Novartis Streamlines Oncology Pipeline, Discontinues Six Phase 1 Cancer Programs
核心洞察
Novartis discontinued six Phase 1 oncology programs during Q4 2025, including the actinium-based PSMA (搜索)-targeting ligand Ac-PSMA-R2 (搜索) and Werner helicase (搜索) inhibitor HRO761.
The company added two new Phase 1 assets to its pipeline: AMO959 (搜索), a DNA-PK (搜索) inhibitor for prostate cancer (搜索) developed by Chengdu Baiyu (搜索), and GCJ904 (搜索) for solid tumors.
Despite the discontinuations, Novartis reported strong oncology performance with over $54.5 billion in net sales for 2025, driven by growth in Kisqali and Scemblix.
Novartis has discontinued six Phase 1 oncology programs while adding two new candidates to its pipeline, reflecting the company's strategic focus on advancing only the highest-value medicines. The Swiss pharmaceutical giant revealed these changes during its fourth-quarter 2025 earnings presentation, marking a significant reshuffling of its early-stage cancer portfolio.
Major Discontinuations Signal Strategic Refinement
The most notable discontinuation was Ac-PSMA-R2 (搜索) (AAA802), a next-generation actinium-225-based radioligand therapy targeting PSMA (搜索) for prostate cancer (搜索). This project faced multiple setbacks, with recruitment into the Phase 1/2 Satisfaction study stopped at 29 patients out of a planned 100. The Phase 1/2 NeoPSMA trial in neoadjuvant prostate cancer was withdrawn in December 2025, with clinical trial records citing "acceptable safety but limited benefit."
Novartis also terminated HRO761, a Werner helicase (搜索) inhibitor that had been in Phase 1 trials for solid tumors since 2023. The decision followed disappointing data presented at the ESMO 2025 meeting, adding to a pattern of failures in this target class, with Roche and GSK previously abandoning similar Werner helicase programs.
Other discontinued programs included KFA115, an undisclosed protein degrader; MGY825, an NFE2L2/KEAP1/CUL3 inhibitor terminated in NSCLC; DFV890, an NLRP3 inhibitor acquired through the 2019 IFM Tre acquisition for $310 million upfront; and PIT565, a CD19 (搜索) x CD2 (搜索) trispecific T-cell engager that had been in Phase 1 since 2022.
New Additions Strengthen Pipeline Focus
Despite the discontinuations, Novartis introduced two new Phase 1 assets. AMO959 (搜索), a DNA-PK (搜索) inhibitor originated by Chengdu Baiyu (搜索) and also coded BY101298, entered a Phase 1/2 combination trial with Pluvicto in PSMA (搜索)-positive metastatic castration-resistant prostate cancer (搜索) in December 2025. The asset appears to be part of a licensing deal Novartis signed with Baiyu in October 2024.
The company also added GCJ904 (搜索), described as a "mystery compound" for solid tumors, though no additional details were disclosed about its mechanism of action or development timeline.
Strong Financial Performance Supports Strategic Decisions
The pipeline refinement comes amid robust financial performance, with Novartis reporting over $54.5 billion in net sales for 2025, representing 8% year-over-year growth. Oncology remained the primary growth driver, with Kisqali achieving $4.78 billion in sales (57% increase) and Scemblix reaching $1.29 billion (85% increase).
Continued Commitment to Early-Stage Innovation
CEO Vas Narasimhan emphasized during a media call that the discontinuations do not represent a retreat from early-stage investments. "We've been really consistent in wanting to build out our early-stage pipeline," Narasimhan stated, particularly through acquisitions in the "sub-$2-billion range."
A company spokesperson confirmed that Novartis is "refining its portfolio to ensure we are advancing only the highest value medicines," noting that discontinued assets are "balanced by the addition of new projects entering our pipeline."
The strategic portfolio management reflects broader industry trends toward more selective development approaches, as companies face increasing pressure to demonstrate clear differentiation and commercial potential in crowded therapeutic areas. Novartis continues to maintain its focus on PSMA (搜索)-targeting therapies, with Ac-PSMA-617 advancing into Phase 3 trials using the same actinium-225 platform as the discontinued Ac-PSMA-R2 (搜索).