On March 6, 2024 Heidelberg Pharma AG (FSE: HPHA), a clinical stage biotech company developing innovative Antibody Drug Conjugates (ADCs) reported that it will be presenting first efficacy data on its Phase I clinical trial with ATAC candidate HDP-101 as well as preclinical data on other drug candidates from its proprietary ADC technology platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held in San Diego, California on the 5 – 10 April 2024 (Press release, Heidelberg Pharma, MAR 6, 2024, View Source [SID1234640855]).
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Details of the conference and poster presentations are as follow:
Late Breaking Research: Poster: Multimeric linker-exatecan-based ADC targeting Guanylyl cyclase C (GCC) as novel therapeutic modality for treatment of colorectal cancer
Abstract number:
LB059, Section 53
Session:
Late-Breaking Research: Experimental and Molecular Therapeutics 1
Presentation time:
7 April 2024, 1:30 pm – 5:00 pm PDT
Speaker:
Dr. Sarah-Jane Neuberth
Link to abstract:
Late-breaking abstracts are available on 5 April 2024.
Clinical Trials 1: Poster: The anti-BCMA antibody-drug conjugate HDP-101 with a novel amanitin payload shows promising initial first in human results in relapsed multiple myeloma
Abstract number:
CT067, Section 48
Session:
Phase I Clinical Trials 1
Presentation time:
8 April 2024, 9:00 am – 12:30 pm PDT
Speaker:
Dr. András Strassz
Link to abstract:
Clinical-trials abstracts are available on 5 April 2024.
Poster: HDP-102 – a CD37-targeting Amanitin-based-ADC for the treatment of NHL – non-clinical data package
Abstract number:
1865, Section 22
Session:
Antibody-Based Technologies and New Inhibitors
Presentation time:
8 April 2024, 9:00 am – 12:30 pm PDT
Speaker:
Dr. Sarah-Jane Neuberth
Link to abstract:
View Source!/20272/presentation/8116
The poster presentation details preclinical data on ATAC candidate HDP-102, an Amanitin-based-ADC that is directed against the target molecule CD37. CD37 is found exclusively on immune cells, primarily B cells, and is overexpressed in malignant B-cell diseases such as Non-Hodgkin’s lymphoma (NHL).
HDP-102 has demonstrated excellent anti-tumor efficacy in in-Vivo-studies after a single administration and initial preclinical studies display good tolerability, indicating HDP-102 as a potential new treatment option for patients with NHL.
Poster: Liver toxicity of Amanitin-based Antibody drug conjugates (ATACs) is caused by unspecific uptake of the ATAC into liver cells
Abstract number:
7183, Section 24
Session:
Pharmacology and Pharmacogenetics
Presentation time:
10 April 2024, 9:00 am – 12:30 pm PDT
Speaker:
Dr. Christian Orlik
Link to abstract:
View Source!/20272/presentation/8047
The use of antibody-drug conjugates (ADCs), which combine high efficacy of cytotoxins with the specificity of antibodies, is still often limited by side effects. These include the binding of the ADCs independently of the target antigen (off-target toxicity mechanisms), which is responsible, for example, for the premature release of the transported cytotoxins.
The study details, the off-target toxicity mechanisms of ADCs that use amatoxins (RNA polymerase II inhibitors) as payload, so-called ATACs, were deciphered. The data reveals that liver toxicity is caused by non-specific uptake of the ATACs into liver cells. The substitution of two amino acids of the antibody (LALA mutation) that are responsible for the unspecific binding of the ATAC reduces the off-target toxicity. This significantly increases the tolerability of ATACs while leaving the antitumor efficacy unaffected, resulting in an improved therapeutic window of ATACs.