RG-7827

Roche’s clear-out was accompanied by an influx of other assets. Roche has removed eight phase 1 and 2 oncology and neurology candidates from its pipeline as part of a set of “trade-offs” intended to “increase the overall portfolio value and speed up development.” In the fourth quarter (PDF), Roche removed eight drug candidates and replaced them with eight different prospects, shifting the balance of its pipeline away from neurology and, to a lesser extent, oncology and toward immunology, cardiovascular and metabolism in the process. The number of neurology prospects fell from 18 to 12, although one of those was moved to another part of the pipeline. CEO Thomas Schinecker said the the resources will be shifted "to projects we want to accelerate." He also foreshadowed similar pipeline cuts to come in the first quarter during a fourth quarter earnings call Thursday.  Basmisanil is one of the candidates Roche is kicking to the curb. The drugmaker trialed the GABAA α5 receptor negative allosteric modulator in ischemic stroke and schizophrenia patients from 2016 to 2019. The discovery of an EEG biomarker of dup15q, a developmental disorder, spurred interest in treating the syndrome by reducing GABA activity in the brain and led Roche to start enrolling patients in a phase 2 trial in 2022. ClinicalTrials.gov lists the study as recruiting, but Roche removed the asset from its pipeline.  Roche also axed balovaptan, a small-molecule vasopressin V1A receptor antagonist that previously made it to phase 3 in autism spectrum disorder only to fail to move the needle. The drugmaker tried again in the aftermath of the failure, kicking off a phase 2 study in post-traumatic stress disorder. Roche finished that trial last year and promptly removed balovaptan from its pipeline.  News of the other neurology changes preceded the fourth-quarter update. AC Immune said Roche had returned the Alzheimer’s disease prospects crenezumab and semorinemab last month, and details of the decision to drop Angelman syndrome candidate rugonersen emerged via the patient community last year.  On the oncology side, Roche removed three phase 1 candidates from the pipeline. The drugmaker dealt a second blow to the hopes of treating solid tumors by targeting FAP. Having already stopped studying a FAP-IL-2v candidate, Roche removed the solid tumor FAP-CD40 prospect RG6189 from its pipeline in the fourth quarter. A phase 1b trial of a FAP-4-1BBL candidate, RG7827, is continuing.   The other two axed oncology assets are the EGFRvIIIxCD3 bispecific antibody RG6156, which Roche was studying in brain cancer, and another bispecific designed to bind to HLA-G on tumor cells and CD3 on T cells.  Roche’s clear-out was accompanied by an influx of other assets, including candidates acquired through the takeovers of Carmot Therapeutics and Telavant. A longer-term bet delivered a clinical candidate, too, with Roche moving a covalent inhibitor of WRN, the synthetic lethal target at the heart of a $135 million deal with Vividion Therapeutics, into phase 1.