TT-301 / OPKO Health, Johns Hopkins University - LARVOL DELTA

BEACH TRIAL OF THE NOVEL ANTI-NEUROINFLAMMATORY SMALL MOLECULE THERAPEUTIC CANDIDATE MW189 IN NON-TRAUMATIC ICH: UPDATE ON PROGRESS (ADPD 2026) - "BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute CNS injury. In addition, the exploratory analyses in BEACH may identify mechanisms and biological responses to this new potential neuroprotective therapy targeted toward neuroinflammation."

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation

Drug Development. (PubMed, Alzheimers Dement) - "Our drug discovery efforts have taught us several important lessons: 1) Focus efforts on disease-relevant pathophysiology processes integrated with strategic compound design. 2) Fail fast and early. 3) Complex diseases such as AD require interventions that target complementary disease drivers and therapeutic intervention time windows. 4) Dosing is the pharmacological basis of successful therapeutic intervention: what, when, and how - the RIGHT drug(s) at the RIGHT time(s) for the RIGHT disease mechanism. 5) The cytokine/synaptic dysfunction axis is a viable pathophysiology process for therapeutic intervention where proinflammatory cytokine dysregulation is part of the disease progression mechanism."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Johns Hopkins University | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Dec 2025 ➔ Nov 2026

Biomarker • Trial completion date • Trial primary completion date • Cerebral Hemorrhage • Hematological Disorders

Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (NCT05020535) (ISC 2025) - P2 | "The Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (NCT05020535) phase 2a pilot study is a first-in-patient study to assess the safety and tolerability of MW189 in patients with intracerebral hemorrhage (ICH)...The trial is led by Linda Van Eldik (University of Kentucky) and Daniel F. Hanley (Johns Hopkins University). The trial website provides further information https://biostraining.com/BEACH/."

Biomarker • Cerebral Hemorrhage • Hematological Disorders • Inflammation • Vascular Neurology • IL10

BIOMARKER AND EDEMA ATTENUATION IN INTRACEREBRAL HEMORRHAGE (BEACH): A PHASE 2A PROOF-OF-CONCEPT STUDY OF AN ANTI-NEUROINFLAMMATORY SMALL MOLECULE DRUG CANDIDATE (ADPD 2024) - "Preclinical studies in acute brain injury models have shown that the investigational drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes... BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute CNS injury."

Biomarker • P2a data • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology

Biomarker And Edema Attenuation In Intracerebral Hemorrhage Trial (ISC 2024) - P2 | "The Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (NCT05020535) phase 2a pilot study is a first-in-patient study to assess the safety and tolerability of MW189 in patients with intracerebral hemorrhage (ICH)...The trial website provides further information https://biostraining.com/BEACH/. BEACH is funded by a grant from the National Institute on Aging (Grant: R01AG069930) with design and planning work through the Trial Innovation Network JHU Trial Innovation Center (Grant:U24TR004440)."

Biomarker • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • IL10

Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Johns Hopkins University | Phase classification: P2a ➔ P2 | Trial completion date: Jun 2026 ➔ Oct 2026

Biomarker • Phase classification • Trial completion date • Cerebral Hemorrhage • Hematological Disorders

Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage. (PubMed, Neurocrit Care) - "Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury."

Clinical • Journal • P2a data • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology

Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH): a phase 2a proof-of-concept trial of a novel anti-neuroinflammatory small molecule drug candidate (CTAD 2023) - P2a | "Success with MW189 in ICH patients will further de-risk the compound for subsequent larger trials of acute CNS injury and/or to develop the drug for Alzheimer’s and other age-related dementias. The study will also generate important information about the utility of targeting the acute proinflammatory cytokine aspects of neuroinflammation in older adults with vascular disease."

Biomarker • P2a data • Alzheimer's Disease • Cardiovascular • Cerebral Hemorrhage • Cognitive Disorders • Dementia • Hematological Disorders • Hypertension • Inflammation • Vascular Neurology

Partial Depletion of Microglia Attenuates Long-Term Potentiation Deficits following Repeated Blast Traumatic Brain Injury in Organotypic Hippocampal Slice Cultures. (PubMed, J Neurotrauma) - "Treatment with the novel drug, MW-189, prevented LTP deficits when administered immediately following a repeated bTBI and even when administered only for an acute period (24 h) between two blast injuries. These findings could inform the development of therapeutic strategies to treat the neurological deficits of repeated bTBI suggesting that microglia play a major role in functional neuronal deficits and may be a viable therapeutic target to lessen the neurophysiological deficits after bTBI."

Journal • CNS Disorders • Vascular Neurology • CD68 • IL10 • MRC1

Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (clinicaltrials.gov) - P2a | N=120 | Recruiting | Sponsor: Johns Hopkins University | Trial completion date: Oct 2026 ➔ Jun 2026

Biomarker • Trial completion date • Cerebral Hemorrhage • Hematological Disorders

Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (clinicaltrials.gov) - P2a | N=120 | Recruiting | Sponsor: Johns Hopkins University | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • Cerebral Hemorrhage • Hematological Disorders

Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) (clinicaltrials.gov) - P2a; N=120; Not yet recruiting; Sponsor: Johns Hopkins University

Biomarker • New P2a trial • Cerebral Hemorrhage • Hematological Disorders

Suppression of established rat collagen-induced arthritis and inhibition of TNF-α with small molecule aminopyridizines (ACR/ARHP 2011) - In stimulated RAW264.7 macrophages and synovial fibroblasts, TT301 and TT302 dose-dependently inhibited the induction of key cytokines relevant to RA pathology including TNF-α, IL-6, and MCP-1

In vitro study • Rheumatoid Arthritis