Frontrunners in Next-Generation Radiotherapeutics

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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).

Technology

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).

Acquisitions

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).

Partnerships

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.

Investor funding

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).

Competitor companies

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.

Pharma activity

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:

• PNT20021 is a prostate-specific membrane antigen (PSMA) targeted radioligand therapy in development for patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on hormonal treatment.
• PNT20031 is an SSTR-targeted radioligand therapy in development for the treatment of patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

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).

The future of radiotherapeutics

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.

References

1. EQT Group. EQT Life Sciences Announces Launch and Series A Financing Round of portfolio company Ariceum Therapeutics. Press Release. 10 Jun. 2023.
2. Ariceum Therapeutics. Our Technology. ariceum-therapeutics.com (accessed 12 Oct. 2023).
3. Wild, D.; Grønbæk. H.; Navalkissoor, S. et al. A Phase I/II Study of the Safety and Efficacy of [177Lu]Lu-satoreotide Tetraxetan in Advanced Somatostatin Receptor-positive Neuroendocrine Tumors. Eur J Nucl Med Mol Imaging. 2023 Sep 18. doi: 10.1007/s00259-023-06383-1. Epub ahead of print. PMID: 37721581.
4. An International, Multicenter, Open-label Study to Evaluate Safety, Tolerability, Biodistribution, Dosimetry, and Preliminary Efficacy of 177Lu-OPS201 for the Therapy of Somatostatin Receptor-positive Neuroendocrine Tumors (NETs), NCT02592707. ClinicalTrials.gov, (accessed 12 Oct. 2023).
5. A Multicentre Surveillance Study to Evaluate the Long-term Safety in Participants Who Have Been Previously Treated With 177Lu-IPN01072 in an Ipsen-sponsored Clinical Study. NCT05017662. ClinicalTrials.gov (accessed 12 Oct. 2023).
6. Virgolini, I.; Bahri, S.; Kjaer, A.; et al. A Randomized, Factorial Phase II Study to Determine the Optimal Dosing Regimen for 68Ga-Satoreotide Trizoxetan as an Imaging Agent in Patients with Gastroenteropancreatic Neuroendocrine Tumors. J Nucl Med. 2022, 63 (3), 376–383. doi: 10.2967/jnumed.121.261936. Epub 2021 Jul 2. PMID: 34215673; PMCID: PMC8978200.
7. Ariceum Therapeutics, Pipeline. ariceum-therapeutics.com (accessed 12 Oct. 2023).
8. Young, R.J.; Demétrio De Souza França P.; Pirovano, G.; et al. Preclinical and First-in-Human-Brain-cancer Applications of [18F]poly (ADP-ribose) Polymerase Inhibitor PET/MR. Neurooncol Adv. 2020 Sep 15;2(1):vdaa119. doi: 10.1093/noajnl/vdaa119. PMID: 33392502; PMCID: PMC7758909.
9. Schöder, H.; França, PDS.; Nakajima, R.; et al. Safety and Feasibility of PARP1/2 Imaging with 18F-PARPi in Patients with Head and Neck Cancer. Clin Cancer Res. 2020, 26 (13), 3110–3116. doi: 10.1158/1078-0432.CCR-19-3484. Epub 2020 Apr 3. PMID: 32245901; PMCID: PMC7421489.
10. Ariceum Therapeutics. Ariceum Therapeutics Announces Extension of Series A Financing to EUR 47.75M to Advance its Next Generation Radiopharmaceutical Clinical Pipeline. Press Release. 1 Jun. 2023.
11. Ariceum Therapeutics. Ariceum Therapeutics, and Eurofins CDMO Sign a Pharmaceutical Multi-Project Agreement. Press Release. 26 Jun. 2023.
12. Ariceum Therapeutics. Andera Partners, and Earlybird Venture Capital Join Existing Investor, Pureos Bioventures. Press Release. 18 Apr. 2023
13. PeptiDream. PeptiDream Announces Collaboration and License Agreement with Genentech for the Discovery and Development of Novel Peptide-Radioisotope Drug Conjugates. Press Release. 19 Sept.2023.
14. Eli Lilly. Lilly to Acquire POINT Biopharma to Expand Oncology Capabilities into Next-Generation Radioligand Therapies. Press Release. 3 Oct. 2023.
15. Novartis. Novartis Executes Sandoz Spin-off, Completing the Strategic Transformation into a Leading, Focused Innovative Medicines Company. Press Release. 4 Oct. 2023.
16. Bloomberg. Novartis Weighs Selling Assets from Radiopharma Unit. Press Release. 3 Oct. 2023.

About the author

Cheryl Barton is director of PharmaVision, info@pharmavision.co.uk.

Article details

Pharmaceutical Technology Europe
Vol. 35, No. 11
November 2023
Pages: 13-15

Citation

When referring to this article, please cite it as Barton, C. Frontrunners in Next-Generation Radiotherapeutics. Pharmaceutical Technology Europe 2023 35 (11).