C4X, a biotechnology company based in Manchester, is making significant strides in the field of immune-mediated inflammatory disease, where it is executing a new and ‘evolutionary’ strategy.
In an exclusive interview, the company’s Chief Scientific Officer (CSO) Nick Ray and Chief Business Officer Bhavna Hunjan shed light on the company’s use of non-biologic oral therapies to treat inherited and autoimmune disease.
A Strategic Shift
In November 2022, C4X secured a worldwide exclusive license worth up to US$402 million for its NRF2 Activator programme, marking a significant milestone for the company, led by Deputy Chair of the UK’s Vaccine Taskforce chief executive Clive Dix.
AstraZeneca will take the programme forward by commercialising oral medicines, such as pills taken by mouth, to treat inflammatory and respiratory disease, especially chronic obstructive pulmonary disease (COPD).
The move forms part of the company’s strategy to focus on immuno-inflammatory pathways, a core shift in its business model initiated last year.
C4X’s researchers are experts in discovering small molecule-based medicines that can treat immune-mediated inflammatory diseases and migrate them towards commercial development by partnering with big pharmaceutical groups.
In August, the company entered into an asset purchase agreement with London Stock Exchange-listed pharmaceutical business Indivior.
For a nameplate price of US$20 million (£15.95 million), it shed its orexin-1 receptor antagonist, called C4X_3256 (INDV-2000), used to treat substance-use disorder, to the pharma group.
Most of the company’s research revolves around transcription factors, which have the ability to “turn genes on or off”, Ray explained.
Its research has implications for a number of genes and could potentially impact the treatment of chronic respiratory diseases like COPD, currently a focus area for its commercial partner AstraZeneca.
Financial Milestones and Partnerships
C4X reached a financial milestone this week, securing an £11 million payment triggered under the partnership deal with AstraZeneca.
The company has also received milestone payments (€7 million to €13 million in 2022) from Sanofi under a licensing deal for its IL-17A Inhibitor therapeutics, used to treat conditions such as psoriasis, Bhavna said. That agreement with Sanofi is worth up to €414 million.
Its existing contracts with AstraZeneca and Sanofi represent approximately US$800 million of proceeds combined, Bhavna added, part of which could possibly be banked this year upon the completion of further milestones.
The company’s business lead said C4X is focused on executing on its partnership strategy to transition the company’s research to a clinical setting, emphasising that the business will prioritise in-house research. Two of the company’s projects have moved into operations and are both well-capitalised, she said.
A particular focus for the company’s research activities this year will be its alpha 4 beta 7 programme, which will progress possible treatments for inflammatory bowel disease (IBD).
Unique Technology and Future Prospects
C4X’s unique technology allows the biotech company to look at the shape of molecules in solutions and see how they behave, a capability that sets them apart from others in the field, Ray explained.
The company uses nuclear magnetic resonance technology, alongside proprietary software, to determine the structure of molecules in situ, which enables its researchers to identify unique molecular structures. For example, these molecules might behave differently when “floating about” nature, such as in a liquid, he said.
This differs from older techniques such as X-ray crystallography that effectively take a “snapshot” of a molecule frozen in time, Ray added.
He explained that the company’s software gives unique insights into the shape of molecules, including those with potential therapeutic properties.
The company’s drugs target prions, which play a role in transcription processes in the body. One such drug targets NRF2, a transcription factor that can reduce oxidative stress on organs by governing antioxidant synthesis through an augmentation process.
These techniques could potentially be used by companies such as AstraZeneca to treat serious autoimmune diseases like multiple sclerosis, a neurological disorder, though development is currently focused on the treatment of respiratory diseases.
An evolutionary year
Bhavna said that C4X is always in discussions with potential partners that can take its molecular drug discoveries forward to a clinical setting, something that could eventually happen with its ongoing work on irritable bowel disorder.
The company is also planning to publish results from two phase three clinical trials for Parkinson’s with the Garvan Institute of Medical Research.
In response to those trials, C4X has developed a technique to “stratify” possible candidates who could respond better to treatment based on their genetic profiles, using PatientSeek software, which Bhavna said can also be applied to other treatment pathways.
She explained that the aim of this work is to “build trust” and move the company’s in-house research forward.
With a background in discovery rather than clinical work, C4X is a company that is not afraid to innovate and push boundaries.
Its strategic focus on inflammatory pathways, unique technology, and ambitious plans for the future make C4X a company to watch in the biotechnology sector.