C4X Discovery happy in the pre-clinical world as partner list grows

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C4X Discovery Holdings PLC (LON:C4XD) has made pre-clinical work the centre of its focus.

The firm aims to create the world’s most productive drug discovery engine by designing small-molecule medicines that can be easily delivered to the affected area of the patient’s body.

READ: C4X Discovery strikes Sanofi licensing deal worth up to €414mln

“We don’t plan to become a clinical company and we remain in the early phase, and the reason for that is we have a couple of very good technologies which we believe make a big difference in that phase and differentiates us from the rest,” chief executive Clive Dix told Proactive.

“We plan to always have a portfolio of projects that we work on using our technologies to find really good molecules, high-quality molecules, which we take anywhere from starting point all the way through to a clinical candidate ready to go in the clinic.”

The portfolio is focused on inflammation, neurodegeneration and oncology, including immuno-oncology, with the aim of replenishing big pharma discovery pipelines and driving returns through revenue-generating pre-clinical licensing deals.

C4X has recently clinched its second major licensing deal with French group Sanofi, worth up to €414mln for its oral IL-17A inhibitor programme.

At the moment both the UK company and its partner are a long way from commercial launch.

However, they are working on a hugely promising potential treatment for inflammatory diseases, tapping into a multi-billion-dollar market.

Currently, IL-17 monoclonal antibodies are administered by injection, so having an oral version represents a significant breakthrough.

“Everybody wants an oral IL-17 inhibitor – all the companies that have an antibody want an oral molecule, a small molecule that you can pop a pill, and all the companies that haven’t gotten IL-17 but are in the inflammatory space also want a small molecule, so there’s a lot of demand,” Dix, who is also interim chair of the UK Vaccines Task Force, explained.

“Because we’ve got differentiated technologies we can crack some problems that maybe others can’t, or if they can, it’s quite hard for them to.”

The company’s first major deal dates back to March 2018, when it agreed to supply its treatment to FTSE 250-listed Indivior for opioid use disorder into the clinic as part of a deal worth US$294mln.

Phase I trials for the drug, which aims to treat opioid addiction by targeting the “craving” process, started last summer.

The first part of the two-part study is double-blind, placebo-controlled and randomised, with a single-ascending dose given to fasting volunteers.

The second part is an open-label study, in which the patients are aware of what they are given, with a single dose to be administered once under fasting conditions and once after eating a standard US Food & Drug Administration (FDA) high-fat breakfast.

The trial benefits from funding by the US National Institutes of Health (NIH), made to Indivior in 2019 to develop medications to prevent and treat opioid addiction, as the US continues to battle an opioid crisis.

But C4X doesn’t rest on its laurels and continues looking for the rest of its portfolio.

“[The programmes] are in areas where we know there’s a lot of interest, both medical interest and unmet need, and companies are looking to get molecules in these areas,” Dix noted.

The oral NRF-2 activator programme is also targeting inflammatory diseases activating the NRF-2 pathway, which is important in mediating illnesses such as sickle cell disease, chronic obstructive pulmonary disease, pulmonary arterial hypertension and others.

“It worked in lots of areas,” Dix said, “in fact, the companies who are interested can’t make their mind up which area they think is the best.”

“We have our own views but it’s not really down to us to decide. We want the partners to look at it, and in many cases now we’re already talking to partners and we do material transfer agreements and they test them in their specific model systems.”

According to Dix, this molecule is “a little bit like a steroid” as it causes powerful anti-inflammatory responses but also has antioxidant properties, so it helps against the destruction of tissue which inevitably happens when the disease hits.

There’s also the oral α4β7 integrin inhibitor programme, which received an InnovateUK Feasibility Award to fund the early stages.

Clinical tests showed that it was effective in avoiding too many white blood cells to migrate into the tissue when paired with an antibody.

“We have looked to see if we can find small molecules that do the same as the antibody yet again and we’ve got some really nice early molecules,” Dix continued.

“There’s a lot of interest already in that programme and we’ll be developing the full data package on that and, as we go through, companies will keep coming and looking at it and talking to us and at some point we will decide to initiate a full licensing programme there again.”

Finally, there’s the collaboration with medical research charity LifeArc as part of the Medical Research Council’s out-licensing and drug discovery programme.

The pair entered a partnership in 2018 to work on programmes for oncology and inflammation indications.

Similarly to other work done by C4X, the scope is to develop oral, potent and selective small molecule drug candidates in areas of high unmet clinical need.

Shares were trading at 42.99p on Wednesday, having climbed 34% in the year to date.

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