Emerging as a new class of drugs, radiopharmaceuticals are all the rage in cancer treatment research, at present. Pharma giant Novartis’ $1 billion acquisition of Massachusetts-based Mariana Oncology is proof of this growing fascination with this class of therapeutics.
The American radiopharmaceutical company would also receive an additional $750 million in milestone payments in exchange for Novartis’ rights to its preclinical radiopharmaceutical portfolio to treat solid tumors. This adds to the Swiss multinational’s own portfolio of radiopharmaceuticals that include U.S. Food and Drug Administration (FDA)-approved drugs Lutathera and Pluvicto.
The purchase comes after Eli Lilly’s oversubscribed $175 million investment in the biotech last year in hopes of moving Mariana’s lead asset MC-339 to the clinic.
Eli Lilly has been quite keen on fostering radiopharma companies in the past year. It snapped up American clinical-stage company Point Biopharma for $1.4 billion last year, marking one of the most significant mergers and acquisitions (M&A) deals of all time. More recently, it paid American biotech Aktis Oncology $60 million to develop a pipeline against solid tumors.
The pharma giant acquired all of Point Biopharma’s drug candidates including its pan-cancer program targeting fibroblast activation protein-α (FAP-α), and its drug candidate for people with metastatic castration-resistant prostate cancer (mCRPC).
The billion-dollar buyouts have become part of a larger market trend witnessed by the radiopharmaceutical industry. But first, how do these drugs target cancer?
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How do radiopharmaceuticals work?
When an imaging radioactive isotope of an element – like fluorine-18, gallium-68, zirconium-89 and technetium-99m – is bound to a drug or monoclonal antibody and delivered intravenously to a patient with cancer, it attaches itself to cancer cells, much like a key to a lock. Then, with the help of nuclear imaging, the radioisotope can be spotted, therefore locating the tumor cells.
Once the target cells have been identified, a therapeutic radioisotope – namely, actinium-225, iodine-131, yttrium-90 and astatine-211, among others – that is linked to the same kind of vector that was previously used in detecting the target, enters the cancer cells. The radioactive compound then breaks down, releasing energy that damages cancer cells, as these cells are particularly sensitive to DNA damage that is caused by radiation. This is the mechanism behind radiopharmaceutical drugs.
With a market value of $6.3 billion this year, which is forecasted to more than double over the next decade, according to a report by Statista, the radiopharmaceutical industry is growing, as more companies are becoming invested in the field.
Radiopharmaceutical market thrives with funding surge and notable mergers in 2023 and 2024
American multinational Bristol Myers Squibb is also going up against Novartis and Eli Lilly as it has spent $4.1 billion on a major player in the industry, RayzeBio. The California-based startup’s lead candidate RYZ101 is currently in phase 3 clinical trials for patients with neuroendocrine tumors, which is poised to be the first actinium-225 (Ac225) approved drug. RYZ101 is a targeted therapy that is designed to deliver Ac225 to tumors that express the somatostatin receptor type 2 (SSTR2) – both a biomarker and a therapeutic target that many radiopharmaceuticals are focused on drugging.
It had previously swayed investors when it reeled in $160 million in a series D round last year, and then went public with a $311 million initial public offering (IPO) in September.
Meanwhile, British multinational AstraZeneca has taken over Canadian clinical-stage company Fusion Pharmaceuticals. The $2 billion deal will allow AstraZeneca to get its hands on the phase 2 candidate FPI-2265 to treat mCRPC. If approved, it could become the first actinium-based radiopharmaceutical for mCRPC.
AstraZeneca has taken a shine to the therapeutic space of late as it also contributed to a series A funding round for Nucleus RadioPharma in which the biotech had initially raised $56 million to streamline its supply chains last year.
Amid this radiopharma buyout craze, German biotech ITM Radiopharma secured around $205 million this month as it looks to have a piece of Novartis’ pie as its lutetium-177 drug looks to take on Lutathera. Earlier this year, Massachusetts-based Ratio Therapeutics raised $50 million to launch clinical trials for its solid tumor candidates. California-based Radionetics Oncology also completed a $52.5 million fundraising to advance its radiopharma pipeline.
Moreover, last year was a turning point for various other biotechs focused on delivering radiopharmaceutical drugs to patients with cancer. Canadian startup Abdera Therapeutics emerged out of stealth with a $142 million combined series A and B funding, with which it is advancing its pipeline of antibody-based precision radiotherapeutics. Its lead candidate designed to treat small cell lung cancer (SCLC) is slated to go to the clinic soon as it has received the go-ahead from the FDA.
2023 also saw more funding deals like American company Convergent Therapeutics closing its $90 million series A round. Now, its prostate cancer drug’s Investigational New Drug (IND) application has been cleared by the FDA.
Radiopharmaceutical advantages and challenges
As the theranostics landscape evolves, radiopharmaceuticals – unlike chemotherapy and immunotherapy where months of treatment is required before the benefits of the drugs kick in – can show therapeutic responses after a few injections, according to Jamal Temsamani, drug development director at Vect-Horus, who told Labiotech.
Moreover, because these drugs are better equipped at targeting cancer cells compared to radiation therapy – thereby regarded as a powerful tool in precision medicine – they seem to have fewer side effects on patients. On the other hand, radiation therapy has been linked to side effects like nausea, hair loss, mouth sores, difficulty swallowing, and various others that come with the part of the body where the therapy is aimed.
However, developing radio-labeled drugs is no picnic. Steffen Schuster, CEO of ITM Group in Germany explained in a Labiotech article in 2022, that many companies do not understand the supply chain for radiopharmaceuticals, and underestimate how short the half-life of the drug is – due to the presence of a radioisotope. And so, factoring in elements like transport, where it must reach different parts of the world before it decays, is essential. Schuster also pointed out that hospitals need to amp up their nuclear medicine departments in order to partake in clinical trials.
To add to that, picking the most suitable radioisotope is key to an effective treatment. While beta particles – which have less charge and mass – can penetrate tissues and have a less damaging outcome, some companies are looking into the power of alpha radiation, which can deliver a lot of energy to nearby cells, making it quite destructive despite traveling a much shorter distance. So, depending on how aggressive the tumor is, providing the right treatment is important.
Keeping the many challenges in mind, radiopharmaceutical companies are now building portfolios that have made funding them hard to resist for investors. Thanks to more and more funding now more than ever, we may see more radiopharmaceutical drug candidates hit the clinic soon.