The 2022 American Association for Cancer Research (AACR) annual meeting will be held from April 8 to 13, 2022 in New Orleans. Along with the American Society of Clinical Oncology (ASCO) Annual Meeting and the European Society of Medical Oncology (ESMO) Annual Meeting, the AACR Annual Meeting is one of the most-attended oncology conferences in the world. It is the annual focus of the cancer research community. Coherent Biopharma (CBP) will present two research posters at the conference. These two posters listed below describe in vitro/in vivo, preclinical activities, evaluation of target-receptor expression levels, and correlation between receptor expression level and anticancer response:
CBP-1008 shows excellent efficacy and desirable drug safety profile in preclinical models
Coherent Biopharma’s leading pipeline product, CBP-1008 consists of two ligands, targeting Folate Receptor Alpha (FRα) and Transient Receptor Potential Vanilloid 6（TRPV6）receptors respectively. Folate Receptor Alpha (FRα) is the high affinity folate transporter and is highly expressed in ovarian, lung and breast cancer. Transient Receptor Potential Vanilloid 6 (TRPV6) calcium channel characterized by its high calcium selectivity is up-regulated in a variety of cancers, such as breast, ovarian and prostate cancer.
Preclinical results showed that FRα+/TRPV6+ tumor responds better than tumors which have at least one marker negative. Within the FRα+/TRPV6+ tumors, tumor growth inhibition (TGI) correlates well with IHC score of FRα. At the upcoming AACR annual meeting, CBP team will release the preclinical research results in a poster, abstract number: 1819:
Compared to ADCs, Bi-XDCs possess several desired physiochemical characteristics like small molecular weight, unambiguous molecular form and structure, straightforward chemical synthesis with better quality control. In this poster, results demonstrated Bi-XDCs’ highly desired PK/PD profiles such as high binding affinity & ability to overcome competition, fast tissue penetration and rapid enrichment in tumor cells, superior in vivo efficacy correlating to receptors’ expression level, fast clearance from normal tissue and blood circulation and desirable drug safety profile.
Clinically, the Ib clinical trial of CBP-1008 in more than a dozen hospitals has achieved promising results in treating patients with advanced recurrent ovarian cancer for which no standard of cares. A phase II clinical trial for target-enriched, advanced, recurrent ovarian cancer patients planned.
Evaluation of FRα/TRPV6 Expression in Gynecological Cancer
CBP’s first Bi-XDC clinical pipeline product CBP-1008 takes advantage of dual-targeting with Folate Receptor Alpha (FRα) and Transient Receptor Potential Vanilloid 6 (TRPV6). Both markers are highly expressed in ovarian cancer, an evaluation of expression of FRα and TRPV6 in a panel of gynecological cancers is of great importance. Using validated immunohistochemistry (IHC) assays, expression of both FRα and TRPV6 were evaluated in 200+ FFPE samples. Researchers at Clinical Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, and Coherent Biopharma will present “Evaluation of FRα/TRPV6 Expression in Gynecological Cancer” under Abstract number 6275.
Our results shows FRα and TRPV6 are both highly expressed in gynecological cancer. However, expression levels of FRα and TRPV6 in different histological subtypes of ovarian cancer are various. FRα shows highest expression in high grade serous ovarian cancer (HGSC); expressions in clear cell ovarian cancer (CCC) and low grade serous ovarian cancer (LGSC) are much lower. Whereas TRPV6 shows highest expression in CCC. Co-expression rate of FRα and TRPV6 is 51% in ovarian cancer, indicating synergetic effect for molecularly-targeted therapies for those two targets. This study result further verifies CBP’s clinical effort in treating patients with recurrent ovarian cancer. Preliminary results of CBP-1008 studies have shown potent anticancer activities and acceptable safety profile.