Helus Pharma (HELP) investor relations material

Company and program overview

• Developing novel serotonergic agonists for mental health, with a platform approach and multiple programs in late, mid, and early stages.

• Lead program HLP-003 (deuterated psilocin) is in phase III for adjunctive major depressive disorder (MDD), with a first phase III readout expected in Q4 2026 and an NDA filing anticipated in 2028.

• HLP-004 (deuterated DMT) is in phase II for generalized anxiety disorder, and HLP-005 is an early-stage program with a lead candidate expected to advance in 2027.

• Strong intellectual property portfolio underpins clinical development and future commercialization.

HLP-003 scientific and clinical rationale

• Deuterated psilocin offers improved brain penetration, higher exposure, and reduced drug load compared to psilocybin.

• Preclinical studies show HLP-003 achieves higher Cmax and AUC at lower doses than psilocybin, with altered metabolism reducing drug-drug interaction risk.

• Phase III APPROACH study uses two 16 mg doses three weeks apart, with primary endpoint at six weeks and secondary at 12 weeks.

• Inclusion criteria require moderate to severe MDD (MADRS ≥24) and stable background antidepressant use, excluding MAOIs, tricyclics, antipsychotics, and mood stabilizers.

Efficacy, safety, and regulatory considerations

• Phase II showed a 13-point MADRS improvement after one dose, with an additional 5.5 points after a second dose.

• Phase III is powered similarly to other late-stage trials in the class; primary and key secondary endpoints, plus safety data, will be released at top-line.

• Clinically meaningful effect size is considered 3 points on MADRS, with 4-5 points seen as strong, especially given the safety and durability advantages over adjunctive antipsychotics.

• Safety profile to date shows mostly mild to moderate, transient adverse events; discharge criteria after dosing include physiological and mental status assessments.

• Suicidality is monitored rigorously, with regulators focusing on imbalances between active and placebo arms.