Q3 Radiopharmaceutical Report—Pt.2 Manufacturing &Supply Chain Announcements

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As the interest in the field of Radiopharmaceuticals grows, I endeavour to publish a quarterly review on the latest developments in the field and also provide some personal commentary as context on specific areas of interest. I will publish the quarterly reports in digestable sections covering? General announcements, Fund raising & Financial updates, manufacturing & supply chain notices, and clinical & strategic partnerships annoucements.

Commentary: As the Radiopharma industry matures it is following a similar tragectory as the cell & gene therapy sector did in the early-to-mid teens in terms of the need for manufacturing capacity. CDMO services in Radiopharma also have the added overlay that the barriers to entry into this highly specialized manufacturing space, also incur a heavier administrative burden in the forms of radiation regulation and a robust safety and monitoring program. Therefore, it is unsurprising that many Radiopharmacentric biotechs are opting to offshore manufacturing to 3rd parties. There are only a handful of specialized rCDMOs with a proven track record in the space. Those include SpectronRX, Cardinal, AtomVie, to name a few and the new kid on the block which has made a big splash with recent construction and expansion announcements, Nucleus Radiopharma. The race to lock up both manufacturing capacity and isotope supply continued in Q3, and a trend is now starting to form within the rCDMO space with major players looking to become fully integrated one-stop-shops to capture much of the value in the supply chain by also producing medical isotopes as well as radiolabeling and fill/finish services.

There are niche players as well which have flown under the radar. The most noticeable being RadioMedix which has made their manufacturing expertise available to the broader ecosystem and has demonstrated their capabilities both in the areas of generator manufacturing, and finished clinical dose production. ?

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Manufacturing & Supply Chain Announcements:

Curium— announced today that it has officially opened an additional and new facility in Petten, Netherlands to produce non-carrier added lutetium-177 (Lu-177) to meet the growing global demand for Lu-177 for the treatment of cancer patients. Using in-licensed technology from Turkey-based Eczac?ba??-Monrol, the facility will initially include two production lines (with ability to scale via further lines as needed in the future) to supply Curium’s proprietary Lu-177 product pipeline, as well as external pharmaceutical and hospital customers.

Convergent Therapeutics—announced the signing of a strategic contract manufacturing services agreement. Convergent’s lead asset CONV01-α is a prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody linked to Ac-225 and is currently being investigated as a treatment for prostate cancer. Under the terms of the expanded collaboration, NorthStar will provide Convergent with its environmentally preferred, high purity non-carrier-added (n.c.a) Ac-225 for use in CONV01-α and Utilize its new, state-of-the-art contract development and manufacturing facility to manufacture CONV01-α to serve patients in Convergent’s clinical trials, and perform research and development activities to support continued development of CONV01-α and other Convergent assets.

GlyTherix— announce a new global clinical supply agreement with Wisconsin-based SHINE Technologies, a pioneer in next-generation fusion-based technology and North America's largest producer of non-carrier added lutetium-177 (n.c.a. Lu-177) chloride. SHINE will supply its n.c.a. Lu-177 chloride, Ilumira, for use in GlyTherix's clinical trials focused on innovative treatments for aggressive and invasive cancers. GlyTherix's radiotherapy combines Lu-177 with a molecule targeting Glypican-1, a protein in aggressive cancers, to deliver localized radiation while sparing healthy tissue. Their 177Lu-DOTA-Miltuximab? will enter Phase Ib trials in early 2025. GlyTherix will use 177Lu-DOTA-Miltuximab targeting tumours expressing Glypican-1 in its planned Australian Phase Ib therapeutic dose escalation trial scheduled to commence early 2025. Glypican-1 is an attractive tumour target that occurs in several aggressive and invasive cancers including prostate, pancreatic, bladder, lung, glioblastoma and ovarian cancer.

Nucleus Radiopharma— unveiled expansions at sites in Mesa, Arizona, and Springhouse, Pennsylvania, that are expected to boost the company’s production capacity by 200% and add about 100 total new jobs. The 53,000-square-foot Mesa, Ariz. site and the 48,000-square-foot facility in Spring House Innovation Park north of Philadelphia are strategically positioned to serve key markets. Prominent Nucleus backers, including Fox Chase Cancer Center and Mayo Clinic, will benefit from the increased scale and geographical proximity these facilities provide.

SpectroRx— said it inked a binding agreement to complete its first European radiolabeling plant at the Belgian Nuclear Research Center in Mol, Belgium. The build-out of the new facility is expected to wrap up next month, with SpectronRx noting that it hopes to kick off operations by 2025’s first quarter, pending manufacturing certification. SpectronRx will provide state-of-the-art equipment and a Quality System with GMP-qualified procedures, whereas SCK CEN will supply the necessary resources to meet the development objectives.

Northstar Medical Radioisotopes— hosted a grand opening event and ribbon-cutting at the state-of-the-art NorthStar Dose Manufacturing Center in Beloit, Wis., on October 3, 2024. Guest speakers joined with other industry and healthcare leaders, NorthStar customers, suppliers, and partners to share perspectives on the exciting growth of nuclear medicine, the need for reliable U.S. radioisotope supply to support better patient outcomes and how NorthStar is critical to this success. NorthStar’s additional facility will play a critical role in the advancement of diagnostic and therapeutic radiopharmaceuticals as the capacity will lead to further options for biopharmaceutical and pharmaceutical companies, and will provide them with customized solutions to help navigate the complexities of radioisotope research, development and manufacturing. The purpose-built design will add much needed capacity to the industry, and will allow for NorthStar to continue to add more services to meet the demand and regulatory guidelines of customers around the world.

Novartis—is investing more than $200 million to further bolster its radiotherapy infrastructure with a brand-new facility and the expansion of an existing site. Novartis is establishing its third radioligand therapy manufacturing site in the U.S. Joining the company’s two existing locations stateside in Millburn, New Jersey, and Indianapolis, Indiana, the new facility is located in Carlsbad, California, to help optimize the delivery of doses to patients on the West Coast. Separately, the Indianapolis site is getting an important upgrade. Novartis has broken ground on a new plant at the campus to produce radioactive isotopes, which are the critical backbone of radiopharmaceuticals. All told, Novartis is investing more than $200 million in expansions, a company spokesperson told Fierce Pharma. Qualifications and regulatory approvals of the new facilities are expected to be completed by 2026, the spokesperson said. Both facilities will be built with room for further expansion, according to the company. The Indianapolis facility is slated to be the first Novartis-owned isotope production source in the U.S., the Novartis spokesperson confirmed to Fierce Pharma. The company will continue to partner with external isotope suppliers for the international market.

Radiopharm— announced a strategic partnership with BAMF Health, a global leader in molecular imaging and theranostics. The company’s platform also includes world-class Contract Development and Manufacturing Organization (CDMO) services for manufacturing PET isotopes. BAMF Health will manufacture 18F-RAD 101, Radiopharm’s proprietary 18F-tagged radiotracer for the detection and characterization of brain metastasis. BAMF Health is also anticipated to be the first clinical site to open and dose patients with brain metastasis as part of Radiopharm’s Phase 2b imaging study of 18F-RAD 101. RAD 101 is a novel imaging small molecule that targets fatty acid synthase (FASN), a multi-enzyme protein that catalyzes fatty acid synthesis and is overexpressed in many solid tumors, including cerebral metastasis. In October 2022, positive data from the Imperial College of London’s Phase 2a imaging trial of RAD 101 in patients with brain metastases showed significant tumor uptake that was consistent with and independent from the tumor of origin. The US multicenter Phase 2b trial is an open-label, single dose, single arm study to establish the imaging performance of 18F-RAD 101 in participants with suspected recurrent brain metastases from solid tumors of different origins and is anticipated to very shortly enroll the first patient in Q4 2024. BAMF Health’s state-of-the-art radiopharmacy is equipped with dual cyclotrons, a solid target system, and multiple synthesis platforms, enabling the production of a broad spectrum of PET isotopes. The organization has the capacity and flexibility to manufacture a high volume of novel radiopharmaceuticals at a rapid pace. In addition, BAMF Health’s high-efficiency clinical trial platform, world-class imaging capabilities, and comprehensive clinical expertise pave the way for it to be the first site to activate as part of Radiopharm’s Phase 2b study.

Global Morpho Pharma— announced a strategic partnership with Femto Isotope GmbH, a new player in the supply of irradiation services and medical isotopes. This partnership aims to enhance the production and the distribution of key radioisotopes used in cancer diagnostics and targeted therapies. The collaboration consists in the provision of irradiation services and distribution of medical radioisotopes globally, wherein Femto Isotope will leverage its full access to the irradiation capacity and isotope portfolio of the ETRR-2 reactor, and Global Morpho Pharma will leverage its extensive customer network and market expertise. The ETRR-2 research reactor, owned and operated by the Egyptian Atomic Energy Agency, is an INVAP reactor that achieved initial criticality in 1997. Its thermal flux is comparable with that of the other research reactors irradiating targets for the production of nca Lu-177 or Mo-99.

Pharmalogic— announced the official opening of its radiopharmaceutical production and research facility in Salt Lake City, Utah. This state-of-the-art facility represents a major step forward in PharmaLogic's mission to deliver life-saving diagnostic and therapeutic radiopharmaceuticals to patients across North America. The decision to establish the facility in Salt Lake City underscores PharmaLogic’s dedication to expanding patient access to clinically essential radiopharmaceuticals, many of which are currently unavailable in the broader Canyons region. The new production and laboratory space is designed to support not only the scaling of existing operations but also to foster research and development of novel radiopharmaceuticals.

Nusano—and Starget Pharma, a clinical-stage biotechnology company developing precision peptide radioligand therapies focused on difficult to treat cancers, today announced a supply agreement to advance the development of Starget’s Smart Targeted Radioligands (STRs). The supply agreement is expected to support Starget’s STR isotope needs from discovery through commercialization and will include both common radioisotopes as well as rare alpha particle-emitters such as Astatine-211, Lead-212, and Actinium-225. Starget’s STR platform is advancing the field of molecular radiation using its proprietary backbone cyclization technology to create innovative and diversified peptide radioligand candidates with enhanced properties. These STRs are designed to bind and deliver a payload of radiation specifically to biological targets that are overexpressed in cancer compared to normal cells. This highly focused radiation then damages the DNA in the cancer cells, leading to selective cell death and tumor shrinkage. Due to their unique molecular interaction with the target, STRs act with high sensitivity and precision, enabling effective radiation targeting tumors and metastasis.

AtomVie Global Radiopharma— has entered into an agreement with Radiopharm Ventures (RV), a Joint Venture between Radiopharm Theranostics (RAD) and MD Anderson Cancer Center (MDACC), to develop and manufacture 177Lu-BetaBart, a 177Lutetium-conjugated B7-H3 targeting radioantibody. This partnership leverages both companies' expertise to advance novel radiotherapeutic solutions in areas of high unmet medical needs. B7-H3 is an immune checkpoint molecule that is overexpressed in several tumor types and represents a highly attractive target for antibody-based cancer immunotherapy. Deregulated B7-H3 expression is linked with tumor aggressiveness and poor outcomes. 177Lu-BetaBart is the first targeted radiopharmaceutical in development against the 4Ig subtype of B7-H3, which is the most common subtype expressed on human tumors. The monoclonal antibody, invented at MDACC, has been specifically engineered with a shorter blood circulation time and reduced affinity for on-target off-tissue toxicity, leading to a final molecule that is highly promising for human use in clinical settings. Phase I/II First-In-Human therapeutic trial with 177Lu-BetaBart in multiple tumor types in the US, is expected for mid-2025.

Telix Pharmaceuticals— announced that it has selected Cardinal Health, Inc. as a commercial radiopharmaceutical distributor to supply finished unit doses of its PET agent, Zircaix? (TLX250-CDx) for the imaging of kidney cancer in the United States (U.S.), subject to regulatory approval.

Eckert & Ziegler—announced a new global clinical supply agreement. Eckert & Ziegler will provide its GMP grade non-carrier added Lutetium-177 chloride (n.c.a. Lu-177) for use in GlyTherix’s clinical trials focused on innovative treatments for aggressive and invasive cancers. GlyTherix’s radiotherapy approach combines Lu-177 with an antibody targeting Glypican-1, a protein found in aggressive cancers, to deliver localized radiation while sparing healthy tissue. Glypican-1 is an attractive tumor target that occurs in several aggressive and invasive cancers including prostate, pancreatic, bladder, lung, glioblastoma and ovarian cancer. GlyTherix plans to use 177Lu-DOTA-Miltuximab? in its planned Australian Phase Ib in early 2025, followed by US Phase II trials in 2026.

Clarity Pharmaceuticals— announced it has entered into a Clinical Manufacturing Agreement with SpectronRx for the production of the diagnostic 64Cu-SAR-bisPSMA product for its Phase III trials. This agreement builds on the earlier Master Services Agreement and Supply Agreement for the production of the 64Cu isotope, now allowing for a streamlined manufacturing process of both the isotope and the 64Cu-SAR-bisPSMA product at the same facility. SpectronRx’s facility enables on-demand 64Cu-SAR-bisPSMA manufacturing and distribution to all 50 states. This provides reliable, universal access of 64Cu-SAR-bisPSMA in the U.S. for Clarity’s Phase III trials, including the ongoing CLARIFY trial in the pre-prostatectomy setting, as well as the upcoming pivotal trial for prostate cancer patients with biochemical recurrence (BCR). The agreement with SpectronRx complements Clarity’s existing supply network, providing a layered and abundant supply approach, which is unique in the radiopharmaceutical space.

AdvanCell— has commenced drug product manufacture from its facility in Richlands for the ongoing TheraPb trial.? On Wednesday, October 2nd, the first patient was successfully dosed with 212Pb-ADVC001 produced at the Company’s 40,000-square-foot flagship manufacturing site. Previous trial doses had been made at licensed research facilities and collaborator sites.? This manufacture from AdvanCell’s own premises marks a new chapter – enabling higher activity doses to meet the demands of the rapidly progressing trial.