Cantanhede – November 05, 2026 -- Mondego Bio has started a first-in-human Phase 1 study of MB-388, an oral dual PTPN2/PTPN1 inhibitor built to overcome resistance to cancer immunotherapy, with initial human pharmacokinetic and pharmacodynamic data due in December 2026.
Phase 1a tests dose escalation in healthy volunteers
The randomized, double-blind, placebo-controlled study will evaluate single and multiple ascending doses of MB-388. It will assess safety and tolerability, characterize pharmacokinetics and measure target engagement using blood-based pharmacodynamic biomarkers.
CEO Nikolay Savchuk said the study will define the relationship between exposure, pathway engagement and tolerability ahead of the planned patient study.
Preclinical data position MB-388 against osunprotafib
Mondego designed MB-388 to deliver sustained target coverage orally while keeping a therapeutic window wide enough for combination with checkpoint inhibitors. In head-to-head preclinical studies against osunprotafib, the leading clinical-stage PTPN2/PTPN1 inhibitor, MB-388 showed a substantially higher unbound fraction in human plasma, higher oral exposure and longer target coverage.
The compound also showed more than 1,000-fold selectivity over unrelated targets. Rodent and non-rodent safety studies showed favorable exposure margins.
In tumor models that respond to or resist PD-1 blockade, MB-388 was active as monotherapy and combined with anti-PD-1 treatment. Treatment increased intratumoral CD8-positive T cells and granzyme B.
Phase 1b in advanced solid tumors is slated for January 2027
The Phase 1b study will enroll patients with advanced solid tumors who have progressed on or after standard therapy, including those previously treated with checkpoint inhibitors. It will first evaluate MB-388 as monotherapy. A combination run-in with PD-(L)1 blockade will follow once initial monotherapy dose levels have been cleared.
The combination program will include both checkpoint-refractory and checkpoint-naive patients. Mondego plans a readout from combination dose escalation in December 2027.