Y-mAbs Therapeutics, Inc. (YMAB) Earnings Call Transcript & Summary

Good morning. Welcome to Y-mAbs Therapeutics virtual Radiopharmaceutical R&D update webcast and conference call. As a reminder, today's conference will be recorded. I would now like to turn the call over to Y-mAbs Head of Investor Relations, Courtney Dugan. Please go ahead.

Thank you, operator, and good morning, everyone. Welcome to the Y-mAbs virtual Radiopharmaceutical R&D update, webcast and conference call. We issued a press release this morning before the market opened, highlighting key takeaways from today's discussion. The press release and accompanying slides are available on the IR section of our website. Let me quickly remind you that the following discussion contains certain statements that are considered forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about preclinical and clinical data, regulatory matters, clinical trial timing and plans, the achievement of clinical and commercial milestones, the potential benefits of the company's programs and product candidates, and other statements that are not historical facts. Because forward-looking statements involve risks and uncertainties, actual results may differ materially from those expressed or implied by such statements due to a variety of factors, including those risk factors discussed in the company's previously filed report on Form 10-K for the year-ended December 31, 2024, as supplemented by the risk factors discussed in the company's quarterly report on Form 10-Q for the quarter ended March 31, 2025. I will now turn the call over to our President and Chief Executive Officer, Mike Rossi.

Thank you for joining us today during our virtual Radiopharmaceutical R&D update. Joining me today is Natalie Tucker, our Radiopharmaceutical Business Unit Head; and Norman LaFrance, our Chief Medical and Development Officer. We also have our Chief Financial Officer, Peter Pfreundschuh, joining during the Q&A portion of today's update. I will make a few opening remarks and then hand the call over to Natalie. At Y-mAbs, our vision is to pioneer and develop next generation therapies, leveraging our novel immunotherapy and Radiopharmaceutical platforms to transform patient care for a broad ranges of diseases, starting with cancer. Y-mAbs Therapeutics was founded 10 years ago with the urgent mission to make innovative cancer therapies available to patients worldwide. Since then, we have brought an important and differentiated antibody therapy, DANYELZA, to market in the pediatric oncology space, meeting our mission of helping to improve the lives of patients and their families. DANYELZA has provided and continues to provide invaluable quality time for patients with relapsed/refractory high-risk neuroblastoma in the bone and bone marrow out of the hospital setting, giving the gift of childhood back to patients. This legacy of impact and improving people's lives is something we are working to expand with our Radiopharmaceutical platform and programs. With the establishment of 2 distinct business units announced earlier this year, we have the people and resources in place to further maximize the full potential of DANYELZA in and beyond neuroblastoma, while at the same time, accelerating the strategic advancement of our novel self-assembling and disassembling pre-targeted radioimmunotherapy or SADA PRIT technology platform and programs across targeted disease areas. We are excited to provide you with several updates across our radiopharmaceutical business today. Within our radiopharmaceutical business, we have 5 strategic enablers, which define our vision for growth, which you can see here. Each of these addresses a significant gap in the current radiopharma space. First, we believe pretargeting will address the challenge of off-target toxicity associated with many Radiopharmaceuticals. Second, we are working toward building a fully operational theranostic platform, encompassing both novel radioimmunotherapies and accompanying diagnostic tools. Third, we will leverage the multi-isotope modularity of our platform, which will pair the appropriate isotope to the patient-specific disease characteristics. Fourth, we are putting our investment towards strategic R&D and clinical advancement rather than building large manufacturing facilities for complicated radiochemistries. Lastly, we are enhancing physician participation in patient treatment, allowing for a more collaborative and efficient treatment patient journey. Let me touch on these areas a bit more. By executing our vision for our Radiopharmaceutical business, we are well positioned to potentially disrupt both the existing treatment paradigm and the commercial pathway for Radiopharmaceuticals with much lower cost and increased access for patients and physicians alike. As I mentioned with SADA, we have no need to spend hundreds of millions of dollars on new infrastructure and physical manufacturing plants. With our pretargeted approach, the assembly of the protein and radioisotope happens in the patient as opposed to a Radiopharmaceutical production facility. This allows us to focus our investments on strategic R&D and clinical advancement of high-value target programs and helps keep our overall cost of goods down. Physician participation is a challenge right now with current radioimmunotherapies. Oncology and nuclear medicine largely operate independently when delivering Radiopharmaceuticals. SADA better utilizes the existing physician infrastructure as the first dose or the pretargeted dose can be administered anywhere by the oncologist. Then after the appropriate clearance interval, the patient will receive the isotope injection by a radiation oncologist or a nuclear medicine physician. With SADA, each physician plays a role in the delivery of the therapy. SADA is patient-centric and it can accommodate a variety of different isotopes using modular designs. Physicians would essentially personalize their radioimmunotherapy treatment for a specific patient. And finally, with SADA's pretargeted approach, we can deliver an optimal therapeutic dose directly to the tumor while significantly decreasing potential off-target toxicity. Let's take a quick look at the progress we have made over the past 1.5 years. Since joining the company in November 2023, Y-mAbs has reinforced its commitment to Radiopharmaceuticals and is leading a brand-new generation of truly patient-centric theranostics. 2024 was a year of execution for Y-mAbs. In the past 12 months alone, we have brought an incredible level of radiopharma expertise, in particular, with Dr. Norman LaFrance and Natalie Tucker and many others across our clinical, quality, regulatory and scientific teams. We have learned a lot from our GD2-SADA Phase I Part A data and the additional molecule optimization work has been completed. We have set a path for strategic growth and clinical advancement, which we will share with you today. Looking to 2026 and 2027, we have several potential high-value inflection points and clinical milestones ahead. You will hear more about this later today. Today, we will report on the progress of our Radiopharmaceutical pipeline and release the results of our completed Trial 1001 Part A data, including our plans for future studies. Let me pass the call to Natalie, who will discuss the results from Phase I Part A of our GD2-SADA Trial 1001.

Thank you, Mike. I want to highlight the important takeaways and learnings gained from recent insights across our SADA platform. First and foremost, we are pleased to achieve the primary endpoint of Trial 1001 Part A that GD2-SADA is safe and well tolerated. This indicates that we will be able to advance this, our first ever in-human SADA program through further clinical development and continue to execute on new additional programs, which I will speak about later. In addition, in Part A, we confirmed the pharmacokinetics of our GD2-SADA protein and our Lu-DOTA radiohapten behaved as expected based on our preclinical studies with allometric scaling to human models. Importantly, the GD2-SADA PK presented close patient-to-patient repeatability within cohorts, which validates the performance of our protein and is imperative for determining the optimal time of Lu-DOTA administration. Within our operations, we are moving forward with improvements to streamline our study design and overall operations in order to accelerate our clinical trials. Recent insights collected will benefit our entire platform and support the strategic advancement of high-value targets. Now let's dive into results from Part A, our GD2-SADA Phase I Clinical Trial 1001. Earlier this year, we shared an initial look into data from Part A of Trial 1001. Today, we will provide a more comprehensive overview of safety, PK, and dose symmetry from the 6 dosing cohorts in Part A. Additionally, we will share how we are using this data in collaboration with feedback from our KOLs to pave the way for the next steps in both our GD2-SADA program and benefit our entire platform and operations across an expanded therapeutic and molecular imaging pipeline. We will begin with the trial background and design. Following extensive preclinical and IND-enabling studies with GD2-SADA and Lu-DOTA, Trial 1001 was initiated in 2023 as a first-in-human study of this novel pretargeting approach; 7 study sites have been activated to date. The key objective of the Phase I study was safety. Secondarily, we evaluated the PK, dosimetry and immunogenicity of GD2-SADA Lu-DOTA. The original Phase I design included 3 parts: A, B and C. In Part A, which we're reviewing today, the GD2-SADA protein was given over increasing doses from 0.3, 1 and 3 milligram per kilogram with varying clearance intervals spanning 2 to 5 days. A few key items to note. The trial covered multiple indications, including sarcoma, melanoma, small cell lung cancer and in the final cohort, high-risk neuroblastoma. Patients were eligible with recurrent or refractory metastatic solid tumors with a valuable disease and standard ECoG in liver, renal and hematological functions. We restricted prior systemic treatment within 3 weeks of dosing with GD2-SADA. For Part A, the design was split into imaging and therapy stages. All participants first underwent the imaging stage where they were evaluated with CT anatomical imaging. A maximum of 5 lesions were selected to follow by the local study site team. Patients subsequently received a dose of GD2-SADA protein followed by a clearance interval and a 30 mCi dose of Lu-DOTA. All participants had blood drawn to monitor GD2 protein and Lu-DOTA pharmacokinetics, as well as GD2-SADA immunogenicity, and received nuclear imaging to determine tumor uptake and radiation absorbed doses to the tumor and organs. Tumor uptake was determined qualitatively as a clear difference in lesion to background activity with a contrast to noise ratio greater than 3. Like target lesion determinations, tumor uptake was assessed locally and at the discretion of the site. At least 1 of the target lesions had to show positive uptake as determined by the site to become eligible for the therapy stage, where they subsequently received another dose of GD2-SADA protein and a therapeutic dose of Lu-DOTA, either 100 mCi or 200 mCi. Only the previously selected lesions were eligible for evaluation of tumor uptake. As noted, we had a heavily pretreated multi-indication patient population. Of the 31 patients screened, 23 were enrolled and treated with GD2-SADA protein in the imaging phase. Reasons for screen failures vary, including no measurable disease, lab values out of inclusion criteria and serious intercurrent illness, among others. All 23 patients are included in our safety set. 22 patients subsequently received Lu-DOTA following GD2-SADA protein administration. These patients are included in our imaging set. Of the 9 patients with tumor uptake as determined per protocol, 7 went on to the therapy stage with 3 receiving 200 mCi of Lu-DOTA and 4 receiving 100 Lu-DOTA; 2 of these patients withdrew before completing their final day 43 blood draw. Across all 23 patients enrolled, we had nearly equal representation for male and females across a wide range of ages spanning 16 to 76. Patients were heavily pretreated with radiotherapy, surgery, chemotherapy, and immunotherapy. Most were metastatic to the liver, bone, lung and/or brain, and there was a wide range of tumor lesion sizes. Of patients selected for imaging, an average of 3.1 tumors were selected per patient by the site for further evaluation. As previously noted, the determination of tumor uptake was conducted locally and per the discretion of the site staff. As we showed during our full year 2024 earnings call, 9 participants showed tumor uptake per protocol across sarcoma and melanoma. The small cell lung cancer and the 2 enrolled high-risk neuroblastoma adult patients did not show uptake. Notably, these high-risk neuroblastoma patients were over the age of 16 and heavily treated with prior GD2-directed therapy. Our Chief Medical and Development Officer, Dr. Norman LaFrance, will now present our safety, PK and dosimetry data.

Thank you, Natalie. Part A of Trial 1001 was our first in-human study of the SADA-based pretargeting platform with safety as the primary objective. As you will see, an acceptable robust safety profile was met. As previously reported, Part A demonstrated a robust safety signal. Administration of GD2-SADA up to 3 mg/kg and Lu-DOTA, up to 200 mCi, with clearance intervals ranging from 2 to 5 days were shown to be safe and well tolerated across all 6 dosing cohorts. Importantly, there were no dose-limiting toxicities or treatment-related serious adverse events observed and no adverse event trends across the dosing cohorts. Per protocol, the DLT observation period was 6 weeks of first GD2-SADA administration. Dose-limiting toxicity evaluable patients, therefore, included patients who completed both imaging and therapy stages, effectively receiving 2 doses of GD2-SADA and 2 doses of Lu-DOTA as well as those who were on study for 6 weeks from the first GD2-SADA administration. A significant finding in our safety analysis was the majority of AEs were not related to the treatment. Those that were related were predominantly Grade 1, 70%, and Grade 2, 27.5%. The single Grade 3 related adverse event was abdominal pain the day of the first GD2-SADA administration, which we'll cover later as 1 of the 3 adverse events of special interest. To emphasize, we did not observe any DLTs or treatment-related serious adverse events over the 6 cohorts. In this data-rich slide, the most common AEs were nausea, lymphopenia, and constipation. However, going back to our demographics, the 23 patients enrolled had diverse primary cancers, were metastatic and progressive, had undergone a number of pretreatments ranging from surgery to immunotherapy and were on significant concomitant meds to address their cancer. Hence, the AE profile is not surprising. For related AEs, the most common observed included nausea and chills of grades 1 and 2, all of which resolved spontaneously or with minor treatment. Notably, we did not see any dose-dependent AE trends that you would expect to see with the usual GD2 binding such as pain or hypotension, even with increasing amounts of protein over the study cohorts, indicating as expected that the GD2-SADA construct, at least to the 3 mg/kg currently studied does not share nor is as severe as the existing anti-GD2 therapies. Similarly, and despite the fact that 7 patients received 2 doses of Lu-DOTA totaling up to 230 mCi, we did not see any dose-dependent radiation-related adverse event trends. To that end, we saw only 2 patients with a total of 3 adverse events of special interest. One patient reported abdominal pain with the first GD2-SADA protein infusion and did not continue with the subsequent Lu-DOTA dose. The pain observed was non-serious and the patient recovered on the same day. Notably, this patient had a prior history of cancer pain, nausea and diarrhea and had been treated with conmeds to manage those. A second patient had a history of elevated liver enzymes, which were maintained following the imaging stage and eventually reached grade 3 while on study. However, they were deemed non-serious and unrelated to study drug. In summary, the safety data from Phase I confirms the safety observations that GD2-SADA protein and Lu-DOTA pretargeting platform provide a robust, well-tolerated approach, delivering radioactivity to the tumor without any notable dose-dependent adverse effect trends. Secondary objectives of the 1001 trial included analysis of the GD2-SADA protein PK, the Lu-DOTA PK and tumor and organ dosimetry. This section will show that the PK of our GD2-SADA product is dose-dependent, predictable based on preclinical modeling and demonstrates expected characteristics around Cmax and clearance rates over time. The next few sections will provide more details on these findings. The PK and other preclinical evaluations per standard, mice were utilized to evaluate our pretargeting platform. This model was also chosen because GD2 is expressed comparably across tissues and GD2-SADA protein had a comparable binding affinity to GD2 expressing murine and human cell lines. In our murine models, we described the importance of the concept known as SADA trough, which refers to the nature of circulating SADA protein as determined by PK analysis of blood samples over time. The SADA trough is a function of the amount of administered GD2-SADA protein and the clearance interval prior to the Lu-DOTA administration. Preclinically, we observed that optimal tumor-to-organ ratios were seen when the SADA trough was less or equal to 1 microgram/ml prior to giving Lu-DOTA. Using standard scaling coefficients from mouse to human, we modeled the PK profiles of various administered doses of GD2-SADA protein as shown here in the figure on the left. The modeling indicated a longer clearance interval was required to reach the equivalent SADA trough threshold seen in the murine experiments for a given scaled protein administered dose. The clinical trial commenced with a study design that sought to investigate the GD2-SADA PK over varying protein concentration and clearance interval combinations. As predicted, we observed that higher concentrations of GD2-SADA showed slower clearance rates from blood than lower concentrations of GD2-SADA, which was highly reproducible when looked at on a per patient basis by cohort, indicating that even among highly variable patient population, GD2-SADA's PK performance is largely a factor of its administered dose. With regard to the SADA trough, the highest delivered concentration, 3 mg/kg did not reach 1 microgram per mL until approximately 120 hours after the administration, which was expected. Lower doses reached the SADA trough in less time as evidenced by the 0.3 and 1 mg/kg cohorts. When the GD2-SADA PK was normalized by the concentration of the administered protein dose, all dose concentrations had similar Cmax and clearance rates. Interestingly, the 0.3 mg/kg cohort did appear to have a faster clearance rate compared to the other 2 cohorts. While more data is required to better characterize this difference in our preclinical models, we did see the plasma concentration profiles were dose proportional for doses greater than 20 mg/kg, but lower than dose proportional for doses of 2.5, 4 and 10 mg/kg, which were described to higher levels of monomers at low concentrations having faster clearance than tetramers. Taken together, the first-in-human study of the GD2-SADA protein and associated PK profiles over varying administered doses shows that GD2-SADA protein PK provides a road map for determining the SADA trough and provides valuable key learnings that can be utilized to further refine murine-to-human modeling for current and future targets. We next evaluated the PK of the radiohapten Lu-DOTA, determine serial blood measurements following its administration. The key takeaway is, unsurprisingly, that Lu-DOTA PK is dependent on both the concentration of the GD2-SADA protein at the time of administration and the clearance interval between GD2-SADA protein and Lu-DOTA dosing. When Lu-DOTA is plotted against the GD2-SADA protein PK, you see a positive correlation between circulating Lu-DOTA and circulating GD2-SADA protein. For example, the 3 mg/kg GD2-SADA cohort had the highest circulating Lu-DOTA over time. This protein concentration to Lu-DOTA PK is expected and a positive study finding. When looking at Lu-DOTA PK group by cohort, we can further see the impact of the initial GD2-SADA protein concentration on elimination rates. The 2 cohorts at the bottom here are both 5-day intervals, one with the 0.3 mg/kg and one with the 1 mg/kg administered GD2-SADA. Notably, the top group here is a 3 mg/kg, which is also at a 5-day interval. In this case, even though the 3 mg/kg was given after a 5-day interval, the higher protein load significantly slowed the elimination of the Lu-DOTA. This reinforces the importance of these data and will allow us to maximize the reduction in circulating GD2-SADA protein at the time of Lu-DOTA administration and, most importantly, minimize and mitigate off-target effects. Lastly, we investigated tumor and organ dosimetry. As originally noted per protocol, up to 5 target lesions were determined locally by each site via CT prior to GD2-SADA protein dosing. Only target lesions identified at the site, which were later deemed to have a contrast to noise ratio of greater than 3 on SPECT/CT at the site's discretion were considered to be uptake positive. Only these tumors were further analyzed by dosimetry. Briefly, serial whole body planar SPECT imaging supplemented by blood sampling were used for radioactivity measurements following the imaging stage dosing only. Dosimetry is conducted using a hybrid SPECT-CD planar approach using a dose factored-based approach as commonly found in the commercially available OLINDA/EXM software. Secondarily, in order to understand the performance of our GD2-SADA- Lu-DOTA complex holistically, we performed an expanded assessment using the Torch software, which uses voxel-level dose calculations based on the direct Monte Carlo method. In this expanded evaluation, all 22 patients receiving Lu-DOTA were assessed and all tumors included for evaluation regardless on their status as a CT-defined target lesion. For the 9 patients with protocol-defined uptake, absorbed dose to the target lesions were modest with organ uptake to the kidney, spleen and red marrow also evaluated. Unlike what we observed in the preclinical setting and expected in this Phase I Part A study, no cohort demonstrated an optimal therapeutic index. As a note of clarification, all dosimetry shown is based on the 30 mCi imaging dose of Lu-DOTA. However, when we expanded the dosimetry assessment to all patients and all tumors, we discovered 16 out of 22 patients had tumor uptake that would have otherwise qualified them for the therapy stage. The column colors here represent the different cohorts, and the table is divided into the original set to the left and the expanded set to the right. All data and calculations were performed with Torch software. Critically, in the expanded evaluation, we observed a higher tumor uptake in a number of lesions. In some cases, we also observed an improved therapeutic index. Notably, at least 2 tumors received over 1 grade even with the 30 mCi Lu-DOTA dose. Compared to our original uptake list by indication, we now see that all osteosarcoma patients had uptake in addition to most of the other sarcoma patients. Almost all melanoma patients showed uptake and the patient with small cell lung cancer also had uptake. Taken together, these indicate GD2-SADA is binding despite a variable patient population with heterogeneous GD2-expressing tumors. To further illustrate the power of expanded evaluation, the image on the left shows tumor uptake in a lesion that was not noted as a target lesion. But because the patient had at least one target lesion with uptake, they were eligible per protocol for the therapy stage. The right picture shows a patient who is not eligible because the preselected target lesions did not show uptake. However, as evidenced in the image, non-target lesions did show uptake. These data underscore how a broad review of tumors and their uptake is required to better understand the impact of our pretargeted platform across patients and tumors. Let me now pass the call back to Natalie, who will recap these findings and our key learnings.

Thank you, Norman. In summary, the primary objective for Part A of our 1001 trial was safety, and we demonstrated a robust safety profile across 23 patients treated with the GD2-SADA protein, which includes the 22 patients treated with both the GD2-SADA protein and Lu-DOTA. Notably, the safety included 7 patients receiving 2 doses of both protein and radiohapten across the imaging and therapy stages. The GD2-SADA protein PK was precise and predictable when evaluated over multiple doses and clearance intervals. Importantly, understanding the GD2-SADA protein PK prior to subsequent radiohapten administration is key to informing the optimal trough and clearance interval as related to a given antigen sink and will be incorporated into future study designs. We believe this PK insight and positive safety profile will enable parallel cohort testing, thereby accelerating development. When opening up the tumor uptake analysis beyond the 5 tumors allowed per protocol and using SPECT/CT as a determining factor, we observed a far greater number of patients with tumor uptake. Critically, this expanded evaluation with concomitant streamlined dosimetry analysis will be built into future designs to allow us to make rapid clinical decisions. Lastly, dosimetry indicated we did not see renal tumor uptake or therapeutic index and indicated optimization studies were necessary. We, therefore, embarked upon a series of preclinical optimization studies with the intent to bring key learnings back to the 1001 trial. In the multivariable preclinical studies on the left conducted earlier this year, we tested each component of the existing GD2-SADA Lu-DOTA molecule for optimization, building permutations of the current molecule and integrating innovative design features. We were able to identify a new molecule with almost double the AUC of tumor uptake compared to our existing molecule used in 1001 with no meaningful change to organ uptake. Our second study also conducted earlier this year used our existing GD2-SADA protein with the same optimizations as evaluated in Study 1 in a small cell lung cancer model using actinium-225 as the radioisotope. In this study, our optimized molecule was able to achieve greater than fivefold improvement in area under the curve of tumor uptake, again, with no meaningful change to organ uptake. As described, we evaluated 3 components of the existing GD2-SADA complex, including the protein itself, the radiohaptens and the formulation. Data indicated no change is required for the GD2-SADA protein itself and will allow us to utilize our already existing manufactured protein for ongoing trials. Key changes to the new molecule include a new proprietary hapten and a new formulation. These together are anticipated to increase residence time of the conjugated molecule on the tumor. Our new radiohapten expands our access to a range of isotopes with theranostic applications. Like Lu-DOTA, Proteus binds to SADA through an anti-lanthonide DOTA domain with picomolar affinity. Unlike DOTA, Proteus is a universal radiohapten, which, in addition to its better tumor uptake and characteristics, supports a more streamlined development process that can rapidly scale across the therapeutic alphas and betas as well as optimal diagnostic isotopes for molecular imaging to support patient selection and treatment response monitoring. Proteus will be a key component of our modular platform and will enable isotope modularity as described in our vision for growth. In closing, the combined data from Part A of our 1001 trial and the subsequent nonclinical optimization studies are paving the way for the next steps in the 1001 study. We aim to add a bridge study to quickly evaluate Proteus with variable mass doses at fixed GD2-SADA concentration in clearance in adults. We plan for this bridge study to start in the first half of 2026, and we anticipate study results in the second half of 2026. We believe that the molecular improvements will provide a more favorable tumor-to-organ ratio and pave the way for Part B, where we will increase the Lu-DOTA administered dose, which we plan to kick off in early 2027 with data results anticipated before the end of 2027. Notably, we are working closely with the FDA on our next IND on a new GD2 PET diagnostic with filing expected by the end of this year. This GD2 diagnostic will be instrumental in speeding development of this program and will be incorporated into Part B to inform patient selection. Now let's discuss our expanded development pipeline, beginning with a brief overview of our target evaluation. Earlier this year, our team conducted an in-depth target selection work evaluating the next potential high-value targets for our pre-targeting platform. We started with a database of over 1200 targets and narrowed that down based on incidents, unmet need and focusing on tumors that are known to have radiation sensitivity. Secondarily, we looked at target-specific attributes such as cellular location, tumor expression and healthy tissue expression. We landed on 40 to 50 assets suitable for further evaluation. We then considered market opportunity, competitive intensity and development risk to prioritize approximately 15 targets for our platform. We forthranked these 15 targets to develop a mix of archetypes that we believe will diversify our development risk over the coming years. We are focusing short-term activities on targets that are a good fit for our platform and have good scientific validation. As mentioned, the new targets will focus in areas of high unmet need with 5-year overall survival rates at or below 50%. These cancers are primarily in 3 focus areas, namely lung cancers, women's cancer and gastrointestinal cancers. By focusing on franchise opportunities, we will be able to leverage development and clinical synergies, thereby allowing the appropriate development focus. Aligned with our belief that a theranostic pretargeting approach will accelerate development, our Radiopharmaceutical pipeline now includes molecular imaging. We plan to pair a direct targeted PET diagnostic with each of our therapeutic assets with the first moving into IND later this year. This molecular imaging asset will be the first of its kind to identify GD2 expression in the clinic. We anticipate the first patient to be dosed early next year. Also notable in our pipeline is our next-generation therapeutic asset focusing on metastatic colorectal cancer. Development of this asset has already begun with preclinical studies underway. This study leverages our proprietary and universal radiohapten Proteus and will be our entry into alpha therapies with planned testing of actinium-225. Accompanying this target is our diagnostic asset, where testing of both zirconium-89 and copper-64 will begin this year. We plan to file an IND on this asset in the first half of 2027 and anticipate the first patient to be dosed in the second half of 2027. Since the beginning of this year, we have completed 2 optimization studies, and we're currently manufacturing our new universal hapten. We have redesigned our operations, and we anticipate leveraging learnings from Part A to accelerate future and ongoing development. These accomplishments have led to multiple high-value inflection points ahead. First, we plan to submit an IND for our GD2 PET diagnostic later this year using zirconium-89, and we anticipate to see initial study results in 2026. We believe the benefits of a GD2 diagnostic will not only benefit SADA development, but our entire business, helping to expand naxitamab indications as well. We anticipate results from our GD2 Bridge Study in 2026, and we plan to immediately initiate our dose escalation trial in adult patients and separately initiate a pediatric GD2-SADA study upon receipt of meaningful results. To reiterate, we also plan to dose our first metastatic colorectal cancer patient in 2027 using an alpha therapy. I will now pass it back to Mike to close us out for today.

Thank you, Natalie. Before we open the call for Q&A, I want to reiterate key takeaways from today's discussion. Data from Part A of Trial 1001 demonstrates that our GD2-SADA protein is safe and well tolerated. In addition, the protein PK can be used to optimize the dosing interval and maximize the therapeutic index. We believe our new universal radiohapten benefits our entire platform, accelerating development, streamlining regulatory efforts, enabling patient-centric treatment through isotope interchangeability. The new target franchise opportunities in oncology we plan to advance are scientifically and commercially fit for purpose and addresses large unmet medical needs. And together, with the proven safety of our SADA platform, the precision and predictable PK and our redesigned operations, we believe we will accelerate the development of our next-generation SADA platform. I'm proud of the extensive work and progress our team has made across our Radiopharmaceutical business. We believe we are well positioned to potentially disrupt both the existing treatment paradigm and the commercial pathway for Radiopharmaceuticals.

[Operator Instructions] And our first question will come from [ Bill Mann with Clear Street ].

So just thinking through the addressable patient population -- I know after infusing the lutetium, you found patients who would not have otherwise qualified. Do you think that this expands, I guess, the definition of what would be a GD2-positive patient? And then when you layer in a diagnostic on top of that, do you expect to find the broader patient population versus maybe what you would have found earlier, if that makes sense? And then do you expect efficacy to be similar in both that initial positive patient population and the expanded positive?

Bill, thank you for the question. Just as we look at this, just to make sure I'm understanding it correctly, you're asking about expanding beyond the initial 9 patients with the positivity. Yes, so as we look at this -- and I'll kind of set this up and I'll turn it over to Norman -- but as we looked at this, the clear differentiator between the 9 and the additional patients is stepping from what the original protocol was and looking at specific predefined tumors on CT to where the uptake occurs throughout the body. So in a short answer, I'd say, yes, these patients appear to have GD2 positive because they have uptake. And when you're binding to those receptors, you're not constrained by what was seen on CT. And with nuclear medicine, you have the ability to see that receptor expression regardless of where it is, even at smaller quantities that may not be visible on CT -- picked up on CT or even tumors that have been so heavily pretreated, they've -- I don't want to say encapsulate it, but you've destroyed kind of the receptors that are on those. And it's some of the newer metastases, some of the newer untreated that tend to see the uptake. But -- Norman?

Yes. Thanks, Mike. And Bill, the question makes total sense, and you kind of indirectly answered it yourself. Clearly, with the expanded approach to take benefit of not only the anatomical direction of the CT, which as Mike just mentioned was the protocol design, we emphasized utilizing all the available information, particularly the targeted information that as we presented showed more patients with the GD2 tumor avidity. This is also presented, emphasized and showed us that the GD2 protein was fine. That's recognizing the GD2 tumors very well and will help us design future protocols, utilizing all the information. You brought in a diagnostic, having patient selection is always desirable. What we found here is the design with the lutetium imaging dose, which many people do, is one option to -- for patient identification. But as you've heard, we are developing a diagnostic, and we feel this will have even better patient identification capabilities, which will likely further expand the success of this GD2 platform. Hopefully, that answers your question. If you want any more clarification, let us know.

Yes, Bill, just one additional thing. The last thing you asked about was efficacy. I think as we look at this, it's clear -- you can't predict efficacy. But what we can predict is the better the GD2 expression or any targeted expression, the better the opportunity to deliver the isotope to the affected cells and then increase your therapeutic index on that. So I think that the better we select these patients, the better you see them upfront, the more opportunity you have to have at least similar, if not better efficacy than you have with other products.

And since we've seen it in GD2, do you expect this kind of expanded ability to identify patients to be applicable to other targets as well?

Yes. I think it's really target independent. So as we look at this, the beautiful thing about nuclear medicine is it's functional imaging. You actually see what's happening. You see the organ working. In this case, you see the expression. We see it with the other targeted Radiopharmaceuticals that are in the market today. You determine the expression first with diagnostics and then go for the therapeutics. So with that, it's very common in the targeting to make sure that we target those that have good expression, and we're able to treat when the expression is the highest.

And the next question will come from Li Watsek with Cantor Fitzgerald.

I guess just first one on tumor uptake. It looks like there's some variability here, maybe a lower uptake in some tumor types like in small cell lung or neuroblastoma. Just wondering why do you think that's the case? Are these patients positive for GD2? And then for the next-generation hapten, I mean, what do you hope to achieve with the therapeutic index just from a dosimetry standpoint?

Yes. So we'll take that in kind of 2 parts. First, we'll talk about the tumor uptake and then we could really dive into kind of what the hapten will do. So what I'll do is turn it over to Norman first to discuss the tumor uptake and the variability, what we see. And then, I think Natalie will be in a good position to talk about the hapten and what that will do.

Yes. Thanks, Li. As we pointed out, the Phase I was directed to safety, but we opened it up to all tumors that have had prior descriptions of GD2 avidity, which vary by the diagnosis, as everyone knows. What we showed with the additional evaluation with Torch that initially, when we thought some of the tumors were not showing avidity, it was because basically they were preselected by only CT target lesion criteria. When we opened that up to include the SPECT data, the lutetium DOTA imaging dose, many of these other tumors, and we had a slide that showed that all the osteosarcomas, majority of the sarcomas, a lot of the tumors showed the GD2 avidity that was consistent with the published GD2 expression that people know. This gets back to Mike's comments earlier and what I think we've all said, and I've heard from many of you that patient selection ahead of time for GD2 avidity will likely be an important part of the treatment paradigm for GD2. And I might emphasize, although there are some tumors like pediatric -- early pediatric neuroblastoma that is known to have very high GD2 avidity. There are other tumors that would benefit from this therapy, sarcoma, for example, osteosarcoma, melanomas, triple-negative breast, lung cancer. These are the ones that will likely really be available for a GD2 therapeutic intervention, particularly with the availability of a GD2 diagnostic. Hopefully, that helps.

And Li, just as a follow-up to that, the thing to be cognizant of too, of all the dosimetry is based on a 30- millicurie dosimetric dose and not the therapeutic doses. So these when you look at that uptick, it's at the diagnostic levels. And it's also -- that needs to be optimized, which leads us to the radiohapten change and what our plans are for the future with that. So Natalie?

Yes, sure. And thank you, Li, for the question. So going back in terms of the impact of the optimization on the therapeutic index. So just to recap, we're expecting to make 2 changes, and we're planning on those changes right now, one to the radiohapten and one to the formulation. The hapten itself has 2 big benefits. Number 1, it is universal. So we'll be able to use it across all of our different formats, including our diagnostic. And also, critically important, the tumor uptake. So you did see in the preclinical studies that we saw tumor uptake area under the curve, 2x to 5x. And what's so important about that, if it wasn't evident, was the time retention on the tumor. Because it retains so long on the tumor, you're able to extend that dosing interval, allow the protein to clear from the blood while you still have tumor retention, and then dose the lutetium. So it really does add an improvement to the therapeutic index for that reason. And again, we're seeing those increase in tumor uptake 2x to 5x. In terms of the formulation, we're also doing a change there where we increase the amount of Proteus that we deliver, effectively increasing the mass. And what that actually does is it acts as a clearing agent in a way to clear the protein from the blood so that you can also increase your therapeutic index. And it actually -- what we've seen is marginally reduces the off-tumor effects so that we really could see the upside on 2 fronts, both from the hapten on the increased tumor uptake as well as the formulation on the decreased off-tumor uptake. So hopefully, that addressed your question.

And the next question comes from John Newman with Canaccord.

So you've talked a lot about the PET diagnostic going forward that this will be refined and sort of designed for each specific indication. I'm just wondering if at any point in time going forward, you'll be able to develop an additional assay for GD2, perhaps something more similar to some of the assays used for other targets such as IHC, although that may not be applicable here? Or if we should expect that at least for GD2, you'll be relying on the PET diagnostic?

Yes. It's -- John, thank you for the question. It is a great question. The challenge with GD2 is something that the industry has been fighting with for a long time. Many institutions have tried. We have tried several different ways to get a conventional IHC in order to move forward. In order to get a validated test, you really need to be able to preserve it. And it's generally a paraffin-based test, which the paraffin destroys the GD2 receptors. So it doesn't allow you to look at it. There's been some fresh frozen that show GD2 expression, but it's very difficult to validate because it is institution-by-institution. So as hard as we've tried over the years, it's been very difficult to do. That's why it was so exciting to get GD2-SADA into patients and actually start seeing that receptor expression. Maybe I'm a bit tainted as a nuclear medicine person, but when you can actually see something live and you see the amount of expression, you see that affinity, it gives you a much better direction on which patients to select, which indications. So I think with GD2 and again, I defer to others as well, I think our best option going forward is a Nuclear medicine imaging agent, a PET agent to patient select for GD2, both for a radiotherapy as well as DANYELZA.

And one additional question. You mentioned in your prepared remarks that you're looking to potentially have data in the second half of '26 for the Part 2A study with the optimized Proteus Radiohapten. I'm just curious if perhaps maybe internally, will you be able to take a look at PK ahead of that? Or should we expect all that data to sort of come in second half of '26?

Yes, John, good question. And we're actually building that time line as we speak. We're looking at both the bridging study as well as the Part B as part of that as rolling it forward. It's -- for me, the PK is much easier to have those conversations about on a patient-by-patient basis, and we've seen a lot of consistency across all of the patients on the PK. So it gives us a level of reassurance on how SADA is performing, what that looks like, what the clearance looks like. Ultimately, when we start looking at the therapy and the imaging, I think it's important that we aggregate and look at least groupings of patients so that we're not looking at this as results coming in from individuals. You want to see what the overall evidence says across a larger group. So I'll turn it over to Natalie on kind of what the plan is. But I think overall, it's important for us to look at this and aggregate the data so that we know exactly what we're looking at and not make assumptions based on a single patient.

Yes. Good point. Thanks, Mike, and thank you, John for the question. So in terms of that Part A2 study for the Bridge, I mean, we're really looking at running 2 parallel cohorts. We mentioned this earlier today and our opportunity to accelerate. And that first cohort number 1, we'll be really evaluating -- we'll be swapping out that Lu-DOTA for Lu-Proteus and evaluating the safety, PK and dosimetry. So exactly what you said, our goal and what we've mentioned today is PK really drives our dosing interval and our therapeutic index. So we'll be looking at the PK very early, and we want to run a parallel cohort where we also adjust the mass dose, so our formulation change. So we are thinking around 6 patients based on study -- statistics that we could run in parallel. So that's why we hope to have that data by the end of 2026.

And the next question comes from Alec Stranahan with Bank of America.

A few from us. I guess, first, are there any optimizations to the tumor binding motif of the GD2-SADA construct you're contemplating to maybe make it a bit stickier for the tumor? Or is the path forward really on this piece with the hapten and the formulation? And secondarily to this, I guess, is this maybe more of a GD2 like a target issue or a SADA issue in your view? Just reading through to your other programs.

Yes, Alec, good questions. As we look at this, we're not planning any changes to the GD2-SADA protein itself. For us, it's optimizing the Radiohapten to increase the affinity. And that becomes platform -- a platform change. So when we look at moving forward with the Proteus, it will be used on all. GD2, again, the only validated GD2 target is pediatric neuroblastoma. So a lot of this is a bit of a learning experience. And it's an NM1. So we'll learn more about the additional targets as we move forward on the best way to optimize those. I think also looking at our development plan forward, as Natalie had discussed, we're looking at manufacturing for phase specific development, which will give us the opportunity to tweak that protein on the high-value targets to make sure that both the lead sequence and the SADA itself has the highest tumor affinity, combining that with the proprietary Radiohapten will allow us to maximize the therapeutic index on these. Natalie, is there anything else?

No, I think just going to Alec's question regarding is the issue GD2 itself. I think that speaks to the fact and the importance of having a diagnostic so that we can preselect those patients for therapy because it is a very heterogeneous population of tumors. And so, it's really hard to predict what should be showing uptake and what shouldn't. So that GD2 diagnostic will really benefit us as we go into the later studies later next year.

Okay. Got it. And then just on the CD38 program, curious if this is also impacted by the planned inclusion of Proteus? Or I guess, what's sort of the path forward given the first patient, I think was initiated in the first half of this year in that study?

Yes. Alec, good question again. We're continuing with the CD38 study and evaluating each patient as they come in. It will have an effect as we move forward with the program to then take that bridging study and that will be completed for that Radiohapten, we could plug that into any of the SADA trials to increase the overall affinity. But ultimately, again, similar to our 1001 Trial, the 1201 is a safety study with the protein. So no changes needed at this point to get the information we need from a safety and a PK. And then as we start looking at moving into efficacy is where we'll move into the Proteus.

The next question comes from Justin Walsh with JonesTrading.

So maybe the first one, can you confirm if the new alpha therapies, are those making -- that you're planning on using the SADA platform for those?

Yes.

Got it. And then maybe you can give us a little color on where you see the opportunity in metastatic castration-resistant prostate cancer. I think that's listed as the new target for the IND submission first half of 2027. Obviously, there's a lot in PSMA out there, but others are working on some novel targets in prostate cancer. So curious how you view the landscape. And I'm sure you can't give too many specifics right now, but just wondering on the positioning.

I appreciate it. I'll turn that over to Norman, who can definitely help walk through that.

That's a great question. I guess the short answer is there's applicability of our platform to the PSMA. I guess I'd summarize it that the 2-step is feasible against PSMA even as an internalizing target. We've looked at various clones, some with excellent potential in the castrate-resistant prostate carcinoma. We've done some comparisons and they're promising. I really can't go into detail now, and we're -- and that's not by being secretive. It's just we have additional data to do. So -- and the feasibility, again, for targets even internalized seem to be promising here. So we've gotten some very provocative preliminary data. We're running more experiments and stay tuned for that development. I think I'd add also besides your question on prostate, we are looking also at colorectal cancer. There's some very promising data on that target that I'll defer to Mike on how much we disclose.

Justin, as we look at these, for us, we're going to focus in 3 franchises and for what we want to commercialize. And things like prostate, although the platform is very good for that, we'll make that decision as we move forward on if it's something that we help somebody else get into the 2-step, whether it's something that we consider doing down the road or if it's something that is good enough where it is. But at the end of the day, it's all part of the evaluation in both from an internally commercialized product as well as potential BD partnerships.

Got it. One more, if I can. I'm curious, as we're kind of moving forward and we have this optimized Radiohapten we're working with and then also you're moving into trying things with alpha therapies. Is there a certain tumor to kidney ratio that you define as a sort of a SADA success from a broad sense, obviously, I'm sure it's kind of dependent on the particular cancer and some of those other details, but curious what your thoughts are moving forward?

Yes -- no, as we look at these, I wouldn't say there's one single number on a tumor kidney, especially difference between alphas and betas. And then 2, looking at the overall half-life of the isotope, where we have a lot of flexibility with SADA is using shorter-lived isotopes. So if you have a situation where you've got great tumor affinity for a short period of time, using the shortest-lived alpha isotopes gives you the best therapeutic index on that and the best ratio between the tumor and kidney. A lot of the kidney data is all based on external beam. So there's so much happening right now in collecting the data on systemic radiotherapy and understanding what the appropriate levels are. Again, the larger the difference between the tumor and the off-target, the better it's going to be. But as we look at this, we want to make sure that we're focused on tumor absorption. We're looking at kidney function, liver function because it's ultimately, is it causing damage, both short and long-term? Is it reversible or not? And is that the right way to move forward? So again, with the betas, you want a much bigger tumor-to-kidney ratio. The alphas is maybe not so much, and it gives you a lot more flexibility. With our platform as well, what we know is the lower the nadir in the blood upon injection, the less toxicity you see off target. So to me, the one key for us is making sure that we're injecting at the right period of time, whether it's an alpha or beta, and you will create that differentiation you're looking for.

And the next question will come from Nicole Germino with Truist.

So I noticed that there is no tumor uptake with the 2 neuroblastoma patients. Can you explain why or was it not enough dose? And then should we think of GD2-SADA as part of the life cycle management for DANYELZA, given that you already have so much expertise in the GD2 space with DANYELZA already. Would that be more -- or is this more of a proof of concept and this will be used as a format to kind of help build the foundation for the pipeline? Or will this also be a key target for further clinical and commercial development for GF2?

Yes. So I'll break that into kind of the 2 halves on the -- we'll start with the kind of the tumor uptake and what we see on that and what kind of the expectations are. And that I'll turn it over to Norman to talk about that. And as far as moving forward with GD2, I'll address that upfront. I think all of these -- as we look at them, DANYELZA is a fantastic product, and it has its own life cycle plan for continued expansion. And that's part of the reason for getting into the GD2 diagnostic for us to be able to really patient select for things like for breast, for lung, for sarcomas. So we plan on continuing to invest in DANYELZA and move that forward. Now as far as the GD2 product itself as SADA-GD2, that too may have its opportunities to go after some similar indications, and it may be in conjunction with, it may be sequenced. Time will tell as we develop the evidence on that. But it's not a plan to replace DANYELZA in any stretch of imagination. But as we look at this, the diagnostic can enhance the opportunity to continue to grow DANYELZA. And then the GD2 as a separate commercial product, if we see that it is a benefit to continue that. So I'll turn it over to Norman to talk a little bit about the tumor uptake.

Yes. Thanks, Mike. Nicole, it's a good question on neuroblastoma. You'd expect morbidity, which I think is what you're getting at. I want to emphasize both of these were older patients for neuroblastoma, I think one in 20s, one in 30, so -- in early 30s. And the way I'd approach it, even though neuroblastoma de novo, particularly in the early presentation, kids are 2 to 4 years old, for example, oftentimes, it's well known their GD avidity is north of 90% -- expression, excuse me, is north of 90%. The biology for these older kids typically present in late teenage years and then extend on as we have with these 2 patients. The biology is different. The GD2 expression likely differs. Importantly, in these patients, there was a lot of pretreatment, multiple pretreatments, all of which I think probably influenced it. So different biology, heavily pretreated. And we saw with the data presented over many tumor types, it really wasn't the antibody issue because we saw avidity across many tumors. And when we had the additional evaluation with the Torch methodology and looked at all the data, we had a broad representation of recognizing tumors if they had GD2 avidity available. So I think it was -- in this case, these 2 older patients with the different biology of a later neuroblastoma development were negative, and that's what happens. It gets back to Mike's point on the having a diagnostic product to be able to patient select. And I'll add as a caveat, I just came from the ANR meetings, the Association for Neuroblastoma Research and a lot of excitement there, a lot of pure antibody approach for their treatments, of course, and much of it GD2. I got as many questions about our diagnostic and the need for that even with the high expression in neuroblastoma. So it's not just us waiting the flag for a needed diagnostic, I think, as people recognize, it's the KOLs.

And our next question will come from Mike Ulz with Morgan Stanley.

Maybe just a follow-up on some of the tumor uptake questions. And just curious what other factors might influence the uptake. It sounds like tumor expression is -- or target expression on the tumor is key, but just curious if you're learning other factors that may influence this, for example, tumor size or maybe tumor location?

Yes. Mike, I appreciate it. And again, as we look at the variability on tumor uptake, there are several variables, and I'll let Norman address that. But -- and one thing to keep in mind, too on these are, these were all heavily pretreated patients, many of which who had received anti-GD2 therapy, which we know. If you're failing on that therapy, generally, it's a receptor-driven issue. But I'll turn it over to Norman to kind of talk about what some of the variables are in there.

Yes. I think we've tried to approach the tumor avidity part and with the extra evaluation. So the antibody per se is fine, and we showed with the additional evaluation that it was positive in a broad array of tumors that we presented. Importantly, people want to see the osteosarcoma, and when you look at all the data, we saw a much better percentage of avidity. And I think it points out to really protocol design that you don't limit yourself to, say, an anatomical selection of the biggest tumors and you rattle off some of the criteria that can influence things. But the strength of some of the diagnostic process, you could have a small tumor that resolution could be an issue. But if you have the avidity or the expression density, you will pick up that tumor. The other advantage is, for example, a GD2 assay was raised, and everyone has tried that for decades. Imaging will give you not only the presence or absence of that target, but the location of the target. And at the end of the day, I think having a diagnostic product and making sure you utilize all the data available will be most important. And that's, I think, one of the big learnings we had here that when we did the initial analysis, a broader array of tumors were positive. And it's -- and we found that the radiohapten, we had avidity and sometimes if you don't have the proper radiohapten, particularly with the chelate linker for the antibody, you might miss it. So it wasn't an antibody issue. It was a radiohapten that we discovered and have optimized. So hopefully, that makes sense to you, and thanks for the question.

And the next question will come from Jeff Jones with Oppenheimer.

I guess a lot of questions have been answered really on the PKPD. I just -- I guess, at this point, where is your head in terms of thinking about the optimal isotope delivery timing versus SADA dosing that seemed to be pretty consistent in just SADA driven. And as part of that, was there any impact of the tumor burden on that SADA trough?

Jeff, thank you for the question. As we look at this, I'll turn this over to Natalie, who could talk a little bit about what the optimal window is as well as what we expect on tumor burden.

Yes. Thank you, Mike, and thanks, Jeff, for the question. When we talk about the optimal isotope delivery timing, it really is driven by the PK. So I think you mentioned that, really it's getting below that trough level and timing the dose of the radiohapten when we reach the nadir. And so, we saw that in our preclinical, and we did see it play out in the human trial, which was really exciting. So we are going to use that PK in all of our trials going forward to identify the optimal timing to deliver the hapten and the isotope. Your second question, the impact on tumor burden, the tumor burden impact the trough. We didn't see that, right? Because if you look across cohorts, they were very variable, right? We had 6 different cohorts of different proteins, protein loads. And yet at the same point in time, we saw a precise and predictable PK across those cohorts. So those patients presented with anywhere from 1 to 5 tumors, but yet we did see that repeatability. So kind of directly answering your question, no, there was no direct impact of the tumor burden on the trough because that PK was quite precise and predictable.

Great. And as we think about the CD38 program and switching to the new hapten, should we be thinking about a similar time line for the SADA program for Part B, so sort of a 2027 start there?

Jeff, I'd say on this, the CD38 is still under review. We've dosed 1 patient in a very difficult to acquire patient population. So we're looking at patient-by-patient, and we'll make those determinations. If it moves forward beyond the safety study, we would absolutely be moving forward with the Proteus Radiohapten. However, that's still under -- it's still very early in that program.

And the next question will come from Chiara Montironi with Kempen.

A quick follow-up regarding the PET diagnostic. I was wondering, could you please help us understand the market opportunity for diagnostic with your SADA approach for GD2 and also beyond GD2?

Yes, Chiara, great question. As we look at the PET diagnostic -- I'll let Natalie address kind of what the business case looks like. But going back to any diagnostic, as we look at this Radiopharmaceutical space, and I'll use prostate for an example. Right now, the prostate PET diagnostic market is north of $1.5 billion just in the diagnostics, right? In the therapeutic, you're looking at $2 billion to $4 billion at this point. So the diagnostics themselves, depending on the size of the patient population, incidence rates, prevalence pools, how it's being used, there are significant opportunities, even in the rare disease space like neuroendocrine tumors, we see the diagnostic north of $200 million in sales. So even in the rare disease space, the potential on the diagnostic is very high. In this case, there is a lot of excitement around the GD2, especially because there is no other alternative to determine GD2 expression. And there's a lot of patients that really need to be treated and to be selected. So for us, it's an opportunity for us on both the diagnostic and the therapeutic. But more importantly, it's selecting patients that are going to best benefit from the therapies going forward. Natalie, if there's anything you want to add on the diagnostic?

Yes. Thanks, Mike, and thank you for the question. So I think Mike spoke pretty well about the opportunity beyond GD2. With this first product, on our PET diagnostic that we're going to bring to market, that is specifically for GD2. And when we look at the population for our trials, we're going to be looking at pediatric neuroblastoma as well as osteosarcoma and a second cohort, including our adult patients, including neuroblastoma, malignant melanoma, small cell lung cancer and TNBC, which is identical to our 1001, as you will notice. And really, when you look across all of those different study populations, the opportunity is quite large. If you look at any other diagnostic on the market, I'll take the prostate that Mike gave it. And as an example, you really need to think about it in 3 different approaches on how a clinical site will use that diagnostic. Obviously, you think about it from the inclusion criteria, but you'll see that the majority of use cases are in the response to treatment as well as the ongoing monitoring. So those can be 2x to 3x the population and the use cases as the inclusion. So really, it's kind of 3 phases. And when you look at your modeling, we need to look at all 3 of those, the inclusion in the response to treatment, as well as monitoring when we think about diagnostics.

The next question will come from Kemp Dolliver with Brookline Capital Markets.

Great. Earlier on, you said that this experience is giving you some potential, I guess, opportunities to speed up execution. So since you're going through this process a few more times, at least in the next couple of years, how much of a benefit should we see with regard to the speed of execution in these early-stage trials?

Yes, Kevin, very good question. I'll turn that over to Natalie. But before I do, just as we went into this, the GD2-SADA in both GD2 and CD38, the goal was to get into patients very quickly and to really start looking at the feasibility of the 2-step approach. And for us, it was speed into patients, get that information and understand what we have. Now that we've learned from that, I can let Natalie discuss a little bit of how we plan to get this data much more quickly and how we plan to move forward and benefit from that across multiple products.

Thanks, Mike, and thanks, Kemp for the question. So just kind of talking about speed of execution, I do want to reiterate what we've done since the beginning of the year. So we did move into these 2 business units early in the year. And since then, we've been able to run 2 preclinical trials in order to optimize our molecule, and we've already had that molecule in manufacturing. So -- when you look at speed of execution, we've already started to deliver on our promises there, as we've been able to execute a lot since the beginning of the year. When we look at our upcoming trials and our ongoing trials, and what we're going to expect to see, you're going to see a lot of the benefits when we look at parallel cohorts, number 1, that's going to accelerate tremendously. You're also going to see a lot of acceleration when we look at dosimetry. So we've been able to identify opportunities to improve with centralized imaging with real-time dosimetry and with ways to really gather our data much quicker. With that, we expect to see, if you take, for example, our 1001 Part A, that's been 14, 15 months, but yet on our Bridge Study, we think we can get it done in about 6 months. So we're looking at accelerating mostly because we've been able to prove the safety of GD2-SADA. And once we've proven the safety, that will allow us to quickly accelerate going forward.

Kemp, thank you very much, and I appreciate everyone for joining. We're up on time. So I just want to thank you again for joining today's call and hearing about the progress made across our Radiopharmaceutical business. We look forward to providing updates on key milestones and inflection points across our pipeline. I appreciate you joining, and have a great day.

Thank you for participating. This does conclude the call for today, and you may now disconnect.