Although a niche area, market interest in radiopharmaceuticals is on the rise as certain bio/pharma majors and smaller companies strike drug-development deals and CDMOs/CMOs specializing in this area expand production capacity. 

By Patricia Van Arnum, Editorial Director, DCAT, pvanarnum@dcat.org

Niche but growing market
Radiopharmaceuticals are a niche segment in the global bio/pharmaceutical market, but are showing solid growth and increased interest by the bio/pharmaceutical majors and smaller companies. The global radiopharmaceuticals market was estimated at $5.97 billion in 2023 and is expected to increase at a compound annual growth rate of 8.2% to reach $13.67 billion by 2033, according to Precedence Research, an Ottawa, Canada-based market research firm. The market is driven by radiopharmaceuticals’ use in cancer treatments and other precision medicines as well as for diagnostics.

Several of the large bio/pharmaceutical companies have recently struck $1-billion-plus deals to advance their position in radiopharmaceuticals. Some of the key moves are outlined below.

Novartis. Among the bio/pharma major, Novartis is positioned with two radioligand therapies, Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for treating certain types of gastroenteropancreatic neuroendocrine tumors, and Lutathera (lutetium Lu 177 dotatate) for treating metastatic castration-resistant prostate cancer.

In 2024, Novartis has made moves on both the manufacturing and drug development fronts. In September (September 2024) Novartis began the construction of two new radioligand therapy (RLT) manufacturing facilities in the US. Novartis broke ground on a new facility at its site in Indianapolis, Indiana, which will produce radioisotopes for the manufacturing of RLTs. In Carlsbad, California, Novartis is establishing its third RLT manufacturing site in the US. Both facilities will be built with room for further expansion to enable the potential production of different isotopes, ligands, and RLTs. 

On the drug-development front, in May (May 2024), Novartis agreed to acquire Mariana Oncology, a Watertown, Massachusetts-based bio/pharmaceutical company developing RTLs to treat cancers, in a deal worth up to $1.75 billion ($1 billion upfront and $750 million in potential milestone payments). The acquisition encompasses a portfolio of RLT programs spanning lead optimization to early development across a range of solid tumor indications, such as breast, prostate and lung cancer. The assets also include a development candidate, MC-339, an actinium-based RLT being investigated in small cell-lung cancer.

Earlier this month (November 2024), Novartis entered into an exclusive worldwide license and collaboration agreement with Ratio Therapeutics, a Boston-based clinical-stage radiopharmaceutical company, for the discovery and development of a somatostatin receptor 2 (SSTR2) radiotherapeutic candidate for cancer, in a deal worth up to $745 million. 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.  

Bristol-Myers Squibb. In February (February 2024), Bristol-Myers Squibb (BMS) completed its $4.1-billion acquisition of RayzeBio, a San Diego, California-based clinical-stage radiopharmaceutical company. RayzeBio has a position in actinium-based radiopharmaceutical therapeutics targeting solid tumors, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), small-cell lung cancer, hepatocellular carcinoma, and other cancers.  

Its lead program is RYZ101 (225Ac-dotatate), a small-cell lung cancer drug candidate in Phase III development targeting somatostatin receptor 2 (SSTR2) in patients with SSTR-positive GEP-NETs who have previously been treated with lutetium-177-based somatostatin therapies. Its pipeline also includes: RYZ801, a proprietary peptide for treating hepatocellular carcinoma, now in investigational new drug (IND)-enabling studies; an asset targeting CA9, which is expressed in renal cell cancer and currently in IND-enabling studies; and multiple preclinical assets to treat solid tumors. 

On the manufacturing side, BMS gains a radiopharmaceutical manufacturing facility. At the time of the acquisition, RayzeBio was completing construction of an in-house manufacturing facility in Indianapolis, Indiana, with GMP drug production slated to begin production in the first half of 2024. 

AstraZeneca. In June (June 2024), AstraZeneca completed its acquisition of Fusion Pharmaceuticals, a Hamilton, Ontario, Canada-based clinical-stage bio/pharmaceutical developing radioconjugates to treat cancer, in a $2.4-billion deal (includes $2 billion upfront). Fusion Pharmaceuticals specializes in developing radioconjugates to treat cancer to deliver a radioactive isotope directly to cancer cells through precise targeting using molecules such as antibodies, peptides, or small molecules. The acquisition also includes R&D and manufacturing facilities.  

Fusion’s lead candidate is FPI-2265, an actinium-based radioconjugate as a potential new treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), currently in a Phase II trial. FPI-2265 targets prostate-specific membrane antigen (PSMA), a protein that is highly expressed in mCRPC, according to information from AstraZeneca

Sanofi. Last month (October 2024), Sanofi and Orano Med, a Paris-based developer and producer of radiopharmaceuticals, entered into an agreement under which they will invest in a new entity, operating under the Orano Med brand, and focused on the discovery, design, and clinical development of RLTs based on lead-212 (²¹²Pb) alpha-emitting isotopes. 

The agreement follows Sanofi’s announcement of an exclusive licensing agreement with Orano Med and RadioMedix, a Houston, Texas-based bio/pharma company, to advance RLTs in rare cancers with a focus on one late-stage project, AlphaMedix (²¹²Pb-dotamtate), a targeted alpha therapy currently being evaluated for treating adult patients with unresectable or metastatic, progressive somatostatin-receptor expressing neuroendocrine tumors.

Under the agreement, Sanofi will make an equity investment of EUR 300 million ($325 million) for an approximate 16% equity stake in the new entity valued at EUR 1.9 billion ($2.1 billion). This agreement is subject to standard regulatory approvals required for transactions of this nature.

Eli Lilly and Company. In July (July 2024), Lilly inked a $1.1-billion deal with Radionetics Oncology, a San Diego, California-based bio/pharmaceutical company developing small molecule G protein coupled receptor (GPCR) targeted radiopharmaceuticals for treating a broad range of solid tumors. Under the deal, Radionetics received a $140-million upfront cash payment, and Lilly obtained the exclusive right to acquire Radionetics upon conclusion of an exercise period for $1 billion.

This was the second $1-plus deal thus far this year by Lilly to build its position in radiopharmaceuticals. In May (May 2024), Lilly formed a $1.1-billion strategic collaboration with Aktis Oncology, a Boston-based radiopharmaceutical company. Under the deal, Aktis received a $60-million upfront cash payment for the collaboration in addition to an equity investment in Aktis by Lilly. In addition, Aktis will be eligible to receive up to an additional $1.1 billion in potential preclinical, clinical, regulatory, and commercial milestones, as well as tiered royalties. In exchange, Lilly will receive worldwide rights to develop radiopharmaceutical therapeutic and diagnostic products discovered by Aktis on a defined set of targets selected by Lilly.

These deals are in addition to another large move by Lilly to increase its position in radiopharmaceuticals. Last December (December 2023), Lilly completed its $1.4-billion acquisition of Point Biopharma, an Indianapolis, Indiana-based radiopharmaceutical company with a pipeline of preclinical and clinical radioligand therapies in development for the treatment of cancer. Point Biopharma’s lead programs are in late-phase development: PNT20021, a prostate-specific membrane antigen (PSMA) targeted RTL for treating metastatic castration-resistant prostate cancer, and PNT20031, a somatostatin receptor (SSTR) targeted RTL for treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs). With the acquisition, Lilly also gained a  180,000-square-foot radiopharmaceutical manufacturing campus in Indianapolis, Indiana, as well as a radiopharmaceutical research and development center in Toronto, Canada.  

Smaller companies and radiopharma start-ups
Orano Med. In addition to its partnership with Sanofi, Orano Med is advancing its position in radiopharmaceuticals for its own products and is increasing manufacturing capacity to support those products. Earlier this month (November 2024), Orano Med broke ground for a EUR 250-million ($262 million) facility in Bessines-sur-Gartempe in Haute-Vienne,  France, for the production of thorium-228, a precursor of lead-212. The facility has over 7,000 m² of floor space and is scheduled for commissioning in 2027 and will increase current production to support clinical and commercial-scale production. In 10 years, the company estimates that its industrial platform will enable the production of 100,000 doses of its lead-212 radiopharmaceuticals.

Earlier this year (2024), Orano Med also broke ground on a EUR 29 million ($31 million) laboratory for producing lead-212 based RTLs in Onnaing, France. The facility will have over 3,000 m² of floor space and will focus on the production of lead-212 therapies developed by Orano Med and their distribution in Europe. Orano Med was slated to inaugurate a similar facility this year (2024) in Indianapolis. 

Telix Pharmaceuticals/Rhine Pharma. Last month (October 2024), Telix Pharmaceuticals, a Melbourne, Australia-based bio/pharmaceutical company, announced the spin-off of Rhine Pharma, a radiopharmaceutical company. Rhine Pharma was formed following a collaboration between Telix and Heidelberg University Hospital, which created a theranostic compound, RHN0014, which Rhine Pharma is now advancing into a Phase I/IIa theranostic clinical study to evaluate the safety profile and efficacy of both 99mTc-RHN001 and 188Re-RHN001 for treating advanced prostate cancer.

PanTera. PanTera, a Mol, Belgium-based producer of radioisotopes, announced in September (September 2024) that it had raised EUR 94 million ($102 million) for the construction of a production facility in Belgium. PanTera raised the money through EQT Life Sciences, an investment firm. PanTera was founded in 2022 with the primary goal of enabling large-scale production of actinium-225 (²²⁵Ac), which is used in a new class of targeted cancer treatments known as targeted alpha therapyies Targeted alpha therapies enable delivery of radiation to cancer cells by radioisotopes that emit highly energetic alpha particles. The company says that the radiation effect of the alpha particle is more localized compared to other approaches and as such can destroy the cancer cells to which it is attached without harming surrounding healthy tissue.  

CDMOs/CMOs expand
The increased interest in radiopharmaceuticals has also spawned manufacturing expansions by certain CDMOs/CMOs specializing is this area as outlined below.

Nucleus RadioPharma. Last month (October 2024),Nucleus RadioPharma, a Rochester, Minnesota-based CDMO of radiopharmaceuticals, announced it is expanding radiopharmaceutical development and manufacturing capacity with two new facilities totaling over 100,000 square feet in Mesa, Arizona, and Springhouse, Pennsylvania. The 53,000-square-foot Mesa site and the 48,000-square-foot facility in Spring House will create approximately 50 new jobs in each location.

NorthStar Medical Radioisotopes. Also, last month (October 2024), NorthStar Medical Radioisotopes, a Beloit, Wisconsin-based CDMO of radiopharmaceuticals, opened a new manufacturing center in Beloit, Wisconsin. The facility will provide development services and dose-manufacturing capacity for medical radioisotopes, including Ac-²²⁵, Lu-1⁷⁷, Cu-⁶⁴, Cu-⁶⁷, and In-¹¹¹. The 52,000-square-foot facility will increase capacity for diagnostic and therapeutic radiopharmaceuticals.

PharmaLogic. In April (April 2024), PharmaLogic, a Boca Raton, Florida-based CDMO of radiopharmaceuticals, opened a new radiopharmaceutical production and research facility in Cincinnati, Ohio. The new production and laboratory space is equipped for PharmaLogic to expand current production and focus additional efforts on research and development of compounds.