After decades of neglect from big pharma, radiopharmaceuticals are generating major oncology deals globally. This could lead to a boom in cancer drugs that can serve as both treatments and diagnostics, or ‘theranostics.’
Over the last several months, there has been big activity from companies developing drugs that use radioactivity to destroy tumors. Just this week, we’ve seen the Australian firm Telix Pharmaceuticals licensing its portfolio to China Grand Pharma in a deal worth €242M (AU $400M). Not long after a €182M ($212M) IPO in June, the US-based Fusion Pharma was recently recruited by the big pharma AstraZeneca to co-develop radiotherapies for cancer. And in mid-October, the US radiopharmaceuticals startup RayzeBio launched with a €39M ($45M) Series A.
“The market is clearly hot at the moment and, whilst the majority of the investment has been in the US, we are also seeing a high level of interest and activity in Europe and the Far East,” said Paul Edwards, NanoMab’s CEO.
On a smaller scale, European companies have also been staking their claims in the sector. In September, the Belgian company Camel-IDS rebranded as Precirix as it advanced its lead candidate radiopharmaceutical into phase I/II. The firm NanoMab moved its headquarters from China to the UK in Spring and is preparing to enter phase II. We also saw Vect-Horus (France) raising €6.7M in September and Pentixapharm (Germany) raking in a €15M Series A in February.
Nuclear medicine involves using radioactivity for the diagnosis or treatment of a range of diseases. In cancer, for instance, a radioactive atom called a radionuclide can be attached to a drug that can hunt down tumors in the body. This opens up avenues for theranostics, where you can image tumors and destroy them more easily than with conventional therapies such as chemotherapy.
“If you look at chemotherapy or immunotherapy, once you start the treatment, you have to wait a few months in order to get it resolved,” said Jamal Temsamani, Drug Development Director at Vect-Horus. “You stop [the radiotherapy] and you can have the results right away.”
A classic theranostic method that has been used since the 1950s is radioactive iodine; one isotope of iodine can be used to image the spread of thyroid tumors, and another can be used to destroy them.
A newer approach, developed by the French company Advanced Accelerator Applications (AAA), tackles neuroendocrine tumors by using a molecule called dotatate. This drug seeks out proteins on the surface of some tumors. One radionuclide can be attached to dotatate to image the tumors and another can be attached to eliminate them.
For decades, the clinical development of radiopharmaceuticals was mainly restricted to academic efforts. However, AAA’s efforts with dotatate in the last several years meant the field began to be taken more seriously by big pharma.
Following AAA’s acquisition by Novartis for around €3.3B in 2017, the FDA approved AAA’s dotatate therapy Lutathera in 2018. Novartis would go on to acquire another radiopharmaceutical developer, the US-based Endocyte, for around €1.8B in 2018. In late 2019, the US nuclear medicine biotech Progenics — with several radiopharmaceutical therapies approved by the FDA — was acquired by the US company Lantheus Holdings.
“It was really AAA coming along and doing a formal prospective, randomized controlled study that has been a game-changer,” noted Greg Mullen, CEO of the UK company Theragnostics. “If you look at how Novartis sees radionuclide therapy, it sees it as one of the pillars that it wants to develop as a cancer therapy.”
There are a number of nuclear medicine options available for cancer patients, particularly in diagnostics. However, to really fulfil the potential of theranostics in precision medicine, the range of technology available needs to be expanded.
“The current theranostics field is still tending to focus on just a few small molecules and specific radioisotopes,” said Edwards. He added that the drugs need to be able to target many more biomarkers, and to be able to carry more types of radionuclides.
The firm Theragnostics aims to expand the range of theranostics by harnessing a class of drugs called PARP inhibitors. These drugs, which include AstraZeneca’s Lynparza, prevent cancer cells from repairing damaged DNA, and can work in a wide range of tumor types.
Theragnostics licensed AstraZeneca’s PARP inhibitor intellectual property last year with the plan to radiolabel some of these drugs. A diagnostic version is currently in phase I, and a therapeutic version is entering phase I.
“That’s what’s different from all of the other cancers where you have a specific marker for a specific cancer and even an indication,” said Mullen. “Here, you have what I call a potential pan-cancer market.”
Meanwhile, NanoMab and Precirix are developing radiolabeled drugs based on antibodies from the camelid family, which include camels, llamas, and alpacas. These antibodies are smaller and more stable than human antibodies, allowing them to penetrate tumors more easily. Precirix’s phase II-stage lead candidate is designed to treat breast cancer that has spread to the brain, while NanoMab is developing a diagnostic that could noninvasively check whether checkpoint inhibitor drugs are working.
Vect-Horus is a relative newcomer to the theranostics field, as it’s mainly a supplier of peptide vectors for drug delivery. However, with a recent €6.7M fundraise, the company is preparing to start phase I development of a theranostic glioblastoma drug for in 2021 with US partner RadioMedix.
The European life sciences scene was one of the main driving forces in kickstarting theranostics, with companies such as AAA, Novartis, and AstraZeneca leading the way. However, the same might not be true for the future of the field.
“Some of the newer generations of nuclear medicine companies will come out of the US; we’re probably behind on the startups,” Mullen told me.
Additionally, like many other therapies, the clinical development of theranostics is vulnerable to the ongoing Covid-19 pandemic. This is partly because radiotherapy requires patients to travel to hospitals, which are currently struggling with Covid-19 outbreaks.
“For instance, the collaboration with RadioMedix was affected by the pandemic,” said Vect-Horus’ Temsamani. “It’s obviously slowed down the development of our compound.”
Nevertheless, theranostics continues to gain momentum, and will likely be able to expand its range to new cancer biomarkers and indications going forward.
“Immunotherapy took the best part of 15 to 20 years to get going,” reflected Mullen. “Now nuclear medicine is the next immunotherapy.”
Image from Elena Resko