Bristol Myers Squibb has axed the degrader-antibody conjugate (DAC) it bought from Orum Therapeutics for $100 million, walking away from the asset after seeing phase 1 data.
Orum, which disclosed (PDF) the news in a financial filing, sold the DAC to BMS in 2023. The therapy, dubbed ORM-6151, delivers a GSPT1 degrader to cells expressing CD33. Degrading the housekeeping protein GSPT1 can lead to cell death. Because acute myeloid leukemia and myelodysplastic syndrome cells often express CD33, ORM-6151 could theoretically selectively eliminate the blood cancers.
BMS began testing that idea in 2024, starting a phase 1 clinical trial of ORM-6151 as a monotherapy and in double and triple combination with azacitidine and venetoclax. The study was due to wrap up in February 2027, according to the federal trials register.
But Orum disclosed that BMS has now stopped developing the DAC after reviewing clinical data. The termination of work on ORM-6151, which BMS called BMS-986497, deprived Orum of the chance to earn (PDF) up to $80 million in milestones tied to clinical development.
The program is one of many projects that BMS has jettisoned since Christopher Boerner, Ph.D., took over as CEO in 2023. BMS struck the Orum deal days into Boerner’s time as CEO, suggesting that the agreement was largely forged by the previous regime. Early in Boerner’s reign, the Big Pharma axed multiple internal and partnered projects advanced by the old leadership.
BMS’ termination of ORM-6151 is another blow to the DAC field. AbbVie beat BMS to the clinic by starting a phase 1 trial in 2023 of ABBV-787, a CD33-directed DAC with a BET degrader payload. But AbbVie terminated the study last year, citing strategic considerations.
The focus on CD33 DACs echoes the early years of antibody-drug conjugate (ADC) development. In 2000, Wyeth, now part of Pfizer, won (PDF) accelerated FDA approval for its CD33-directed ADC, Mylotarg. Orum based the antibody in ORM-6151 on the targeting molecule in Mylotarg, gemtuzumab, limiting its changes to modifications intended to support manufacturing and improve safety.