OLX07010 / Oligomerix - LARVOL DELTA

Oligomerix Published Results from a Preclinical Therapeutic Treatment Study on an Oral Experimental Drug in Development for Alzheimer’s and Rare Neurodegenerative Diseases (Businesswire) - "Oligomerix, Inc...announced today the publication of a preclinical study demonstrating in vivo proof of concept for therapeutic treatment with its oral small molecule OLX-07010 blocking the progression of tau aggregation and ameliorating motor deficits...'This study shows that treatment of mice with pre-existing tau aggregates with OLX-07010 can block the further accumulation of tau aggregates. This is important for Alzheimer’s patients because the progression of tau aggregation begins years before clinical symptoms are apparent.'...OLX-07010 is presently being tested in a Phase 1a clinical trial in healthy volunteers to demonstrate its safety and pharmacokinetic exposure that is expected to be completed in 2025."

P1 data • Preclinical • Alzheimer's Disease

Therapeutic Treatment With OLX-07010 Inhibited Tau Aggregation and Ameliorated Motor Deficits in an Aged Mouse Model of Tauopathy. (PubMed, J Neurochem) - "Treatment prevented the accumulation of tau aggregates above baseline, and in parallel, treatment groups had improved motor behavior in a Rotarod assay compared to baseline and vehicle control groups, suggesting that treatment was rescuing motor impairment in aged mice. The functional and biochemical readouts suggest that this small molecule has potential for treating neurodegenerative diseases characterized by tau aggregation such as AD and progressive supranuclear palsy."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Movement Disorders • Progressive Supranuclear Palsy

Drug Development. (PubMed, Alzheimers Dement) - "Four weeks of daily oral dosing was sufficient to demonstrate a dose dependent therapeutic effect on tau pathology and motor function supporting clinical development of OLX-07010. This molecule, selected for inhibiting tau self-association in vitro, may also improve the clearance of protein aggregates in vivo, further supporting its therapeutic potential."

Journal

Acute daily treatment with OLX-07010, an oral, small molecule inhibitor of tau self-association, caused dose dependent reduction of tau aggregates in aged JNPL3 mice and improved motor function (Neuroscience 2024) - "The dose dependent increase in LC3-II suggestsincreased autophagy for clearance of protein aggregates. If the acute treatment strategytranslates to the clinic, then changes in biomarkers of tau aggregation and functional readoutsmay enable shorter timelines for trials."

Preclinical • CNS Disorders • Mood Disorders • Psychiatry

Therapeutic treatment of APPSWE-Tau (TAPP) mice with small molecule OLX-07010 inhibitor of tau self-association (Neuroscience 2024) - "Data from ongoing biochemical studies will add on and clarify OLX-07010’s effects in a more representative AD mouse model. In summary, this approach will provide a more robust understanding of OLX-07010’s potential as a novel treatment strategy against AD."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Phase 1 Study of OLX-07010 in Healthy Adult and Elderly Participants (clinicaltrials.gov) - P1 | N=88 | Enrolling by invitation | Sponsor: Oligomerix, Inc | Active, not recruiting ➔ Enrolling by invitation

Enrollment open • Alzheimer's Disease • CNS Disorders

Acute treatment with OLX-07010 reduced tau aggregates and upregulated a marker of autophagy with dose dependence in aged P301L tau JNPL3 mice (AAIC 2024) - "Four weeks of daily oral dosing was sufficient to demonstrate a dose dependent therapeutic effect on tau pathology and motor function supporting clinical development of OLX-07010. This molecule, selected for inhibiting tau self-association in vitro, may also improve the clearance of protein aggregates in vivo, further supporting its therapeutic potential."

Preclinical • Alzheimer's Disease

Preclinical evaluation of a small molecule that inhibits tau self-association in transgenic mouse exhibiting mutant tau and APP (Neuroscience 2023) - "The 9-month treatment study has started, and the 3-month study is timed to conclude in parallel with the 9-month study. This study is targeted towards studying the efficacy of our lead small molecule in reducing tau aggregation in the context of concurrent Aβ expression and inflammation for better evaluation of the pharmacology of OLX-07010 for clinical studies in AD."

Preclinical • Alzheimer's Disease • CNS Disorders

Treatment with OLX-07010 inhibits the aggregation of human P301lL tau in aged JNPL3 mice with dose dependence (Neuroscience 2023) - "However, analysis of human P301L by immunoblot showed greater dose dependence as the 80 mg/kg dose was consistently more effective than 40 mg/kg dose for inhibiting tau aggregation. Although the immunoblot approach yields semiquantitative data, it enabled the visualization of the spectrum of human tau monomer and aggregated species via resolution on a gradient gel and demonstrated greater dose dependence for the inhibition of P301L tau aggregation by treatment with OLX-07010."

Preclinical • CNS Disorders

Small molecule inhibitor of tau self-association in a mouse model of tauopathy: A preventive study in P301L tau JNPL3 mice. (PubMed, PLoS One) - "Here, we evaluated OLX-07010, a small molecule inhibitor of tau self-association, for the prevention of tau aggregation...In the cortex, the levels of insoluble tau were similar in the Baseline and Vehicle groups, indicating that the pathological phenotype of these mice was beginning to emerge at the study endpoint and that there was a delay in the development of the phenotype of the model as originally characterized. No drug-related adverse effects were observed during the 4-month treatment period."

IO biomarker • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

Oligomerix Publishes Preclinical Data on Novel Small Molecule Therapeutic in Development for Alzheimer’s Disease and Rare Neurodegenerative Diseases (Businesswire) - "Oligomerix...announced today the publication of preclinical data demonstrating that the oral small molecule OLX-07010 inhibits tau aggregation in a model for inherited tauopathies such as progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD)....In a paper published in the journal PLOS ONE...researchers reported that the experimental drug OLX-07010 reduced the accumulation of tau aggregates. Compared to controls, oral treatment with the drug over four months significantly prevented the development of tau aggregates in this mouse model."

Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Progressive Supranuclear Palsy • Tauopathies And Synucleinopathies

Phase 1 Study of OLX-07010 in Healthy Adult and Elderly Participants (clinicaltrials.gov) - P1 | N=88 | Active, not recruiting | Sponsor: Oligomerix, Inc | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Enrollment closed • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Oligomerix Announces First-in-Human Dosing of Tau Self-Association Inhibitor OLX-07010 (Businesswire) - “Oligomerix, Inc…announced the dosing of its first subjects in the company’s Phase 1a clinical trial evaluating lead candidate OLX-07010. This lead compound is a novel oral, small molecule inhibitor of tau self-association being assessed for the treatment of Alzheimer’s disease and other neurodegenerative disorders. The objective of the Phase 1a study is to evaluate the safety and tolerability of OLX-07010 in single-ascending and multiple-ascending dose regimens in healthy volunteers, followed by the evaluation in a cohort of healthy elderly volunteers, the intended population.”

Trial status • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Tauopathies And Synucleinopathies

Phase 1 Study of OLX-07010 in Healthy Adult and Elderly Participants (clinicaltrials.gov) - P1 | N=88 | Enrolling by invitation | Sponsor: Oligomerix, Inc

New P1 trial • Alzheimer's Disease • CNS Disorders

Oligomerix Announces Issuance of Key U.S. Patent for Lead Tau-Targeting Candidate OLX-07010 to Treat Neurodegenerative Diseases (Businesswire) - “Oligomerix, Inc…announced that the U.S. Patent and Trademark Office (USPTO) issued U.S. patent 11,472,776 (the ‘776 patent) titled, ‘Novel Quinazolinones that Inhibit the Formation of Tau Oligomers.’ The ‘776 patent further strengthens the company’s intellectual property position and coverage for their tau oligomer formation inhibitors and provides product protection for Oligomerix’s lead clinical candidate, OLX-07010, including composition of matter and methods of use until October 2037.”

Patent • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Tauopathies And Synucleinopathies

OVERVIEW OF THE PRECLINICAL PROGRAM FOR OLX-07010 - A NOVEL INHIBITOR OF TAU SELFASSOCIATION. (CTAD 2022) - "The preclinical development program demonstrated that OLX-07010 is an excellent candidate for clinical development. Long-term treatment for chronic diseases such as AD requires safe, effective, and economically feasible approaches. This small molecule, CNS drug-like lead substantially fulfills these requirements based on our preliminary results and the fact that it would not need cold-storage nor expensive infusion centers for administration for ease of treatment to address the unmet global health crisis."

Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Immunology • MAPT

Oligomerix Presents Data from IND-Enabling Studies on Clinical Candidate at Clinical Trials on Alzheimer's Disease (CTAD) and Neuroscience 2022 Meetings (Businesswire) - “At the meetings, the company presented data from IND-enabling studies demonstrating the safety and pharmacokinetic profile of OLX-07010 in in vitro and in vivo preclinical studies. In multiple animal species, OLX-07010…demonstrated good oral bioavailability, with no significant adverse effects reported at the highest dose levels tested. Furthermore, in in vitro studies, OLX-07010 demonstrated a low potential for interactions with other commonly prescribed medicines when administered at the anticipated efficacious dose. These results further support OLX-07010’s potential as a clinical candidate for Alzheimer’s disease and other dementias where tau plays a significant role….‘We have been working closely with FDA and our funder, the National Institute on Aging (NIA)…to finalize our protocol for our first-in-human study, and we look forward to initiating our Phase 1a study of OLX-07010 in the coming months.’”

New P1 trial • Preclinical • Alzheimer's Disease • CNS Disorders

Preclinical profiling of pharmacokinetic and pharmacodynamic readouts of a small molecule inhibitor of tau self-association in a mouse model of tauopathy (Neuroscience 2022) - "Motor behavior phenotype will be evaluated using Open-field and Rotarod tests. Overall, the most informative markers of efficacy will be used to develop a PK/PD model for supporting the dose selection of OLX-07010 in future clinical studies."

PK/PD data • Preclinical • Alzheimer's Disease • CNS Disorders

Preclinical evaluation of the exposure and safety of a small molecule inhibitor of tau self-association (Neuroscience 2022) - "No adverse effects were observed, and the NOAEL was the highest dose tested in each species. Based on the above-described non-clinical pharmacokinetic and associated in vitro studies, the absence of cytochrome P450 inhibition with minimal induction, no effects on transporters, and the relatively modest toxicity seen in the 28-day GLP toxicity studies, OLX-07010 appears to be an excellent candidate for clinical development for neurodegenerative diseases."

Preclinical • Alzheimer's Disease • CNS Disorders • Dementia

Oligomerix Awarded $2.49M from NIH to Further Support Clinical Development of Tau-Targeting Alzheimer’s Disease Therapy Candidate OLX-07010 (Businesswire) - "Oligomerix, Inc...announced an award of $2.49 million from the National Institute on Aging of the National Institutes of Health to support clinical development of its lead program OLX-07010, an oral tau self-association small molecule inhibitor....Oligomerix has completed the preclinical work needed to support an investigational new drug (IND) application with the U.S. Food and Drug Administration, which was filed in mid-2022 to enable the initiation of a first-in-human, Phase 1a study to evaluate the safety, tolerability and pharmacokinetics of OLX-07010 in healthy subjects."

Financing • IND • Alzheimer's Disease • CNS Disorders

Oligomerix Awarded $3.35M from NIH to Support Clinical Development of Tau-Targeting Alzheimer’s Disease Therapy (Businesswire) - “Oligomerix, Inc…announced an award of $3.35 million from the National Institute on Aging of the National Institutes of Health to support clinical development of its lead program OLX-07010, an oral tau self-association small molecule inhibitor. Oligomerix plans to begin a Phase 1a clinical trial in healthy volunteers in 2022….‘Our NIH R01 grant will support a Phase 1a double-blind, randomized, three-part study designed to evaluate the safety, tolerability, and pharmacokinetics of OLX-07010 in single ascending doses, multiple ascending doses, and a single dose in healthy elderly…’”

Financing • Alzheimer's Disease • CNS Disorders

Oligomerix Awarded $3.35M from NIH to Support Clinical Development of Tau-Targeting Alzheimer’s Disease Therapy (Businesswire) - "Oligomerix, Inc...announced an award of $3.35 million from the National Institute on Aging of the National Institutes of Health to support clinical development of its lead program OLX-07010, an oral tau self-association small molecule inhibitor. Oligomerix plans to begin a Phase 1a clinical trial in healthy volunteers in 2022."

Financing • New P1 trial • Alzheimer's Disease • CNS Disorders

TREATMENT WITH A SMALL MOLECULE INHIBITOR OF TAU SELF-ASSOCIATION REDUCED TAU AGGREGATION IN TWO MOUSE MODELS OF TAUOPATHY USING BOTH PREVENTIVE AND THERAPEUTIC STUDY DESIGNS (ADPD 2022) - "Treatment with OLX-07010 was effective in preventing the accumulation of tau aggregates in young mice and in inhibiting the progression of tau aggregation in aged mice in models representing tau aggregation in 4R tauopathies and Alzheimer’s disease showing the broad potential application of this treatment for Alzheimer’s disease and rare tauopathies supporting its preclinical development for clinical studies."

Preclinical • Alzheimer's Disease • CNS Disorders

Reduction of tau to baseline levels and rescue of motor impairment in a therapeutic study in aged JNPL3 mice treated with small molecule OLX-07010 targeting tau self-association (Neuroscience 2021) - "Moreover, the reduction in tau aggregation in the cortex and its aberrant phosphorylation correlated with improved motor performance in the Rotarod assay and in open field arena analyses. Preclinical studies are being performed for an IND submission to the FDA to enable planned first-in-human studies.; Grant Support: NIH Grant AG029777; NIH Grant AG057325; ADDF Grant NS49442; NIH Grant AG066384; NIH Grant AG033474; NIH Grant AG053150; NIH Grant AG062021"

Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • MAPT

Oral treatment with OLX-07010, a small molecule inhibitor of tau self-association, reduced tau aggregation to baseline in a therapeutic study of aged tau P301L JNPL3 mice (CTAD 2021) - "Treatment with the lead caused significant reduction in tau aggregates in blinded preventive studies in the htau model and showed efficacy in both preventive and therapeutic studies in JNPL3 mice modeling 4R tau aggregation in tauopathies. Taken together these studies support the development OLX-07010 for the reduction of tau oligomers and larger aggregates to modify the course of AD and rare tauopathies. Our small molecule approach allows for ease of administration, complementary therapy and, importantly, a cost-effective treatment option."

Late-breaking abstract • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • Movement Disorders • Progressive Supranuclear Palsy • MAPT