Step Pharma bags cash for CTPS1 autoimmune R&D drive

Paris, France, where Step Pharma is based.

Step Pharma has closed a €14.5 million ($17.0 million) series A round. The financing equips the lean French biotech to prepare its CTPS1 inhibitors for clinical testing in autoimmune disorders.

Paris, France-based Step is built on a discovery made by researchers at the Imagine Institute. They sequenced the genomes of eight patients who suffered from the early onset of severe chronic viral infections, leading them to identify a mutation in CTPS1 that impaired T cell proliferation in the children. That suggested inhibition of CTPS1 may result in highly targeted immunosuppression.

Step spun out of the institute with a target it felt was genetically validated in humans but without chemical structures. Working with the institute and CRO Sygnature Discovery, the biotech built an assay platform from the ground up and identified selective inhibitors of the target, the most advanced of which are now in lead optimization.

That led Pontifax Venture Capital to join with existing investors including Kurma Partners and Bpifrance for an €8.6 million second closing of the series A, bringing the total size of the round up to €14.5 million. 

“Now we can finish lead optimization of our molecules,” Step CEO Geoffroy de Ribains said.

Beyond that, Step will push into regulatory preclinical development while working to understand which indication to target in the clinic. Ultimately, de Ribains thinks the approach is applicable to a breadth of autoimmune disorders. But, as a small biotech, the focus is on getting clinical validation before branching out to unlock the full potential of the mechanism.

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Step will perform this work through the Imagine Institute and Sygnature, both of which came on board early in the biotech’s history. Sygnature provides Step with FTEs—16 at the last count—in return for equity in the startup.   

“In that way they were completely aligned with the objectives of the other shareholders and they were also completely engaged with the project,” de Ribains said.

Working this way allowed Step to run as a virtual biotech. The startup now employs two FTEs. Two more will join before the end of the year, with another two following in 2018 as the biotech gears up for the clinic. 

De Ribains also attributes Step’s ability to work through some early difficulties in its attempts to drug CTPS1 to the coalition that formed around the company early on. VCs and Sygnature came on board far earlier in Step’s growth than is typical for biotechs, particularly in Europe, and this meant the company’s tiny team had access to the input of experienced people from its earliest days.

Step’s ability to attract that early support stems from its target. The biotech began life with clinical evidence that CTPS1 is critical in promoting T cell proliferation. 

“If CTPS1-specific inhibitors can be designed, they would potentially be highly specific immunosuppressive drugs able to inhibit auto- or allogenic-specific T-cell and B-cell responses without additional toxicity given the lymphocyte specificity of the CTPS1-deficiency phenotype,” the Imagine Institute team wrote in a 2014 Nature paper.

At that stage, Step lacked molecules to hit the target, but other research groups had already shown it is possible to develop nucleotide synthesis inhibitors and use them to treat autoimmune disease. 

Now, Step is closing in on the day it will learn whether dialing up the specificity of the molecules will enable the safe delivery of high doses of its nucleotide synthesis inhibitors, opening the door to their use in any situation in which lymphocyte activity needs dampening.