NorthStar Medical Radioisotopes Provides Updates on Corporate Progress and Upcoming Milestones

− NorthStar positioned for continued strong growth and setting leadership standards for domestic, environmentally sustainable radioisotope production across its portfolio to meet needs of health systems, radiopharmacies and patients –

− NorthStar continues as the only U.S. commercial producer of diagnostic imaging radioisotopes non-uranium molybdenum-99 (Mo-99)/technetium-99m (Tc-99m), for more than three years −

− Company poised as first commercial-scale producer of therapeutic radioisotopes actinium-225 (Ac-225) and copper-67 (Cu-67), using environmentally preferable technology −

BELOIT, Wis.--(BUSINESS WIRE)--NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic and medical imaging applications, today announced a corporate update highlighting progress across its key programs during the past twelve months, and upcoming milestones.

“NorthStar has made tremendous strides in advancing our portfolio over the past year and we are very excited about the future,” said Stephen Merrick, President and Chief Executive Officer of NorthStar Medical Radioisotopes. “Our plans to ensure reliable, environmentally friendly, non-uranium based radioisotope supply for the United States continue to progress. RadioGenix® System (technetium Tc 99m generator) utilization is increasing. We are well on our way to having dual production and processing pathways for Mo-99 to ensure additional domestic capacity and supply security to best meet customer demand. Our Mo-99 facility expansions are nearing completion and moving to the final phase of activities required for licensure and FDA approval.

Mr. Merrick continued, “NorthStar is rapidly expanding its leadership position in the emerging area of therapeutic radiopharmaceuticals by defining the supply chain for commercial-scale, reliable and environmentally preferred therapeutic radioisotope production. Using electron accelerator technology, we are well-positioned to be the first commercial-scale producer of copper-67 (Cu-67) and actinium-225 (Ac-225). We have built out the production space and ordered processing equipment for Cu-67 production. Cu-67, given its clean manufacturing process, allows for high volume production, with no issues associated with access to stable target material or generation of long-lived radioactive waste. NorthStar is further investing in the future with a first-of-its-kind Actinium-225 Production facility, exclusively dedicated to commercial-scale production of our no-carrier added (n.c.a.) Ac-225. Illustrating NorthStar’s commitment to commercial-scale manufacture of this isotope, a third Rhodotron® TT-300 HE accelerator was ordered from IBA in November 2021.

“During the year, we expanded our SPECT pipeline through an agreement with GE Healthcare to manufacture and distribute iodine-123 capsules for imaging of thyroid cancer and other diseases, to be available pending appropriate licensure and FDA approval, which is expected in early 2023. FibroScint, a novel cardiovascular SPECT imaging agent, is advancing towards exploratory IND-enabling studies, and NorthStar is collaborating with Monopar Therapeutics to develop a targeted Ac-225 based radiotherapeutic agent for cancer and severe COVID-19. We continue to evaluate additional potential opportunities with specialized SPECT radiopharmaceuticals and therapeutic radioisotopes to address unmet healthcare needs. NorthStar anticipates sustained progress and growth as we expand our horizons and execute strongly in our mission to provide patients with global access to our game-changing radiopharmaceuticals.”

A deep commitment to environmentally responsible radioisotope production
NorthStar is committed to ensuring that health systems have access to innovative, clean solutions that minimize the environmental footprint of their nuclear medicine departments. All NorthStar processes are non-uranium based and employ the Company’s “Reduce, Recover, Reuse” approach for reliable, domestic and environmentally sound medical radioisotope production. The Company continues to set leadership standards for domestic, environmentally sound radioisotope production across its portfolio to meet the needs of health systems and patients.

• NorthStar’s unique production technology for Mo-99 offers a highly differentiated environmental advantage over traditional uranium-based methods. This results in comparatively benign, short-lived and easily managed waste streams, in contrast to uranium-based methods that result in highly radioactive, long-lived waste with significant burdens to global waste streams.
• Like all NorthStar processes, electron accelerator production of Mo-99, Ac-225 and Cu-67 radioisotopes is non-uranium based and highly efficient. For example, the Rhodotron accelerator uses significantly less electricity when compared to older linear accelerators.
• NorthStar is utilizing environmentally preferred production technology for its high purity non-carrier-added (n.c.a.) Ac-225. Electron accelerators will produce n.c.a. Ac-225 that is free of long-lived radioactive contaminants and byproducts associated with many other production methods, which pose regulatory and waste management challenges for hospitals and health systems.
• Northstar’s production of Cu-67 is both high volume and highly sustainable, allowing for the direct substitution of reactor-based therapeutic isotopes such as lutetium-177. The process is highly efficient with no associated long-lived radioactive contaminants.

Corporate development and industry leadership
NorthStar is firmly positioned for sustained long term growth and increasing global industry prominence.

New executives

• Frank Scholz, Ph.D., was appointed as NorthStar’s Senior Vice President and Chief Operating Officer. Dr. Scholz has extensive operational experience in the pharmaceutical and life sciences industries, and will help lead the next phase of NorthStar’s growth. With oversight of the Company’s Strategic Execution, Regulatory Affairs, Engineering & Technology, Manufacturing Operations & Supply Chain, and Advanced Radioisotope & Therapeutic Technologies teams, he will be instrumental in driving NorthStar’s initiatives across its portfolio.
• NorthStar appointed Adam D. Lynch as Vice President, Corporate Development and External Affairs. Mr. Lynch’s deep experience in healthcare, business and finance will help progress NorthStar’s corporate development efforts. His initial focus is to work with health systems so that they can realize the economic and social benefits of using domestically produced medical radioisotopes that are manufactured in a way that minimizes environment impact.

Industry leadership

• In August 2021, NorthStar was awarded $37 million in new cooperative agreement funds with the U.S. Department of Energy’s National Nuclear Security Administration (DOE/NNSA) as part of an industry outreach initiative to establish reliable domestic Mo-99 production without the use of highly enriched uranium (HEU). NorthStar is the first and only company to achieve commercialized Mo-99 production through collaboration with the DOE/NNSA. With inclusion of the current and past awards, NorthStar has been awarded a total of over $100 million in cooperative agreement funds by DOE/NNSA.
• NorthStar is widely recognized for its leadership position in radioisotope technology development and commercialization and the nuclear medicine industry.
  • In June 2021, NorthStar hosted an Industry User Meeting in conjunction with the Society of Nuclear Medicine and Molecular Imaging (SNMMI), “Accelerating the Future of Nuclear Medicine: Advances in Radioisotope and Therapeutic Technologies.” In addition, NorthStar President and Chief Executive Officer Stephen Merrick also participated in a CEO Summit and Panel discussion, “The Potential, Promise and Future of Therapeutics.”

Commercial U.S. Mo-99 manufacturing and production expansion
Currently, and for more than three years, NorthStar remains the only commercialized U.S. producer of Mo-99. The Company is aggressively expanding and establishing environmentally sound dual production and processing hubs for additional Mo-99 capacity to better meet customer demand and to ensure sustainable U.S. supply. Two facility expansion projects nearing completion in Beloit, Wisconsin, will augment current Mo-99 production and processing in Columbia, Missouri, conducted in partnership with the University of Missouri Research Reactor (MURR®).

• NorthStar’s Beloit, Wis., Accelerator Production facility expansion will ensure additional Mo‑99 capacity, enable flexible production scheduling, including Sunday production, and minimize customer supply risks.
  • In April 2021, NorthStar announced a major milestone in its efforts to expand U.S. production capacity for Mo-99 with the delivery of two custom-built IBA Rhodotron® TT 300-HE (High Energy) electron beam accelerators at its facility in Beloit, Wis.
  • In January 2022, NorthStar announced that both of its Rhodotron TT 300-HE electron beam accelerators achieved full beam energy of 40 MeV, validating its approach for commercial-scale production. Equipment testing is underway, with commercial production expected early in 2023, pending appropriate licensure and FDA approval.
• NorthStar’s Beloit, Wis., Isotope Processing facility will complement current Columbia processing capacity for Mo-99 source vessels. The facility will enable NorthStar to more than double its current Mo-99 processing capabilities.
  • Equipment testing and validation are underway, with commercial production planned for early 2023, pending appropriate licensure and FDA approval.
  • As part of NorthStar’s “Reduce, Recover, Reuse” initiative, the facility houses a reclamation suite, featuring proprietary technology to recover and purify either Mo-98 or Mo-100 source material, which are reused to manufacture new targets that will be irradiated to produce Mo-99.

RadioGenix^® System commercial progress
NorthStar’s innovative, high tech radioisotope separation platform, the RadioGenix System, uses U.S.-produced, non-uranium based Mo-99 to produce Tc-99m, the most widely used medical radioisotope that informs patient management decisions in 40,000 U.S. imaging studies daily. Ongoing product development programs continue to maximize operational utility and efficiency of RadioGenix Systems in producing Tc-99m, and include plans for next generation Tc-99m production.

• RadioGenix Systems have generated well over one million doses of Tc-99m for patients’ diagnostic imaging studies to date, with utilization continuing to steadily increase. RadioGenix Systems have provided reliable Tc-99m supply for customers with U.S.-produced Mo-99 despite intermittent shortages from suppliers using legacy, uranium-based production methods.
• In March 2022, NorthStar and RLS (USA) Inc. expanded their supply agreement to provide RLS’ nationwide radiopharmacy network with additional domestically-produced Mo-99. RLS plans to install additional RadioGenix Systems in its radiopharmacies, increasing availability of NorthStar’s non-uranium Mo-99. The agreement is part of both companies’ shared commitment to broaden access to reliable, environmentally sound Mo-99/Tc-99m, to help health systems and the RLS nationwide radiopharmacy network meet corporate sustainability objectives.

Commercial-scale therapeutic radioisotope production − Ac-225 and Cu-67
NorthStar is poised to be the first commercial-scale supplier of the important therapeutic radioisotopes Ac-225 and Cu-67, both used to deliver therapeutic doses of radiation to destroy cancer cells in patients with serious disease while sparing healthy tissue. Development of Ac-225 based therapies has been severely constrained by limitations in current production technology and very limited supply. Development of Cu-67 has also been historically hampered by the lack of commercial chelators to securely hold copper without leaking it in vivo, which limited demand for the isotope. The recent development of Clarity Pharmaceuticals’ Targeted Copper Theranostics platform using chelators that are able to securely hold copper is now reaching later stage development and commercialization, driving Cu‑67 demand.

• NorthStar is applying its commercial-scale radioisotope production experience with Mo-99 to provide reliable Ac-225 and Cu-67 supply to advance clinical research and for commercial radiopharmaceutical products. The Company is leveraging technology expertise demonstrated by the successful launch of the RadioGenix System and non-uranium based Mo-99 supply, as well as key learnings from sophisticated techniques required in constructing its advanced Accelerator Production and Isotope Processing facilities.
• In November 2021, NorthStar announced a contract with IBA to purchase a third Rhodotron® TT300 HE electron beam accelerator, exclusively dedicated for Ac-225 production. The accelerator will be built in parallel with construction of NorthStar’s Actinium-225 Production facility.
• In September 2021, NorthStar broke ground on its first-in-kind Actinium-225 Accelerator Production facility. Construction has begun as of mid-March, 2022, and initial production of radiochemical grade Ac-225 planned for late 2023. A Drug Master File will be submitted to the FDA in mid-2024, which, upon FDA acceptance, will allow NorthStar to provide cGMP grade Ac‑225.
• NorthStar has multiple supply agreements already in place to provide clinical trial supply and commercial-scale quantities of Ac-225 and Cu-67, and expects additional supply agreements during 2022.
  • In March 2022, NorthStar and Convergent Therapeutics signed a supply agreement for NorthStar’s high purity non-carrier-added (n.c.a.) Ac-225. Convergent will use NorthStar’s Ac-225 to radiolabel its lead asset, CONV01-α, a prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody, currently being investigated as a treatment for prostate cancer.
  • In September 2021, NorthStar and POINT Biopharma signed a supply agreement under which NorthStar will provide POINT with its n.c.a. Ac-225. POINT will use NorthStar’s Ac‑225 in investigational studies of PNT2001, a next-generation Prostate-Specific Membrane Antigen (PSMA) for non-metastatic castrate-sensitive prostate cancer (nmCSPC); PNT2004, a Fibroblast Activation Protein-α candidate with potential pan-cancer applications; and to advance its novel Tumor Microenvironment (TME) tumor-targeting technology platform.
  • In May 2021, NorthStar and Clarity Pharmaceuticals entered into an exclusive U.S. supply agreement for Cu-67, for the supply of Cu-67 towards Clarity’s Targeted Copper Theranostics programs to treat neuroblastoma, breast and prostate cancers, among others. NorthStar anticipates that production of radiochemical grade Cu-67 will begin in late 2022.
  • Other supply agreements have been signed, but not disclosed, under confidentiality agreements with NorthStar pharmaceutical partners.
• NorthStar and Monopar Therapeutics continue their collaboration on Ac-225-labeled MNPR-101, an investigational diagnostic and therapeutic radiopharmaceutical for cancer and severe COVID-19. In May 2021, the companies announced filing of two provisional patents relating to a unique and highly efficient chelating technology. Pathways to initiating a first-in-human clinical study are currently being evaluated.
• NorthStar is evaluating additional potential opportunities for the production and commercialization of other novel radioisotopes to support the needs of researchers and pharmaceutical drug developers.

Specialized SPECT portfolio
NorthStar is actively developing and growing its strategic portfolio of specialized single photon emission computed tomography (SPECT) radiopharmaceuticals to meet increasing clinical needs for SPECT imaging, driven by scientific advancements in cardiology and oncology.

• NorthStar has an exclusive, global licensing agreement with Capella Imaging, Inc. for FibroScint, a novel fibrin-specific diagnostic imaging agent labeled with Tc-99m for SPECT imaging. Pending successful development, FibroScint will have an initial application in the imaging of thrombus (blood clots) associated with left ventricular assist devices (LVADs), and other potential imaging applications in deep vein thrombosis and pulmonary embolism. NorthStar intends to use RadioGenix System-produced Tc-99m in planned clinical studies of FibroScint. A Phase 2 SBIR funding submission is planned for Q4 2022, with an exploratory Investigational New Drug (IND) filing for a Phase 1 study planned for early 2023.
• In June, 2021, NorthStar expanded its pipeline through an exclusive U.S. manufacturing and distribution agreement with GE Healthcare to produce and distribute iodine-123 (I-123) capsules. I-123 is the proven radiopharmaceutical standard in diagnostic imaging studies for thyroid disease. GE Healthcare’s Pharmaceutical Diagnostics unit will manufacture and supply NorthStar with I-123 capsules under the NorthStar label using a new, state-of-the-art production system. Upon regulatory approvals, NorthStar will retain exclusive U.S. marketing and distribution rights for I-123 capsules in 100 µCi and 200 µCi formulations. FDA approval is expected in early 2023.
• NorthStar is evaluating additional potential opportunities in specialized SPECT radiopharmaceuticals to address unmet healthcare needs and synergies with its product portfolio.

About the RadioGenix^® System (Technetium Tc 99m Generator)
The RadioGenix System is an innovative, high tech separation platform that is approved for processing non-uranium based molybdenum-99 (Mo-99) for the production of the important medical radioisotope, technetium-99m (Tc-99m). Prior to availability of RadioGenix technology, the U.S. supply chain for Mo-99 has been subject to frequent and sometimes severe interruptions that negatively impacted patient health care. Approved by the U.S. Food and Drug Administration (FDA) in 2018, the RadioGenix System is the first and only on-site, automated isotope separation system of its kind for use with non-uranium based Mo-99, designed to help alleviate shortage situations and expand domestic supply.

Indication and Important Risk Information about the RadioGenix^® System and Sodium Pertechnetate Tc 99m Injection USP

INDICATION
The RadioGenix^® System is a technetium Tc-99m generator used to produce Sodium Pertechnetate Tc 99m Injection, USP. Sodium Pertechnetate Tc 99m Injection is a radioactive diagnostic agent and can be used in the preparation of FDA-approved diagnostic radiopharmaceuticals.
Sodium Pertechnetate Tc 99m Injection is also indicated in:

• Adults for Salivary Gland Imaging and Nasolacrimal Drainage System Imaging (dacryoscintigraphy).
• Adults and pediatric patients for Thyroid Imaging and Vesicoureteral Imaging (direct isotopic cystography) for detection of vesicoureteral reflux.

IMPORTANT RISK INFORMATION

• Allergic reactions (skin rash, hives, or itching) including anaphylaxis have been reported following the administration of Sodium Pertechnetate Tc 99m Injection. Monitor all patients for hypersensitivity reactions.
• Sodium Pertechnetate Tc 99m Injection contributes to a patient’s long-term cumulative radiation exposure. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure. Use the lowest dose of Sodium Pertechnetate Tc 99m Injection necessary for imaging and ensure safe handling and preparation to protect the patient and health care worker from unintentional radiation exposure. Encourage patients to drink fluids and void as frequently as possible after intravenous or intravesicular administration. Advise patients to blow their nose and wash their eyes with water after ophthalmic administration.
• Radiation risks associated with the use of Sodium Pertechnetate Tc 99m Injection are greater in children than in adults and, in general, the younger the child, the greater the risk owing to greater absorbed radiation doses and longer life expectancy. These greater risks should be taken firmly into account in all benefit-risk assessments involving children. Long-term cumulative radiation exposure may be associated with an increased risk of cancer.
• Temporarily discontinue breastfeeding. A lactating woman should pump and discard breastmilk for 12 to 24 hours after Sodium Pertechnetate Tc 99m Injection administration.
• Sodium Pertechnetate Tc 99m Injection should be given to pregnant women only if the expected benefits to be gained clearly outweigh the potential hazards.
• Only use potassium molybdate Mo-99, processing reagents, saline and other supplies, including kit/packs, provided by NorthStar Medical Radioisotopes. Do not administer Sodium Pertechnetate Tc 99m Injection after the 0.15 microCi of Mo-99/mCi of Tc-99m limit has been reached or when the 24 hour expiration time from elution is reached, whichever occurs earlier. Follow step-by-step instructions for use provided in the Operator’s Guide, RadioGenix System 1.2.

To report SUSPECTED ADVERSE REACTIONS, contact NorthStar^® Medical Radioisotopes, LLC at 1-844-438-6659; or FDA at 1-800-332-1088 or www.fda.gov/medwatch.

For RadioGenix^® System version 1.2 Full Prescribing Information, click here or visit https://www.northstarnm.com/wp-content/uploads/2022/03/Radiogenix-System-SYS-0051-Rev-06.pdf.

About NorthStar Medical Radioisotopes, LLC (NorthStar)
NorthStar Medical Radioisotopes is a commercial-stage nuclear medicine company that manufactures and distributes diagnostic and therapeutic radioisotopes and radiopharmaceuticals. The Company’s proprietary state-of-the-art technology and proven management team have propelled it to the forefront of U.S. medical radioisotope production as the sole domestic producer of the diagnostic imaging radioisotope molybdenum-99 (Mo-99). Mo-99 is used to generate technetium-99m (Tc-99m), the standard of care in diagnostic imaging to assess the extent and severity of heart disease and cancer. NorthStar’s unique Mo-99 production process is non-uranium based and environmentally friendly. NorthStar is expanding its industry-leading position in the emerging area of therapeutic radioisotopes, which are used in targeted radiopharmaceutical therapy to treat cancer, respiratory and other diseases. Using first-in-kind and environmentally-sound electron accelerator technology, NorthStar is poised to be the first commercial-scale producer of therapeutic radioisotopes actinium-225 (Ac-225) and copper-67 (Cu-67). NorthStar also collaborates with other companies in the development of radiopharmaceuticals. For more information about NorthStar’s comprehensive radiopharmaceutical portfolio, visit: www.northstarnm.com.