One-carbon therapeutics AB is developing an MTHFD2 first-in-class inhibitor to the one-carbon metabolism representing a novel way of attacking the DNA damage response (DDR).

 Co-founded by the Helleday Laboratory, we are taking our previous success of discovering the PARP inhibitor concept for treatment of BRCA mutated cancer to a new level; exploiting cancer-specific metabolism to target the DDR, and cause cancer-specific DNA damage at replication forks.

Many DDR companies are targeting either DNA damage signalling or DNA repair, with difficulties obtaining cancer selectivity and a good therapeutic index. One-carbon therapeutics has instead a unique strategy targeting cancer metabolism pathways underpinning the DDR. This strategy ensures selectivity towards cancer over normal cells

 

 

Our primary target is MTHFD2, an oncofoetal protein, expressed during embryogenesis, silenced in adult normal cells and then re-expressed in cancer. MTHFD2 has been validated as an anti-cancer target by numerous independent laboratories. At one-carbon therapeutics, we are proud to announce a first-in-class, low nanomolar potent inhibitor of MTHFD2 clinical development.

A key hallmark of all DDR inhibitors is to cause replication stress and death of cancer cells, but the trouble is doing this selectively in cancer cells. Using the DNA fiber assay (DNA combing) we can visualise replicating DNA molecules and show a slower, cancer cell-specific replication fork speed with MTHFD2 inhibitors (MTHFD2i). The controls methotrexate (MTX) or ATR inhibitor (ATRi) cause replication stress in both cancer and normal cells, which could explain the adverse effects seen with these drugs in the clinic

Pioneering team

Many years’ experience in oncology drug discovery and development, identified and brought first-in-class DDR targets to clinical  trials.

The co-founder of one-carbon therapeutics pioneered the PARP-BRCA synthetic lethal concept

First-in-class

Building on frontline research and developing first-in-class treatments for a new emerging area within the DDR space.

Frontline structure-guided medicinal chemistry and unique mechanism of action

Biomarker-driven

Targeting cancers with high unmet clinical need using state-of-the-art ex vivo screening and defined biomarker-driven patient selection.

Employing emerging ex vivo screening methods for increased accuracy

One-carbon therapeutics AB is a Swedish company exploiting cutting-edge science to develop first-in-class treatments to MTHFD2 and related targets and developing these with advanced biomarkers identified using primary cancer patients tumours