CytomX slumps as BMS bails on 3 partnered projects

Biotech also puts a PD-1 inhibitor candidate on an indefinite hold. (CytomX)

Amid an R&D update from CytomX is the news that Bristol-Myers Squibb has abandoned three programs, putting pressure on the biotech’s share price.

Investors appear to have voted with their feet after the company revealed that BMS had dropped three discovery-stage projects from their long-established $3.6 billion collaboration, along with the news that it had decided to postpone trials of PD-1-targeting Probody drug CX-188 indefinitely due to a “portfolio prioritization.”

Shares in the San Francisco biotech fell by almost a third in the wake of the R&D update amid fears that BMS’ big takeover of Celgene could mean further cuts to its early-stage pipeline. However, CytomX insisted that the move doesn’t affect other discovery and development activities in the partnership.

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While it's never wise to count the backloaded payments in such deals until the "biobuck" eggs have hatched, it’s worth noting that each of the three programs was potentially worth up to $448 million through various development, regulatory and commercial milestones plus royalties, according to the 2017 agreement between the two companies.

It’s also not the first time CytomX has had projects cut by a big pharma partner. Last year, Pfizer ducked out of a longstanding collaboration with the biotech on antibody-drug conjugates for cancer, although it still has active projects in place with Amgen and AbbVie along with BMS, pocketing substantial upfront payments in each case.

Analysts at Jefferies said the sell-off was "overdone" and "unwarranted," however, pointing to encouraging results with two of CytomX's wholly owned programs.

Indeed, CytomX was at pains to emphasize the other elements in its R&D update—including BMS’ decision to advance CTLA-4 Probody therapeutic BMS-986249 into a phase 1/2 trial that should generate results before the end of the year—but that was overshadowed by investor jitters about the cuts.

It also highlighted the progress made with its two lead programs, namely anti-PD-L1 Probody CX-072 and CX-2009, billed as a first-in-class CD166-targeting Probody drug conjugate.

Probody therapeutics are designed to take advantage of conditions in the tumor microenvironment to enhance the tumor-targeting features of an antibody, all the while reducing its impact on healthy tissues, and thus adverse events.

New data from a phase 1/2 study of CX-072 in patients with triple negative breast cancer (TNBC), undifferentiated pleomorphic sarcoma (UPS), cutaneous squamous cell carcinoma (cSCC) and anal squamous cell carcinoma (SCC) revealed “a preliminary pattern of anti-cancer activity generally consistent with historical data for other PD inhibitors," and favorable safety profile, according to the biotech.

A combination arm of the trial in which CX-072 was given alongside BMS’ CTLA4 inhibitor Yervoy (ipilimumab) revealed that 4 of 19 patients (21%) had a response, including one complete response and two confirmed partial responses as of the Feb. 6 cutoff date.

Jefferies said the data show "signs of safety differentiation and durable response from CX-072."

Meanwhile, CytomX said it has completed a dose escalation trial of CX-2009 in patients with breast, castration-resistant prostate, cholangiocarcinoma, endometrial, head and neck, non-small cell lung and ovarian cancers, with evidence of tumor activity—including tumor shrinkage—at higher doses.

The drug also seemed to work in subjects with cancer resistant to PD-1/PD-L1 inhibitors, according to the company, although some patents have ocular toxicity that has required the use of prophylactic measures.

“Several years ago, we set out to reimagine and reinvent therapeutic antibodies so we could make a big difference for cancer patients,” said Sean McCarthy, D. Phil, CytomX’s president and CEO.

“The emerging clinical data from our two lead programs support the utility of our Probody technology in achieving this vision and sets us on a path to building the long-term, integrated biotechnology company we have always envisaged.”

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