Signal Pharma

Signal Pharma is a business angel-funded joint venture from the Universities of Aberdeen and Toronto, founded in 2013, focussing on the discovery and preclinical development of drugs for the treatment of diseases which are not adequately served by current therapies.  These programmes include novel approaches to the treatment of diastolic heart failure, angina, cancer, neuropathic pain, inflammatory pain and type 2 diabetes.

Diastolic Heart Failure   Diastolic Heart Failure The most advanced programme at Signal Pharma is a novel drug for the treatment of cardiovascular disorders, most especially diastolic heart failure.

Cardiovascular diseases are the leading cause of death in the developed world and are now on track to become the leading cause of death in the developing world. One particular manifestation, heart failure (HF), is dramatically increasing in frequency and is now the leading cause of hospitalisation in the over 60s. There is an even split between a) systolic heart failure, which is moderately well-served pharmacologically by a number of agents including loop diuretics, beta-blockers and ACE inhibitors, but despite these the 5 year survival rate (less than half) is worse than for most common cancers, and b) diastolic heart failure, which has no effective treatments and mortality comparable to that of systolic heart failure. It is becoming apparent that altered myocardial energetics plays a prominent role in the pathogenesis of HF, that optimisation of myocardial metabolic efficiency is a highly promising approach to treatment of HF, and that this approach can be additive or synergistic with other therapies.

We have discovered a drug which can shift myocardial metabolism from fatty acid to carbohydrate utilisation (improved substrate utilisation), enhancing ATP synthesis without affecting oxygen consumption (enhanced cellular energetics). This has been shown to give a functional benefit even for heart failure patients already receiving optimal drug therapy
Harnessing the Potential of Cannabinoids for Pain Relief   Neuropathic and Inflammatory Pain Prior to licensing to Signal Pharma, researchers in the Kosterlitz Centre for Therapeutics achieved experimental proof of principle for a new strategy for the treatment of pain and developed potent patentable drug-like small molecule compounds, with funding from the BBSRC Follow on Fund and Canadian Institutes of Health Research. The programme has now been licensed to Signal Pharma.

The endocannabinoid system is one of the most important natural painkilling systems in the body; endocannabinoids are released on demand as and when they are required, and act on cannabinoid CB1 receptors. These are heterogeneously expressed through the brain and are located on both central and peripheral pain processing pathways. Currently available compounds (cannabinoid agonists) include Sativex, a cannabis extract approved in Canada for the treatment of spasticity and pain in multiple sclerosis; it is also in development in cancer pain and neuropathic pain of various origins. There are currently around 40,000 people across Canada approved to use medical marijuana, soon to be provided by growers licensed by Health Canada. Clearly, cannabis has proven efficacy in a number of medical conditions. However, global activation of cannabinoid CB1 receptor by direct agonists (including THC contained in cannabis) leads to psychoactive side effects and abuse liability. There is both an opportunity and a need to provide safer and more effective ways of harnessing the therapeutic benefits of CB1 receptor activation. Our approach of targeting the allosteric binding site on the CB1 receptor using positive allosteric modulators (PAMs) has the advantage of increasing endocannabinoid effects only at the site of release (spinal and brain pain processing centres), thus providing the are expected to be free of the psychoactive side-effects associated with direct agonism of CB1. We have developed and validated a novel and potent CB1 PAM, showing it is effective as in relieving pain in animal models of neuropathic and inflammatory pain; crucially, we have also shown that it does not induce the psychoactive side effects that are characteristic of CB1 receptor orthosteric agonists.