Dover, Delaware, United States, November 9, 2026
Eilean Therapeutics, LLC, a clinical-stage biotechnology company developing targeted protein degraders, has announced encouraging first-in-human results for ZE66-0205, an investigational oral degrader targeting mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). The company reported that a single oral dose produced a 57% reduction in MALT1 protein levels in peripheral blood mononuclear cells (PBMCs) of healthy volunteers at drug exposures projected to be therapeutically relevant. The findings provide early clinical evidence that ZE66-0205 can reach and degrade its intended biological target in humans. The announcement also included encouraging results from three-month good laboratory practice (GLP) toxicology studies in non-human primates, in which the candidate was reportedly well tolerated at all tested doses. Based on these findings, Eilean is advancing two clinical studies in parallel: a first-in-human study in healthy volunteers and a Phase 1b study involving patients with relapsed or refractory B-cell and T-cell lymphomas and chronic lymphocytic leukemia (CLL). The development programme represents an important step in exploring targeted protein degradation as an oral treatment strategy for hematological cancers.
ZE66-0205 Demonstrates 57% MALT1 Reduction in Humans
The first-in-human findings come from the single-ascending-dose portion of Eilean’s ongoing Phase 1 clinical study in healthy volunteers. Following a single oral administration, ZE66-0205 demonstrated dose-dependent degradation of MALT1 protein in blood mononuclear cells. At the dose achieving projected therapeutic exposure, the company observed a 57% reduction in MALT1 levels between 24 and 72 hours after administration. The reduction was temporary, with MALT1 levels returning towards baseline after dosing stopped, indicating that the degradation effect was reversible. This is an important pharmacodynamic finding because it demonstrates that the investigational drug can engage its intended target in humans. The company also reported that ZE66-0205 was well tolerated in the study to date, with no drug-related adverse events or dose-limiting safety findings at exposures considered therapeutically relevant. However, these observations are preliminary and come from an early-stage study involving healthy volunteers. Further dose escalation and evaluation in larger patient populations will be required to establish the candidate’s safety profile, optimal dose and potential therapeutic benefit.
Preclinical Safety Studies Support Clinical Development
In addition to the human target-engagement results, Eilean reported findings from three-month GLP toxicology studies in cynomolgus monkeys. Animals received daily doses of 30, 100 and 500 mg/kg, with no adverse findings reported across clinical observations, body weight, electrocardiographic measurements, cardiovascular and respiratory parameters, clinical pathology, immune-cell subsets or organ histopathology. The company identified 500 mg/kg/day as the no-observed-adverse-effect level (NOAEL), the highest dose evaluated. The studies also demonstrated approximately 90% MALT1 degradation in primate blood mononuclear cells within 4 to 24 hours following the first dose, with suppression maintained through Day 28. MALT1 levels subsequently returned to baseline after treatment stopped. Additional 28-day GLP studies in mice also reportedly showed no adverse effects at the highest tested dose. These findings provide supportive preclinical safety and pharmacology information for continued investigation. Nevertheless, animal toxicology findings cannot establish human safety, and longer-term clinical monitoring remains essential as dose escalation progresses.
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Phase 1b Trial Targets Lymphomas and CLL
ZE66-0205 is an oral, cereblon-based protein degrader designed to remove MALT1 rather than simply inhibit its enzymatic activity. MALT1 plays an important role in activating the NF-κB signaling pathway downstream of B-cell and T-cell receptors. This pathway contributes to the survival, proliferation and drug resistance of several lymphoid malignancies, including certain forms of diffuse large B-cell lymphoma and CLL. By degrading MALT1, ZE66-0205 is designed to disrupt both its enzymatic and scaffolding functions, potentially affecting multiple cancer-associated signaling processes. Eilean is advancing a Phase 1b clinical study in adults with relapsed or refractory B-cell and T-cell lymphomas and CLL, including patients who have received at least two previous lines of treatment. The study will assess safety, tolerability, pharmacokinetics, MALT1 degradation in blood and tumor samples, and preliminary anti-tumor activity. The programme includes dose escalation followed by dose optimization to identify a recommended Phase 2 dose. Eilean aims to support the initiation of Phase 2 development in 2027, depending on clinical progress. ZE66-0205 remains investigational, and its safety and efficacy have not been established by regulatory authorities.
Source: Eilean Therapeutics press release
