Eisbach Bio gets FDA nod for IND application of EIS-12656, first allosteric ALC1 inhibitor

Eisbach Bio GmbH, a clinical-stage biotechnology company based in Martinsried, Germany, has received clearance from the United States Food and Drug Administration (FDA) for its investigational new drug (IND) application for EIS-12656. This innovative drug is a first-in-class, orally available, and blood-brain barrier-penetrant allosteric inhibitor targeting ALC1 (CHD1L), a crucial player in DNA repair mechanisms.

EIS-12656 focuses on cancers deficient in homologous recombination repair. The drug's anticipated superior safety profile is expected to enable new combination therapies, potentially surpassing the limitations faced by current PARP inhibitors in treating hard-to-treat cancers. Eisbach Bio plans to start enrolling patients in clinical trials by the second quarter of 2024.

The announcement was made on May 6, 2024, by Eisbach Bio. EIS-12656 functions by inhibiting the chromatin helicase ALC1 through allosteric mechanisms, thereby suppressing genome reorganization triggered by DNA damage. This mechanism leads to the trapping of ALC1 within the chromatin, resulting in the targeted killing of cancer cells.

EIS-12656 has shown significant inhibition of tumor growth in preclinical models, including when used in combination with standard-of-care therapies. Its allosteric mechanism of action provides a level of selectivity that enhances safety, as demonstrated in preclinical trials.

According to Dr. Adrian Schomburg, Founder and CEO of Eisbach Bio, "EIS-12656 selectively targets tumors without affecting normal tissues. Our clinical study will also explore combination therapies previously limited due to combinatorial toxicity."

The discovery of EIS-12656 stems from the pioneering research led by Eisbach founder Prof. Andreas Ladurner. His team found that PARP effects in cancer cells depend on chromatin remodeling by ALC1. Utilizing this insight, Eisbach designed a first-in-class, once-daily small molecule therapy that directly targets cancer genome reorganization induced by DNA damage, specifically the PARP-activated helicase ALC1.

The upcoming Phase 1/2 clinical trial will be an open-label study evaluating the safety, tolerability, and efficacy of EIS-12656 in patients with genetically defined advanced solid tumors. The study will be led by Principal Investigator Dr. Timothy A. Yap, Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. The trial will begin with dose escalation of EIS-12656 monotherapy, followed by dose expansion modules and evaluation in patients who are progressing under PARP inhibitor treatment.

Eisbach Bio is a leader in precision oncology, focusing on developing allosteric drugs that selectively disrupt essential molecular machines involved in tumor genome reorganization. By leveraging genetic vulnerabilities and its proprietary ALLOS platform, Eisbach is pioneering first-in-class therapies designed to reduce side effects.