August 18 2022: the clinical stage of ITM’s lead candidate was corrected to phase 3.
Radiopharmaceuticals have been a relatively niche area of cancer therapy for decades. Steffen Schuster, the CEO of Germany’s ITM Group, outlines how the space is heating up, and how much nuclear medicine centers still need to grow.
There are many areas in oncology research that are generating investor excitement, including immuno-oncology, DNA damage repair and protein degradation. Another emerging area with huge potential is the treatment of cancer using drugs that carry radioactive molecules, known as radiopharmaceuticals.
“This space is hot right now,” said Steffen Schuster, CEO of the German firm ITM Group. “You see acquisitions in the field and you see the money flowing in, in terms of venture capital, private equity and growth capital.” Some notable acquisitions in the last decade include Novartis’ takeover of Advanced Accelerator Applications and Endocyte, and Bayer’s purchase of Noria Therapeutics and its subsidiary PSMA Therapeutics.
Radiopharmaceuticals typically consist of a tumor-hunting drug that is chemically attached to a radioactive molecule called a radioisotope. If you attach one type of radioisotope to the drug, you can image where it binds to a tumor target in a diagnostics setting. By attaching a different radioisotope, you can zap the tumor cells with radiation at point-blank range. This strategy is also known as theranostics.
“When we give a drug to the patient, we know already that the receptors are being addressed with the diagnostic targeting molecule. That’s the beauty of the concept,” explained Schuster.
ITM has been in the radiopharmaceuticals business since 2004, and has positioned itself as a central supplier for many other companies in the same space. After he served as a general partner at TVM Capital, Schuster took the helm at ITM in 2011, and has driven the company to become a drug developer in its own right.
ITM has long specialized in the production of a radioisotope called lutetium-177, which is the radioisotope used in the approved radiopharmaceutical Lutathera. This molecule is fast becoming the workhorse of the radiopharmaceutical space because it can shoot electrons, or beta radiation, at cancer cells. The specific form of lutetium-177 produced by ITM — named no carrier added lutetium-177 (lutetium-177 NCA) — has a half-life of around 6.7 days. This means it can be delivered worldwide before decaying, and is also easier to dispose of in hospitals than compounds with longer half-lives.
“We’ve been the only party in the world able to manufacture this lutetium-177 NCA in large volumes,” explained Schuster. One example of ITM’s agreements is with Novartis to supply their recently approved drug Pluvicto.
In addition, ITM has its own pipeline of radiopharmaceutical drugs in development, with its lead candidate in phase 3 trials to treat rare cancers called gastroenteropancreatic neuroendocrine tumors.
“We have a very nice business model where we generate nice cash flows on the side of the radioisotopes and, on the other hand, we develop drugs,” elaborated Schuster.
Much of the growth in the radiopharmaceuticals space is thanks to the growing range of radioisotopes available, in addition to an increasing number of drugs that deliver the cargo to tumors. However, it’s a tricky field to navigate for beginners, as the logistics of radiopharmaceutical drugs are very different from those of regular drugs.
“Many companies completely underestimate the complexity of radiopharmaceuticals, because they don’t understand the supply chain,” said Schuster. “In many big pharma companies, they are used to drugs where you put them on the shelf for two years and you forget about them. That’s very difficult with a product with a half-life of 6.7 days.”
Other challenges to developing these treatments include the necessity for a reliable manufacturing supply, being able to transport the molecule around the world before it decays, and the fact that hospitals need experienced nuclear medicine departments in order to participate in clinical trials.
Another crucial decision in radiopharmaceuticals is deciding which type of radiation you will use to blast tumor cells. In addition to beta radiation, which can travel millimeters in the body, some companies are working with alpha radiation, which travels only several cell widths, but delivers a lot of energy into nearby cells.
“For example, in more aggressive tumors, I would rather go with an alpha emitter: high energy, but low range,” commented Schuster. “But in less aggressive tumors, I would go with beta emitters. It’s better tolerated by the healthy tissue.”
In spite of the challenges, radiopharmaceuticals are maturing to the point where they could compete with immuno-oncology and chemotherapy.
“We are of the conviction that radiopharmaceuticals, which traditionally have been used in the later lines of therapy, will move into earlier lines,” said Schuster. He added that some of the patients in ITM’s ongoing trials are in their first line of cancer treatment.
“When you look at the side effects, if you just compare chemotherapy and radiotherapy, it’s an amazing difference. And we think that, in many cases, radiopharmaceuticals are superior.”
However, there are also many opportunities for synergy between radiopharmaceuticals and other fields. For example, the firm Theragnostics is working on radiolabeling a class of cancer drugs called DNA damage repair inhibitors.
Nonetheless, to really unchain the field, Schuster noted that more capacity is needed in nuclear medicine departments at hospitals to allow more patients to benefit. To facilitate this expansion, the German non-profit organization the International Centers for Precision Oncology Foundation was set up in 2019. The mandate of the organization is to work with national health systems to allow more patients access to lifesaving radiopharmaceuticals. Part of this mission is dedicated to increasing the number of beds available in hospitals.
“We don’t have enough hospital beds for nuclear medicine,” warned Schuster. “It’s not a German or European thing; this is something affecting the whole world. We need nuclear medicine departments to grow.”