Hamlet BioPharma (HAMLET) Investor update summary

Pipeline and clinical progress

• Phase II bladder cancer study reported an 88% reduction in tumor size at higher doses; visible tumor-size reduction occurred in 82% of tumors at the high dose and 45% at the lower dose.

• Phase III trial of Alpha1H in non-muscle invasive bladder cancer began enrolling after protocol approval by European and U.S. authorities; study coordinator is Professor Marek Babjuk.

• Phase III design uses six bladder instillations of Alpha1H at 8.5 mM before surgery, followed by standard care for up to 12 months; event-free survival, including recurrence, is monitored.

• Carcinoma in situ completed Phase II; a University of Iowa collaboration will address CIS, while an acute pyelonephritis study is planned.

• Separate U.S. clinical study is also being advanced; Alpha1H production has been scaled to kilogram levels.

Alpha1H mechanism and development

• Alpha1H induces tumor-cell shedding and apoptosis, inhibits cancer-related gene expression and activates a protective immune response described as similar to BCG.

• Research indicates Alpha1H disrupts multiple adhesion systems, including tight junctions, adherens junctions and focal adhesions, unlike therapies targeting a single molecule.

• Patient samples showed detached cells and apoptosis after two hours; treated tumors showed suppressed gene expression and cell-death markers.

• Potential development includes adjuvant use after surgery, alone or in combination; plans depend on neoadjuvant study data.

• Management said Phase III treatment appeared to be working well, while official data await a sufficient patient count; 8.5 mM was selected after higher-dose solubility constraints, with a lower eventual marketing dose possible.

Non-antibiotic infection and pain programs

• Phase II recurrent cystitis study compared five days of anakinra with nitrofurantoin; both reduced symptoms, while anakinra also inhibited immune hyperactivation.

• Six-month follow-up showed fewer recurrent UTIs and improved quality-of-life scores; the approach aims to limit antibiotic resistance pressure and effects on normal flora.

• Preclinical host-directed candidates suppressed excessive inflammation and accelerated bacterial clearance, including in models involving antibiotic-resistant bacteria.

• Host therapy was reported to help many patients with treatment-resistant bladder pain, with some returning to more normal lives and continuing treatment.