CytomX Therapeutics, Inc. products

CytomX is developing CX-2009, a Probody drug conjugate (PDC) conjugated with DM4, a highly potent cytotoxic drug, targeting CD166, also known as ALCAM. CD166 is a molecule widely and highly expressed on solid tumor cells and previously considered “undruggable” given its expression on normal tissues. In preclinical studies, Probody drug conjugates targeting CD166, have led to complete regressions in models of breast and lung cancer at therapeutically relevant doses, and are well tolerated in non-human primates. Updated Phase 1 results of CX-2009 in selected tumor types were announced at ASCO 2020  demonstrating durable clinical activity in HER2 negative (HER2-) breast cancer. In December 2019, CytomX initiated a Phase 2 expansion study in patients with hormone receptor (ER, PR) positive, HER2- breast cancer.

CX-072 is a wholly owned PD-L1-targeting Probody therapeutic for the treatment of cancer. Initial clinical data presented at the ASCO and ESMO 2018 Annual Meetings showed that CX-072 demonstrated tolerability and anti-tumor activity, while reducing activation of the immune system outside the tumor. Initial clinical translation data presented at SITC confirmed that CX-072 is unmasked, activated and has biological activity in patient tumors while remaining predominantly masked and intact in circulation. Following a recent program and portfolio prioritization, CytomX has also made the strategic decision to terminate the Phase 2 trial of the anti-PD-L1 Probody CX-072 in combination with Yervoy® (ipilimumab) in melanoma. This allows CytomX to focus on its potential first-in-class assets, including the combination of CX-072 and CX-2009.

CytomX and AbbVie are co-developing CX-2029, a PDC directed against CD71, the transferrin receptor that is highly expressed on a number of solid and hematologic tumors, as well as many normal tissues. CytomX is evaluating CX-2029 in a Phase 1/2 clinical trial as monotherapy. CD71 is an excellent “internalizer,” which has the potential to efficiently deliver toxin to tumor cells. Historically, CD71 has not been widely pursued as a target given its expression on normal tissues and potential for causing toxicities. CytomX presented initial Phase 1 data at ASCO 2020 validating CD71 as a first-in-class oncology target with encouraging clinical activity observed. CytomX is preparing to advance the CX-2029 into 4 dose-expansion cohorts in patients with head and neck cancer, squamous non-small cell lung cancer, esophageal carcinoma, and diffuse large B cell lymphoma.

CX-188 is our wholly owned PD-1-targeting Probody therapeutic. As with anti-PD-L1 therapies, PD-1 monotherapy and combinations have been associated with significant toxicities. Our preclinical studies have shown that CX-188 has the potential for an improved therapeutic index relative to PD-1 antibodies. The IND for CX-188 was cleared by the FDA. Following a program and portfolio prioritization, CytomX has decided to indefinitely postpone the clinical trials of CX-188, a PD-1 Probody. CytomX may elect to initiate clinical trials of CX-188 in the future.