The two companies had partnered back in 2016 in a deal worth up to $500m to co-develop and co-commercialise ADCs against a target called CD71. This molecule is highly expressed in many types of solid cancers, but is often found in healthy tissue as well, making it tough to target using ADCs and other drugs.
CytomX’s ADC technology, called Probody, is designed to be much more selective than other ADCs. The company’s ADCs are equipped with a ‘mask’ that stops the drug from binding to CD71 in healthy tissue, where there are few proteases around to remove the mask. However, once the drug reaches the tumor microenvironment, high amounts of nearby proteases unmask the ADC. The drug is then able to bind to and destroy tumor cells expressing CD71.
The 2016 collaboration with AbbVie led to the candidate CX-2029, which is in a phase 1 trial for the treatment of head and neck cancer, squamous non-small cell lung cancer, and squamous esophageal carcinoma. According to results released in January 2023, one of the drug’s most encouraging results was a 21% objective response rate in squamous esophageal cancer. However, many patients experienced anemia as a side effect, which had to be managed with transfusions, dose delays, and reductions.
Strategic decision
Following these results, AbbVie had the option to take the candidate into further clinical development. In its recent 2022 earnings report, however, CytomX revealed that AbbVie decided not to continue the clinical development of CX-2029 for “strategic portfolio reasons,” and the collaboration would come to an end.
“While we are disappointed with AbbVie's decision, in our work to date on CD71, we have pushed new scientific boundaries and demonstrated for the first-time that targeting CD71 with an antibody drug conjugate can lead to tumor shrinkage in late-stage cancer patients,” said Sean McCarthy, CytomX's CEO and chairman in an investor call.
As a consequence of AbbVie’s decision, CytomX has regained full rights to CD71 as a target. The biotech is also in the process of negotiating with AbbVie for regaining full rights to CX-2029.
“Going forward, CytomX will be evaluating next steps for CX-2029 while also continuing to pursue next-generation strategies targeting CD71,” stated McCarthy. “We would like to thank AbbVie for their partnership in helping us bring CX-2029 and our CD71 program to this stage in its development.”
Ongoing collaborations
Nonetheless, CytomX emphasised other ongoing collaborations as reasons for optimism. For example, the firm is working with Amgen to develop CX-904, a T-cell engaging bispecific Probody drug in solid tumors in phase 1, while Bristol Myers Squibb is testing a masked version of the approved cancer antibody treatment Yervoy in a phase 1/2a trial in patients with solid tumors. CytomX also launched new collaborations with Regeneron and the mRNA giant Moderna for $30m and $35m upfront respectively.
In the same business update, CytomX reported $194m cash reserves at the end of 2022, compared to $305m at the end of 2021. The company’s total revenue from 2022 was $53m, beating 2021’s total of $37.3m, which CytomX attributed to progress in collaborations with AbbVie, Astellas and Bristol Myers Squibb.
Investors were spooked by CytomX’s latest company update, and the biotech’s Nasdaq stock price slumped by 10% Wednesday.