followed by therapeutic approach. We believe we are well-positioned to explore partnership options to leverage our proprietary SADA platform. And our strategy here is to seek partnership for the adult indications while focusing on the pediatric indications. We also plan to potentially optimize and repurpose previously failed late-stage clinical targets that have already been proven safe in humans by implementing them into a SADA construct, as we believe these SADA targets could potentially significantly enhance the therapeutic indices, as evidenced by the PK attributes of the SADA platform, and further unlock the potential of pre-targeted radiopharmaceuticals in tumors that have not historically demonstrated any meaningful responses to therapeutic agents. Moving to the Y-Biclone platform, the IND for our CD33 bispecific pediatric AML has been cleared, and we believe this is a promising treatment that can potentially address an important pediatric unmet need, as AML remains one of the most challenging treatments hematologically malignancies for children. We treated the first AML patient in June, and we look forward to reporting the progress of this study as it unfolds. We've decided to seek out licensing partners for Nivotrutamab in order to preserve capital as our GD2 solder is so close to the clinic, and to focus our attention on our commercial asset, Danielsa, and the potential launch of Ompertumab. As you know, we've established a partnership with Cyclone Pharmaceuticals for Danielsa and Umberto expansion in Greater China. We are especially excited about Danielsa and the potential approval expected to take place later this year, which will trigger a $15 million regulatory milestone. We have continued to see an uptick in patients treated in the pilot zones in China and expect this market to be an important revenue driver for Danielsa's Asian sales. We continue to work on making sure that Yeltsin and Bertramov, if approved, will have a global footprint. And we have entered into additional partnerships covering Latin, Eastern Europe, and Israel to support this potential and continue to work on widening the footprint. We ended the second quarter of 2022 with $133.7 million in cash. Recall we mentioned in the previous conference call for our first quarter of 2022, that we have reprioritized our programs in an effort to unlock the near-term value of our pipeline through focused internal execution and external partnerships. With a strong cash run rate and a robust pipeline, we believe we are on track to deliver many more clinical and commercial milestones, support the continued commercialization of Danielsa and the potential launch of UmbertoMap, as well as advance our early-stage programs, including the SADA technology constructs. We are very pleased with our current financial position, which Bo Guz, our Chief Financial Officer, will elaborate on in a minute. Thank you. Over to you, Bo.
spk06: Thank you, Thomas. And good morning, everyone.
spk07: Our net revenues of $10.8 million and $21.3 million for the quarter and six months ended June 30, 2022, represented a decrease of 1% and an increase of 30%, respectively, over $11 million and $16.3 million in the comparable periods of 2021. Net revenues in the quarter and six months ended June 30th, 2022 include $1 million worth of license revenue compared to $2 million worth of license revenue in the corresponding periods of 2021. Then the other product revenues for the quarter and six months ended June 30th, 2022 was 9.8 million and 20.3 million respectively, which represented increases of 9% and 42% respectively over the corresponding periods of 2021. The Nielsen product revenues of 10.8 million in the second quarter decreased 7% compared to the first quarter of 2022 net revenues of 10.5 million. the decline included a slight decrease in new U.S. patients earlier in the second quarter, partially offset by a rebound in June and July, while international revenues benefited from increased wealth income from partners' sales, offset by a decrease in volume due to the timing of partner orders. Moving to the operating expenses, our R&D expenses increased by 6.6% and $8 million to $26.4 million and $49.3 million for the quarter and six months ended June 30, 2022, respectively. These net increases in the quarter and six months ended June 30, 2022 reflected increased outsourced manufacturing, inclusive of $2.9 million of Nexidimab inventory vials that were designated for clinical use during the three and six months ended June 30, 2022. increased clinical trial activity with a particular focus on the Nielsen, Umberto Mupp, and the Sarah constructs. SG&A expenses increased by $9.6 million and $11.1 million to $23.1 million and $36.5 million for the quarter and six months ended June 30, 2022. The increases in SG&A expenses in both periods were primarily the result of a $10.7 million charge related to contractual severance-related benefits for our former Chief Executive Officer, which were inclusive of $1.4 million of compensation-related accruals and $9.3 million of non-cash share-based compensation expense, and, to a lesser extent, the launch and commercialization of the Nielsen, which included employee-related costs and commercial expenses. We reported a net loss for the quarter in the June 30, 2022, of $41.1 million, or 94 cents per share, basic and diluted, compared to a net loss of 22.9 million, or 53 cents per share, basic and diluted, for the quarter ended June 30th, 2021. The decrease in earnings in the second quarter of 2022 reflects the unfavorable impact of the $10.7 million charge related to the contractual severance-related benefits for our former chief executive officer and increased R&D expenses, as noted. Additionally, we reported the net loss for the six months in the June 30th, 2022 of 69.2 million or $1.58 per share basic and diluted compared to a net income of 10.5 million or 25 cents per basic share and 23 cents per diluted share for the six months in the June 30th, 2021. The net income in the six months in the June 30th, 2021 included a $62 million gain from the sale of our Danielsa Priority Review Voucher after sharing 40% of the net proceeds from the sale with MSK as per the license agreement. The decrease in earnings in the six months ended June 30, 2022, also reflects the unfavorable impact of the charge related to contractual severance-related benefits for a former chief executive officer and increased R&D expenses, as noted above, partially offset by the favorable impact of Danielsa's growing revenues. We ended the second quarter of 2022 with a cash position of $133.7 million compared to $181.6 million at year-end 2021. The decrease was 47.9 million years paid, and the decrease of 23 million compared to the first quarter cash balance reflects that the cash burn was reduced by about 8% during the second quarter of 2022. Our cash burn is driven by the cash used in our operating activities. Consistent with the prior quarter, we believe that our current cash position is sufficient to fund our current operations into mid-2024. We believe our cash position of $133.7 million as of June 30th provides a solid financial runway to support our commercial initiatives and our reprioritized pipeline programs, as Thomas mentioned. As we noted in the prior quarter, the underlying assumptions for this guidance are important to understand, and we did not include any assumption for the net proceeds received on the anticipated POV, which we could sell upon the potential approval of MbernaMath. In addition, no new partnerships or other BD-related sources of income are included in the assumptions. Potential burden operating revenues upon approval are also excluded, and the Danielsa revenues are only assumed to increase modestly by 10% each year for the purposes of this analysis of runway. To be clear, we hope to see an entirely different different growth rate for Danielson in the years to come as we execute our refined commercial strategy and continue to deliver clinical data that could potentially lead to expanded indications and greater physician adoption. In terms of development activities, we have assumed that current programs will be advanced at our own expense and no new programs are assumed at this point. The financial runway forecast benefits from the fact that most of the expenses related to pivotal trials, post-marketing commitments, and regulatory activities are behind us at this point. Also, previously discussed, we continue to expect operating expenses of 162 to 167 million and a total cash burden of 78 to 83 million for 2022. The net cash accruals related to the severance package do not include or do not impact cash projections but increase the estimated full year operating expenses, which are unchanged from the first quarter. For the purpose of the guidance, we have not assumed any equity or debt offerings or borrowings. We believe YMAPS remains in a healthy financial position to execute our strategic mission priorities and support the delivery of multiple milestones. Now, this concludes the financial update. Now, I'll turn the call back to Tom.
spk17: Thank you, Bo. This marks the end of today's prepared remarks. Let's open up the line now, and perhaps we can ask the operator to remind you of the procedures for submitting your questions at this time. Thank you.
spk16: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.
spk15: One moment, please, while we poll for questions. Thank you. Our first question comes from the line of Alex Stranahan with Bank of America.
spk16: Please proceed with your question.
spk01: Hey, guys. Thanks for taking our questions. Just a couple from us. First on VertMEM and just on the commercial preparedness activities ahead of a potential approval in November. Do you plan to take a hospital-centric approach similar to the Danielza launch? And roughly how many salespeople do you think you'll need to attain adequate coverage in the U.S.? And as a follow-up, what are your expectations in the EU? given you maybe haven't had the same level of interaction with EMA as you have with the FDA. And second question, on the SADA platform, could you talk a bit more about the study design? Do you feel like you have a pretty good sense of what the optimal dose of the payload should be at this point, given your preclinical studies? Just trying to think of how quickly you might be able to step through the dose escalation in parts A and B. Thanks.
spk17: Thank you, Alec. Sue, I think you can take the first question on UmbertoMab.
spk14: Yeah, thanks, Alex, for the question. So, the US team is very engaged right now in the preparations for the launch of UmbertoMab, and we're actually in good standing there. We are taking more of a hospital-based approach because they have to be certified in the ability to administer the nuclear medicine capability. Also given the ultra orphan nature of this, we want facilities that will see a slightly higher volume of this very rare CNS leptomeningeal disease so that they have a proficiency in administering. So we are taking that approach and we do feel that we are actually hiring some people specifically for this launch and to start out with such small patient numbers and the synergy with our current Danielza efforts, we feel that we have the right number of people to be successful. In terms of EU expectations, we are continuing to engage with EMA and gain guidance from the agencies. And so, you know, the signs right now, you know, we're continuing with that effort and, you know, hoping obviously for a good outcome. and certainly have prepared our thoughts on the best way to commercialize in the EU should that come to fruition.
spk17: Thank you, Sue. Vinesh, do you want to, I mean, let's not go into deep details of study design. Let's talk about, you know, what we're achieving for the first dose cohort and the timing of the two injections and maybe the starting dose.
spk08: Yes. Well, so thank you very much to Vinesh Ardha, Chief Medical Officer here. This SADA 1001 trial, this is a phase one dose escalation study that will be divided into three separate parts. The three separate trial parts are designated Part A, Part B, and C. Part A being looking at the GD2 SADA dose escalation, Part B looking at the 177 lutetium DOTA dose escalation, and Part 3 will be the repeated dosing analysis. And so each of these parts will only be initiated upon completing the previous part. So part B, for example, where we're looking at dose escalation on lutetium dota, will only be initiated in patients who have completed the dose-limiting toxicity observation for the first part, which is just for the GD2 start-up. So this is, the escalation trial will be based on a classical three plus three trial design with a standard titration stage to establish a maximum tolerated dose. I don't have details with specific doses myself, but the primary objective or primary endpoint, as you can imagine, is occurrence of the DLTs and the number and severity of adverse events. So I hope this answers at least part of your question.
spk01: Yes, it's very helpful. Thanks for the color.
spk16: Our next question comes from the line of Robert Burns with HC Wainwright. Please proceed with your question.
spk05: Hey, guys. Thanks for taking my questions. Just two, if I may. So, for the first one, it seems like the number of centers that you're able to address is slowing as of recently. You know, given this, I'm sort of curious what the average number of neuroblastoma patients are, you know, per year in the centers that you're still trying to get access to. And then my second question is with regard to some of the upcoming catalysts. Are you still planning to initiate a phase two trial for an exitative evidence frontline neuroblastoma? And will we also see another IND submission for an additional SATA construct this year? Thank you.
spk17: Thanks, Robert. Sue, will you take the first question? I can take the second.
spk14: Sure, sure. Thanks, Robert, for your question. Yeah, so in terms of the number of patients, again, sort of putting this into perspective, the, you know, ultra... rare nature of this disease, there are in the U.S. about 700 diagnosed neuroblastoma, about 350 of those patients have high-risk neuroblastoma, and about 310 of those are in our label for high-risk relapsed refractory neuroblastoma in the bone or bone marrow. So the team is acutely aware of, you know, where those patients are and where they are in the accounts, and we see we're very focused on the sources of growth. So we know that We still have a tremendous amount of potential at the priority accounts, which we've segmented into priority key and standard. And we also, you know, the good news is our team can execute well. Eighty-nine percent of our enrollments are coming from the accounts we've prioritized. So I think that, you know, 18 months post-launch, starting to see both second patients, third patients, plus retreatment of patients in those accounts will be a source of growth for us. And given some of the new rare disease efforts we've put in place, we now know sort of the needle in the haystack. We know where those patients are and are following compliantly. So I think that we'll start to see the expansion of those accounts, and also we expect growth from the new lead generation efforts of our new rare disease plans.
spk17: Thank you. And just to address your other question about additional INDs for SADA, we are planning on submitting an additional IND in Q1 of 2023 while we focus on, you know, validating GD2 in the clinic prior to that IND.
spk05: Thank you for that. And are you also planning that front-line neuroblastoma trial for Nuxidimab?
spk17: So front-line neuroblastoma trial, yeah, we are still waiting on gathering some data, and then we will go and address the FDA. But we are not planning on any head-to-head study. We are planning to have discussions with the FDA on a non-inferior basis and see where we can take that.
spk03: Awesome. Thanks, Thomas. Yep.
spk13: Thank you, Roland.
spk15: Our next question comes from the line of Charles with Guggenheim.
spk16: Please proceed with your question.
spk02: Hey, good morning, everyone, and thanks for taking our questions. My first one regarding the map, could you provide any additional color expectation of the types of data we could see for the upcoming PSYOP 2022 presentations, and also regarding specifically B7H3-positive CNS metastases. Could you also provide your thoughts around a potential development, you know, steps, development next steps for this particular asset as a future label expansion opportunity?
spk03: Thanks.
spk17: Yeah. Hi, Vanessa, do you want to take the first one?
spk08: Yes. So, as you just quite rightly alluded, we'll be looking at a SIOP oral presentation later this year for the 101 study, interim analysis. This is the multicenter YMABS-led study that will be given and delivered by Dr. Kramer. And also at the start of 2022, we'll have Dr. Modak giving another oral presentation of the 03-133 study, which was a single center study at Sloan Kettering. So you'll hear more about the details of the safety and efficacy in those presentations. But as we have shared with you, I think in previous calls, The headline news around efficacy concludes that there is a clear clinical benefit in terms of response rates and survival with a manageable safety profile. For example, in the O3-133, where, as you know, we looked at the overall survival, progression-free survival, and we did an indirect comparison with an external control arm to serve as an appropriate comparator. Preliminary data has shown that the overall survival difference doing this indirect comparison, the median overall survival has a difference of roughly 15 months in the control arm versus 43 months in the actual interventional arm, albeit taking into account these are indirect comparisons. Moving to the 101 study where the primary endpoint was response rates, here the primary aim is to look at individual patients looking at response rate at six months after initiation of treatment. Here we have shown, certainly in those patients with measurable disease, which is about 20 patients, roughly 14 patients had a level of disease control, which includes complete response, partial response, as well as stable disease. So I think combined with these two studies, we believe that there is clearly a signal of clinical benefit for these patients who really have no alternative treatments with a very poor prognosis, and this is primarily the clinical arguments we've been submitting in our BLA and will be shared more in detail at the relevant abstract and presentations. I think you added your second question around clinical development of this further. Is that right?
spk02: Yes, specifically for the B7H3 positive CNS mets, yes.
spk08: Yes, I think in theory, if we're able to get past this FDA PDUFA approval, we will be looking to see other areas where umbertumab can be used in those specific patient populations who can benefit from this. So there are a number of neuroectodermal tumors, CNS tumors that express B7H3, not only in pediatrics, but adults. Further details of precisely which tumor indications can be shared in subsequent calls. But at the moment, we're open to supporting not just investigator-led programs, like we have an ongoing study run by the Pediatric Brain Tumor Consortium, the PBTC study, who are looking at medulloblastoma and ependymomas and other neuroectodermal tumors, as well as through YMAP-sponsored studies. So further details will follow, but certainly it is within our strategy to see where we can get the best information risk-balance benefit of umbertumab in these B7H3 tumors.
spk03: Great. Thanks for taking my questions.
spk15: Our next question comes from the line of Joseph Tome with Cowan.
spk16: Please proceed with your question.
spk11: Hi there. Good morning, and thank you for taking my questions. Maybe the first one on the expected October ag-com for umbertumab. Maybe what do you expect that discussion to focus on and how is the team preparing for that decision? And then once we look forward to a hopeful launch here, what are kind of the key drivers? Do we need to wait for inclusion in treatment guidelines, or is it more just kind of these, you know, site-to-site kind of interactions? Anything on that would be helpful. Thank you.
spk17: Thanks, Vanessa. Do you want to just give a short guess?
spk08: Yes, thank you, sir. Okay. Yes, I think for the outcome meeting, I expect or we expect the areas of focus for the committee as well as the FDA will be centered around two or three, I guess, important points, which has been brought up in previous discussions with the FDA. Firstly, of course, we know that the study O3133 is a single arm, single center trial. So the application relies on comparisons with the external control data, which always has limitations, as you know, to serve as an appropriate comparator when you're trying to show incremental treatment effect and survival improvements. And quantifying this treatment effect is important, will be important for the FDA and the outcome in order to make a risk-benefit statement. So a lot of the discussion that we anticipate will be around the robustness of these data, both from the MSK study as well as the indirect control arm, and there will be a number of discussions around the statistical assumptions we have taken to estimate the comparative treatment effects, and we'll be looking at propensity score matching to control for any relevant confounding or selection bias. The other area there will also be discussion is looking at the study 101, and here looking at the response rate we anticipate there will be questions around the number of patients with measurable disease. And because obviously this is still a relatively small study, whether the degree of confidence in the responses seen can be replicated in a larger patient population. So that will be one area I anticipate the outcome to look at. So I think these were the key points I anticipate the most discussion to be. And I should add that all of these points we have discussed been involved in a number of discussions, ongoing discussions with the FDA, and the team are confident we are able to address these, not just the clinical arguments, but also statistical arguments with a high degree of confidence, I should add, because I think we, our case largely, of course, looks at the data that we have. The 13133 data is the single largest study in this patient population. And given the fact that this is a rare disease in an area of unmet medical need with very poor prognosis, we also believe the FDA and the outcome will look at this as an area where flexibility needs to be applied in making any judgments around risk benefit assessments. And in their own guidance, they do provide statements where they allow for this flexibility in determining effectiveness of drugs in rare diseases. So that's really what I expect the discussion to go like in the outcome.
spk13: Thank you, Vinesh.
spk15: Our next question comes from the line of Tess Mormero with JP Morgan.
spk16: Please proceed with your question.
spk09: Hey, guys. Thanks so much for taking our questions. So a question for Sue, if I could. You talked about a new rare disease strategic roadmap for the company. Would you expect to see pull through from the increased sales headcount and other initiatives in the second half of this year? Or should we expect to see that impact more weighted to 2023? And really, my question is, do you believe a second half of the year inflection is still achievable? Thanks so much.
spk14: Thanks, Tess. Yes. I do. I do feel confident that we have the right people in place. We're adding more resources. And, you know, the materials and programs and infrastructure we put into place in second quarter have been adopted by the sales team. They're embracing these new rare disease tools and they're leveraging them. And as you know, in a rare disease, you know, this is ultra orphan. This is not a cardiovascular drug. So when you implement something, it takes some time when you identify an appropriate patient that they may be then relapsed or refractory and appropriate for our product. So you often see in rare disease, maybe a six to 12 month sensitivity, not all the time, but sometimes between when something starts and when you see the appropriate patient. So I think that we, I feel confident we'll hit our forecast this year. And I think to your point, we even have some new things we're putting into place in this third quarter. that will take some time to get their footing. But we are very clear on the sources of growth. We're very focused there. We've already started to see early signs that our, for instance, our pivoted marketing plan is performing above benchmark with a more focused approach on these refined targets. And that our team executes effectively. The majority of our enrollments are coming from our currently prioritized accounts. So I feel that the fundamentals are strong and that we expect the growth to hit our numbers this year and, you know, of course, see additional growth in 2023. Yep.
spk09: And Sue, just one follow-up on that, if I could. You know, I think previously you've talked about sort of, you know, a two-thirds, one-third type of split between sort of patients that have been treated more in the second line versus the third line. I guess, how is the duration of treatment looking at your latest market research? Thanks.
spk14: Sure. So that's another area of strategic focus for us. We're looking at some new ways to refine our messaging, frankly, and we're just in the midst of developing that. I think that what we often see unfortunately at some of these larger centers of excellence is very late stage patients with a shorter duration of therapy of two to three cycles before they go on to hospice. So what we're looking to do is really move earlier in the treatment journey for those primary refractory patients who are in our label and we have great data in bone and bone marrow and that's the most stubborn disease compartment. I think as we look to refine and enhance our approach, we're really looking to shift that to get to the earlier stages. And we really shine there, so we just want to do an even better job of communicating that.
spk09: Thanks so much for taking our questions.
spk15: Thank you.
spk16: Our next question comes from the line of Mike Yules with Morgan Stanley. Please proceed with your question.
spk04: Hey, guys, thanks for taking the question. Maybe just one to start on, Danielle. So just the weakness in patient ads sort of earlier this in 2Q, was there anything specific that drove that or is that more just some quarterly variability we should sort of think about as we move forward here?
spk14: Yeah, I think that that's really just quarterly variability. You know, we did see a rebound from that. And, you know, I mean, I hate to use the analogy of sort of, you know, using a yo-yo when you walk up the stairs, but often in rare disease you will see some variability. And I do think that, you know, the team was, it was two patients off. We're not happy about it. I own it, full accountability. But I do feel that, frankly, you know, the foundation that we have here, our fundamentals are very solid. The team is very engaged. and motivated. So I just see that as a blip, and I really hope to deliver on that and plan to deliver on that this year.
spk04: Got it. That's helpful. And then maybe just a quick follow-up just on Umbertamab and the ADCOM. You know, thanks for all the color on sort of where you expect the focus to be. I'm just curious, has the FDA set a date yet?
spk17: Yeah, no, so we have not disclosed the date yet, but we are hoping to get it very soon.
spk06: Okay, great.
spk17: Thank you.
spk06: Yeah, we will announce it once it becomes available.
spk13: At least sometimes in late October, so.
spk15: Our next question comes from the line of Bill Maugham with Canaccord Genuity.
spk16: Please proceed with your question.
spk12: Hi, good morning and thanks. So my first question is on Danielza. So among these 36 sites that do have access to Danielza, when a doctor is going through their thought process about how to treat these patients and they choose treatment other than Danielza in a patient that is within Danielsa's label. Specifically, I guess, what factor do you think is leading them to choose a competitor versus Danielsa, and how do you change that point in their decision process?
spk14: An excellent question. I'm assuming, Thomas, you want me to take that?
spk17: That can be a long one. Yeah. Go ahead.
spk14: Okay. Okay. Thanks, Bill. So as you know, the other anti-GD2 in the market has been in the market for seven years, and we have been on the market for 19 months. And the unituxin was developed by COG through all of their treatment centers over many years, and our product was developed at Sloan Kettering. So at launch, we didn't have hundreds of COG sites that had experience and the nursing staff having muscle memory, you know, on how to use the product at launch as they did. So I think that the key determinants there really are on looking to highlight where we benefit, which is, you know, we are indicated and have excellent data in clearing the bone and bone marrow, and they do not. And we also are, you know, flexible. We have the ability to use inpatient and outpatient. Those are some of the areas that we are talking with physicians about. When you talk with a lot of these physicians one-on-one, their head is nodding in the right direction. These are some of the areas that we're looking to explore. We have some advisory boards and market research this fall to really look at optimally telling that story. Those are some of the areas that I think we know from current one-on-one interactions with some of the very you know, big center cog physicians, that those are areas that they see that make sense and have value. And also parents are very interested in the flexibility aspect of this product. So I think our DCC patient community and all the efforts we're doing there, that is definitely something that they care about. So there's a number of factors in our omni-channel mix that we're working towards continuing to
spk17: evolve and frankly we're building the danielza story as we're speaking here today so stay tuned um and i think um these are some of the areas the levers that we're working on yeah so just adding danielza was developed in four sites multi-center site versus unit toxin as in approximately 200 sites five years ago six years ago so you know um but we're making great progress
spk12: And then I just wanted to check in on the CEO search. How's that going, and when might we hear an update?
spk17: Yeah, I think it's going very well. You know, YMAPS is an attractive company. It's a strong foundation, and so I think we'll be able to give you an update maybe later this year, but it's going very well in terms of attracting talent. Okay.
spk13: Thank you. Yep.
spk16: As a reminder, if you would like to ask a question, press star 1 on your telephone keypad. Our next question comes from the line of Etzer Darut with BMO Capital Markets. Please proceed with your question.
spk10: Hi, thanks for taking my question. This is Luke Chamoyan for Etzer Darut. Just one from me. Can you touch on the progress of Umberto Nomad, their label expansion, specifically in DIPG and DSRCT, and when we might be able to get some clinical updates for those trials? Thank you.
spk17: So, DIBG, we've changed the isotope from 124 to 131. And we are planning on pending the outcome of on birth map for CNS METS later this year to start a multicenter trial using 131 instead of 121 in DIBG. DSRCT is a very, very small indication that we, it will be very difficult to run a proper trial So I think we will hope to see that that will be a potential label expansion or off-label as we move out in the future.
spk13: Thank you. Thanks.
spk15: We have no further questions at this time.
spk16: I would like to turn the floor back over to management for closing comments.
spk17: Well, thank you everyone for participating today and wish you a great day.
spk13: Thanks.
spk16: Ladies and gentlemen, this does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation, and have a wonderful day.
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