On September 7, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported that the Company presented advances within its conditionally-activated ADC portfolio, including the next generation EpCAM-ADC, CX-2051, at the World ADC conference taking place September 6-9, 2022, in San Diego, CA (Press release, CytomX Therapeutics, SEP 7, 2022, View Source [SID1234619223]).
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"The momentum in the field of ADC therapeutics is incredibly exciting and holds great promise for the innovation and development of novel oncology therapeutics. Our pioneering work and experience in applying our versatile Probody platform to the ADC modality has the potential to expand the universe of addressable targets and to further increase the therapeutic window of future molecules entering the clinic," said Marcia P. Belvin, Ph.D., senior vice president and head of research at CytomX. "CX-2051, our EpCAM-targeted, conditionally activated ADC, is strategically tailored to optimize the therapeutic index for systemic treatment of EpCAM-expressing epithelial cancers, which is an area of high unmet need where, to date, efforts have not been successful due to dose-limiting toxicities."
"Our strategy with CX-2051 is to match payload mechanism of action with tumor sensitivity, and we have selected the topoisomerase-1 inhibitor, camptothecin, as the payload for our newest ADC," Dr. Belvin continued. "Topoisomerase-1 inhibitor-conjugated ADCs are showing impressive clinical activity, and importantly, the safety profiles of camptothecin and its derivatives have been well characterized. Additionally, two camptothecin derivatives, irinotecan and topotecan, have been approved by the U.S. Food and Drug Administration for clinical use – irinotecan for pancreatic and colorectal cancer, and topotecan for ovarian, cervical, and small cell lung cancer. We plan to pursue multiple indications with this new therapeutic candidate and look forward to progressing to an investigational new drug application submission in the second half of 2023."
Presentation highlights include:
Review of clinical activity for the conditionally activated ADCs CX-2029 and praluzatamab ravtansine (CX-2009), targeting CD71 and CD166, respectively. CD71 and CD166 have historically been inaccessible targets for traditional ADCs due to their high expression levels on normal tissues. The data presented demonstrate clinical anti-cancer activity and a therapeutic window for these previously undruggable targets.
The molecular structure of CX-2051, a masked, conditionally activated, EpCAM-targeting ADC with a next generation camptothecin-based linker payload. CX-2051 highlights the potential for CytomX’s Probody technology to unlock a new ADC target (EpCAM/Trop-1), which is a target that has previously yielded promising clinical results only through locally administered therapies.
CX-2051 preclinical data indicating strong anti-cancer activity and tolerability with a favorable predicted therapeutic index.
The full presentation is available at the following link:
Tailoring the Selection of Target, Payload, & Tumor Type to Maximize the Therapeutic Index of Conditionally Activated ADCs
Marcia P. Belvin, Ph.D., Senior Vice President, Head of Research, CytomX Therapeutics
Presentation Link