Editor's Note
This article was published in Pharmaceutical Technology Europe’s November 2023 print issue.
New radiotherapeutic agents are making headway in hard-to-treat cancers.
Ariceum Therapeutics, a private biotechnology company, based in Germany, is focused on developing novel drugs for systemic targeted radiation therapy (STRT) for hard-to-treat cancers. The name Ariceum is an anagram of ‘Marie Curie’ who discovered the elements radium and polonium, which have been hugely influential in the discovery of cancer treatments. The company was co-founded in 2021, and Ipsen transferred assets and all corresponding rights into the company on 22 Oct. 2021. Industry veteran Manfred Rüdiger, PhD, is the CEO of Ariceum, and Sandy McEwan, the company’s chief medical officer, is a world-renowned expert in oncology and nuclear medicine (1).
This article was published in Pharmaceutical Technology Europe’s November 2023 print issue.
Over the past decade, significant advances have been made in radiation therapy, particularly in the development of systemic targeted radiopharmaceuticals to reduce potential side effects. Using an artificial intelligence (AI)-enabled platform, Ariceum has focused on designing novel targeting molecules that either bind to receptors on the tumour cell surface or the DNA within the tumour cells. This allows the radioactive payload to accumulate within the tumour and reduces exposure of healthy tissues to radioactivity (2).
Ariceum’s lead candidate in Phase II trials—beta-emitting lutetium-177 radiolabelled satoreotide tetraxetan (SS0110), a somatostatin type 2 (SST2) receptor antagonist—is being developed as a theranostic for the diagnosis and treatment of hard-to-treat cancers. SST2 receptors are overexpressed in many cancers, such as small cell lung cancer (SCLC), high-grade neuroendocrine tumours (NETs), and neuroblastoma, an aggressive, rare type of cancer that occurs mainly in young children (2). Satoreotide binds to the SST2 receptor on the tumour surface to deliver alpha and beta particles into the cancer cell within a radius of 1–10 mm of the receptor binding site.
The company recently published details of a Phase I/II trial, NCT02592707, assessing the safety and efficacy of satoreotide where it was shown to be safe and effective in patients with progressive, SSTR-positive NETs (3,4). A five-year long-term follow-up study is ongoing, and the study is due to be completed on 1 April 2025 (5). The company is also evaluating satoreotide in Phase II for SCLC, Phase I for Merkel cell carcinoma (MCC), and pre-clinical evaluation in solid tumours. In addition, Ariceum is evaluating SS0120, a gamma-ray-emitting Gallium-68 radiolabelled satoreotide trizoxetan as an imaging agent in patients with gastroenteropancreatic neuroendocrine tumours (6).
Ariceum’s second targeting molecule is a Poly (ADP-ribose) polymerase inhibitor (PARPi) which is expressed at a low level in healthy tissues compared to cancer cells (2). ATT001 is an iodine-125 radiolabelled PARP inhibitor (123I PARPi), which targets activated PARP bound to tumour DNA to release radiation in the cell nuclei through the emission of Auger electron (7). It is due to enter Phase I development for the treatment of glioblastoma following promising results in preclinical and first-human studies (8). In addition, ATD001 a fluorine-18 radiolabelled rPARPi is currently in Phase I clinical trials at Memorial Sloan Kettering Cancer Center. The first clinical study with ATD001 in head and neck cancers completed recruitment in May 2019 and trial data was published in 2020 (9).
In June 2023, Ariceum acquired UK-based biotech Theragnostics Ltd for US$44 million (€42 million)—US$2.5 million (€2.4 million) upfront plus cash and milestone payments totaling up to $41.5 million (€39.4 million)—to help expand its radiotherapeutic pipelines. The deal will enable Ariceum to gain access to NEPHROSCAN, a US Food and Drug Administration (FDA)-approved diagnostic developed in partnership with GE Healthcare, and gallium-68 (68Ga) kit technology intellectual property which is currently licensed to Novartis (10).
In June 2023, Ariceum signed a pharmaceutical multi-project agreement with Eurofins contract development and manufacturing organization (CDMO) to secure clinical trial services to support its Phase I/II clinical trial programme in Australia (11). In May 2023, the company signed a strategic research collaboration with UCB to discover new modalities for the treatment of immune-related diseases and cancers (10). UCB will leverage its proprietary messenger RNA-display platform, ExtremeDiversity, to support Ariceum in the discovery of three new peptide-radioisotope conjugates.
In June 2022, it completed a €25 million Series A financing round led by EQT Life Sciences (formerly LSP) HealthCap and Pureos Bioventures, and these funds will be used to advance its lead radiopharmaceutical product, satoreotide (1). In April 2023, Ariceum extended a Series A financing round to raise an additional €2.75 million funds to advance its clinical pipelines. New investors Andera Partners and Earlybird Venture Capital, join existing investor, Pureos Bioventures (12).
There is significant interest in radiotherapeutics, and several companies in Europe and the United States, including France-based Advanced Accelerator Applications (a Novartis Company) and Curium Pharma, and Germany-based ITM Isotope Technologies Munich SE, Germany, and US-based NuView, Telix Pharmaceuticals, RayzeBio, and Y-mAbs.
On 26 Sep. 2023, Genentech teamed up with Japan-based biopharmaceutical company PeptiDream to discover and develop novel peptide-radioisotope drug conjugates (13). According to the transaction terms, PeptiDream will receive an upfront payment of US$40 million (€38 million) from Genentech. PeptiDream will be eligible for potentially up to US$1 billion (€949 million) in payments based on certain development, regulatory, and commercial milestones.
On 3 Oct. 2023, Eli Lilly acquired POINT Biopharma for US$1.4 billion (€1.3 billion) to expand its oncology capabilities and gain access to next-generation radiotherapeutics (14). POINT’s lead programs in late-phase development include:
On 4 Oct. 2023, Novartis AG announced that it was considering selling part of the radiopharmaceuticals company, Advance Accelerator Applications (AAAs) as part of its business strategy to focus on high-risk, high-reward business units (15). AAAs pipeline includes Lutathera (lutetium-177 oxodotreotide) a first-line therapy against GEP-NETs, Netspot, and SomaKit which use 68Ga labelled somatostatin analogue to target neuroendocrine tumours, Locametz a 68Ga labelled prostate-specific antigen (PSA) and Gluscan, which tracks glucose metabolism with fluoride-18 (16).
Although radiation therapy has been used for years in the treatment of cancer technological radiotherapeutics are relatively new on the scene. Technological advances have improved the targeting of radiation therapy at the cellular level, and reduced side effects. Many of the larger pharma companies including AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck & Co, and Novartis have invested in this area and several agents have entered late-stage clinical development and/or entered the market. The next-generation radiotherapeutics offer significant potential to revolutionize the treatment of hard-to-treat cancers such as glioblastoma and neuroendocrine tumours, which up until now evaded treatment through traditional methods.
Cheryl Barton is director of PharmaVision, info@pharmavision.co.uk.
Pharmaceutical Technology Europe
Vol. 35, No. 11
November 2023
Pages: 13-15
When referring to this article, please cite it as Barton, C. Frontrunners in Next-Generation Radiotherapeutics. Pharmaceutical Technology Europe 2023 35 (11).