Heidelberg Pharma Initiates Phase I Trial of HDP-102 for Non-Hodgkin Lymphoma as Second Amanitin-Based ADC Enters Clinic
核心洞察
Heidelberg Pharma has dosed the first patient with HDP-102, an amanitin-based antibody-drug conjugate targeting CD37 (搜索), in a Phase I study for relapsed or refractory non-Hodgkin lymphoma.
The multicenter trial will evaluate safety, tolerability, and pharmacokinetics across Moldova, Israel, and selected EU countries, with plans for dose escalation followed by expansion phases.
HDP-102 represents the company's second ATAC technology candidate to reach clinical development, following encouraging safety and efficacy data from HDP-101 in multiple myeloma.
Heidelberg Pharma AG has announced the dosing of the first patient with HDP-102, marking a significant milestone as the company's second amanitin-based antibody-drug conjugate (ADC) enters clinical development for non-Hodgkin lymphoma (NHL). The Phase I study represents an important advancement in the company's proprietary ATAC (Amanitin-based ADC technology) platform, which utilizes compounds derived from the green death cap mushroom.
Novel CD37-Targeting Approach
HDP-102 targets CD37 (搜索), a key antigen expressed on many B-cell lymphoma cells, and has the potential to successfully treat patients across multiple NHL indications. The compound leverages Heidelberg Pharma's unique position as the first company to use amanitin from the green death cap mushroom in cancer therapy, representing a new therapeutic modality that combines antibody specificity with cytotoxic efficacy.
Dr András Strassz, Chief Medical Officer of Heidelberg Pharma, emphasized the significance of this development: "Moving our second ATAC program, HDP-102, into clinical development in patients with non-Hodgkin lymphoma is a significant milestone. Building on the encouraging safety and efficacy data we have seen with HDP-101 in multiple myeloma, we are optimistic that HDP-102 will deliver similarly promising results."
Study Design and Global Scope
The first patient was dosed with HDP-102 at a study center in the Republic of Moldova as part of a multicenter, multinational, open-label study. The trial is designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of HDP-102 in patients with relapsed or refractory B-cell malignancies, while determining the recommended dose for future studies.
The study will be conducted across multiple regions, including Moldova, Israel, and selected EU countries. Following the initial dose escalation phase, the study is planned to enter an expansion phase to further evaluate the safety and potential efficacy of HDP-102 at the optimal dose.
Preclinical Foundation
Heidelberg Pharma presented preclinical data for HDP-102 at the American Association for Cancer Research (AACR) 2024 Annual Meeting, demonstrating strong anti-tumor efficacy and favorable tolerability following a single administration. These results provided the foundation for advancing the compound into human clinical trials.
Addressing Significant Medical Need
Non-Hodgkin lymphoma represents one of the more common types of cancer, with more than 550,000 new cases diagnosed each year. The disease leads to the death of two to three patients per 100,000 people annually. Among the various NHL subtypes, diffuse large B-cell lymphoma (DLBCL) is the most aggressive and accounts for approximately 32% of cases, while other common B-cell lymphoma subtypes include follicular lymphoma (17%), marginal zone lymphoma (8%), and mantle cell lymphoma (4%).
Despite treatment advances over the last three decades with combination immunotherapies, a significant proportion of NHL patients either relapse or fail to respond to current treatments. While conventional chemotherapy achieves response rates of over 50%, relapse remains common, highlighting the urgent need for more durable and effective treatment options.
ATAC Technology Platform
Heidelberg Pharma's ADC approach combines the specificity of antibodies with the efficacy of toxins to fight cancer. Selected antibodies are loaded with cytotoxic compounds, called payloads, that are transported into diseased cells where the toxins unleash their effect and kill the diseased cells. The company has built up an ADC toolbox that overcomes tumor resistance via numerous pathways and addresses different types of cancer using various antibodies.
The biological mechanism of action of amanitin represents a new therapeutic modality and is used as a compound in the Amanitin-based ADC technology. The goal is to develop targeted and highly effective ADCs for the treatment of a variety of malignant hematologic and solid tumors.