Heidelberg Pharma (HPHA) Status Update summary

Clinical development highlights

• HDP-101 is an amanitin-based antibody-drug conjugate (ADC) targeting BCMA with a novel payload derived from mushroom toxin, inhibiting RNA polymerase II, a previously untargeted, cell cycle-independent mechanism.

• The ADC efficiently kills both dividing and dormant tumor cells, with no known resistance mechanisms and is effective even in ultra-low BCMA-expressing cells.

• Preclinical and early clinical data show strong activity against myeloma cells, including those resistant to other therapies, and a favorable safety profile.

Phase I trial results and safety

• In heavily pretreated, triple-class exposed multiple myeloma patients, HDP-101 demonstrated multiple responses, including a stringent complete remission lasting over 19 months.

• Dose escalation cohorts revealed that split dosing strategies mitigated transient thrombocytopenia, with no significant ocular, renal, or liver toxicities observed.

• No dose-limiting toxicities were seen up to 112.5 mcg/kg, and the trial is enrolling at 140 mcg/kg.

• The safety profile is notably mild, with no cumulative toxicity observed in long-term treated patients.

Efficacy and future development

• Responses were observed at doses above 90 mcg/kg, with ongoing durable partial and complete responses.

• The recommended phase II dose is expected by year-end, with plans to expand into phase II, including monotherapy and combination regimens.

• The drug is positioned for post-BCMA relapse/refractory myeloma and earlier lines in combination, aiming for accelerated or conditional approval by 2030.

• Additional amanitin-based ADCs targeting CD37, PSMA, and GCC are in early development for other cancers.