By: Robert Mittendorff MD, Jason Grosz and Jack Grimes

 

B Capital is proud to partner with ARTBIO, an oncology biotech company pioneering the development of radioligand therapies (RLTs) based on the radionuclide lead-212 (Pb-212), a short-lived alpha-emitting isotope that has the potential to broaden the therapeutic index of radiopharmaceuticals.

ARTBIO has developed a differentiated pipeline of RLTs for both validated and first-in-class targets, with its lead program, AB001, entering a Phase 1 trial this year for metastatic castration-resistant prostate cancer (mCRPC), an advanced form of prostate cancer that has spread beyond the prostate and progressed on androgen deprivation therapy. With a robust technological foundation, proprietary isotope production platform, and a highly experienced team, we believe ARTBIO has the potential to define the next chapter of precision oncology.

 

RLTs: A Transformative Modality in Oncology

Radiopharmaceuticals have emerged as a transformative modality in oncology, delivering paradigm-shifting clinical results and poised to become a cornerstone of cancer treatment. RLTs, which consist of a targeting vector linked to a radioactive isotope, enable the systemic delivery of radiation precisely to tumor cells that express a target receptor. This targeted approach enables the systemic delivery of radiation while minimizing damage to surrounding healthy tissue. The clinical success of two approved RLTs that rely on the beta-emitting isotope lutetium-177 (Lu-177) –Pluvicto for prostate cancer and Lutathera for neuroendocrine tumors – are rapidly becoming the standard-of-care for their respective indications while enjoying commercial success. However, these first-generation therapies represent just the tip of the iceberg for this modality, with RLTs exploiting novel targets and more potent radioactive isotopes poised to improve efficacy, combat resistance, and enable indication expansion.

Looking forward we believe that alpha emitters, and Pb-212 in particular, are positioned to unlock the full therapeutic potential of RLTs.

 

Pb-212: A Differentiated Alpha-Emitting Isotope

ARTBIO’s differentiation stems from its use of Pb-212 as the radioactive payload, which we believe to be the ideal isotope for maximizing both safety and efficacy. When compared to beta emitters like Lu-177, we believe Pb-212 offers several key advantages:

• Higher linear energy transfer (LET): Alpha particles cause double-stranded DNA breaks that rapidly trigger cancer programmed cell death (apoptosis), while beta particles typically cause single-stranded breaks that cells can more easily repair through normal DNA damage response mechanisms.
• Shorter path length: The alpha particles’ shorter emission range limits the radioactive exposure to healthy tissues surrounding the tumor, improving the therapeutic index.
• Short half-life: Pb-212’s short half-life (10.6 hours) allows for a higher dose rate – meaning a greater quantity of radiation is absorbed over a shorter time period – which may enhance efficacy and enable more frequent dosing. The shorter half-life of Pb-212 also aligns well with the half-life of commonly used ligands (e.g., small molecules, peptides), potentially translating to a better safety profile by reducing off-target toxicity to healthy tissues.

While Pb-212 is not the only alpha emitter in development, we have strong reason to believe that it will be a best-in-class alpha emitter. The most common alpha emitter in the clinic today, actinium-225 (Ac-225), has a significantly longer half-life than Pb-212 (~10 days vs. 10.6 hours), resulting in prolonged radiation exposure and a narrower therapeutic index.

We believe the ability to irradiate the tumor more rapidly while eliminating the long tail of radiation exposure to healthy tissues will meaningfully expand the therapeutic index of radiopharmaceuticals based on Pb-212.

Early clinical experience with Pb-212 RLTs from academic centers and Pb-212 focused biotechs have provided preliminary confirmation of the theoretical advantages of Pb-212. In small datasets, these trials have demonstrated the potential of:

• Encouraging efficacy signals: Response rates have been striking, even in Lu-177-resistant patients.
• Favorable safety profile: Pb-212 shows improved safety compared to Ac-225, with less myelosuppression (bone marrow suppression) and minimal salivary gland uptake, thereby reducing off-target radiation damage to sensitive tissues and improving patient tolerability.

These early findings suggest that Pb-212 may unlock the next phase of radioligand therapy—delivering potent, targeted radiation with a more favorable safety profile.

 

Innovating on Multiple Fronts: A Broad Pipeline & Best-In-Class Pb-212 Generator

ARTBIO’s lead program, AB001, targets PSMA, a clinically validated target for prostate cancer. This program is designed to address key unmet needs in metastatic castration-resistant prostate cancer (mCRPC)—an advanced form of prostate cancer that no longer responds to hormone therapy—with the potential to benefit both Pluvicto-naïve and Pluvicto-experienced patients. Beyond AB001, ARTBIO has built a deep pipeline of novel targets with broad applicability across many solid tumors through both internal R&D and external partnerships with companies like 3B Pharmaceuticals, a leader in peptide-based radiopharmaceutical development, and Parabilis, a biotech pioneering a new class of helical peptides called Helicons.

ARTBIO has also developed a proprietary Pb-212 generator, AlphaDirect, which will be able to reliably produce clinical- and commercial-scale supply of Pb-212. This will allow ARTBIO to overcome the production challenges that have plagued other centrally-manufactured alpha emitters like Ac-225. AlphaDirect delivers >99.9% isotope purity and enables the distributed manufacturing network required to successfully deliver an isotope with a 10.6-hour half-life to patients.

In parallel, ARTBIO has built a strong operational backbone through partnerships with leading regional contract development and manufacturing organizations (CDMOs), including Nucleus RadioPharma, PharmaLogic, SpectronRx, and others. These specialized partners will support the production and distribution of ARTBIO’s Pb-212-based radiopharmaceuticals, positioning ARTBIO for success as it advances multiple RLTs into the clinic.

 

A Highly Experienced Leadership Team Well-Positioned to Shape the Future of Radiopharmaceuticals

The expertise of ARTBIO’s management team and their strategic approach to RLT development is highly impressive. The team has the right combination of commercial experience, scientific acumen, clinical development strategy, and manufacturing expertise:

• Emanuele Ostuni, PhD (CEO) – Former Head of Europe for Cell & Gene Therapies at Novartis, where he oversaw the commercialization of Kymriah.
• Nick Pullen, PhD (Chief Scientific Officer) – Former Head of Research at Jnana Therapeutics (biotech specializing in chemoproteomics-driven small molecule drug discovery for rare and immunemediated diseases), which was acquired for $800M by Otsuka (up to $1.1B with milestones).
• Margaret Yu, MD (Chief Medical Officer) – Led clinical development for the prostate cancer drugs Zytiga and Erleada as the Prostate Disease Area Leader at Janssen.
• Philippe Dasse, PharmD (Chief Technical Officer) – Former Head of Technical Operations at Advanced Accelerator Applications (France-based nuclear medicine specialist that developed Lutathera) and continued in that role at Novartis following its $3.9B acquisition. At Novartis, Philippe built and scaled the infrastructure for the commercial launch of Pluvicto.

With a differentiated isotope, broad pipeline, proprietary generator, and a proven leadership team, we believe ARTBIO is uniquely positioned to shape the future of alpha radioligand therapy.

 

 

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