Genomic instability is a hallmark of cancer, and represents a targetable vulnerability, yet is underdeveloped as a therapeutic area. The central goal of this Phase 2 program is to complete the early preclinical development of a new class of new cancer therapeutics that uniquely target RAD51, delivering effective cancer-cell selective therapy in subsets of biomarker-defined leukemia and lymphoma. Two key challenges in current cancer therapy are overcoming tumor cell evolution that drives cancer progression and therapy resistance; and minimizing the side effects due to off-target toxicity. Therapies that target genomic instability mechanisms have the potential to meet these critical clinical challenges. In recent years, the B-cell specific DNA mutase/recombinase Activation Induced Cytidine Deaminase (AID) has been implicated as a driver of oncogenic genomic instability. While its expression is normally restricted to activated, germinal center B-cells, AID is also overexpressed in a range of human neoplasms, especially B-cell non-Hodgkin's lymphomas (NHL) and chronic lymphocytic leukemia (CLL). Cyteir Therapeutics, Inc., in partnership with The Jackson Laboratory, has demonstrated the feasibility of targeting RAD51 in these cancers and has developed new lead candidate compound. Our novel therapeutic approach takes advantage of the discoveries that: (1) AID is both a biomarker and a DNA damage driver, creating widespread DNA double strand breaks (DSBs) throughout the genome; and (2) RAD51 has a unique role in the repair of these malignant, AID-induced DSBs and is, therefore, critical for viability in transformed, AID+ cells. Cyteir's lead RAD51 inhibitor is potent, highly selective for cells that are AID+, effective against NHL and CLL cells in vitro and in vivo, and is extremely well tolerated in preclinical animal models.
The aims of this Phase 2 study are to complete early preclinical testing and development required prior to the filing of investigational new drug (IND) application and commencement of phase I clinical trials. We will develop a clinical dosage form for our lead compound, carry out single- and multiple-dose tolerability and range finding studies, establish pharmacokinetics and toxicokinetics for the clinical dose form, and generate comprehensive comparative efficacy data using human- to-mouse xenograft models of NHL and CLL. We have assembled an impressive team of academic and industry leaders, complemented by an advisory panel of top thought leaders, to advance this program and build the Cyteir drug discovery engine. One of our strengths is the continuing partnership with The Jackson Laboratory, providing both an academic foundation for our R&D efforts and a platform of unique in vivo testing technologies to enable rapid translation to the clinical phase. Our commercialization plan for this program calls for completion of the proposed preclinical studies, commencement of clinical trials and partnership or out licensing after either phase I or phase II trials, to create company and investor value and generate revenue to continue building a sustainable drug development pipeline.
There are roughly 137,000 new cases of lymphoma, leukemia and multiple myeloma in the United States annually, and in excess of 54,000 deaths. Although therapies have improved somewhat, these cancers are still increasing in incidence worldwide. Owing to the rigors of chemotherapy, there are significant long-term health concerns relating to survivorship. The conventional first-line therapies for lymphoid cancers can produce difficult and sometimes life threatening side effects, but are often non-curative. Thus, there is a significant, unmet need for new therapeutics that effectively treat the cancer but elicit fewer side effects. Our novel therapeutic strategy promises to selectively target lymphoid cancer cells for self-destruction and minimize the side effects associated with conventional chemotherapies. Given the continued increase in global lymphoma and leukemia incidence, and the insufficiency of current therapies, there is a significant clinical and commercial market for effective and selectiv therapeutics, both domestically and worldwide. In this context, we have potential to positively impact a substantial cancer patient population, and to improve the quality of life of many who require chemotherapy treatment.
