Nuvectis Pharma (NVCT) investor relations material

Precision medicine strategy and pipeline

• Focus on developing targeted therapies for serious oncology conditions with unmet needs.

• NXP900 is a novel, highly selective YES1/SRC kinase inhibitor discovered at the University of Edinburgh.

• Phase 1a dose escalation and drug-drug interaction (DDI) studies completed; Phase 1b program ongoing with monotherapy and combination arms.

• Potential indications include YES1/SRC-driven solid tumors, squamous cell cancers, and ALK/EGFR-mutated NSCLC.

• Management team has a strong track record with three approved drugs in four indications in the US and EU.

Clinical progress and safety

• Phase 1a study in advanced solid tumors showed robust pharmacodynamic response with ~90% SRC inhibition at ≥150 mg/day.

• Acceptable safety profile; no dose-limiting toxicity identified.

• Most common adverse events: diarrhea, fatigue, nausea, decreased appetite, and dyspnea, mostly mild to moderate.

• DDI study in healthy volunteers showed NXP900 is a weak inhibitor of CYP3A and CYP2B6, with no serious adverse events.

• Rapid and sustained reduction of pSRC in PBMCs observed after dosing.

Scientific rationale and preclinical validation

• Hippo pathway mutations and YES1 amplification linked to NXP900 sensitivity; strong preclinical efficacy in lung, esophageal, and head and neck cancer models.

• NXP900 achieves complete shut-down of YES1/SRC pathways, differentiating it from other multi-kinase inhibitors.

• More selective and potent SRC inhibition compared to saracatinib, with enrichment strategy for patient selection.

• Preclinical synergy demonstrated with ALK/EGFR inhibitors and RAS inhibitors, reversing resistance in NSCLC models.

• SRC, YES1, and YAP1 activation validated as drivers of resistance to targeted therapies.