S-pindolol (ACM-001)

S-pindolol (ACM-001) is our lead candidate and is chemically-related to a well-established beta-blocker for hypertension and angina (pindolol). A clinical development programme of S-pindolol (ACM-001) is in planning to confirm and expand upon the positive results demonstrated in a proof of concept Phase II study in patients with cancer-related cachexia.

Mode of action

S-pindolol (ACM-001) is an anabolic/catabolic transforming agent with a multifunctional effect on three key pharmacological targets relevant for cancer cachexia:

  β-1receptor antagonism that blocks catabolism1

•  Increased anabolism and muscle growth, through partial β2 receptor agonism1

  Central 5-HT1A antagonism that can stimulate appetite and thereby improve overall patient outcomes as well as improving fatigue2,3,4,5,6,7

This trio of anti-catabolic and pro-anabolic pharmacology makes S-pindolol (ACM-001) a unique candidate for development in cancer cachexia.

Clinical data

The ACT-ONE8 Phase II clinical study of S-pindolol (ACM-001) was a proof of concept exploratory, randomised, double-blind, placebo-controlled study in 87 patients with NSCLC (non-small-cell lung cancer) or colorectal cancer (CRC). The trial demonstrated that S-pindolol (ACM-001) was well-tolerated and that patients receiving high-dose S-pindolol (ACM-001) 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.

Patients receiving S-pindolol (ACM-001) also demonstrated improved hand-grip strength.

Actimed has initiated its first clinical study of the pharmacokinetics and pharmacodynamics (PK/PD) for a new salt of S-pindolol (ACM-001.1) under development as a treatment for cancer cachexia. The study will be conducted in healthy subjects in two parts. It will compare ACM-001.1 to pindolol and will investigate both single and multiple dose PK and assess a range of doses of ACM-001.1. This study is a prelude to the commencement of a Phase IIb clinical programme in patients and the results from this data, if positive, will be used to inform the Phase IIb programme.


1Pötsch MS, Tschirner A, Palus S, von Haehling S, Doehner W, Beadle J, Coats AJ, Anker SD, Springer J. 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

2Newman-Tancredi A, Chaput C, Gavaudan S, Verriele L, Millan MJ. Agonist and antagonist actions of (-) pindolol, at recombinant, human serotonin 1A (5-HT1A) receptors.  Neuropsychopharmacology. 1998  May; 18(5):395-398

3Andree B, Thorburg SO, Halldin C, Farde L. Pindolol binding to 5-HT1a receptors in the human brain confirmed with positron emission tomography. Psychopharmacology (Berl). 1999 June; 144(3) 303-305

4Martinez D, Hwang D, Mawlawi O, Slifstein M, Kent J, Simpson N, Parsey RV, Hashimoto T, Huang Y, Shinn A, Van Heertum R, Abi-Dargham A, Caltabiano S, Malizia A, Cowley H, Mann JJ, Laruelle M. Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans. Neuropsychopharmacology. 2001 Mar;24(3):209-29.

5Castro ME, Harrison PJ, Pazos A, Sharp T. Affinity of (+/-)-pindolol, (-)-penbutolol, and (-)-tertatolol for pre- and postsynaptic serotonin 5-HT(1A) receptors in human and rat brain. J Neurochem. 2000 Aug;75(2):755-62.

6Yan H and Lewander T. Differential tissue distribution of the enantiomers of racemic pindolol in the rat. Eur Neuropsychopharmacol. 1999 Dec; 10(1): 59-62

7Olver Js, Cryan JF, Burrows GD, Norman TR. Pindolol augmentation of antidepressants: a review and rationale. Aust. NZ. J. Psychiatry 2000 Feb;34 (1): 71-79

8A Coats et al Espindolol for treatment and prevention of cachexia: the ACT-ONE trial. J Cachexia Sarcopenia Muscle 2016; 7: 355–365