C4X makes solid progress across portfolio of programmes

Drug discovery company C4X Discovery Holdings announced progress across a number of key programmes in line with its strategy on Tuesday, reporting that it was continuing to progress its strategy to deliver programmes for out-licensing its NRF-2 activator, IL-17 inhibitor and LifeArc collaboration.

The AIM-traded firm said it was also progressing its early-stage multi-target disease area opportunities for novel targets identified from its proprietary technology and collaborations, including the Horizon Discovery Group and Taxonomy3-derived Parkinson's disease projects.

On the oral NRF-2 activator programme, C4X said it was progressing a series of novel potent activators of the NRF-2 pathway for the treatment of inflammatory diseases.

In its studies, multiple lead compounds showed a duration of at least 12 hours of action following low oral dosing on activation of NRF-2 in key tissues such as lung and liver, as well as blood.

Pre-candidate nomination studies were currently underway, with candidate selection anticipated for the first quarter of 2020.

“Partnering discussions to date have confirmed commercial interest for NRF-2 in Sickle Cell Disease (SCD),” the C4X board said in its statement.

“NRF-2 activators are shown to directly increase foetal haemoglobin and reduce oxidative stress and inflammation, with significant potential for the treatment of haemolysis-related complications in SCD.

“The board believes that upcoming C4X data will be valuable in driving a competitive out-licensing process focused on SCD.”

Looking at its oral IL-17 inhibitor programme, C4X explained that it had identified small molecules that could selectively block IL-17 activity, while keeping molecular size of the molecule in the traditional ‘drug-like’ range.

In its studies, optimisation of lead oral compounds continued to achieve effective drug concentration in the blood.

Based on recent industry disclosures, the company said that level of drug concentration was predicted to be efficacious in pre-clinical inflammatory models.

C4X said it was continuing to receive strong interest from potential partners for the high value target, particularly driven by the C4X series profiles.

On its LifeArc oncology and inflammation collaboration, the company said the initial phase of the collaboration had been successful.

In initial studies, multiple hit compounds had progressed with the aim of generating a lead series with in vivo activity for oncology and inflammatory indications by the second quarter of 2020.

“Significant industry activity from multiple pharmaceutical companies for the target of interest at recent scientific meetings supports the ongoing partnering potential of this programme,” the board said.

Looking at its oral Orexin-1 receptor antagonist programme, in March last year, Indivior entered a license agreement to obtain exclusive global rights to develop and commercialize ‘C4X3256’ for the treatment of opioid use disorder.

On 27 September, Indivior was awarded a National Institutes of Health grant to advance C4X3256 from preclinical status through phase 1 clinical evaluation, and perform the necessary toxicology and drug metabolism studies to enable phase 2 studies, the company noted.

On the firm’s early-stage multi-Target disease area opportunities, in its Horizon oncology collaboration, C4X noted that itself and Horizon had entered into an exclusive target discovery partnership in December to take forward high-value novel synthetic lethal oncology targets discovered through in-depth CRISPR-Cas9 analyses conducted by Horizon, which it said had the potential to offer an alternative route to creating new oncology drugs.

The collaboration had made “rapid” progress, and had now generated comprehensive in vitro validation data packages for the lead novel target in the collaboration.

“In vitro studies have confirmed that inhibition of this target induces cell death that is dependent on the presence of cancer-specific mutations, thereby demonstrating synthetic lethality.

“Additional in vivo studies have shown that knock out of the gene inhibits growth of implanted colon cancer cells with a KRAS mutant background.

“As an enzyme, the target is expected to be highly amenable to targeting with small molecules and is nearing progression into C4X-led drug discovery programmes, with additional targets to follow the development pathway.”

Finally, on its Taxonomy3-derived Parkinson's disease projects, C4X said it was continuing to progress the validation of its proprietary novel targets for Parkinson's, utilising a diversified strategic approach.

It said its internally-led biological validation studies were near completion for targets with existing tool compounds, which provided a low-risk starting point from which to rapidly initiate drug discovery programmes for promising targets with some known chemistry and biology.

The Phoremost collaboration initiated in June used Phoremost's ‘SITESEEKER’ platform to generate biological validation for all Taxonomy3 targets, as well as providing chemical starting points for “highly novel” Taxonomy targets without existing chemistry in the literature.

That enabled the progression of more challenging, but high potential targets, the board explained.

The e-therapeutics collaboration had identified additional novel biological pathways derived from Taxonomy3's novel genes, which were currently being evaluated to identify additional targets, with the potential to start new drug discovery programmes.

“Momentum continues to build within the C4X Discovery portfolio,” said C4X chief executive officer Dr Clive Dix.

“Recent exciting new industry sickle cell disease data supports the potential of our NRF-2 activator programme as an alternative treatment for poorly served patients.

“This new data supplements learnings from our early discussions and increases our confidence towards a sickle-cell disease focused out-licensing.”

In order to maximise the value for shareholders, Dr Dix said the company had focused on rapidly advancing the next wave of potential revenue-generating assets, while maintaining its considered approach to the deployment of available funds.

In particular, he said the firm was planning to progress the lead target from its collaboration with Horizon Discovery into a C4X-led commercial drug discovery programme.

“We are excited that the world class drug discovery being carried out by the team at C4X Discovery has built a highly valuable portfolio of new medicines that will allow us to strike further lucrative deals with pharma partners, as demonstrated by Indivior's grant awarded by NIH HEAL to initiate phase 1 clinical studies of our Orexin 1 programme for the treatment of opioid use disorder.

“We are very confident about delivering these deals in the near future and beyond.”