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Actimed has conducted a Phase 1 Pharmacokinetic and Pharmacodynamic (PK/PD) comparative bioavailability study of S-pindolol benzoate in healthy subjects (NCT06028321). This study was published in the Journal of Cachexia, Sarcopenia and Muscle in December 2024 and demonstrated that S-pindolol, when administered as the single enantiomer, was essentially bioequivalent to an equivalent dose of S-pindolol when administered as part of a racemic mixture of pindolol (the authorised product). The study also demonstrated the lack of in vivo racemization of S-pindolol to R-pindolol.
Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers. Misselwitz, F., Henderson, D., Menakuru, S., Morten, E., Roe, C., Whitaker, G., Wohlfeil, S. and McDermott, J. (2024). The publication may be accessed here.
Following this successful PK/PD study, a Phase 2b/3 clinical development programme in cancer cachexia, the IMPACT Programme (Improving cancer cachexia with ACTAs), is planned to expand upon the positive results demonstrated in an exploratory proof of concept Phase 2a trial for S-pindolol, (ACT-ONE)2.
The IMPACT programme will consist of two trials of identical design: one in patients with non-small cell lung cancer (NSCLC) and the other in colorectal cancer (CRC), both groups with a diagnosis of cachexia. The studies are designated IMPACT-NSCLC and IMPACT-CRC respectively.
A US Investigational New Drug Application was approved for the IMPACT programme in August 2023 and the Company plans to dose the first patients once funding is secured.
In view of its multi-modal pharmacology, S-pindolol is an obvious candidate to evaluate in this setting. In May 2025, Actimed initiated a new development programme investigating the potential benefits of using S-pindolol benzoate (ACM-001.1) during and post-GLP-1 receptor agonist (GLP-1RA) therapy in the management of obesity and related metabolic conditions.
This new initiative comprises a two-part programme:
- A preclinical programme, designed to explore the pharmacological mechanisms, safety and efficacy of S-pindolol in a diet-induced model of obesity in animals who are receiving or who have received a GLP-1 RA. The in vivo phase of these studies has completed, and they will be reported in the coming months.
- PROACT (Preserving, Restoring, and Optimising (lean mass and muscle) with ACTAs) – a Phase 2a , randomised, placebo clinical trial, which will assess the safety and efficacy of S-pindolol benzoate in obese patients during and post-GLP-1 RA therapy. The first patient is expected to be enrolled by mid-year 2025. This study will include up to 60 patients.
Mode of action
S-pindolol has been described as an anabolic/catabolic transforming agent1 with a multifunctional effect on three key pharmacological targets relevant for cachexia and muscle wasting:
• Reduction of catabolism via β-1 receptor antagonism3,4,5
• Increased anabolism and muscle growth, through partial β2 receptor agonism1
• Improvement in appetite and fatigue via central 5-HT1a antagonism6,7,8,9,10,11
This trio of anti-catabolic and pro-anabolic pharmacology makes S-pindolol a highly promising candidate for development in muscle wasting diseases.
- Provides extended UK patent coverage relating to lead compound S-pindolol benzoate (ACM-001.1) to 2040
- International patent application also filed in March 2021
London, UK – 4 May 2022. Actimed Therapeutics Ltd, a clinical stage company focused on bringing innovation to the treatment of muscle wasting disorders, today announced the grant of a new UK Patent (GB 2593902 B) covering new salts of S-pindolol for use in the treatment or prevention of cachexia with an expiry date in 2040.
An international patent application has also been filed under the Patent Cooperation Treaty (PCT) and was published in October 2021, which seeks to extend patent protection for new S-pindolol salts to all relevant major international markets out to 2041.
S-pindolol benzoate (ACM-001.1) is the leading development candidate of Actimed and is protected by the patent for use in the treatment of cachexia. Actimed plans on initiating Phase 2b/3 clinical studies of S-pindolol benzoate in 2023.
Robin Bhattacherjee, CEO of Actimed commented “We are thrilled to confirm the grant of this new patent which includes protection of our new benzoate salt form of S-pindolol for use in the treatment of cachexia. Strengthening our intellectual property portfolio is fundamental to the commercial value of S-pindolol and supports our plans to develop the first globally approved treatment for cancer cachexia, which affects 50 to 80% of cancer patients worldwide. The granted patent provides enhanced and extended protection of S-pindolol benzoate for use in cachexia until 2040 adding significant value to our lead asset and to the Company as a whole.”
Cachexia is a wasting syndrome that can be difficult to reverse and remains a significant hurdle in the treatment of cancer. It causes sudden loss of weight, appetite and muscle and accounts for up to 20% of all cancer deaths1. In nonclinical models, S-pindolol is an anabolic/catabolic transforming agent2 with a multifunctional effect on a trio of pharmacological targets which could make it an important candidate for development in cancer cachexia.
The potential clinical utility of S-pindolol benzoate as a therapeutic for the treatment of cancer cachexia is supported by data from the ACT-ONE3 Phase II clinical study of S-pindolol (ACM-001) which was a proof of concept exploratory, randomised, double-blind, placebo-controlled study in 87 patients with non-small-cell lung cancer (NSCLC) or colorectal cancer (CRC). The trial demonstrated that S-pindolol was well-tolerated and that patients receiving the highest dose showed a median weight gain of 2.74kg compared to a median 1.09kg weight loss in patients receiving placebo over a 4-month period.
The newly granted patent follows the commencement in December 2021 of a pharmacokinetic and pharmacodynamic (PK/PD) clinical study of S-pindolol benzoate (ACM001.1) in healthy subjects. Data from this study are expected in the first half of 2022 and will be used to further inform the Phase 2b/3 programme.
1Argilés JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14:754–62.
2Pötsch MS, et al. The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats. J Cachexia Sarcopenia Muscle. 2014 Jun;5(2):149-58
3Coats AJS, et al. Espindolol for the treatment and prevention of cachexia: a randomized, double-blind, placebo-controlled, international multicentre phase II study (the ACT-ONE trial). J. Cachexia Sarcopenia and Muscle 2016 Jun; 7(3):355-365.
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