Pivot Uterine & Triple-Negative Breast Cancer Portfolio

Pyrrolobenzodiazepine dimers (PBDs) Provide a Novel “Synthetic Lethal” Approach for the Treatment of Resistant Cancers such as Metastatic Endometrial, Triple-Negative Breast, and/or Metastatic Colorectal Cancers:

Pivot’s novel PBDs are active in cancers associated with the loss of tumor suppression, DNA repair and/or homologous recombination gene function, which are responsible for some of the refractory nature of cancers such as metastatic endometrial, triple-negative breast and/or metastatic colorectal cancers through a novel DNA Damage Response (DDR) pathway. Furthermore, PBDs also exhibit ‘synthetic lethality’, which results in its ability to promote cytotoxicity and death of refractory cancers that have mutations in tumor suppressor functions.

There are no effective treatments available for tumors that have “functional deficiencies” in genes like BRCA1 or BRCA2 (breast cancer); DNA mismatch repair (colon, endometrial, glioblastoma and bladder); PTEN (colon, endometrial, leukemia and breast) and ERCC1 (melanoma). Such tumors remain a highly unmet clinical need and currently few drugs are under development that would specifically target tumors with such ‘loss of function’ in tumor suppressor genes.

Pivot has identified several ‘synthetic lethal’ (SL) relationships in tumor suppressor gene functions, and its proprietary and novel small molecule anticancer drug candidates from the pyrrolobenzodiazepine dimer (PBD) class of drug candidates, that create synthetic lethality in tumor cells that have loss of function in tumor suppressor genes by inhibition of DNA replication in such impaired cells. Thus, these novel PBDs are poised to treat genetically- and/or epigenetically-resistant cancers that result from a loss of function in tumor suppressor genes and/or DNA mismatch repair gene functions in cancers such as refractory/relapsed metastatic endometrial, triple negative breast and/or metastatic colorectal cancers.
* PBDs (pyrrolobenzodiazepine dimers) are DNA Damage Response (DDR) inhibitors that can treat ‘genetically resistant’ women’s cancers
- Metastatic Endometrial Cancer (mEC)
- Metastatic Colorectal Cancer (mCRC)
- Triple-Negative Breast Cancer (TNBC)

* Chemotherapeutics and DNA targeting agents generate large revenues (sales numbers prior to patent expiration & generic competition)
- Revlimid (Lenalidomide) generated over $4.98 Billion in 2014
- Abraxane (protein-bound delivery system for paclitaxel) generated $649 MM in sales in 2013
- Taxotere (Docetaxel) generated $2.9 Billion in net sales in 2009 for Sanofi-Aventis