Single oral dose reduced MALT1 by 57% in healthy volunteers at exposures projected to be therapeutic; three-month GLP primate toxicology showed no adverse findings at the highest dose tested; healthy-volunteer and Phase 1b patient studies advancing in parallel

DOVER, Del., Nov. 9, 2026 /PRNewswire/ — Eilean Therapeutics, LLC (“Eilean”), a clinical-stage biotechnology company applying a hybrid AI/ML platform to the discovery of targeted protein degraders for cancer and immune-mediated disease, today announced new safety and target-engagement data for ZE66‑0205, a first-in-class, orally available degrader of MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), a central driver of NF-κB signaling in malignant B and T cells.

In GLP toxicology studies of up to three months’ duration, ZE66‑0205 was well tolerated in non-human primates at every dose tested, up to 500 mg/kg/day, with no adverse findings and near-complete MALT1 degradation. In the single-ascending-dose (SAD) portion of the ongoing healthy-volunteer study, ZE66‑0205 produced dose-dependent MALT1 degradation, reducing MALT1 protein in blood mononuclear cells by 57% at plasma exposures projected to be therapeutic.

On the strength of these results, Eilean is advancing two clinical studies in parallel: a healthy-volunteer study of safety, tolerability, pharmacokinetics (PK) and biomarkers, and a Phase 1b study in patients with relapsed or refractory B- and T-cell lymphomas and chronic lymphocytic leukemia (CLL).

Safety and target engagement

• Primate safety through three months: In GLP studies in cynomolgus monkeys dosed at 30, 100 and 500 mg/kg/day, ZE66‑0205 produced no adverse effects on clinical signs, body weight, ECG, cardiovascular or respiratory parameters, clinical pathology, immune-cell subsets or organ histopathology. The no-observed-adverse-effect level (NOAEL) was the highest dose tested, 500 mg/kg/day.
• Murine safety: In a 28-day GLP study, the NOAEL was likewise the highest dose tested (500 mg/kg/day), with no effects on central nervous system function or lymphocyte subsets.
• Genetic toxicology and cardiac safety: ZE66‑0205 was negative in GLP Ames and chromosome-aberration assays and showed minimal hERG inhibition.
• Primate target engagement: At all three doses, MALT1 protein in blood mononuclear cells fell by approximately 90% within 4–24 hours of the first dose and remained suppressed through Day 28. MALT1 returned to baseline after dosing stopped, confirming that the effect is reversible.
• Human target engagement: In the SAD portion of the healthy-volunteer study, MALT1 in blood mononuclear cells fell dose-dependently, by 57% at 24–72 hours post-dose, before returning to baseline — again confirming reversibility. Plasma exposure at this dose exceeded the level projected to be effective from preclinical lymphoma models.
• Human safety: ZE66‑0205 has been well tolerated to date, with no drug-related adverse events and no dose-limiting safety findings at doses achieving therapeutically relevant exposure. Dose escalation continues per protocol.

Clinical program: two studies in parallel

Study ZE66‑0205-0001 (healthy volunteers, Australia). A randomized, double-blind, placebo-controlled first-in-human study assessing safety, tolerability, PK and pharmacodynamics, the last measured as MALT1 levels in blood mononuclear cells.

• Single ascending doses starting at 50 mg, with eight participants per cohort (six on active drug, two on placebo)
• Additional cohorts evaluating higher doses and the effect of food on absorption

Phase 1b study (patients). An open-label, international, multicenter dose-escalation and expansion study in adults with relapsed or refractory B- or T-cell lymphoma or CLL/small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy.

• Indications: activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL), including after CAR-T therapy; marginal zone lymphoma, including MALT lymphoma; follicular lymphoma; mantle cell lymphoma; Waldenström’s macroglobulinemia; CLL/SLL following BTK and BCL2 inhibitors; and peripheral T-cell lymphoma
• Part A — dose escalation: once-daily oral dosing in 28-day cycles, beginning at a dose already cleared in healthy volunteers. Escalation follows a Bayesian optimal interval (BOIN) design guided by safety, PK and MALT1 degradation.
• Part B — dose optimization and expansion: a randomized comparison of two doses, consistent with FDA Project Optimus guidance, to select the recommended Phase 2 dose
• Endpoints: dose-limiting toxicities and adverse events (primary); PK, MALT1 degradation in blood and tumor biopsies, and NF-κB pathway biomarkers including IL-2 and IL-10 (secondary). Preliminary response is assessed using Lugano, iwCLL and IWWM-6 criteria.

Running both studies in parallel is designed to identify the optimal biologically active dose rapidly and to support initiation of Phase 2 in 2027.

Management comment

“Achieving upto a 57% dose dependent reduction in MALT1 after a single oral dosing in humans, alongside a clean three-month primate safety profile, is a significant milestone for ZE66‑0205,” said Iain Dukes, D.Phil., Chief Executive Officer of Eilean Therapeutics. “Removing the MALT1 protein, rather than merely blocking its protease activity, shuts down both its scaffolding and its enzymatic roles in NF-κB signaling. Running our healthy-volunteer and patient studies in parallel allows us to move quickly toward the dose that delivers maximal target suppression for patients with lymphoma and CLL.”

About MALT1 and ZE66‑0205

MALT1 is essential for NF-κB activation downstream of the B-cell and T-cell receptors. This pathway drives the survival, proliferation and drug resistance of many lymphoid cancers, including ABC-DLBCL and CLL that has progressed on BTK inhibitors. ZE66‑0205 is an oral, cereblon-based protein degrader. In preclinical studies it degraded MALT1 at low-nanomolar concentrations (DC50 of approximately 3 nM) with high selectivity across the proteome, and extended survival in a MALT1-dependent DLBCL model.

About Eilean Therapeutics

Eilean Therapeutics develops first-in-class therapies, including oral protein degraders, directed at escape mechanisms in solid and hematological cancers. Its lead program, ZE66‑0205, is an oral MALT1 degrader for hematological malignancies. For more information, visit

www.eileanther.com.

Forward-looking statements

This press release contains forward-looking statements, including statements regarding the design, timing and anticipated results of clinical studies, the projected therapeutic exposure of ZE66‑0205 and its therapeutic potential. Such statements involve known and unknown risks and uncertainties, and actual results may differ materially from those expressed or implied. ZE66‑0205 is an investigational product and has not been approved by the U.S. Food and Drug Administration or any other regulatory authority; its safety and efficacy have not been established. Eilean undertakes no obligation to update these statements except as required by law.

Contact
Amy Burd, Ph.D.
Chief Scientific Officer, Eilean Therapeutics
aburd@eileanther.com

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SOURCE Eilean Therapeutics, Inc