Q4 2024 Radiopharmaceutical Report: Part 3—Clinical Announcements & Strategic Partnerships

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Commentary:

Welcome back Radiopharma fans! In Part 3 of the 2024 Q4 recap, we have Ph.I/II announcements from Pentixpharm, PeptiDream, Monopar, and Oncoinvent. Ratio makes a big splash with a biobucks deal with Novartis. Not to be outdone, Radiopharm announced a co-development deal with Lantheus on various solid tumor targets. Korea’s SK biopharma announced collaboration agreements with ProEn Therapeutics for 2 preclinical candidates using their proprietary ArtBody platform, a dual target binding tech. They also announced a discovery collaboration with the Korea Institute of Radiological and Medical Sciences (KIRAMS). Telix and Curium both provided updates on their Ph. III programs. Curium has completed enrollment of the SOLAR-RECUR 64Cu PSMA I&T PET/CT trial as well as announcing that the primary endpoint of the pivotal ECLIPSE 177Lu-PSMA I&T trial has been met. This sets the stage for market entry and competing with Novartis’s PLUVICTO. It will be interesting to see how the market will develop and how this will impact alpha PSMA I&T products in development (ahemmm……Fusion/AstraZeneca). Telix has dosed it’s first patient in the Ph.III ZIRCON-CP trial of TLX250-CDx PET imaging agent for clear cell renal cell carcinoma (ccRCC).

Cardinal Health—announced the start of weekly production of actinium-225 (Ac-225) through its Center for Theranostics Advancement in Indianapolis, IN, in collaboration with TerraPower Isotopes. The routine production will increase the availability of Ac-225 for the manufacturing of investigational therapeutic drug products and provide for the future commercial manufacturing of novel therapies that will help advance patient care. Cardinal Health’s investments in its Center for Theranostics Advancement have supported the growth of theranostics globally, as the company works with pharmaceutical innovators across their product lifecycles, from concept to commercialization. Growth of the Center for Theranostics Advancement has enabled the company to create strategic collaborations with pharmaceutical manufacturers to support the development and commercialization of new precision medicines as well as the growing demand for cGMP Ac-225.

Jubilant Radiopharma— and Simplified Imaging Solutions (SIS), a leading Diagnostic Services Organization (DSO), are proud to announce a strategic partnership aimed at enhancing the operational efficiencies of nuclear medicine services to healthcare facilities and physician offices nationwide. This is a first of its kind comprehensive full-service nuclear medicine solution that combines a national network of radiopharmacies with a Diagnostic Services Organization in the United States. This strategic partnership combines the national network of 43 SPECT radiopharmacies and 3 PET manufacturing facilities of Jubilant Radiopharma with the fixed and mobile diagnostic solutions of Simplified Imaging Solutions. The strategic collaboration of Jubilant Radiopharma and SIS will be able to provide all products and services ranging from equipment, technicians, management services, FDA approved radiopharmaceuticals, licensing, accreditation, physicists, camera service or any other additional support required for efficient and affordable testing experience. The objective of this partnership will be to provide clients with a turnkey, consolidated, lower cost option of providing in-house diagnostics in both existing and new labs. Under this business model, nuclear laboratory practices can combine all costs associated with their operations into one flat fee per test. By consolidating all aspects of nuclear laboratory operations—including radioisotopes, staffing, equipment, services, physicists, supplies and quality control—into one single, cohesive offering, the partnership seeks to significantly reduce the complexities and administrative burdens traditionally associated with running a nuclear lab.

PeptiDream—marked a milestone following the initiation of a Phase 1 clinical study of a radioligand therapy by Swiss-based Novartis Pharma AG in connection with the companies’ 2019 research and collaboration agreement and PeptiDream’s Peptide Discovery Platform System (“PDPS”). The Phase 1 study is being conducted to investigate the safety, tolerability, dosimetry and preliminary efficacy of 177Lu-NNS309 (a 177Lu-labelled radiotherapeutic) and the safety and imaging properties of 68Ga-NNS309 (a 68Ga-labelled radiodiagnostic) in patients aged ≥ 18 years with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer (BC), triple negative breast cancer (TNBC) and colorectal cancer (CRC) (ClinicalTrials.gov Identifier; NCT06562192). The initiation of the Phase 1 study triggered an undisclosed milestone payment from Novartis to PeptiDream, which will be accounted for in PeptiDream’s FY24-Q4.

?Oncoinvent— announced an interim data readout of the Phase 1/2a studies of Radspherin for the treatment of peritoneal carcinomatoses. The studies were closed for recruitment at the end of 2023, and patients are currently in long-term follow-up. The readout confirmed the previously published results on efficacy and adds further confidence in the ongoing randomized controlled Phase 2 clinical trial for Radspherin? in patients with ovarian cancer. In the first interim readout from the Phase 1 study in ovarian cancer, only 1 patient out of the 10 receiving the selected dose (10%) had peritoneal recurrence at the 12-month interim readout, compared to an expected recurrence rate of 25% in similar populations. Correspondingly, in the second intermediate readout of the colorectal cancer study, only 3 of 20 patients (15%) receiving the selected dose of 7 MBq had peritoneal recurrence after the full 18 months follow-up period.? With current standard therapy, the expected peritoneal recurrence rate is approximately 50% after 18 months. 36 patients with colorectal cancer have received the selected dose, with results from the final 16 patients still pending full follow-up.

Pentixapharm— announced that the first patient has been treated in a Phase I/II clinical trial evaluating the safety and efficacy of Lu177-PentixaTher, a novel radiopharmaceutical therapy, in adults for relapsed/refractory CXCR4 positive acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The trial, funded by the French Ministry of Health and led by a renowned investigator team from the University Hospital in Nantes, represents a significant step toward expanding targeted radiotherapy options for hematologic malignancies. The investor-initiated study, named PENTILULA (ClinicalTrials.gov ID: NCT06356922) is a multicenter, open-label trial in which up to 21 patients with relapsed/refractory AML or ALL will be enrolled over a period of 24 months, with a total study duration of 36 months. The primary objective is to determine the maximal tolerated dose (MTD) of Lu177-PentixaTher, and to examine key efficacy parameters such as overall response rate (ORR) and complete remission (CR) after infusion of the novel radiotherapeutic agent. The study is significant for Pentixapharm insofar as the incidence of ALL and AML, and hence the medical need, is much higher than that for T-Cell lymphoma. The PENTILULA trial is the first trial that combines PentixaTher with Lutetium-177, a radioisotope widely and successfully used for the treatment of castration resistant prostate cancer or neuroendocrine tumors. Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are aggressive and life-threatening blood cancers that affect thousands of people worldwide each year. AML is the most common type of acute leukemia in adults, with an incidence of approximately 20,000 new cases per year and low five-year survival rate of 31.9% in the United States [1]. ALL is the most common type of cancer in children, with a high incidence in adults as well. Current treatment options often involve intensive chemotherapy and stem cell transplantation, which can have severe side effects. Effective radiotherapies in other indications are currently reimbursed with more than 100,000 USD per patient.

Ratio Therapeutics— entered today into an exclusive worldwide license and collaboration agreement with Novartis Pharma AG, a subsidiary of Novartis AG. The collaboration leverages Ratio's radioligand therapy discovery and development expertise as well as its technology platforms for the development of a Somatostatin Receptor 2 (SSTR2) radiotherapeutic candidate for cancer.? Under the terms of the agreement, Ratio will receive combined upfront and potential milestone payments up to $745m, and is eligible to receive tiered royalty payments. Ratio will collaborate with Novartis to drive preclinical activities to research and select an SSTR2-targeting development candidate. Novartis will assume responsibility for all remaining development, manufacturing, and commercialization activities.?

Radiopharm—announced that it has entered into a strategic co-development partnership with Lantheus to advance the clinical development of innovative radiopharmaceuticals in Australia. Under the agreement, Radiopharm will lead clinical development efforts in Australia, leveraging its extensive experience and infrastructure to drive advancements in the field. The collaboration includes plans for a basket clinical trial targeting multiple solid tumors, underscoring both companies' commitment to addressing unmet medical needs in oncology. As part of the partnership, Lantheus will cover all clinical development costs associated with the program. Additionally, Radiopharm will receive up to USD 2 million as milestone payments upon achieving key clinical development objectives, including ethics committee approval, first patient dosing, and completion of patient enrolment, for the first imaging trial subject to this agreement.

Curium— announced that it has completed enrollment of its Phase 3 SOLAR-RECUR clinical trial.? The trial is a multicenter, open-label study to evaluate the diagnostic performance of copper Cu 64 PSMA I&T PET/CT in men with suspected biochemical recurrence of prostate cancer after radical prostatectomy or radiation therapy.? The additional Phase 3 trial, SOLAR-STAGE, a multicenter, open-label study to evaluate the diagnostic performance of copper Cu 64 PSMA I&T PET/CT in staging of men with newly diagnosed unfavorable intermediate-risk, high-risk or very-high-risk prostate cancer electing to undergo radical prostatectomy with pelvic lymph node dissection continues to enroll patients at sites in the U.S. and will soon open locations in Europe.

Curium—announced its ECLIPSE trial met its primary endpoint.? ECLIPSE is a pivotal Phase 3, multi-center, open-label, randomized clinical trial comparing the safety and efficacy of 177Lu-PSMA-I&T (INN: lutetium (177Lu) zadavotide guraxetan) versus hormone therapy in patients with metastatic castration-resistant prostate cancer. The ECLIPSE trial demonstrated a statistically significant and clinically meaningful improvement in the median radiographic progression-free survival (rPFS) of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration-resistant prostate cancer (mCRPC) after treatment with up to 6 doses of 200 mCi (7.4 GBq) of 177Lu-PSMA-I&T in patients previously treated with an androgen receptor pathway inhibitor (ARPI) compared to a change in ARPI.

Curasight— announced today that it has entered into a clinical supply agreement with Curium for the supply of non-carrier-added Lutetium-177 for Curasight’s uTREAT. The agreement announced today leverages Curium’s uniquely diversified irradiation network and large-scale manufacturing capacity recently announced in its Petten, Netherlands facility, which will largely cover the future requirements for uTREAT? Phase III trials and commercialization, in particular in the US and Europe.

Oncoinvent & Artbio—have entered into an agreement where Artbio rents premises and equipment and gets access to parts of Oncoinvent's expertise in radiation protection and analytical services - as well as buying selected R&D equipment. The agreement between Oncoinvent and Artbio is a joint commitment to maximize resource utilization and operational efficiency in a field that is limited by a limited supply of such specialized facilities worldwide.

Monopar—announced the first patient ever dosed with MNPR-101-Lu. This novel therapeutic radiopharmaceutical combines MNPR-101, Monopar’s antibody that selectively targets the urokinase plasminogen activator receptor (uPAR), with the therapeutic radioisotope lutetium-177. uPAR is involved in tumor growth and metastasis, and is found in some of the most aggressive, deadly cancers, including pancreatic, ovarian, triple negative breast, and colorectal cancers. The MNPR-101-Lu intravenous infusion was well-tolerated with no serious adverse reactions reported. This patient, dosed under a compassionate use protocol in the US, has metastatic pancreatic cancer, and prior to dosing, the cancer was imaged using MNPR-101-Zr (a zirconium-89 imaging radioisotope conjugated to MNPR-101) with a PET/CT scanner and showed uPAR expression. Monopar is actively enrolling participants in two Phase 1 clinical studies in Australia, evaluating MNPR-101-Zr for imaging and MNPR-101-Lu for treatment of advanced solid tumors. Further information about the MNPR-101-Lu Phase 1a trial is available at www.ClinicalTrials.gov under study identifier NCT06617169.

MTTI—published preclinical study results for their proprietary 225 Ac-EBTATE against SSTR2 NET cancers online in the European Journal of Nuclear Medicine. Professor Humphrey Fonge of the Université de Laval and lead author commented, “At just 40% of the administered dose reported for 225 Ac-DOTATATE, 225 Ac-EBTATE produces enhanced anti-tumor efficacy in Small Cell lung cancer (SCLC) and Pan-neuroendocrine tumor (NET) models as shown with complete tumor remissions. At a therapeutic dose of 2x 34 kBq, 225 Ac-EBTATE showed general safety for 28 days after blood biochemistry analysis, CBC, and histopathological examination of major organs and tissues. We demonstrated that 225 Ac-EBTATE was effective against human small-cell lung cancer (SCLC) with 80% complete remission and 100% survival in preclinical models.” MTTI has licensed commercial use rights for the patented Evans blue (EB) technology from the National Institute of Biomedical Imaging and Bioengineering (“ NIBIB ”), part of the National Institutes of Health. EB binds to serum albumin, extending in vivo circulatory half-life and tumor residence time, enhancing up to 30-fold uptake at a tumor and enabling good efficacy with significantly lower radiopharmaceutical activity and fewer dosing cycles vs. the current standard of care.

BAMF—BAMF Health is creating a global destination for intelligence-based precision medicine through the construction of a comprehensive Theranostics center in downtown Detroit. BAMF’s new facility will be located within Bedrock’s 14-acre Gratiot Site campus, establishing a hub for global leaders in precision medicine, radiopharmaceutical development, radioligand clinical trials, and more. In partnership with Bedrock, Michigan Innovation Headquarters (MI-HQ), Ferris State University, Wayne State University, and TechTown, the site will serve as a catalyst for cultivating talent, conducting research, and advancing medical technology. Early on, BAMF Health promised to deliver its comprehensive platform to the people of southeast Michigan and to create a bridge for care delivery that would reach statewide. BAMF Health’s facility will reside within the Gratiot Site’s Life Science Innovation Building and occupy 45,000 square feet on the first floor. The site will include a molecular imaging clinic, molecular therapy clinic, and a commercial manufacturing radiopharmacy. The site is currently home to the now-vacant juvenile detention facility. Demolition of that facility has already begun.

PeptiDream—announced its second wholly-owned peptide radiopharmaceutical development candidate arising from the company’s ongoing internal peptide radiopharmaceutical discovery and development efforts. The development candidate (“PD-29875”) is a novel first-in-class highly-selective macrocyclic peptide-radioisotope (RI) conjugate against Claudin 18.2 (“CLDN18.2”), a member of the claudin family of proteins that are integral components of tight junctions found in epithelial tissues. CLDN18.2 is expressed in a variety of solid tumors, including gastric cancer, pancreatic cancer, biliary cancer, genitourinary tract cancers, and colorectal cancer, and others. PD-29875 was discovered using PeptiDream’s proprietary PDPS technology and further optimized at PeptiDream with in vivo imaging and efficacy studies conducted at PDRadiopharma, our wholly owned subsidiary. PeptiDream has initiated IND-enabling studies of PD-29875 and intends to initially develop the therapeutic (225Ac-PD-29875) and paired diagnostic imaging agent (64Cu-PD-29875) for the diagnosis and treatment of gastric cancer. The paired diagnostic imaging agent, which consists of the same peptide and chelator as the therapeutic, will enable us to screen and identify patients, both in clinical trials and in clinical practice, who have CLDN18.2 expressing tumors that are most likely to have a favorable clinical response from PD-29875 treatment. PeptiDream is additionally planning to initiate human Ph0 imaging studies of 64Cu-PD-29875 in 2025, prior to the start of a Phase 1 study.

SK Biopharmaceuticals—announced a research collaboration agreement with ProEn Therapeutics, a biotech company dedicated to advancing oncology treatments, to further extend its oncology research capability and expand its pipeline of radiopharmaceutical therapies (RPT). Under this agreement, both sides seek to advance up to two preclinical candidates for the development of novel radiopharmaceutical drugs by 2027 – the year when SK Biopharmaceuticals aims to become a global leading RPT player, via strengthened internal and external resources. This joint research builds on a series of SK Biopharmaceuticals' global strategic partnerships, including the in-licensing of a radiopharmaceutical compound, and a supply agreement to secure actinium-225, an alpha-particle emitting radioisotope, since the company unveiled its "RPT Roadmap" to gain a competitive edge in the rapidly growing field of nuclear medicine. SK Biopharmaceuticals will leverage ProEn Therapeutics' ArtBody platform, a dual-target binding technology that incorporates small proteins to identify and target specific tumor antigens – enhancing tumor selectivity – for the development of potential cancer treatments, while minimizing damage to healthy tissues. ArtBody, which has intrinsic advantages of high stability and structural robustness, can be mass-produced using bacteria, making it ideal for industrial applications.

SK Biopharmaceuticals—announced that it has entered into an agreement with the Korea Institute of Radiological and Medical Sciences (KIRAMS), Korea's premier research institution dedicated to the study and advancement of radiological and medical sciences, to collaborate on discovering and developing preclinical radiopharmaceutical drug candidates. This marks the first collaborative research agreement in which both sides will aim to discover radiopharmaceutical compounds and investigate novel oncological treatments, using actinium-225 (225Ac), an alpha-particle emitting radioisotope that selectively kills cancer cells. The research for radiopharmaceutical therapy (RPT) focuses on this application that has been gaining attention for its high potential in nuclear medicine. SK Biopharmaceuticals has already initiated its 225Ac-based research as it secured a supply of the radioisotope from TerraPower Isotopes, a subsidiary of TerraPower, a nuclear innovation company whose investors include SK Biopharmaceuticals' parent SK Inc. and Bill Gates. SK Biopharmaceuticals and KIRAMS will seek to submit an Investigational New Drug application by 2027, as they leverage each other's resources to optimize their drug discovery efforts. SK Biopharmaceuticals said it could significantly reduce the time and cost of new drug development, with KIRAMS' researchers, facilities and equipment using the radioisotope, enabling the company to further accelerate in securing and expanding its RPT pipeline and capability. The agreement is in line with SK Biopharmaceuticals' so-called "RPT Roadmap" recently introduced to become a global leading RPT player by 2027, as the company will fortify its RPT business by discovering new drug compounds, extending supply and production capacities, and developing a tech platform, via strengthened internal assets and strategic partnerships. In addition to the 225Ac supply agreement aligned with its roadmap, the company has in-licensed SKL35501 (FL-091) radiopharmaceutical compound targeting neurotensin receptor 1 (NTSR1) solid tumors.

Telix Pharmaceuticals— announce that the first patient has been dosed in the Phase III ZIRCON-CP trial of TLX250-CDx positron emission tomography (PET) imaging of clear cell renal cell carcinoma (ccRCC). The patient was successfully dosed and imaged at Beijing Cancer Hospital in Beijing, China. ZIRCON-CP is a multi-centre Phase III registration trial in China intended to bridge to Telix’s global Phase III ZIRCON trial, which met all co-primary and secondary endpoints, including showing 86% sensitivity and 87% specificity, and a mean positive-predictive value (PPV) of 93% for ccRCC. The trial, which will enrol up to 82 patients, is being conducted in collaboration with the Company’s strategic partner for the Greater China region, Grand Pharma, to demonstrate that the diagnostic utility of TLX250-CDx is equivalent in Chinese and Western populations. The clinical data from ZIRCON-CP is intended to support future marketing authorisation applications for this breakthrough technology. Greater China represents a major market opportunity for radiopharmaceuticals, including TLX250-CDx, driven by increasing cancer incidence rates and an investment in installation of PET/CT cameras. In China alone – 73,000 people are newly diagnosed with kidney cancer each year.

Clarity Pharmaceuticals— announce that the last patient has completed their final assessment in the Phase II diagnostic 64Cu-SARTATE trial, DISCO (NCT04438304), for patients with known or suspected neuroendocrine tumours (NETs). DISCO, which derives from “Diagnostic Imaging Study of 64COpper-SARTATE Using PET on Patients with Known or Suspected Neuroendocrine Tumours”, is assessing the performance of Clarity’s SARTATE imaging product as a potential new method to diagnose and manage NETs. The DISCO trial recruited participants with Gastroenteropancreatic NETs (GEP-NETs) across four sites in Australia, comparing the diagnostic performance of 64Cu-SARTATE at approximately 4 hrs and 20 hrs post-administration to 68Ga-DOTATATE at one hour. The trial was originally planned for up to 63 patients based on an expected discordance level between imaging with Clarity’s 64Cu-SARTATE and the current standard of care, 68Ga-DOTATATE. The sample size was adjusted to 45 patients based on the results of the pre-planned early assessment of the images collected during the trial with the aim of generating sufficient evidence to plan for a Phase III trial in this indication. This enabled recruitment to successfully close early. The trial aims to build on earlier work with SARTATE in patients with NETs, which demonstrated that imaging at later time points, enabled by the longer half-life of copper-64 in comparison to gallium-68, may lead to better identification of disease2. Delayed imaging (at 4 hrs and 24 hrs vs 1 hr) showed a progressive increase in lesion-to-liver ratio.

Telix Pharmaceuticals— announces a partnership with California-based Subtle Medical, Inc. (Subtle Medical) for artificial intelligence (AI)-powered positron emission tomography (PET) imaging with Telix’s commercial PSMA-PET product, Illuccix? (68Ga-PSMA-11). Subtle Medical’s SubtlePET is a U.S. Food and Drug Administration (FDA) cleared AI-driven solution to enhance the efficiency and effectiveness of imaging procedures. The proprietary deep-learning algorithm allows for faster PET scanning – up to 75% time savings without compromising image quality. The technology represents a significant advancement in the field, offering numerous benefits to patients, physicians, and medical facilities. SubtlePET’s ability to expedite the imaging process reduces patient wait times and increases comfort, with the patient required to remain motionless under the camera for a shorter period of time, contributing to an overall more positive healthcare experience. Additionally, a shorter scan time for Illuccix will allow healthcare providers to further optimise workflows and resource utilisation. Most importantly for facilities, SubtlePET seamlessly integrates into existing imaging center workflows, empowering healthcare providers to achieve faster PET imaging on any scanner, regardless of manufacturer or model. The technology can also extend scanner life through improved performance.