On November 5, 2026 Mondego Bio reported the initiation of a first-in-human Phase 1 clinical study of MB‑388, an oral dual PTPN2/PTPN1 inhibitor designed to overcome resistance to cancer immunotherapy by acting in both tumor cells and immune cells.
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The randomized, double-blind, placebo-controlled Phase 1a study will evaluate single and multiple ascending doses of MB‑388 in healthy volunteers. It will assess safety and tolerability, characterize pharmacokinetics (PK) and measure target engagement using blood-based pharmacodynamic (PD) biomarkers.
MB‑388 was designed to address a central limitation of this inhibitor class: achieving sustained target coverage with an oral molecule while preserving a therapeutic window broad 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. MB‑388 also showed more than 1,000-fold selectivity over unrelated targets and favorable exposure margins in rodent and non-rodent safety studies.
In preclinical tumor models that respond to or resist PD‑1 blockade, MB‑388 was active both as monotherapy and in combination with anti-PD‑1 treatment. Treatment increased intratumoral CD8-positive T cells and granzyme B, consistent with the intended immune-mediated mechanism.
"Starting the first clinical study of MB‑388 is an important milestone for Mondego," said Nikolay Savchuk, PhD, Chief Executive Officer of Mondego Bio. "The Phase 1a study will define the relationship between exposure, pathway engagement and tolerability, giving us the data to move efficiently into our planned study in patients with cancer."
Mondego plans to begin a Phase 1b study in January 2027 in patients with advanced solid tumors who have progressed on or after standard therapy, including patients previously treated with checkpoint inhibitors. The study will first evaluate MB‑388 as monotherapy, then add a combination run-in with PD‑(L)1 blockade once initial monotherapy dose levels have been cleared. The combination program will include both checkpoint-refractory and checkpoint-naive patients.
Initial human PK and PD data are expected in December 2026, and a readout from combination dose escalation is planned for December 2027.
(Press release, Mondego Bio, NOV 5, 2026, View Source [SID1234674357])