Germany-based Eisbach Bio GmbH has published a US patent application (US20260216344A1) covering allosteric small molecule inhibitors of ALC1 (CHD1L; Chromodomain-helicase-DNA-binding protein 1-like) and their combination with PARP inhibitors (PARPi) for treating proliferative diseases, including BRCA-deficient cancers. The application, published July 30, 2026, expands intellectual property protection around Eisbach Bio's clinical-stage ALC1 inhibitor program, describing an allosteric strategy designed to enhance the activity of PARP inhibitors and potentially overcome acquired PARPi resistance.
A Novel Allosteric Target Within ALC1
ALC1 an ATP-dependent chromatin remodeling enzyme implicated in DNA damage repair and tumor progression that is recruited to DNA damage sites through its PAR-binding macrodomain following PARP activation. The company said its inventors identified a previously undescribed allosteric binding pocket within the ATPase domain of ALC1, formed by amino acid residues 101–219 of the protein, which is spatially distinct from the ATP-binding site. Compounds targeting this pocket inhibit ALC1's nucleosome remodeling activity without competing with intracellular ATP — an advantage the filing explicitly attributes to the allosteric mechanism.
Cell-based experiments described in the application suggest the inhibitors increase PARP retention at DNA damage sites, a hallmark associated with enhanced PARP trapping. The company reported that combining ALC1 inhibitors with veliparib, a weak PARP-trapping agent, produced synergistic cancer cell killing in BRCA1-deficient SUM-149-PT cells that exceeded the effect of either agent alone.
The application seeks protection for the compounds themselves, their therapeutic use alone and in combination with PARP inhibitors, and related PROTAC degraders. Intended therapeutic applications span BRCA1/2-deficient tumors, homologous recombination-deficient tumors more broadly, tumors with elevated ALC1 or PARP expression, and specifically named indications including hepatocellular carcinoma, breast cancer, ovarian cancer, prostate cancer, and colorectal cancer. The filing also describes bifunctional proteolysis-targeting chimera (PROTAC)-type compounds that link the ALC1 inhibitor to an E3 ubiquitin ligase recruiter, extending the platform into targeted protein degradation.
Pipeline and Competitive Context
Founded in 2019 as a spinout from Ludwig Maximilian University (LMU) Munich's Biomedical Center, Eisbach Bio is translating research from the laboratory of chromatin biologist Andreas Ladurner, whose work on PARP signaling and the ATP-dependent chromatin remodeler ALC1 underpins the company's proprietary ALLOS drug discovery platform. The ongoing Phase 1/2 development of EIS-12656 represents one of the earliest clinical tests of that research in patients with homologous recombination-deficient solid tumors.
The application is a continuation of a US national phase entry (Ser. No. 18/039,740) originating from PCT/EP2021/084089, which itself claims priority to a European application filed December 3, 2020, giving the underlying technology a priority date now approaching six years. The filing remains a pending application; no grant date has been issued.