J&J sidelines a novel project

Johnson & Johnson seems to have quietly terminated JNJ-88998377, which went into the clinic nearly two years ago. At the time, the asset’s target was a mystery, but it’s since emerged that it hits TRPV1 – a modality that’s more commonly associated with analgesia.

Meanwhile, the future also looks uncertain for several other J&J projects, including its KLK2-targeting radioconjugate and Car-T therapy, based on recruitment changes on the clinicaltrials.gov registry. 

TRPV1 pain

This month, the entry for JNJ-88998377’s phase 1 trial in relapsed/​refractory B-cell non-Hodgkin's lymphoma was changed from “recruiting” to “active, not recruiting”, and its enrolment stopped at 58 versus a planned 170 – both signs that all is not well.

When asked by ApexOnco J&J declined to confirm that the asset had been discontinued, only saying that “data analyses are ongoing, and the results will be reported through appropriate scientific channels as they become available”.

According to OncologyPipeline, no other TRPV1 antagonists are currently being developed in oncology. This target has been investigated as a treatment for pain, although projects have been linked with body temperature regulation issues such as hyperthermia, and no TRPV1 blockers have been approved.

KLK2 doubts

The writing could also be on the wall for J&J’s JNJ-90009530 (a CD20 Car-T originated by AbelZeta), JNJ-80948543 (a CD79b x CD20-targeting trispecific T-cell engager), JNJ-69086420 (KLK2-targeting radioconjugate) and JNJ-75229414 (anti-KLK2 Car-T).

J&J also refused to comment on the status of these projects.

The KLK2-targeting assets are particularly notable because J&J has had several shots against this target, the most advanced being the T-cell engager pasritamig, in phase 3.

The phase 1 trial of the radioconjugate contender, JNJ-6420, was modified in December to “active, not recruiting”, and its enrolment stopped at 144, from a planned 247. There have been doubts about this project since patient deaths were reported at ASCO 2024, although at the time J&J said it was testing a new dosing strategy. No news has emerged from the study since then.

Meanwhile, the phase 1 study of the KLK2 Car-T project, in metastatic castrate-resistant prostate cancer, initially sought to enrol 60 patients, but it ended up recruiting only 15. This change happened in 2023, and there is still no data available from this trial.

J&J also has another high-profile prostate asset in JNJ-95298177, a PSMA-targeting ADC gained through the $2bn purchase of Ambrx. Development of this project appears to have stalled, although a J&J spokesperson previously told ApexOnco that this project was still in play. Notably, a phase 1 trial of JNJ-95298177 plus pasritamig began last year.  

The group recently splashed out $3bn on Halda, to get that group’s androgen receptor-targeting HLD-0915. With so many prostate cancer shots, some attrition is to be expected.

Trispecific trouble?

There are also doubts about the CD79b x CD20-targeting T-cell engager JNJ-80948543, especially since J&J recently started a phase 1 trial with the similarly acting JNJ-95566692. 

A phase 1 study of JNJ-8543 in relapsed/refractory B-cell non-Hodgkin’s lymphoma looks to have been curtailed in November. Another phase 1 study of JNJ-8543 completed last October, and has yet to yield data, while a separate trial testing a combo with the CD20 x CD28-targeting bispecific antibody JNJ-87801493 finished in January.

Notable J&J trial changes

Source: OncologyPipeline & clinicaltrials.gov.