Summary of Radiopharm Theranostics (RADX) Update / Briefing Company and Industry Overview - **Company**: Radiopharm Theranostics (RADX) - **Industry**: Prostate cancer treatment and radiopharmaceuticals Key Points and Arguments 1. **Prostate Cancer Treatment Landscape**: - Significant advancements in prostate cancer treatments, particularly with radiotherapy options like radium-223 combined with enzalutamide and targeted therapies such as PSMA radiotherapeutics like Pluvicto [3][4] - Pluvicto has shown efficacy in prostate cancer patients both before and after chemotherapy, as evidenced by the PSMA-4 and VISION trials [3] 2. **Unmet Medical Needs**: - Despite advancements, there remains a substantial medical need for new therapies, especially targeted radiotherapy, as all patients receiving PSMA-targeting treatments will eventually relapse [4] 3. **Introduction of Betabart**: - Betabart, a monoclonal antibody targeting B7-H3, is being developed as a new treatment option. It has a modified half-life to reduce side effects while maintaining strong target affinity [4][5] - The upcoming study will enroll patients with various tumors, including those with prostate cancer who have previously received Pluvicto [5] 4. **KLK3 Targeting**: - KLK3 (PSA) is identified as a promising new target for prostate cancer therapy, with a focus on its specific expression in prostate tissues compared to PSMA, which is expressed in multiple organs [7][8] - The KLK3-targeted study is set to begin in Australia early next year [8] 5. **Preclinical Data**: - Preclinical studies show that KLK2 and KLK3 are highly specific to prostate tissues, with KLK3 exhibiting higher expression levels than KLK2 [9][19] - The therapeutic efficacy of KLK2-targeted therapies has been demonstrated in advanced mouse models, showing significant tumor reduction [13][14] 6. **Mechanism of Action**: - The therapeutic approach exploits the upregulation of androgen receptors (AR) in response to DNA damage, which increases the expression of KLK2 and KLK3, enhancing the targeting efficacy over time [16][29] 7. **Comparison with Other Therapies**: - KLK3-targeted therapies are positioned as a more advanced approach compared to KLK2, with a higher expression level and a more extensive research background [20][29] - The antibody developed for KLK3 is designed to avoid targeting PSA in circulation, focusing instead on the free form of PSA in tissues [28] 8. **Clinical Development Plans**: - RAD402 (KLK3 targeting molecule) is expected to enter clinical studies in Australia before the end of the year, alongside RV-01 (B7-H3 targeting molecule) in the U.S. [48] Additional Important Content - **Market Potential**: - The arrival of radiopharmaceuticals has significantly changed the metastatic prostate cancer treatment landscape, with improved patient survival rates [45] - There is a recognition that existing treatments like Pluvicto are not perfect, indicating a need for further scientific advancements [46] - **Future Directions**: - The company is exploring new targets and approaches to enhance treatment efficacy and patient outcomes in metastatic prostate cancer [46][47] - **Community Engagement**: - The webinars have attracted significant interest, indicating a strong community engagement and support for ongoing research and development in prostate cancer therapies [45]

Summary of Radiopharm Theranostics (RADX) Update / Briefing August 26, 2025 Company and Industry Overview - **Company**: Radiopharm Theranostics (RADX) - **Industry**: Oncology, specifically focusing on prostate cancer treatment and radiopharmaceutical therapies Key Points and Arguments 1. **Prostate Cancer Treatment Landscape**: The treatment of prostate cancer has evolved significantly, moving from traditional methods like surgery and chemotherapy to incorporating genetics, molecular imaging, and targeted therapies, including immunotherapy and radiopharmaceuticals [11][12][30] 2. **B7-H3 as a Target**: B7-H3 is highlighted as a promising new target for prostate cancer treatment, being highly expressed in various tumors, including 93% of castrate-resistant prostate cancer cases. This makes it a viable alternative to PSMA-targeted therapies, especially in cases where PSMA expression is low [39][41][43] 3. **Need for New Therapies**: There is a critical need for more effective therapies for metastatic castration-resistant prostate cancer, as current treatments often provide limited survival benefits [18][30] 4. **NCCN Guidelines**: The National Comprehensive Cancer Network (NCCN) guidelines are discussed, emphasizing the importance of treatment sequencing and the variety of options available based on prior therapies [19][20] 5. **Theranostics Concept**: The concept of theranostics is introduced, where ligands are designed to bind to specific cancer cell targets, allowing for both diagnosis and treatment using radiopharmaceuticals [24][25] 6. **Clinical Trials and FDA Approvals**: The presentation mentions several clinical trials demonstrating survival benefits from new therapies, including the FDA approval of Plavicto (lutetium-177) for prostate cancer treatment [27][28][51] 7. **BetaBART Development**: The development of BetaBART, a humanized monoclonal antibody targeting the four Ig isoform of B7-H3, is presented as a novel approach in radioimmunotherapy, with plans for a Phase 1 trial in 2025 [51][66] 8. **Competitive Landscape**: The competitive landscape for B7-H3 targeting is discussed, noting that while there are other modalities like ADCs and CAR T-cell therapies, the unique properties of BetaBART provide a competitive advantage [75][78][87] 9. **Immunological Memory**: Evidence of secondary immune memory from prior treatments suggests that BetaBART may not only target tumors but also enhance the immune response against them [64][66] 10. **Market Potential**: The potential market for B7-H3 targeting therapies is significant, with opportunities extending beyond prostate cancer to other solid tumors [46][51] Other Important but Overlooked Content 1. **Challenges with Current Therapies**: The limitations of existing therapies, including the need for better options post-Plavicto treatment, are emphasized, highlighting the urgency for innovation in this space [30][102] 2. **Mechanism of Action**: The mechanism of action for BetaBART is discussed, focusing on its ability to selectively target the four Ig isoform of B7-H3 while minimizing off-target effects and toxicity [49][66] 3. **Future Directions**: The discussion includes the need for randomized control groups in future trials to better assess the efficacy of new treatments [31] This summary encapsulates the critical insights from the briefing, focusing on the advancements in prostate cancer treatment, the significance of B7-H3 as a target, and the innovative approaches being developed by Radiopharm Theranostics.

Core Insights - Radiopharm Theranostics is advancing its clinical pipeline with significant milestones, including FDA Fast Track Designation for RAD101 and clearance for higher dosing of RAD204 [3][5][6] - The company confirmed a cash runway extending through mid-2026, with a year-end cash balance of $29.12 million, up from $18.58 million the previous year [10][12] Program and Business Updates - RAD204, a nanobody targeting PD-L1, is on track for higher dosing at 60mCi of Lu177, with enrollment for the second cohort expected to complete soon [6] - RAD202, targeting HER2, has initiated its Phase 1 HEAT trial, with preliminary data anticipated by the end of 2025 [6] - The company has established supply agreements for key radioisotopes, enhancing its clinical trial capabilities [3][12] Financial Update - For the fiscal year ending June 30, 2025, net cash outflows from operating activities totaled $36.67 million, primarily due to research and development expenditures [10][12] - The company received $4.58 million for research and development tax incentives for the 2024 financial year [12]

Core Insights - The FDA has granted clearance for Radiopharm Theranostics to initiate a first-in-human Phase 1 clinical trial of RV-01, a Lu177-B7H3 monoclonal antibody targeting the 4Ig isoform of B7-H3, which is overexpressed in tumors [1][2] - RV-01 is expected to provide a novel treatment option for patients with aggressive solid tumors, with the first patient dosing anticipated later in 2025 [2][5] Company Overview - Radiopharm Theranostics is a clinical-stage biopharmaceutical company focused on developing innovative oncology radiopharmaceuticals for high unmet medical needs, listed on ASX (RAD) and NASDAQ (RADX) [6] - The company has a diverse pipeline that includes distinct technologies such as peptides, small molecules, and monoclonal antibodies, with ongoing clinical trials for various solid tumors [6] Product Details - RV-01 is the first radiopharmaceutical therapeutic agent developed through a joint venture with MD Anderson Cancer Center, demonstrating tumor shrinkage and prolonged survival in preclinical studies [5] - The unique hepatic clearance of RV-01 may minimize adverse effects compared to other radiotherapeutics, which often have renal excretion pathways associated with higher toxicity risks [2][3] Scientific Significance - B7-H3 is an immune checkpoint molecule linked to tumor aggressiveness and poor clinical outcomes, making it a compelling target for antibody-based cancer immunotherapy [4] - The high affinity of RV-01 for the 4Ig isoform allows for enhanced targeting of tumors while avoiding immune complex formation in circulation [3][4]

Core Insights - Radiopharm Theranostics has appointed Dr. Oliver Sartor to its Scientific Advisory Board, enhancing its expertise in oncology radiopharmaceuticals [1][5]. Company Overview - Radiopharm Theranostics is a clinical-stage biopharmaceutical company focused on developing innovative oncology radiopharmaceuticals for high unmet medical needs [1][5]. - The company is listed on ASX (RAD) and NASDAQ (RADX) and has a pipeline that includes one Phase 2 and three Phase 1 trials targeting various solid tumor cancers, including lung, breast, and brain metastases [5]. Dr. Oliver Sartor's Background - Dr. Sartor is a recognized expert in prostate cancer and radiopharmaceutical therapies, currently serving as Director of Radiopharmaceutical Clinical Trials at Mayo Clinic [2][3]. - He has authored over 500 peer-reviewed publications and led pivotal Phase 3 trials that resulted in FDA approvals for several therapies [4]. Strategic Importance - The addition of Dr. Sartor to the Scientific Advisory Board is expected to provide invaluable insights and leadership as the company advances its radiopharmaceutical pipeline [5].

Core Insights - Radiopharm Theranostics has completed the preclinical data package for RAD 402, an anti-Kallikrein Related Peptidase 3 (KLK3) monoclonal antibody radiotherapeutic, and is preparing to initiate a Phase 1 clinical trial for prostate cancer in the second half of 2025 [1][2][3] Company Overview - Radiopharm Theranostics is a clinical-stage biopharmaceutical company focused on developing innovative oncology radiopharmaceuticals for high unmet medical needs, listed on ASX (RAD) and NASDAQ (RADX) [5] - The company has a diverse pipeline that includes one Phase 2 and three Phase 1 trials targeting various solid tumors, including lung, breast, and brain cancers [5] Partnership and Development - A supply agreement has been signed with Cyclotek to radiolabel RAD 402 with Terbium-161 (Tb), which is crucial for the upcoming Phase 1 clinical trial [1][3] - Cyclotek, a leading radiopharmaceutical manufacturer in Australia and New Zealand, will produce and provide doses of Tb-labeled RAD 402 [6][4] Therapeutic Focus - RAD 402 is designed to target KLK3, which is highly expressed in prostate tissue, potentially leading to improved therapeutic efficacy due to the unique properties of Tb compared to other radionuclides [2][4] - The partnership aims to enhance patient outcomes by improving the accessibility of radiopharmaceuticals [7][8]

Core Insights - The FDA has granted Fast Track Designation for RAD101, a novel imaging small molecule developed by Radiopharm Theranostics, aimed at distinguishing between recurrent disease and treatment effects in brain metastases from solid tumors [1][3] - RAD101 targets fatty acid synthase (FASN), which is overexpressed in many solid tumors, including cerebral metastases, potentially improving diagnostic precision for over 300,000 patients diagnosed annually in the U.S. [2][3] Company Overview - Radiopharm Theranostics is a clinical-stage biopharmaceutical company focused on developing innovative oncology radiopharmaceuticals for high unmet medical needs, listed on ASX (RAD) and NASDAQ (RADX) [6] - The company has a pipeline that includes one Phase 2 and three Phase 1 trials targeting various solid tumor cancers, including lung, breast, and brain metastases [6] Clinical Trial Details - The Phase 2b clinical trial of RAD101 is a multicenter, open-label study evaluating the diagnostic performance of 18F-RAD101 in 30 individuals with confirmed recurrent brain metastases [4] - The primary objective is to assess the concordance between 18F-RAD101 positive lesions and those identified through conventional imaging (MRI with gadolinium) [4] - Secondary endpoints include the accuracy, sensitivity, and specificity of RAD101 in differentiating tumor recurrence from radiation necrosis in previously treated brain metastases [4] Product Information - RAD101 is designed to allow for more accurate detection of cancer cells by targeting FASN activity, representing a clinically relevant method for imaging brain metastases [5] - Positive data from a Phase 2a imaging trial indicated significant tumor uptake independent of the tumor's origin, suggesting potential for non-invasive prediction of overall survival [5]

Core Insights - The company has initiated the Phase 1 'HEAT' clinical trial for RAD202, targeting HER2-positive advanced solid tumors, marking a significant milestone in its transition to a clinical-stage entity [1][3][4] - The trial aims to assess the safety, tolerability, and preliminary efficacy of 177Lu-RAD202, with the first patient already dosed [2][3] - RAD202 is a proprietary nanobody that has shown promise in previous studies for treating HER2-positive cancers, including breast cancer [3][5] Company Overview - Radiopharm Theranostics is a clinical-stage biopharmaceutical company focused on developing innovative oncology radiopharmaceuticals for high unmet medical needs [5] - The company is listed on ASX (RAD) and NASDAQ (RADX) and has a diverse pipeline that includes one Phase 2 and three Phase 1 trials targeting various solid tumors [5] - The company aims to provide therapeutic options that improve clinical outcomes for patients with HER2-positive metastatic cancers [3][4]

Core Insights - Radiopharm Theranostics is advancing its RV01 program towards a first-in-human therapeutic basket study targeting solid tumor cancers, with an Investigational New Drug submission planned for mid-2025 and Phase 1 study initiation expected in Q4 2025 [1][7] Group 1: RV01 Program Development - The RV01 therapy is a B7-H3-targeted radiopharmaceutical designed to target solid tumors expressing the B7-H3 protein, which is associated with poor prognosis in various cancers [2] - Preclinical data indicates that RV01 demonstrates favorable biodistribution and high tumor uptake, with modifications in the Fc region leading to a shorter half-life compared to traditional monoclonal antibodies [1][3] - The antibody's faster liver excretion allows for effective tumor targeting while potentially reducing associated toxicities, offering advantages over traditional excretion methods [4] Group 2: Preclinical Data and Efficacy - New preclinical data supports earlier findings of RV01's strong affinity for the cancer-specific 4Ig isoform of the B7-H3 receptor, showing complete regression of established solid tumors and evidence of immune system stimulation [6] - The biodistribution study is the final preclinical work required for the IND application with the U.S. FDA, confirming the timeline for submission and study initiation [7] Group 3: Company Overview - Radiopharm Theranostics is a clinical-stage biopharmaceutical company focused on developing innovative oncology radiopharmaceuticals, with a diverse pipeline including peptides, small molecules, and monoclonal antibodies for cancer treatment [9]

Core Insights - ITM Isotope Technologies Munich SE and Radiopharm Theranostics have signed a supply agreement for non-carrier-added Lutetium-177 (n.c.a. Lu) to support Radiopharm's clinical and potential commercial development of Lu-based molecules [1][2] Company Overview - ITM is a leading radiopharmaceutical biotech company focused on developing therapeutics and diagnostics for hard-to-treat tumors, with a commitment to improving patient outcomes through high-quality radioisotopes [4] - Radiopharm Theranostics is a clinical-stage company developing innovative radiopharmaceutical products for diagnostic and therapeutic applications, with a pipeline that includes one Phase 2 and three Phase 1 trials targeting various solid tumors [5] Agreement Details - The supply agreement allows Radiopharm to utilize ITM's n.c.a. Lu in key clinical programs, including RAD 204, RAD 202, and RV01, aimed at treating solid tumors [2][3] - ITM's n.c.a. Lu is a highly pure beta-emitting radioisotope that can be linked to tumor-specific targeting molecules, enhancing the precision of cancer treatment [3] Strategic Importance - The agreement is seen as a critical step for Radiopharm to ensure the quality and reliability of its clinical development plans, particularly for its advanced assets [3] - ITM emphasizes its commitment to supplying high-quality medical radioisotopes to both its partners and its own pipeline, reflecting a shared dedication to improving cancer treatment options [4]