Grünenthal Announces Successful Completion of Phase I Trial for Investigational Compound with Potential to Become First-in-Class Therapy for Acute and Chronic Pain
Aachen, Germany – Grünenthal, a global leader in pain management and related diseases, announced today the successful completion of a Phase I trial evaluating the safety and tolerability of its proprietary NOP agonist. The investigational compound has a unique mechanism of action and has shown potential to become a first-in-class therapy option for the treatment of acute and chronic pain.
The trial, which involved 113 healthy participants, demonstrated the compound to be safe and well tolerated, with no dose-dependent adverse event pattern observed.[1] Grünenthal is now planning to progress its NOP agonist into a Phase II trial that aims to enroll 400 US-based patients undergoing bunionectomy – a well-established model for evaluating the efficacy and safety of a compound as a treatment for acute pain. The trial will commence later this year, with results expected in the second half of 2027.
“With selective nociceptin receptor activation, Grünenthal hopes to introduce a new mechanism of action into the pain treatment landscape and provide patients with a much-needed alternative therapy option,” says Uli Brödl, MD, Chief Scientific Officer at Grünenthal.
Through its specific selectivity for the nociceptin receptor, the company’s NOP agonist features a unique mechanism of action for the treatment of acute and chronic pain and may present a first-in-class therapy option. The compound has the potential to deliver robust pain relief in a broad range of conditions without the side effects commonly associated with opioids. During the Phase I trial, no such adverse events, including somnolence, constipation, or respiratory depression, or events suggesting any abuse liability potential were observed.
Bunionectomy is the surgical procedure for removing a bunion, an enlargement of bone and soft tissue that develops on the side of the foot. It is a condition that most commonly occurs in the joint at the base of the big toe, where the big toe progressively angles outwards towards the smaller toes, creating a bony bump (hallux valgus deformity). Bunions may be caused by hereditary factors, inflammatory arthritic conditions, or wearing poorly fitting or pointed shoes that constrict the toes.[2] Bunionectomy is accepted by regulatory authorities as a postoperative hard (bony) tissue pain model in which the analgesic effect of an investigational compound may be evaluated as a treatment for acute pain.[3]
The Nociceptin/Orphanin Receptor (NOP) is a G protein-coupled receptor whose natural ligand is the 17-amino-acid neuropeptide nociceptin (N/OFQ). NOP agonists have been shown to act as potent analgesics without the potential for abuse liability in pre-clinical models.[5] Although the NOP receptor shares some sequence identity (~60%) with the opioid receptors μ-OP (MOP), κ-OP (KOP), and δ-OP (DOP), it possesses little or no affinity for opioid peptides or morphine-like compounds. Likewise, opioid receptors possess little affinity towards NOP’s endogenous ligand nociceptin.[6]
Grünenthal is a science-based, fully integrated pharmaceutical company headquartered in Aachen, Germany. With affiliates in 28 countries across Europe, Latin America, and the U.S., its products are available in approximately 100 countries. In 2025, Grünenthal employed around 4,100 people and achieved revenues of €1.8 billion. The company’s purpose is to change lives for the better – and innovation is its passion. It focuses all its activities and efforts on working towards its vision of a World Free of Pain.
For further information, please contact Christopher Jansen, Global Communications at Grünenthal, christopher.jansen@grunenthal.com.
