Lilly Strikes $1.4B-Backed Deal to Advance GPCR-Targeted Radiopharmaceuticals with Radionetics

On June 30, Eli Lilly and Company partnered with Radionetics Oncology to acquire its small-molecule G protein-coupled receptor (GPCR)-targeted radiopharmaceutical technology. Under the terms of the agreement, Radionetics Oncology will receive an upfront payment of $140 million (equivalent to 1.018 billion RMB). The two parties will jointly advance novel small-molecule radiopharmaceuticals targeting GPCRs for the treatment of a wide range of solid tumors.

As part of the strategic cooperation, Eli Lilly and Company has obtained the exclusive right to acquire Radionetics Oncology, Inc., with a potential acquisition amount of 1 billion US dollars and no specified deadline.During the collaboration, Radionetics will apply its proprietary discovery platform to continuously build a small-molecule radioligand therapeutic asset targeting GPCRs.

Peptide-targeted radiotherapeutics have demonstrated significant therapeutic benefits in the treatment of neuroendocrine tumors and advanced prostate cancer, and are rapidly being integrated into first-line treatment standards. Their increasing use is expected to drive infrastructure development and the deployment of more radiopharmaceutical therapies.

G protein-coupled receptors (GPCRs) are the largest family of cell membrane surface receptors in mammals. The human genome encodes approximately 800 different types of GPCRs, which are widely involved in the pathological processes of various major diseases such as metabolic disorders and cancer, making them a popular target for drug development.

Peptide drugs are gradually gaining attention due to their multiple unique advantages, such as clear mechanisms of action, good safety, low production costs, and nearly infinite possibilities in spatial structure. In recent years, with the deepening understanding of GPCR structures, the development of peptide drugs targeting GPCRs has been rapid, with new drugs continuously coming to market.So far, the U.S. Food and Drug Administration (FDA) has approved nearly 50 peptide drugs targeting GPCRs for the treatment of various diseases, including metabolic disorders, neurological conditions, and cancer.

According to the Radionetics website, although GPCRs are one of the most common target categories in drug development, they remain "largely unexplored" in the field of radiopharmaceuticals.

Radionetics Oncology is dedicated to the discovery and development of novel radiotherapeutic drugs for the treatment of various oncology indications.Its proprietary platform technology utilizes small molecule targeting to deliver therapeutic radioisotopes precisely to a broad range of tumors by selectively binding to peptide receptors (GPCRs) that are overexpressed on cancer cells.This small molecule platform technology addresses many of the significant challenges currently faced in peptide and protein-targeted radiotherapy, particularly in the areas of optimizing drug-like properties and manufacturing.

Radionetics stated that its platform is not limited by α or β emitters. The shortage of radionuclide supply has become a significant factor restricting the development of nuclear medicine. Just last month, RYZ101, a drug acquired by BMS through the acquisition of RayzeBio, suspended patient enrollment in its Phase III clinical trial due to supply issues with the radionuclide Actinium-225 (Ac-225). Radionetics' investigational radiopharmaceutical, 68Ga-R8760, is currently in Phase I studies for the treatment of adrenocortical carcinoma and will also initiate clinical trials in breast cancer and lung cancer.

Schematic Diagram of Radionetics Proprietary Technology Platform Design

Radionetics Oncology, Inc. was founded in 2021 as a spin-off from the clinical-stage drug company Crinetics (NASDAQ: CRNX), focusing on the discovery and development of novel radiotherapeutic agents for the treatment of various oncology indications. It was jointly incubated by Crinetics Pharmaceuticals and multiple dollar funds (5AM Ventures, Frazier Healthcare). In January this year, Radionetics completed a $52.5 million Series A financing round.

Reviewing the development process of nuclear medicine, therapeutic nuclear medicines that have shown rapid development in recent years can be divided into targeted and non-targeted nuclear medicines. For example, RDC (Radiopharmaceutical Drug Conjugates) has been a recent hotspot in development. Early approved therapeutic nuclear medicines were all non-targeted drugs, utilizing the inherent in vivo accumulation characteristics of radioisotopes to treat patients, which would damage normal cells and result in significant adverse reactions.

Targeted radiopharmaceuticals deliver targeted damage to the lesion of interest. Taking RDC as an example, its therapeutic mechanism is clear, simple, and direct, relying on physical radiation to break DNA. The development logic is relatively straightforward, and consequently, the success rate of development tends to be higher. In recent years, the approval of RDCs such as Lutathera and Pluvicto has significantly advanced the progress of precision-targeted nuclear medicine.

Overall, therapeutic radiopharmaceuticals in the industrial boom period are showing a trend of centralization and internal competition in terms of medical isotopes, targets, and indications.In China, many RDC development pipelines are targeting the two products already approved by Novartis, focusing on the development of generic or improved new drugs. PSMA (prostate-specific membrane antigen) and SSTR (somatostatin receptor) are popular targets in radiopharmaceutical research and development, with numerous pipelines for prostate cancer and neuroendocrine tumors, showing initial signs of homogenization.

Many Restrictive Factors Still Need to Be Addressed: Challenges in the Mass Production of Medical Isotopes, Fewer Validated Targets Successfully Identified, and Advanced Molecular Exploration Still in Early Stages. Meanwhile, MNCs Are Advancing the Breakthrough of Therapeutic Radiopharmaceuticals Through Strategic Collaborations with Radiopharmaceutical Biotech Companies Worldwide.

As a "newcomer" in the field of radiation therapy, Eli Lilly's strategy in the nuclear medicine sector focuses more on cutting-edge molecular exploration, multi-target discovery, and novel platform technologies.In December 2023, after overcoming numerous challenges, Eli Lilly completed the acquisition of POINT Biopharma for $1.4 billion, gaining access to multiple radiopharmaceutical assets such as [Lu-177]-PNT2002, [Ga-68]-PNT6555, and [Lu-177]-PNT6555, establishing a foundational product base for its radiopharmaceutical strategy. Entering 2024, Eli Lilly announced two strategic collaborations with biotech companies based on proprietary and innovative platform technologies. This includes a multi-target discovery collaboration agreement reached in May with Aktis Oncology focused on Aktis' unique microprotein radiopharmaceutical platform, with a total transaction value exceeding $1.1 billion.

As the "leader" in nuclear medicine and the owner of Lutathere and Pluvicto, Novartis began its strategic layout as early as 2021. In March 2021, Novartis reached a transfer agreement with iTheranostics, a subsidiary of SOFIE Biosciences, to obtain the global exclusive rights for the development and commercialization of therapeutic applications targeting the new FAP (fibroblast activation protein) agents library, including FAPI-46 and FAPI-74.

In April of the same year, Novartis entered into a global collaboration worth $1.3 billion with Artios Pharma, leveraging Artios' proprietary DDR technology platform to develop and validate next-generation DNA Damage Response (DDR) targets, thereby expanding Novartis' Radioligand Therapy (RLT) pipeline.

On May 2, 2024, Novartis made another acquisition of the radiopharmaceutical startup Mariana Oncology for an upfront payment of $1 billion. Utilizing its proprietary Peptide Discovery Platform System (PDPS), Novartis aims to discover and optimize innovative macrocyclic peptides based on specified targets. These macrocyclic peptides may be used for conjugation with radioligands or applied in other therapeutic and diagnostic applications.

The broader competition continues, with pharmaceutical giants such as BMS, AstraZeneca, and Genentech (Roche) also entering the emerging radiopharmaceuticals Biotech space. The acquisitions and collaborations by MNCs have been a key driving force behind the rapid development of therapeutic radiopharmaceuticals over the past decade.In 2017, Novartis also acquired the innovative oncology therapeutic radiopharmaceutical Lutathera for $2.1 billion.