Key Discovery Programmes
Portfolio of high-value pre-clinical small molecule candidates
Oral MALT1 inhibitor
MALT1 is a promising haematological cancer target for Non-Hodgkin’s Lymphoma (NHL) and Chronic Lymphocytic Leukaemia (CLL), with potential as both a monotherapy and in combination with BTK inhibitors such as ibrutinib. In collaboration with LifeArc and the University of Lausanne, C4X has developed novel chemistry which is structurally differentiated from existing patented chemical matter and is progressing multiple series towards the clinic.
Oral α4β7 integrin inhibitor
Effective antibody therapy against α4β7 integrin is already approved, removing the clinical target risk, but effective oral therapy remains highly sought after. C4XD has identified multiple series of novel, potent and selective inhibitors providing a competitive edge for this programme. This reaffirms the capability of C4XD’s Conformetrix technology to discover novel chemical scaffolds for high value challenging drug targets.
Quality partnerships demonstratingthe value of C4XD’s expertise
Oral Orexin-1 Antagonist (C4X_3256/INDV-2000)
We have successfully out-licensed our novel, oral Orexin-1 receptor antagonist (C4X_3256, now known as INDV-2000) to addiction market leaders Indivior, generating $10 million upfront and up to $284 million of potential development, regulatory and commercialisation milestones, in addition to royalties.
The Orexin-1 receptor is considered to be central to the brain’s “craving” and “reward” pathways with pre-clinical efficacy observed in multiple addiction models. Prior to the licensing deal with Indivior, we demonstrated that INDV-200 attenuated cocaine-induced brain dopamine elevation supporting its potential in this important therapeutic area and adding to the compelling pre-clinical efficacy data already achieved in nicotine addiction showing reductions in self- administration and re-instatement. INDV-2000 is currently in a Phase I clinical trial conducted by Indivior for the treatment of opioid dependence.
Oral IL-17A Inhibitor Programme
We have signed an exclusive worldwide licensing agreement with Sanofi (NASD: SNY, PAR: SAN – “Sanofi “), worth up to €414 million, for C4XD’s oral pre-clinical IL-17A inhibitor programme. Under the terms of the agreement, C4XD will receive an upfront payment of €7 million and could receive up to a further €407 million in potential development, regulatory and commercialisation milestones, of which €11 million is in pre-clinical milestones, in addition to single digit royalties.
Interleukin-17 (“IL-17”) is a high value clinically validated target for inflammation and autoimmune diseases such as psoriasis (estimated to be worth $9 billion per annum). Our programme identified small molecules that can selectively block IL-17 activity whilst keeping the molecular size of the molecule in the traditional “drug-like” range. We have completed optimisation of our lead novel oral compounds which have shown that they can inhibit the release of IL-17 induced cytokines in the blood in vivo when administered orally prior to IL-17 administration. Current marketed drugs that target IL-17 are based on injectable monoclonal antibodies so an oral treatment would increase the number of patients who can access drugs targeting this mechanism and offer the pharmaceutical industry an alternative treatment regime.
Oral NRF2 activator
We have developed novel potent and selective activators of the NRF2 pathway for the treatment of a variety of inflammatory diseases including Inflammatory Bowel Disease (IBD), Sickle Cell Disease (SCD), Pulmonary Arterial Hypertension (PAH) and Chronic Obstructive Pulmonary Disorder (COPD). Our lead molecules have been found to significantly activate NRF2 following oral dosing, providing anti-inflammatory and anti-oxidant activity. In C4XD studies, multiple lead compounds show greater than a 12-hour duration of action following low oral dosing on activation of NRF2 in key tissues such as the lung and the liver and in blood.
We have signed an exclusive global out-licensing agreement with AstraZenea (LSE/STO/Nasdaq: AZN), worth up to $402 million, for C4XD’s NRF2 Activator programme. AstraZeneca will develop and commercialise an oral therapy for the treatment of inflammatory and respiratory diseases with a lead focus on chronic obstructive pulmonary disease (COPD). Under the terms of the agreement, C4XD will receive pre-clinical milestone payments worth up to $16 million ahead of the first clinical trial, including $2 million upfront. In addition, C4XD is eligible to receive a further potential $385.8 million in clinical development and commercial milestones and tiered mid-single digit royalties upon commercialisation.
Alliances play a key role in the development, growth and commercial strategy of our business.
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