CAMBRIDGE, United Kingdom — October 12, 2026
Amphista Therapeutics announced that the first patient has been dosed in its Phase 1 clinical trial of AMX-883, an investigational oral targeted protein degrader being developed for acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The first-in-human study, named BRAMLIE (BR(D9) AML Interventional Evaluation), will evaluate the candidate’s safety, pharmacokinetics and preliminary efficacy as a monotherapy. The trial follows authorization from the U.S. Food and Drug Administration in June 2026 and represents the first clinical-stage program for Amphista. AMX-883 is designed to selectively degrade BRD9, a protein associated with the maintenance of leukemic stem-cell characteristics and the suppression of myeloid cell differentiation. The company aims to investigate whether this approach could support a treatment strategy for patients whose disease may not be addressed by mutation-specific targeted therapies.
BRAMLIE Trial to Assess Safety and Preliminary Efficacy
The Phase 1 BRAMLIE trial is expected to enroll approximately 54 participants across multiple clinical sites, including people with AML and high-risk MDS. Researchers will initially assess AMX-883 monotherapy, focusing on its safety, pharmacokinetic profile and preliminary signs of clinical activity. As an early-stage, first-in-human study, the trial is intended to establish foundational evidence about how the investigational medicine behaves in humans and to inform subsequent clinical development. According to Amphista, after the monotherapy profile has been established, a multicenter dose-escalation study is planned to investigate AMX-883 in combination with current standards of care. That subsequent evaluation would include people with relapsed or refractory AML, as well as patients receiving treatment in earlier disease settings. The planned progression will depend on clinical findings and further development decisions. The trial’s initiation marks an important milestone for the company as it transitions its lead asset from preclinical research into human testing. Safety, tolerability, dose selection and pharmacokinetics will be key considerations as the program advances.
Targeted BRD9 Degradation Offers a Potentially Broader AML Approach
AMX-883 uses Amphista’s Targeted Glue™ protein degradation platform, which is designed to direct selected proteins for degradation by recruiting cellular protein-disposal machinery. The candidate is described as a potent, selective and orally bioavailable DCAF16-mediated BRD9 degrader. BRD9 is a subunit of a chromatin-remodeling complex involved in regulating cellular identity and maintaining leukemic stemness. By promoting BRD9 degradation, AMX-883 is designed to encourage myeloid cell differentiation and disrupt biological processes associated with leukemia. The company reports that preclinical studies demonstrated pro-differentiation activity across diverse AML subtypes, independent of karyotype or mutational status. These findings provide the scientific rationale for evaluating the candidate in a clinical population that is not restricted to patients with a specific mutation. However, the reported activity remains preclinical evidence; whether the mechanism translates into meaningful benefit for patients will need to be established through clinical trials. Amphista’s approach seeks to expand targeted protein degradation beyond established cereblon- and VHL-based systems by exploiting alternative E3 ligases, including DCAF16.
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Addressing Unmet Needs in Acute Myeloid Leukemia
AML is an aggressive blood cancer associated with substantial morbidity and mortality, and many patients continue to receive cytotoxic chemotherapy alongside newer targeted medicines where appropriate. Although targeted therapies have expanded treatment options, some are suitable only for particular molecular subgroups, while resistance to existing treatments remains a challenge. Amphista cited the continuing need for therapies that could potentially address a broader range of patients. Dr Eytan Stein, Director of the Program for Drug Development in Leukemia within the Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center and lead investigator for the trial, highlighted the urgency of developing innovative treatments, particularly as resistance to standard therapies such as venetoclax emerges. Amphista Chief Executive Officer Dr Louise Modis said that advancing AMX-883 into clinical development represents a significant milestone in the company’s effort to develop medicines for severe diseases. Amphista focuses on next-generation targeted protein degradation programs, including AMX-883 for AML and programs in non-small cell lung cancer. The Phase 1 study will provide the first clinical evidence needed to assess AMX-883’s safety and potential activity. The candidate remains investigational, and its effectiveness and overall benefit-risk profile have not yet been established.
Source::Amphista Therapeutics,, press release
