Pipeline

Degenerative and behavioural diseases of the brain and nervous system.

Overview

Target Selection Lead Generation Lead Optimisation Pre-Clinical POC IND OD* Phase 1 Phase 2
Chroneuro™ ALS
DAT Inhibitor in MS Fatigue
OX1 Antagonist in BED
OX1 Antagonist in AUD
Chronoscreen Output
TrkB Modulator in PTSD

*Orphan Drug designation planned for ChroneuroTM.

Abbreviations: ALS, Amyotrophic Lateral Sclerosis; AUD, Alcohol Use Disorder; BED, Binge Eating Disorder; DAT, Dopamine Transporter Inhibitor; IND, Investigational New Drug; OX1, orexin-1 antagonist; PTSD, Post Traumatic Stress Disorder; TrkB, tropomyosin receptor kinase B.

ALS – RDC5

Chronos has a dedicated laboratory in Oxford which screens for activity of drugs in brain disease through its proprietary platform, Chronoscreen™.

Re-purposing Molecules

Chronos has an extensive library of re-purposed molecules showing promise for brain and neurological diseases. The lead compound, Chroneuro™ (RDC5), is being developed for the fatal neurodegenerative disease, Amyotrophic Lateral Sclerosis (ALS).

ALS (or Lou Gehrig’s Disease) is characterised by progressive death of the primary motor neurones in the central nervous system.  Symptoms include muscle weakness and muscle wasting, difficulty in swallowing and undertaking everyday tasks. As the disease progresses, the muscles responsible for breathing can fail, gradually causing dyspnoea or difficulty in breathing.

prevalence

ALS has an average prevalence of 2 per 100,000.  Prevalence is higher in the UK and USA than many other countries, up to 5 per 100,000. There are estimated to be over 50,000 patients in the USA and 5,000 patients in the UK with the condition. Mortality rates for ALS sufferers are high with 10 year survival after diagnosis below 10% and average survival 39 months from diagnosis.

There is only one drug currently approved for treatment in the EU and as of 2017, two drugs are approved for the condition in the USA.

FATIGUE – MS CTDP-001

Chronos recently acquired three new chemical entity (NCE) development programmes for CNS diseases. The most advanced of these is a dopamine active transport inhibitor programme targeting fatigue associated with multiple sclerosis.

MS

An estimated 2.3 million people globally have multiple sclerosis (MS) according to the Multiple Sclerosis International Federation. Fatigue is the most common symptom of the disease. It occurs in 75 percent to 95 percent of patients with MS and as many as 40% of patients have described it as the single most disabling symptom of the disease.

Fatigue is a feature of several chronic diseases of the central and peripheral nervous system.

The pathophysiology of central fatigue is complex and often not well-defined. Patients often define this central fatigue as a subjective sensation of weariness, increasing sense of effort, mismatch between effort expended and actual performance, or exhaustion.

Chronos is actively researching the best candidate molecule to provide alleviation of this serious symptom in MS patients.

ADDICTIVE BEHAVIOURS CTDP-002

There are a number of addictive behaviours that represent significant unmet medical needs and require novel treatments. Chronos is developing orexin 1 antagonists to target binge eating, alcohol and nicotine addictions.

Binge Eating

Binge eating is an eating disorder where a person feels compelled to overeat on a regular  basis through regular “binges” or consumption of very large quantities of food over a very short period of time, even when they are not hungry. The condition tends to develop first in young adults, although many people do not seek help until they are in their 30s or 40s.

There is a 1 in 30 to 1 in 50 chance of a person developing binge eating disorder at some point during their life and it can lead to a variety of health problems that can, in extreme circumstances, be life-threatening. Whilst more women suffer from the condition than men, binge eating is not particularly uncommon in men with the prevalence ratio of approximately 1.5 women for every man with the disorder.

Alcohol Use Disorder

Alcohol use disorder (which includes a level that’s sometimes called alcoholism) is a pattern of alcohol use that involves problems controlling your drinking, being preoccupied with alcohol, continuing to use alcohol even when it causes problems, having to drink more to get the same effect, or having withdrawal symptoms when you rapidly decrease or stop drinking.

Excessive alcohol use (as caused by addiction or binging) has caused 10% of deaths among working-age adults aged 20-64 years in the USA with economic costs in 2010 in the USA alone of $249 billion.

The WHO also estimates that harmful alcohol use causes 3.3 million deaths a year, globally. Short-term health risks, most often the result of binge drinking, include accidents, injuries, alcohol poisoning and risky sexual behaviours.

Chronos is currently selecting the best candidate molecules as potential treatments for this serious and distressing condition.

Post-traumatic stress disorder CDTP-003

Post-traumatic stress disorder (PTSD) is a pathological anxiety disorder resulting after exposure to a traumatic event; it is characterised by an inability to extinguish fear memories.

Symptoms

Symptoms can include persistent re-experience of the event, avoidance of stimuli associated with the trauma and hyper-arousal. The 12 month prevalence of PTSD in the US is 7-8 million cases. PTSD cases frequently involve combat or assault experiences, but there are a wide range of events capable of triggering symptoms. Assaultive violence (including sexual assault) accounts for ~50% of PTSD cases whereas combat related causes account for ~10%. Other common causes include childhood maltreatment, witnessing injury/trauma to others as well as serious accidents, illnesses, and natural disasters. Women are four times more likely to suffer from PTSD than men (after adjusting for differences in exposure).

innovative treatments

Current approved medications for treating adults with PTSD are minimally efficacious and in particular re-experience, avoidance and hyper-arousal symptoms are not particularly well treated. This demonstrates that there is a significant unmet medical need; with current therapies having limited efficacy or adverse side effects, PTSD needs new and innovative treatments that do not carry the liabilities of current therapies. This is particularly true as the current understanding of PTSD suggests that unique cognitive impairments exist in this patient population.

Chronos’ programme seeks to find a truly novel approach to treatment and potentially prevention of this significant condition.

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