On July 13, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported plans to focus on its emerging pre-clinical and early clinical pipeline and to realign its capital resources to drive these efforts (Press release, CytomX Therapeutics, JUL 13, 2022, View Source [SID1234616642]).

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"With the Probody therapeutic platform, CytomX has pioneered a new and strategic field of biologics drug discovery and development. Our leadership position will continue as we incorporate learnings from our broad clinical experience and advance our next wave of innovative product candidates," said Sean McCarthy, D.Phil., chief executive officer and chairman at CytomX Therapeutics. "In the context of the challenging current investment climate for biotechnology, we are making a series of changes to ensure CytomX remains well positioned for the future. We are restructuring the organization to focus on our earlier stage capabilities and programs, as well as our partnerships, leveraging our multi-modality Probody platform to accelerate the development of next-generation therapeutics to destroy cancer differently," continued Dr. McCarthy.

Business & Strategy Updates

Strategic realignment to accelerate early-stage pipeline development, including partnered programs, and extend cash runway:
The Company is restructuring its business to prioritize internal investments in its emerging pre-clinical and early clinical pipeline, resulting in a reduction to its workforce, primarily development and general and administrative staff, by approximately 40%.
These changes are expected to extend the Company’s cash runway into 2025.
CytomX is maintaining its robust research, translational, and early development organizations to support ongoing internal pipeline efforts with two Investigational New Drug Applications (INDs) planned for 2023.
CytomX remains committed to its current alliances with AbbVie, Amgen, Astellas, and Bristol Myers Squibb, which include the clinical-stage programs CX-2029, CX-904, and BMS-986249.
The Company will continue to emphasize future business development and new alliance formation as an integral part of its corporate strategy.
Dr. McCarthy continued, "This difficult decision to restructure CytomX regrettably leads to the departure of many valued team members who have been dedicated to our vision and mission and whose contributions have been critical to the Company’s success to date. On behalf of myself and the Board of Directors, we thank them for their efforts and wish everyone the very best in their future endeavors."

Overview of CytomX Pipeline of Conditionally Activated Product Candidates:
New Emerging INDs

Interferon alpha-2b (IFN alpha-2b) program – CX-801 is a wholly-owned IFN alpha-2b Probody. Based on preclinical activity and tolerability studies, CX-801 demonstrated a wide therapeutic index with an enhanced tolerability profile versus unmasked IFN, without compromising its potent antitumor effects. CX-801 has broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. An IND submission is planned in 2023.
EpCAM-directed ADC program – CX-2051 is a wholly-owned conditionally activated ADC directed toward EpCAM, with potential applicability across multiple EpCAM-expressing epithelial cancers. An IND submission is planned in 2023. CX-2043, CytomX’s DM21-conjugated EpCAM-directed ADC, is being deprioritized.
Current Clinical Programs

T-cell-engaging bispecific (TCB) EGFRxCD3 program – CX-904 is designed to target both the epidermal growth factor receptor (EGFR) on cancer cells and the CD3 receptor on T cells. CX-904 is currently in a Phase 1 dose-escalation study and is part of CytomX’s partnership with Amgen.
CD71-directed antibody-drug conjugate (ADC) program – CX-2029 has shown encouraging activity in patients with squamous non-small cell lung cancer in a Phase 2 expansion study. Enrollment in this cohort is complete and a data update is expected in the second half of 2022. CX-2029 is part of CytomX’s partnership with AbbVie.
Ipilimumab Probody program – BMS-986249 and BMS-986288 are Probody versions of the CTLA-4-targeting antibodies, ipilimumab and non-fucosylated ipilimumab, respectively – both being developed by Bristol Myers Squibb. BMS-986249 is being evaluated in a randomized Phase 2 study in combination with nivolumab in patients newly diagnosed with advanced melanoma. This novel combination is also being studied in advanced hepatocellular carcinoma, castration-resistant prostate cancer, and triple-negative breast cancer. BMS-986288 is being evaluated as monotherapy and in combination with nivolumab in a Phase 1 study in advanced solid tumors.
CD166-directed ADC program – Praluzatamab ravtansine demonstrated single-agent activity in a Phase 2 study in heavily-pretreated patients with advanced hormone receptor-positive, HER2-non-amplified breast cancer. As announced on July 6, 2022, based on results of a three-arm Phase 2 study, CytomX is deprioritizing internal investment in this program and will be seeking a partnership to further advance the asset.
Anticipated Future Pipeline Milestones

2022

Data update for CX-2029 from the ongoing Phase 2 expansion study in patients with squamous non-small cell lung cancer
Updated data from the Phase 2 study of praluzatamab ravtansine in advanced breast cancer
2023 – second half

IND submissions for CX-801 and CX-2051
Conference Call & Webcast
CytomX management will host a conference call and a simultaneous webcast today at 6:00 pm ET (3:00 pm PT) to discuss these updates. Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. A live webcast of the call can be accessed via the Events and Presentations page of CytomX’s website at View Source