Phase 1a/b Study for Selective Brain-Penetrant CDK2 Inhibitor AL-605 doses patients; Selective Brain-Penetrant CDK4 Inhibitor AL-433 on Track for First-in-Human Study
SAN DIEGO, May 29, 2026 /PRNewswire/ -- Alaw Therapeutics, Inc. ("Alaw"), a clinical-stage biotechnology company developing precision oncology therapeutics designed to control oncogenic proliferation, tumor survival, and therapeutic resistance, today announced two major pipeline milestones advancing its next-generation cyclin-dependent kinase (CDK) inhibitor portfolio.
The announcements include:
- Dosing of first patients in its Phase 1a/b clinical trial evaluating AL-605, Alaw's selective, brain-penetrant CDK2 inhibitor, in patients with CCNE1-amplified solid tumors
- Drug candidate nomination of AL-433, Alaw's selective, brain-penetrant CDK4 inhibitor, with first-in-human clinical entry planned for Q4 2026
"These milestones represent an important inflection point for Alaw and for CDK-directed oncology," said Idean Marvasty, President and CFO of Alaw. "The inability to achieve meaningful CNS exposure has remained a fundamental limitation, leaving patients with brain metastases and primary CNS tumors underserved by targeted cell-cycle therapies. AL-605 and AL-433 were specifically engineered to address that challenge through enhanced selectivity of CDK inhibition combined with robust brain penetration."
AL-605: Phase 1a/b Study Initiated for Selective Brain-Penetrant CDK2 Inhibitor
Alaw has initiated a Phase 1a/b clinical trial evaluating AL-605 in patients with cyclin E (CCNE1)-amplified solid tumors. The study is designed to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity, while incorporating prospective biomarker-based patient selection strategies intended to enrich for tumors dependent on CDK2 signaling.
The trial is enrolling two biomarker-defined populations:
- Patients with hormone receptor-positive breast cancer that has progressed following CDK4/6 inhibitor therapy and exhibits CCNE1 amplification or overexpression, a setting strongly associated with CDK2-mediated resistance
- Patients with CCNE1-amplified solid tumors more broadly, including ovarian, endometrial, gastric, esophageal, and triple-negative breast cancers
The Phase 1a portion follows a standard dose-escalation design, while Phase 1b expansion cohorts are intended to confirm the recommended Phase 2 dose and evaluate early clinical activity. Interim data are anticipated in the second half of 2026.
Addressing a Critical CNS Limitation in CDK2 Therapy
CDK2 inhibition is increasingly recognized as a central strategy for overcoming resistance to CDK4/6 inhibitors, which have transformed the treatment landscape for hormone receptor-positive breast cancer but are ultimately limited by the emergence of CDK2-driven bypass signaling.
However, currently available and emerging CDK2 inhibitors demonstrate limited blood-brain barrier penetration, leaving the CNS as a pharmacologic sanctuary where resistant tumor cells can survive and proliferate. By achieving robust and selective CNS CDK2 inhibition, AL-605 is designed to address both systemic disease and intracranial tumor progression, including brain metastases arising from CDK2-dependent tumors.
Preclinical studies have demonstrated that AL-605 achieves CNS exposure exceeding leading comparator CDK2 inhibitors and produces meaningful antitumor activity in intracranial tumor models, including glioblastoma and triple-negative breast cancer brain metastases.
AL-433: Selective Brain-Penetrant CDK4 Inhibitor Advances Toward First-in-Human Development
Alaw also announced the nomination of AL-433, its selective, brain-penetrant CDK4 inhibitor, as a development candidate, with first-in-human clinical studies planned for Q4 2026.
AL-433 targets tumors driven by dysregulation of the CDK4-cyclin D1-Rb-E2F axis, a central regulator of G1-to-S phase cell-cycle progression frequently altered across aggressive solid tumors.
The program is designed to address two fundamental limitations of the currently approved CDK4/6 inhibitor class:
- Selective CDK4 Inhibition. AL-433 was engineered for high selectivity toward CDK4 over CDK6 with the goal of preserving antitumor efficacy while substantially improving tolerability. Reduced CDK6 inhibition may enable uninterrupted dosing and expand combination opportunities with immunotherapies and other targeted agents.
- CNS Exposure and Brain Tumor Activity. Approved CDK4/6 inhibitors are substrates for efflux transporters at the blood-brain barrier and achieve minimal CNS exposure, limiting activity against glioblastoma, CDK4-amplified brain tumors, and brain metastases. AL-433 was specifically optimized for brain permeability and is designed to enable clinically meaningful CDK4 inhibition within the CNS.
Preclinical studies demonstrated that AL-433 achieves near-complete blood-brain barrier penetration, resulting in direct intracranial target engagement and antitumor activity in CDK4-dependent CNS tumor models.
AL-433 has been well tolerated in multi-species preclinical safety studies, and GLP toxicology studies are ongoing in support of clinical advancement. Planned clinical studies are expected to permit enrollment of patients with active CNS tumors or brain metastases, a population historically excluded from trials evaluating CDK4/6 inhibitors.
"The convergence of selectivity, brain penetrance, and rational combination strategy is what makes the pipeline fundamentally differentiated," added Marvasty. "We are not developing conventional next-generation CDK inhibitors. We are building the first CDK-directed therapies designed to follow the tumor wherever it goes, including the brain."
About AL-605
AL-605 is a selective, brain-penetrant CDK2 inhibitor designed for the treatment of CCNE1-amplified solid tumors and CDK2-mediated resistance to CDK4/6 inhibitors. The molecule achieves significant CNS exposure and has demonstrated antitumor activity in preclinical intracranial tumor models. AL-605 is currently being evaluated in a Phase 1a/b clinical study.
About AL-433
AL-433 is a selective, brain-penetrant CDK4 inhibitor designed to achieve highly selective inhibition of CDK4 over CDK6 while maintaining near-complete blood-brain barrier penetration. The program is intended to address both the hematologic toxicity and CNS limitations associated with approved CDK4/6 inhibitors and has demonstrated antitumor activity in preclinical CDK4-dependent CNS tumor models, including glioblastoma. Drug candidate nomination has been achieved, and first-in-human clinical studies are planned for Q4 2026.
About Alaw Therapeutics
Alaw Therapeutics, a wholly owned subsidiary of Eilean Therapeutics, is a clinical-stage biotechnology company developing precision oncology therapeutics designed to control oncogenic proliferation, tumor survival, and therapeutic resistance through highly selective small molecules and next-generation targeted degradation approaches.
The company's pipeline includes selective precision oncology programs in clinical and preclinical development, as well as RIPTAC therapeutic programs designed for programmable tumor-selective pathway control. Alaw integrates advanced medicinal chemistry, AI/ML-enabled discovery technologies, and translational biology to develop differentiated therapies for aggressive and resistant cancers.
For more information, visit www.alawtx.com
About Eilean Therapeutics
Eilean Therapeutics is a biotechnology company advancing precision small-molecule therapies for genetically defined diseases. Leveraging proprietary rational drug design capabilities and deep mechanistic expertise, the company is building a differentiated pipeline of targeted therapies, with a focus on delivering first- and best-in-class clinical candidates.
For more information, visit www.eileanther.com
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SOURCE Alaw Therapeutics
