Z Factor Limited, a University of Cambridge spin-out company, has completed a £7 million Series A investment led by existing investor Medicxi. Cambridge Enterprise and Cambridge Innovation Capital have also joined in the founding round. Founded by Jim Huntington, Professor of Molecular Haemostasis at the Cambridge Institute for Medical Research, Z Factor previously raised undisclosed seed funding from Medicxi.

The Z Factor team is engaged in the discovery of new drugs to treat Alpha-1-Antitrypsin Deficiency (AATD). “AATD, which is a significant cause of liver and lung disease, results from a defect in the gene encoding Alpha-1-antitrypsin” said Professor Huntington. “Individuals with two defective copies of the gene, making up around 1 in 2000 of the Western population, typically develop emphysema starting in their 30s. They are also at an increased risk of developing liver diseases such as cirrhosis and cancer. Around 2% of people have one defective copy of this gene, and are at 5-fold increased risk of developing Chronic Obstructive Pulmonary Disease (COPD) as they age.”

The most common mutation causing AATD is called the Z mutation, which disrupts the normal folding of the protein. Professor Huntington and his team at University of Cambridge obtained the crystallographic structure of this mutant form of Alpha-1-antitrypsin, which allowed for the first time the rational design of drugs that could correct folding and prevent the development of associated diseases. “These small molecule drugs act like molecular chaperones for the defective protein, accelerating folding to the correct native state” said Nigel Ramsden at RxCelerate, who together with David Fox, is leading the drug discovery effort for Z Factor.

Z Factor has already identified dozens of molecules that can correct the folding defect caused by the Z mutation, and shown that some of these drug candidates can increase Alpha-1-antitrypsin levels in an in vivo model of AATD. The company is now working to select the best molecules for use as a drug in human trials. “The existing molecules clearly work well in model systems” said David Fox. “The next challenge is to create molecules that will work safely in human clinical trials.” The company expects to reach the clinic with its lead candidate in 2019.
Following closely on the announcement of investments in ApcinteX and SuperX earlier this year, the Z Factor Series A brings the total raised during 2017 by companies founded by Professor Huntington, one of Cambridge’s most successful serial entrepreneurs, to almost £30 million.

Z Factor is based on the Babraham Research Campus, just south of Cambridge, UK. It operates as a virtual biotechnology company, with no internal operations, using an established network of out-sourced drug discovery and development providers, including RxCelerate, co-located on the Babraham campus.