Y-mAbs Therapeutics Inc (YMAB) 2022 Q2 法說會逐字稿

Good morning, and welcome to the Y-mAbs Therapeutics, Inc.'s 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 Gad, the company's Founder, Interim CEO and President. Please go ahead sir.

Thank you. Good morning, everybody, and thank you for joining us today. With me today, we have our CFO, Bo Kruse; our Chief Commercial Officer, Sue Smith; and our Chief Medical Officer, Vignesh Rajah.

I'm very pleased to briefly review with you our complements throughout the second quarter of 2022. First and foremost, the resubmission of the BLA for omburtamab 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-carried isotope from ITM, Isotope Technologies in Munich.

We have secured supply for Phase I through Phase III clinical development of our GD2-SADA. And we expect to treat the first patient with GD2-SADA in the fourth quarter of 2022.

Our partnership with SciClone Pharmaceuticals continued to advance well. In the past quarter, we have worked diligently on DANYELZA expansion to greater China with an expected decision on approval later this year. We firmly believe that Y-mAbs 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 first -- with our first commercial product, DANYELZA, 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 Y-mAbs are truly proud of the launch to date and being able to offer DANYELZA to children nationwide. And we look forward to DANYELZA's potential expansion outside of the U.S.

While DANYELZA's product revenue has 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 DANYELZA's revenues came in $1.3 million below consensus, corresponding to approximately 2 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 DANYELZA in the U.S. and potentially other markets. She has implemented several positive changes. And we are actually starting to see changes implemented by Sue. And I'm very pleased to have her on our call today.

So over to you, Sue, thank you.

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, empowered 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 DANYELZA's adoption and drive the appropriate use of DANYELZA earlier in the patients' journey over time.

In an effort to support caregivers and parents, we also launched a caregiver Facebook Community initiative called the DANYELZA 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 DANYELZA families to educate parents and families on what they can expect with their child's relapsed or refractory high-risk neuroblastoma and also how DANYELZA 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 DANYELZA journey and also entrusting us with their care. Our refined approach appeared to be effective in the first quarter of 2022 as we recorded DANYELZA product revenues of $10.5 million for the first quarter.

We continue to leverage experiences from the first quarter of 2022 and use them to continue delivering DANYELZA to patients. However, our DANYELZA 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 DANYELZA with 36 treatment centers having administered DANYELZA across the U.S. at the end of second quarter, up 6% compared to 34 centers at the end of the prior quarter and 2 new centers added DANYELZA to the formulary in the second quarter.

We're now also starting to see the addition of notable higher potential accounts using DANYELZA. We're seeing geographic expansion based on our new rare leads. And we're seeing patients being re-challenged with DANYELZA 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 million to $50 million for 2022, which includes an incremental benefit from international revenues. 1.5 years into the launch, the team continues to drive DANYELZA's adoption and expand its physical footprint across the U.S. 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 DANYELZA 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.

Thank you, Sue. As you can hear, everybody, we are very excited about the possibilities going forward, potentially expanding the commercial opportunity of DANYELZA 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 DANYELZA with irinotecan, temozolomide and sargramostim GM-CSF in 90 patients with chemo-resistant 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 2 toxicities. This is the first time a GD2 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. Y-mAbs is also committed to introducing DANYELZA into larger adult indications. And we have ongoing partner discussions to address this potential opportunity.

Now moving over to omburtamab. We are thrilled to report that the FDA has accepted our recent submission of omburtamab brand name on OMBLASTYS. The BLA for priority review and a guided advisory committee meeting date to take place in October 2022 and a PDUFA 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, omburtamab will address the significant unmet medical need here. Omburtamab would fit very well into our commercial portfolio as a line extension to DANYELZA; enable us to further leverage our commercial infrastructure without any major additional investments.

Additionally, we believe that omburtamab, 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 B7-H3.

Given that omburtamab 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 the sale of such omburtamab PRV, 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 Y-mAbs 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 advancements it represents for the company and the medical community. The IND for our first SADA construct the GD2-SADA 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 2-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 patient in the fourth quarter. And we look forward to potentially being able to share tumor binding data in 2023 as our SADA development is based on a theragnostic 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 other 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 promising, a promising treatment that can potentially address an important pediatric unmet need as AML remains one of the most challenging hematological 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 nivatrotamab in order to preserve capital as our GD2-SADA is so close to the clinic and to focus our attention on our commercial assets DANYELZA and the potential launch of omburtamab.

As you know, we have established a partnership with SciClone Pharmaceuticals for DANYELZA and omburtamab expansion in greater China. We are especially excited about DANYELZA 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 DANYELZA's Asian sales.

We continue to work on making sure that DANYELZA and omburtamab, if approved, will have a global footprint. And we have entered into additional partnerships covering LatAm, 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 runway and a robust pipeline, we believe we are on track to deliver many more clinical and commercial milestones, support the continued commercialization of DANYELZA and the potential launch of omburtamab as well as advanced our early-stage programs, including the SADA technology constructs.

We are very pleased with our current financial position, which Bo Kruse, our Chief Financial Officer, will elaborate on in a minute.

Thank you, over to you, Bo.

Thank you, Thomas, and good morning, everyone. Our net revenues of $10.8 million and $21.3 million for the quarter and 6 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 6 months ended June 30, 2022, includes $1 million worth of license revenue compared to $2 million worth of license revenue in the corresponding periods of 2021. DANYELZA product revenues for the quarter and 6 months ended June 30, 2022, was $9.8 million and $20.3 million, respectively, which represented increases of 9% and 42%, respectively, over the corresponding periods of 2021.

Our DANYELZA 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 royalty 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 million and $8 million to $26.4 million and $49.3 million for the quarter and 6 months ended June 30, 2022, respectively. These net increases in the quarter and 6 months ended June 30, 2022, reflected increased outsourced manufacturing, inclusive of $2.9 million of naxitamab inventory vials that were designated for clinical use during the 3 and 6 months ended June 30, 2022, and increased clinical trial activity with a particular focus on DANYELZA, omburtamab and the SADA 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 6 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 noncash share-based compensation expense and to a lesser extent, the launch and commercialization of DANYELZA, which included employee-related costs and commercial expenses.

We reported a net loss for the quarter ended June 30, 2022, of $41.1 million or $0.94 per share basic and diluted compared to a net loss of $22.9 million or $0.53 per share basic and diluted for the quarter ended June 30, 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 a net loss for the 6 months ended June 30, 2022, of $69.2 million or $1.58 per share basic and diluted compared to a net income of $10.5 million or $0.25 per basic share and $0.23 per diluted share for the 6 months ended June 30, 2021. The net income in the 6 months ended June 30, 2021 included a $62 million gain from the sale of our DANYELZA 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 6 months ended June 30, 2022, also reflects the unfavorable impact of the charge related to contractual severance related benefits for our former Chief Executive Officer and increased R&D expenses, as we noted above, partially offset by the favorable impact of DANYELZA'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 and a 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 30 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 PRV, which we could sell upon the potential approval of omburtamab. In addition, no new partnerships or the BT-related sources of income are included in the assumptions. Potential omburtamab revenues upon approval are also not included and the DANYELZA 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 growth rate for DANYELZA 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 as previously disclosed, we continue to expect operating expenses of $162 million to $167 million and a total cash burn of $78 million 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 Y-mAbs remains in a healthy financial position to execute our strategic mission, priorities and support the delivery of multiple milestones.

Now, this concludes the financial updates. And I'll now turn the call back to Thomas.

Thank you, Bo. This marks the end of today's prepared remarks. Let's open up the line now. And then perhaps we can ask the operator to remind you of the procedures for submitting your questions at this time. Thank you.

(Operator Instructions) Our first question comes from the line of Alec Stranahan with Bank of America.

Just a couple from us. First, on omburtamab 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 DANYELZA 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 of A&P.

Thank you, Alec. Sue, I think you can take the first question on omburtamab.

Yes. Thanks, Alec, for the question. So the U.S. team is very engaged right now in the preparations for the launch of omburtamab and we're actually in a 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 DANYELZA 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 the signs right now, we're continuing with that effort and hoping, obviously, for that outcome and certainly have prepared our thoughts on the best way to commercialize in the years should that come to fruition.

Thank you, Sue. Vignesh, do you want to -- I mean let's not go into GD-SADA study design to talk about what we're achieving for the first dose cohort and the timing of the 2 injections and maybe the starting dose?

Yes. Well, so thank you very much. It's Vignesh, the Chief Medical Officer here. So this SADA 101 trial, this is a Phase I dose escalation study that will be divided into 3 separate parts. The 3 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 data 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 of lutetium data will only be initiated in patients who have completed a dose-limiting process the observation for the first part, which is just for the GD2-SADA.

So this is -- the escalation trial will be based on a classical 3 plus 3 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.

Our next question comes from the line of Robert Burns with H.C. Wainwright.

Just 2, if I may. So for the first one, it seems like the number of centers that you're able to have been slowing as of recently. Given this, sort of curious what the average number of neuroblastoma patients are 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 II trial for nivatrotamab in frontline neuroblastoma? And will we also see another IND submission for an additional SADA construct this year?

Thanks, Robert. Sue, will you take the first question, and I can take the second.

Sure. Thanks, Robert, for your question. Yes, so in terms of the number of patients, again, sort of putting this into perspective, the 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 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 -- the good news is our team can execute well, 89% of our enrollments are coming from the accounts we've prioritized.

So I think that 18 months post launch, starting to see both a second patient, 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 not 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 plan.

Thank you, Sue. 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 validating GD2 in the clinic prior to that IND.

And are you also planning the Phase -- the frontline neuroblastoma trial for nivatrotamab?

So, frontline, so much. Yes, we are still waiting on gathering some data and then we will go and address the FDA. But I -- we are not planning on any head-to-head study. We're planning to have discussions with the FDA on a non-inferior basis and see where we can take that.

Our next question comes from the line of Charles Zhu with Guggenheim.

My first one regarding omburtamab. Could you provide any additional color or expectation the types of data we could see for the upcoming SIOP presentations? And also regarding specifically B7-H3-positive CNS/metastases, could you also provide your thoughts around a potential development steps, and on the next steps of this particular asset as a future label expansion opportunity.

Vignesh, do you want to take the first one?

Yes. So as you just quite rightly alluded, we will be looking at a SIOP presentation later this year for the 101 study interim analysis. This is the multicenter Y-mAbs-led study that will be delivered by Dr. Kramer.

And also at SIOP 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 benefit -- clinical benefit in terms of response rates and survival with a manageable safety profile. For example, in the 03-133, 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 the indirect comparison the need in overall survival has a difference of roughly 15 months in the control arm versus 43 months in the actual interventional arm, albeit taking to 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 6 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 2 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 have 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?

Yes, specifically, for the B7-H3 positive CNS, yes.

Yes. I think in theory, if we are able to get pass this FDA PDUFA approval, we will be looking to see other areas where omburtamab can be used in those specific patient populations who can benefit from this. So there are a number of nivatrotamab, CNS tumors that express B7-H3, not only in pediatrics, but adults. Further details are 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, ependymomas, and other neuroectodermal tumors as well as through Y-mAbs-sponsored studies.

So further details will follow, but certainly, it is within our strategy to see where we can get the best risk balance benefit of omburtamab in these B7-H3 tumors.

Our next question comes from the line of Joseph Thome with Cowen.

Maybe the first one on the expected October ASCO for omburtamab. 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 one of these site-to-site kinds of interactions? Anything on that would be helpful.

Thanks. Vignesh, do you want to just give a short -- brief on that.

Yes. So I think we -- as for the ASCO meeting, I expect or we expect the areas of focus for the committee as well as the FDA will be centered around 2 or 3, I guess, important points, which has been brought up in previous discussions with the FDA.

Firstly, of course, we know that the Study 03-133 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 the 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 datas, 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 AdCom to look at.

So I think these were the key points I anticipate the most of the discussion to be. And I should add that all of these points, we have 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 have because I think we are -- our case largely, of course, looks at the data that we have, the 03-133 data is the single largest study in this patient population. And given the fact that is a rare disease, in an area of unmet medical need with very poor prognosis, we also believe the FDA and the AdCom 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 AdCom.

Our next question comes from the line of Tessa Romero with JPMorgan.

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, Tess. Yes. So I do. I do feel confident that we have the right people in place. We're adding more resources. And the materials and programs and infrastructure we put into place in the 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, 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/refractory and appropriate for our product. So you start -- you've often seen rare disease maybe 6 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 of course, the additional growth in 2023.

And Sue, just one follow-up on that if I could. I think previously, you've talked about sort of a 2/3, 1/3 type of split between sort of patients that have been treated more in the second line versus the third line. I guess how does the duration of treatment looking at your latest market research?

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 is 2 to 3 cycles before they go into 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 compartments. So 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.

Our next question comes from the line of Mike Ulz with Morgan Stanley.

Maybe just want to start on DANYELZA. Just as the weakness in patient adds sort of earlier this -- in 2Q, was there anything specific that drove that? Or is that more just some quarterly variability we should sort to think about as we move forward here?

Yes. I think that's really just quarterly variability. We did see a rebound from that. And I mean I hate to use the analogy of sort of even a year where you walk up the stairs. But often in rare disease, you will see some variability. And I do think that the June was -- it was 2 patients off. We're not happy about it. We -- I own it, full accountability. But I do feel that, frankly, the foundation that we have here, our fundamentals are very solid, so we're 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.

Got it, that's helpful. And then, maybe just a quick follow-up just on omburtamab and the AdCom. 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?

Yes. No, so we are -- we have not disclosed the date yet, but we are hoping to get it very soon.

Yes and we will announce it once it becomes available.

Sometime in late October.

Our next question comes from the line of Bill Maughan with Canaccord Genuity.

So my first question is on DANYELZA. So among these 36 sites that do have access to DANYELZA, when a doctor is going through their thought process about how to treat these patients, and they choose treatment other than DANYELZA in a patient that is within DANYELZA's label. Specifically, I guess, what factor do you think is leading them to choose a competitor versus DANYELZA? And how do you change that point in their decision process?

An excellent question. I'm assuming Thomas, you want me to take that?

That's -- that can be a long, Yes.

Okay. So as you know, the other anti-GD2 in the market has been in the market for 7 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 as one Kettering. So at launch, we didn't have hundreds of COG sites that had experience in the nursing staff having muscle memory 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 -- we are indicated and have excellent data in clearing the bone and bone marrow and they do not. And we also are flexible. We have the ability to use inpatient and outpatient. So those are some of the areas that we are talking with physicians about. And when you talk with a lot of these physicians one-on-one, their head is nodding in the right direction.

So 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. And those are some of the areas that I think will be -- we know from current one-on-one interactions with some of the very big center COG positions 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 omnichannel mix that we're working towards continuing to evolve. And frankly, we're building the DANYELZA story as we're speaking here today. So stay tuned, and I think these are some of the areas of the levers that we're working on.

Yes. So just adding, DANYELZA was developed in 4 sites, multi-sensor sites versus Unituxin in approximately 200 sites 5 years ago, 6 years ago. But we are making great progress.

And then I just wanted to check in on the CEO search. How is that going and when might we hear an update?

Yes, I think it's going very well. Y-mAbs 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.

(Operator Instructions) Our next question comes from the line of Etzer Darout with BMO Capital Markets.

This is Luke (inaudible) on for Ether Darout. Just one from me, can you touch on the progress of omburtamab, their label expansion, specifically in the DIPG and DSRCT? And when we might be able to get some clinical updates for those trials?

So DIPG, we've changed the isotope from 124 to 131. And we are planning on pending the outcome of omburtamab for CNS/mets later this year to start a multicenter trial using 131 instead of 121 in DIPG. 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 of label as we move out in the future.

We have no further questions at this time. I would like to turn the floor back over to management for closing comments.

Well, thank you, everyone, for participating today and wish you a great day. Thanks.

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.