Xencor could face second challenge from former partner

Until a year ago Xencor and Johnson & Johnson were partners on the former's anti-CD20 T-cell engager plamotamab, but then the deal was canned. Now not one but two J&J molecules have emerged to threaten Xencor's new lead project, XmAb819.

Last week an entry appeared on a listing of trials under way at AdventHealth Research Institute revealing a phase 1 study of JNJ-89862175, described as an ADC against ENPP3. That's important because Xencor's XmAb819 is an anti-ENPP3 T-cell engager that's already being challenged by J&J's own clinical-stage ENPP3-targeting T-cell engager, JNJ-87890387.

It's possible that JNJ-89862175 is an ADC version of JNJ-87890387, and that these two molecules use the same basic antibody. Curiously, however, the new molecule has no entry on clinicaltrials.gov. A J&J spokesperson would only tell ApexOnco that JNJ-89862175 and JNJ-87890387 were "two distinct molecules", adding that the group would share more information about JNJ-89862175 in the future.

Since ApexOnco contacted J&J, the entry for JNJ-89862175's phase 1 trial on the AdventHealth website was removed. ApexOnco has also asked AdventHealth for clarification, but hasn't received a reply.

Principal investigator

AdventHealth describes itself as a faith-based, not-for-profit clinical research organisation. It's headquartered in Altamonte Springs, Florida, and says it runs over 2,000 care sites at more than 55 hospitals in nine states, with operating revenue of around $17.9bn.

According to the now removed AdventHealth entry the phase 1 trial of JNJ-89862175 is coded 89862175LUC1001, and its principal investigator is Dr Guru Sonpavde, who serves as AdventHealth's director of genitourinary oncology and is also director of the bladder cancer programme at Dana-Farber Cancer Institute.

AdventHealth also lists Sonpavde as principal investigator for first-in-human trials of Pheon's PHN-010, Bayer's DGKα inhibitor BAY 2862789, AbbVie's anti-PSMA x Steap1 ADC ABBV-969 and Avistone's type II c-Met inhibitor ANS014004. The studies of these four molecules all have entries on the clinicaltrials.gov registry.

ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase 3) is said by Xencor to be highly expressed on kidney cancer cells, but only to be present at low levels on normal tissues. XmAb819 uses a 2+1 bispecific format, comprising a MAb with two antigen-binding arms targeting ENPP3 and one targeting CD3.

JNJ-87890387 uses a simpler design, with just two binding sites, one for ENPP3 and the other for CD3. Nothing is known about the structure of JNJ-89862175, meanwhile, and OncologyPipeline reveals no other industry projects targeting ENPP3.

Industry work against ENPP3

Source: OncologyPipeline.

This story has been updated to include comments from J&J.