Radiopharma’s new wave: Nuclidium and Actithera raise the stakes 

Just one day after Actithera announced the largest radiopharma series A of 2025, closing $75.5 million, Nuclidium followed with a $98 million (CHF 79 million) series B round. Two major deals in two days, a sign that radiopharmaceuticals and theranostics are drawing growing investor attention. 

These fundings don’t come out of nowhere. The approvals of Lutathera and Pluvicto in recent years showed that radioligand therapy could move beyond nuclear medicine and into mainstream oncology. That success has opened the door for a broader range of companies and investors to take the space seriously. 

But this next generation is doing more than capitalizing on the success of earlier therapies. Companies like Actithera and Nuclidium are developing full platforms from the ground up, combining isotope science, medicinal chemistry, and precision targeting. Radiotheranostics is no longer a side bet. It’s starting to look like a core modality in cancer care, and the bar for what makes a company credible is rising fast. 

Radiopharma companies in the spotlight 

The two recent funding rounds reflect not just growing investor interest in radiopharmaceuticals, but growing expectations. Both radiopharma companies aim to bring more precision and flexibility to radioligand therapy. But while they share a modality, their strategies diverge: one is focused on improving therapeutic performance through chemistry; the other is building a fully integrated theranostic platform. 

Actithera: Tumor retention by design 

Actithera is betting that better chemistry can make radioligand therapies more effective. Rather than trying to discover new targets or invent new isotopes, the company is focused on optimizing how long its molecules stay in tumors, a factor that can be critical to ensuring a therapeutic dose. 

“Tumor residence time is directly linked to therapeutic efficacy in radioligand therapy. The longer a radioconjugate remains in the tumor, the more radiation dose it can deliver to kill cancer cells. Our goal is to combine short systemic half-life, ideally around one to two hours, to minimize exposure to normal tissues, with extended tumor retention to maximize therapeutic impact,” said Andreas Goutopoulos, the company’s founder. 

The company’s platform uses covalent binding and small-molecule design to extend retention in the tumor microenvironment. That design is isotope-agnostic, meaning the same scaffold could potentially be paired with therapeutic or diagnostic radionuclides.  

“We design our ligands to be compatible with multiple radionuclides, allowing us to choose the isotope best suited for the target biology, molecule, and indication. In some settings, alpha emitters are optimal, while in others, such as when target expression is heterogeneous or present in some normal tissues, beta emitters may be preferable,” explained Goutopoulos. 

Their initial target, fibroblast activation protein (FAP), has a mixed track record in drug development. Its expression in the tumor microenvironment makes it accessible but difficult to exploit fully. 

“FAP has proven difficult to effectively drug in radioligand therapy (RLT) due to challenges with sustained tumor retention. That’s precisely the type of problem our platform is built to address. Our model, by having FAP expression levels in the same range as what human tumors express, has been very predictive of the clinical behavior of some of the most important clinical stage compounds that were tested head-to-head with our compounds.” 

And FAP might only be the beginning for Actithera. “Our approach is designed to be modular and target-agnostic. Covalent chemistry, for instance, can now be applied to a wide range of amino acid residues, not just cysteine, opening up a broader landscape of targetable proteins. Once we’ve optimized a ligand’s tumor retention profile, we can test it with various radionuclides. Longer-lived isotopes require more stringent ligand properties, particularly regarding tumor half-life. But by aiming high from the outset, we build flexibility into every program.” 

While Actithera is purely therapeutic, the company acknowledges the growing importance of theranostics. “Although our primary focus is therapeutic, the importance of the theranostic approach is critical, especially for patient selection, dosimetry, and disease monitoring. In some programs, we may use the same ligand with a diagnostic radionuclide, or a surrogate compound; in others, we may partner with companies that have complementary imaging agents. These decisions are driven by the specifics of each target and program,” said the company’s chief executive officer (CEO).  

And theranostics, that’s what Nuclidium, the other company of the hour, is focusing on.  

Nuclidium: Theranostics by design 

While some radiopharmaceutical companies explore either diagnostic imaging agents or therapeutic isotopes, Nuclidium is committed to doing both, and with the same molecule. The company is the only one to pursue true theranostics: a paired approach using a single targeting ligand labeled with both a diagnostic and a therapeutic radionuclide. 

“True theranostic means that we use the exact same targeting molecule for both the diagnostic and therapeutic, labeled with Cu-61 for PET imaging and with Cu-67 for targeted radiotherapy,” said CEO Leila Jaafar-Thiel. 

This pairing allows for more precise patient selection and dose planning, something that separate companion diagnostics often struggle to match. In Nuclidium’s case, the diagnostic agent doesn’t just approximate the therapeutic; it is the same construct, tagged with a different isotope. 

“Our true theranostic concept allows us to significantly de-risk our therapeutic program by leveraging the knowledge gained from the diagnostic trials.” The pairing not only simplifies translation from imaging to treatment but also strengthens the regulatory case for companion approval. 

Another edge for the company lies in its use of copper isotopes. According to Jaafar-Thiel, copper isotopes are produced from more abundant and accessible stable precursors, and their chemistry allows for rapid preparation at the point of care. 

“In terms of waste management, Cu-67 decays into a stable isotope, Zn-67, leaving no radioactive waste for the hospitals or our patients. This will be particularly important as more patients are treated and targeted radiotherapy advances into indications with larger patient populations,” added Jaafar-Thiel. 

The next indication Nuclidium is aiming for is breast cancer, and the $98 million series B round will certainly help. 

The rising bar for radiopharma 

The radiopharma space is heating up, not just in terms of investment, but in what it takes to stand out. For startups, the expectations are no longer just about having a promising molecule. They’re about proving you can do it again, and do it better. 

“Absolutely,” said Goutopoulos, when asked whether platform potential is now expected even before first-in-human trials. “With SSTR2 and PSMA clinically and commercially validated, attention is shifting to the next generation of targets. Investors and partners are now looking for discovery platforms that can repeatedly generate high-quality candidates.” 

This shift in mindset is changing how young companies are built from the start. “That’s why we built Actithera as a platform company from day one. It gives us the ability to pursue multiple targets, rapidly iterate on ligands, and flexibly work with different isotopes.” 

Indeed, investors like Sofinnova, one of the leads in Actithera’s round, are applying a more rigorous lens. “Through our mapping of the landscape, improving the therapeutic index and tumor retention have emerged as key criteria for next generation RLTs: keeping the RLT in the tumor long enough to deliver maximum radiation to cancer cells, while ensuring rapid clearance from the bloodstream to minimize exposure and toxicity in healthy tissues,” said Karl Naegler, parter at Sofinova. 

In other words, it’s not just about hitting the tumor, it’s about how long you stay there, and how little you leave behind elsewhere. And that refined pharmacology is opening up room to tackle more targets. “This optimized pharmacology will enable us to unlock a broader target space,” Naegler noted. “While there is now commercial validation in the field through Pluvicto and Lutathera, more successful products against additional targets are needed to justify the investment in the space and to establish RLT as a true therapeutic pillar.” 

But even with better science, the path isn’t easier. “It’s also true that expectations have risen,”  Goutopoulos acknowledged. “The emergence of the first blockbuster RLT, increasing pharma interest, and several large early-stage deals since 2024 have raised the bar for startups. As a result, series A rounds have grown in both size and ambition.” 

Sofinnova sees opportunity in that pressure around radiopharma, but not without acknowledging the challenges ahead. “Currently approved radioligand therapies are delivering clinically meaningful survival benefits to patients while generally being well tolerated. This justifies the relatively high investment required for supply logistics and infrastructure,” Naegler explained. “However, there is still room to further optimize existing treatments, whether by adjusting dosing schedules, combining isotopes, or integrating RLTs with other therapeutic modalities.” 

What this all amounts to is a rising bar not just in capital or targets, but in how you build. The companies aiming to shape the next wave of radiopharma need to show flexibility, precision, and scale. And increasingly, they need to show it early. 

What’s next in radiopharma? 

The big question now: where does radiopharma go from here? More precisely, can companies change oncology workflows by merging diagnosis and therapy, a shift Nuclidium believes is within reach? 

“Companion diagnostics are fundamental to the success of theranostics. By using the same molecular target and pharmacokinetics in both the diagnostic and therapeutic setting, we can identify the right patients, tailor dosing, and monitor response, all in a highly personalized way,” Jaafar-Thiel said. 

Their vision isn’t theoretical; it reflects growing trends in precision medicine. Companion diagnostics are projected to nearly double from around $5 billion in 2024 to over $8 billion by 2030, as clinicians increasingly demand tests that can guide therapy decisions.  

Nuclidium expects this convergence to reshape clinical practice. “Over time, we believe theranostics will increasingly blur the line between diagnosis and treatment. While parallel diagnostic and therapeutic tracks may still be needed in some cancers, especially where imaging and treatment modalities differ or where radioligand therapies are not yet available in an earlier line of treatment, we do see integrated theranostic workflows becoming the standard in many solid tumors. This approach offers a more efficient, patient-centric model that enables better outcomes through precision targeting.”