Radiopharmaceuticals — a booming market projected to grow from $7.51 billion in 2025 to roughly $14.44 billion by 2034 — are often seen as the future of precision oncology. Yet their development has trailed behind traditional drug classes due to persistent challenges in chemistry, delivery, and clinical application.
Now, biotech startup Actithera is taking a medicinal chemistry-first approach to radioligand therapy (RLT), and investors are betting big on its strategy. Recently, the company closed an oversubscribed $75.5 million Series A round co-led by M Ventures, Sofinnova, Hadean, 4BIO, and Bioqube and alongside a deep syndicate of global life sciences investors.
What sets Actithera apart is its novel discovery platform, which combines molecular modeling with targeted radiotherapy to improve tumor binding and clearance.
“Radiotherapeutics differ fundamentally from ADCs: while ADC payloads are designed to be released only inside tumor cells, the radionuclide payloads used in radiotherapeutics emit radiation systemically as soon as they are administered,” a spokesperson for Actithera told Drug Discovery News. “This creates a unique medicinal chemistry challenge, balancing rapid clearance from healthy tissues to minimize toxicity, while ensuring prolonged retention at the tumor site to maximize efficacy.”
To address this, the company is developing radioconjugates that form irreversible covalent bonds with tumor-associated proteins. “Achieving this pharmacokinetic ‘disconnect’, fast systemic clearance but durable tumor residency, is difficult but essential for optimal therapeutic index,” the spokesperson said.
This critical 'disconnect' is precisely what irreversible covalent bonds are designed to achieve. Unlike traditional approaches that rely on transient, reversible binding, where a drug might bind and then unbind from its target, these covalent bonds create a strong, permanent chemical link. This means that once the radioconjugate binds to a tumor-associated protein, it stays 'locked on.'
This durable tumor residency allows for a sustained delivery of radiation directly to the cancer cells, maximizing their exposure to the therapeutic dose. Simultaneously, because unbound radioconjugates can clear rapidly from healthy tissues (the 'fast systemic clearance' aspect), the overall systemic radiation exposure is significantly reduced, leading to a much improved therapeutic index compared to therapies where the drug's presence in healthy tissue might be prolonged.
The company’s lead program targets fibroblast activation protein (FAP), a well-known but challenging oncology target with theranostic potential. With fresh funding, Actithera plans to move this candidate into clinical trials and expand its preclinical pipeline.
While FAP has attracted significant interest as a biomarker for imaging and therapy, efforts to drug it have stumbled over issues of specificity and pharmacokinetics. Actithera claims its FAP-targeting radioligand achieves best-in-class tumor residence time, marking a potential breakthrough in an area that has long vexed R&D teams.
Incoming board members have praised Actithera’s rigorous chemistry-driven approach, contrasting it with more biologics-focused radiopharma startups. “Actithera is applying Big Pharma discipline to an emerging field with enormous potential,” said Karl Naegler, Partner at Sofinnova. “Its radioligand therapies represent a meaningful shift in oncology, with the opportunity to redefine the therapeutic index.”
Hakan Goker, chairman of Actithera and managing director at M Ventures, described the company’s approach as “an innovative chemistry platform and first-in-class approach targeting FAP [that] have the potential for significant impact in the RLT field.”
With multiple modalities entering oncology, radioligand therapies offer a compelling mix of imaging and treatment capabilities — allowing clinicians to visualize tumors, confirm targeting, and tailor therapy accordingly. This makes them a strong contender for enabling truly personalized medicine. Whether Actithera’s platform can deliver on that promise will be closely watched as its first candidate heads into the clinic.
