Pfizer Cuts PF-07868489 And Two Obesity Programs, Tightening Its Mid-Stage Pipeline

Pfizer has cleared out several clinical programs in its third-quarter update, led by the discontinuation of phase 2 pulmonary arterial hypertension candidate PF-07868489 and a pair of obesity assets. The company said the PAH decision was made on business grounds rather than because of safety or efficacy concerns.

The cuts reach across multiple mechanisms, but they are most notable in obesity because Pfizer has now retreated from both sides of the GIPR debate while continuing to describe obesity as a growth area. That leaves the company appearing more selective about which combinations and targets are worth continued investment, rather than less interested in the category itself.

The pipeline reset

PF-07868489 came from a long-running attempt to treat PAH through BMP9 biology. Pfizer had first explored BMP9 agonists, then shifted to antagonists as evidence emerged that inhibiting the protein protected rodents against the disease. The company started a phase 1/2 trial in 2023 and began a phase 2 open-label extension study in 2025, but has now terminated that study one year after it began. The trial had been due to end in the second half of 2028.

Pfizer also removed the anti-CXCR5 program PF-06835375 from its pipeline. As previously reported, the company had recently stopped a phase 2 trial in primary immune thrombocytopenia early on business grounds. In the latest update, Pfizer also dropped its phase 1 lupus assessment of the same asset.

Four other phase 1 programs were cut in the quarterly review period, including two in obesity and chronic weight management. Pfizer ended development of PF-07999415, an obesity candidate against an undisclosed target that entered the clinic last year.

The company also discontinued a phase 1 trial of two assets acquired from Metsera. That study was testing GIPR agonist PF-08654696 in combination with GLP-1 receptor agonist PF-08653944. Pfizer said it continues to test the GLP-1 candidate in other settings, but this phase 1 program was the only active trial of the GIPR agonist.

What the obesity cuts signal

The GIPR decision stands out because it follows another recent reversal. Three months ago, Pfizer ended development of GIPR antagonist PF-07976016. Scientists have found that both GIPR agonism and antagonism can decrease body weight, and the field still supports both theories: Eli Lilly’s tirzepatide activates GIPR, while Amgen’s late-phase MariTide blocks the receptor.

Pfizer’s withdrawal from both approaches in quick succession does not settle the biology, but it does show how little patience large companies may have for parallel obesity bets that are not emerging as clear internal winners. The company is still willing to back selected obesity assets, yet its latest update suggests breadth alone is no longer the goal.

The quarterly clearout also included two selective KRAS inhibitors in phase 1 solid tumor trials, PF-07985045 and PF-07934040. Pfizer terminated the PF-07985045 study in May on business grounds but had still listed the program as active in second-quarter earnings. In July, the company stopped enrollment in the PF-07934040 trial well short of its recruitment goal.