PARP inhibitors have dramatically altered therapy options for cancer patients with BRCA1/2 mutations, leveraging the Achilles heel of specific tumors. But dose-limiting toxicity has resulted in recent approval withdrawals in some indications, and resistance to PARPi emerges frequently. Eisbach Bio is tackling this complex problem with a transformative small molecule EIS-12656 that is a differentiating approach for homologous recombination deficiency (HRD) tumors. It targets ALC1, a key molecular DNA damage repair machine that acts in concert with PARP. ALC1 inhibition disrupts mutant cancer cells' DNA repair mechanisms, leading to their demise, while sparing non-damaged cells. And unlike the...

Read More

PARP inhibitors have dramatically altered therapy options for cancer patients with BRCA1/2 mutations, leveraging the Achilles heel of specific tumors. But dose-limiting toxicity has resulted in recent approval withdrawals in some indications, and resistance to PARPi emerges frequently. Eisbach Bio is tackling this complex problem with a transformative small molecule EIS-12656 that is a differentiating approach for homologous recombination deficiency (HRD) tumors. It targets ALC1, a key molecular DNA damage repair machine that acts in concert with PARP. ALC1 inhibition disrupts mutant cancer cells' DNA repair mechanisms, leading to their demise, while sparing non-damaged cells. And unlike the members of the PARP enzyme family that have broad cellular functions, ALC1 is specifically involved in DNA damage repair. Thus, ALC1 inhibition allows for a highly targeted therapy, circumventing many of the issues linked to PARP inhibition. EIS-12656 has outstanding tolerability and preclinical efficacy, even in cells resistant to clinical PARP inhibitors. Our initial target indications are breast, ovarian, pancreatic, and prostate cancers (including brain metastases) marked by mutations in BRCA1/2 and other DNA-damage repair genes. Synergistic support by MDACC's Cancer Focus Fund and CPRIT for our MDACC Phase II trial will be used to investigate EIS-12656 as monotherapy, transforming therapy for HRD patients in Texas and beyond.

Read Less