On November 23, 2020 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported the publication of clinical data that provides molecular insight into TRC102’s mechanism of action and patient populations most likely to respond to treatment (Press release, Tracon Pharmaceuticals, NOV 23, 2020, View Source [SID1234571567]). The article, entitled, "Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment," highlights the clinical features and tumor biology of an exceptional responder patient treated with TRC102 at the National Cancer Institute (NCI): View Source
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The patient was diagnosed with metastatic and highly refractory colorectal cancer and received temozolomide (Temodar) and TRC102. Following treatment, the patient was considered an exceptional responder through the achievement of a near compete response lasting 45 months at the most recent follow-up. Detailed molecular analyses of the patient’s tumor showed silencing of DNA repair pathways that may have resulted in sensitivity to the inhibition of DNA base excision repair pathway by TRC102. Specifically, MGMT expression was silenced by promoter methylation, and RAD50, a mediator of DNA double strand break repair, was silenced by genetic mutation and loss of heterozygosity. The publication authors hypothesized that the combination of Temodar and TRC102 was effective because all necessary DNA repair pathways were compromised genetically or through the activity of TRC102. MGMT expression was also assessed in biopsies from 11 colorectal patients who subsequently enrolled in an expansion cohort, one of which demonstrated a partial response. The tumor associated with the partial response did not express MGMT, whereas each of the 10 tumors that did not respond to therapy expressed this enzyme robustly.
TRC102 is being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the NCI through a Cooperative Research and Development Agreement. TRC102 was also evaluated in a Phase 2 trial in combination with Temodar chemotherapy in 19 patients with progressive or recurrent glioblastoma who progressed following Temodar and external beam radiotherapy. Extended survival was observed in two patients for more than two years, both of whom demonstrated activation of the DNA base excision repair pathway and showed hyperactivation of DNA damage response genes prior to treatment with TRC102.
"The Cancer Cell publication supports our belief that patients whose cancers are dependent on the DNA base excision repair pathway to repair DNA damage from chemotherapy may be particularly sensitive to the pharmacologic effects of TRC102," said James Freddo, M.D., Chief Medical Officer of TRACON. "The NCI data are also consistent with the results from the Phase 2 trial of Temodar and TRC102 in refractory glioblastoma. We remain committed to developing TRC102 in collaboration with the NCI and believe that the data generated to date provide strong rationale for studying TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma."
About TRC102
TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA). TRC102 was granted orphan drug designation by the US FDA for the treatment of malignant glioma in 2020. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical-trials.
About Malignant Glioma and GBM
GBM (also called glioblastoma) is a fast-growing malignant glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults (12,630 men and 10,280 women) are diagnosed with brain and other nervous system cancer annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors.