mirodenafil (AR1001) / ariBio, Samjin Pharma, Fosun Pharma, Neuco United - LARVOL DELTA

Phase 2 Trial Data Support AR1001 as Potential Alzheimer Disease Monotherapy (NeurologyLive) - P2 | N=210 | NCT03625622 | Sponsor: AriBio Co., Ltd. | "New phase 2 data (NCT03625622) presented at the 2025 Alzheimer’s Association International Conference...As an oral PDE5 inhibitor with known blood-brain barrier penetration, AR1001 was assessed not only for cognitive outcomes but also for changes in plasma biomarkers of neurodegeneration. Overall, the study’s findings suggest that AR1001 may exert therapeutic effects through multiple mechanisms beyond traditional symptomatic treatment....In the subgroup of participants not receiving concomitant AD medications, 30 mg AR1001 once daily for 26 weeks was associated with a statistically significant 4.019-point improvement from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale 13 (ADAS-Cog-13; P = .012), the primary end point. Plasma concentrations of phosphorylated tau (ptau) biomarkers were also significantly reduced: ptau-181 by 1.361 pg/mL (P = .023)..."

P2 data • Alzheimer's Disease

Phase 3, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants With Early Alzheimer's Disease (Polaris-AD) (clinicaltrials.gov) - P3 | N=1535 | Active, not recruiting | Sponsor: AriBio Co., Ltd. | N=1150 ➔ 1535

Enrollment change • Alzheimer's Disease • CNS Disorders

Fosun Medicine Receives Exclusive License for Alzheimer’s Innovative Drug AR1001 [Google translation] (Fosun Pharma Press Release) - "Shanghai Fosun Pharmaceutical...announced that they have signed an exclusive licensing agreement for the production and commercialization of AR1001 in Greater China, including Mainland China, Hong Kong Special Administrative Region of China and Macau Special Administrative Region of China (License Area). AR1001 is a small molecule oral drug intended to delay the progression of Alzheimer’s disease (AD) disease with a potent, highly selective inhibition of phosphodiesterase-5 (PDE-5)....Under the terms of the agreement, Fosun Pharmaceuticals will receive exclusive production and commercialization rights of AR1001 within the licensed area. Newco continues to coordinate collaboration with AriBio to advance the completion of the global Phase III clinical trial."

Licensing / partnership • Alzheimer's Disease

AriBio licenses Alzheimer’s pill to Arcera in $600 mil. deal as merger partner Solux surges (Korea Biomedical Review) - "Korean biotech AriBio has handed over regional rights to its experimental Alzheimer’s drug in a deal worth up to $600 million, aligning with Arcera to drive commercialization across Latin America, the Middle East, Southern Africa, Ukraine, and parts of Eurasia...the licensing and supply agreement gives Arcera and its Swiss affiliate Acino exclusive rights to market AR1001 (mirodenafil), while AriBio retains manufacturing control...The drug is currently in a global phase 3 trial that has enrolled more than 1,500 patients across 13 countries, exceeding its initial target. Topline data are expected in the first half of 2026."

Licensing / partnership • P3 data: top line • Alzheimer's Disease

Mirodenafil improves cognitive function by reducing microglial activation and blood-brain barrier permeability in ApoE4 KI mice. (PubMed, Front Aging Neurosci) - "These findings suggest that mirodenafil enhances cerebrovascular function, preserves BBB integrity, and mitigates neuroinflammation in ApoE4 KI mice, leading to cognitive improvement. PDE5 inhibition may serve as a promising therapeutic approach for addressing ApoE4-associated cerebrovascular and cognitive dysfunction."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • APOE • Aβ42

Phase 3, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants With Early Alzheimer's Disease (Polaris-AD) (clinicaltrials.gov) - P3 | N=1150 | Active, not recruiting | Sponsor: AriBio Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

DIVERSITY IN A PIVOTAL REGISTRATION TRIAL FOR AR1001 IN THE TREATMENT OF EARLY ALZHEIMER'S DISEASE (ADPD 2025) - "This trial demonstrates that efforts to enroll a diverse population can be successful. AriBio continues to refine its recruitment strategy aimed at a trial population that more closely reflects the diversity of the AD patient community."

Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - P3 | "We demonstrate target engagement of AR1001, a PDE5 inhibitor, by showing an increase in cGMP and BNDF levels in the hippocampus following daily treatment. AR1001 had pronounced effects in recovery of cognitive functions in a transgenic mouse model of AD at a dose equivalent to that being tested in the Phase 3 trial in early AD patients."

Journal • Alzheimer's Disease • CNS Disorders

Aribio, 100 additional patients in domestic phase 3 of 'Alzheimer's treatment' [Google translation] (HIT News) - "AriBio...announced on the 5th that it will expand the domestic phase 3 clinical trial patients for its oral Alzheimer's treatment 'AR1001' by 100 more patients to 250. The number of clinical trial centers will also increase from 21 to 26...The company explained that our country’s high level of medical staff and clinical trial center system led to faster-than-expected patient recruitment and administration."

Enrollment status • Alzheimer's Disease

Aribio, Alzheimer’s Clinical Society ’AR1001’ Phase 3 Status Announcement [Google translation] (Medipana) - "From the 29th to the 1st of next month, Aribio will present the results of a total of four studies, including potential blood evaluations related to the oral Alzheimer's disease treatment 'AR1001' phase 3, at the 17th Clinical Trials of Alzheimer's Disease (2024 CTAD) to be held in Madrid, Spain...Professor Sharon Sha will present research results showing that the analysis of 'pTau-217', a major biomarker of Alzheimer's disease, in the AR1001 phase 3 blood evaluation is excellent in determining the positive and negative status of toxic proteins (amyloid beta). Accordingly, it is explained that using the pTau-217/Aβ42 ratio as a blood biomarker can save time and cost in clinical trial screening for Alzheimer's disease, such as reducing the need for positron emission tomography (PET) and cerebrospinal fluid (CSF) tests."

P3 data • Alzheimer's Disease • CNS Disorders

Diversity in a Registrational Trial for AriBio's AR1001 for Treatment of Early Alzheimer's Disease (CTAD 2024) - No abstract available

Alzheimer's Disease • CNS Disorders

Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats. (PubMed, Neurotherapeutics) - "Using pMCAO and tMCAO rat models of stroke, we determined that mirodenafil improves the recovery of sensorimotor and cognitive functions after MCAO and protects cortical cells from apoptosis and degeneration. Greater benefit was observed with longer duration of treatment, and improvement was seen even when treatment was delayed."

Journal • Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Erectile Dysfunction • CASP3

Adaptive Research Announces it has Begun Enrolling Patients in AriBio’s Phase 3 POLARIS-AD Clinical Trial (GlobeNewswire) - "Adaptive Research...announced two community practices that are part of the Adaptive Research network have begun patient enrollment and randomization in AriBio’s Phase 3, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants With Early Alzheimer's Disease (POLARIS-AD)...AriBio is expected to enroll 1150 participants in this global Phase 3 clinical trial to evaluate the therapeutic potential of AR1001 in the treatment of early Alzheimer’s disease."

Enrollment open • Alzheimer's Disease • CNS Disorders

AriBio announces 'AR1001 global clinical phase 3' at 2024 Asian Dementia Association (ASAD) [Google translation] (Hankyung) - "Aribio recently presented the global phase 3 clinical trial of AR1001, a multi-mechanism oral Alzheimer’s disease treatment, to dementia clinicians from various Asian countries at the 18th Asian Society for Dementia (ASAD) held in Penang, Malaysia. Aribio CEO Jae-Jun Jeong (PhD) appeared as a presenter on August 17 and introduced the main pipeline and the phase 2 clinical data, including the pharmacological action and cognitive function improvement effect and safety of AR1001, and improvement of major biomarkers such as p-Tau181. He also explained the main clinical design, evaluation index, and development strategy of the global phase 3 clinical trial (Polaris-AD) currently underway in multiple countries."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Dementia

Solux, Aribio merger: 'Large-scale clinical trials make rapid listing inevitable' [Google translation] (Hankyung) - "Solux...has absorbed and merged with Aribio. The surviving company after the merger will be Solux, and the disappearing company will be Aribio, but the surviving company's name will be Aribio. The merger ratio is 1 to 2.5032656. The merger date is November 1. Aribio is currently conducting a global phase 3 clinical trial for 'AR1001', the world's first multi-mechanism oral dementia treatment under development."

M&A • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - P2 | "AR1001 had protective effects both in vivo and in vitro models of AD. Furthermore, AR1001 showed more pronounced activity in the modulation of GR and Wnt signaling among the various PDE-5 inhibitors. It is suggested that the multimodal activity of AR1001 contributes to the therapeutic effects of AR1001 observed in the phase 2 clinical trial in AD patients (NCT03625622)."

Journal • Alzheimer's Disease • CNS Disorders • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • CASP3 • DKK1 • NGF • WNT3A

AriBio Co., Ltd. and Fujirebio Diagnostics, Inc. Announce Milestone Achievement to Advance Biomarker Development for Alzheimer’s Disease and Neurodegeneration (Businesswire) - "Fujirebio Holdings Inc., its wholly-owned subsidiary Fujirebio Diagnostics, Inc., and AriBio Co., Ltd. announced today the attainment of the first milestone in a strategic partnership to advance the development of biomarkers for Alzheimer’s disease (AD) and other neurodegenerative conditions. This milestone marks a key achievement which provides Fujirebio access to clinical samples and data collected as part of the ongoing Phase 3 Alzheimer’s disease study, POLARIS-AD. POLARIS-AD will enroll up to 1150 participants with early Alzheimer’s disease using AriBio’s AR1001, a PDE5 inhibitor shown to inhibit neuron apoptosis, promote neurogenesis, increase neuroplasticity and stimulate autophagy activity to remove toxic proteins. The Phase 3 study has now expanded into South Korea, Europe, the United Kingdom and China."

Biomarker • Licensing / partnership • Trial status • Alzheimer's Disease

AriBio Co., Ltd. Announces Strategic Collaboration with Kentucky Clinical Trial Laboratory (KCTL) to Expand Alzheimer’s Disease Testing (Businesswire) - "AriBio Co., Ltd. (AriBio) announces the expansion of testing for Alzheimer’s disease by entering into a strategic collaboration with Kentucky Clinical Trial Laboratory (KCTL) for the testing of cerebral spinal fluid (CSF) to accurately and efficiently aid in the diagnosis of Alzheimer’s disease using the Lumipulse system from FujireBio. Samples from AriBio’s POLARIS-AD (AR1001-ADP3-US01) study...can be tested for Aβ42/40 ratio with the U.S. Food and Drug Administration (FDA) approved assay on the Lumipulse system."

Licensing / partnership • Alzheimer's Disease • CNS Disorders

Target Engagement and Therapeutic Effects of AR1001, a Phosphodiesterase-5 Inhibitor, in Alzheimer’s Disease Models (AAIC 2024) - P3 | "Conclusion : We demonstrate target engagement of AR1001 , a P DE5 inhibitor, by showing a n increase in cGMP and BNDF levels in the hippocampus following daily treatment. AR1001 had pronounced effects in recovery of cognitive functions in a transgenic mouse model of AD at a dose equivalent to t hat being tested in the Phase 3 trial in early AD patients."

Alzheimer's Disease • CNS Disorders

AriBio Receives IND Approval from China’s NMPA for POLARIS-AD, a Phase 3 Trial for the Treatment of Early Alzheimer’s Disease (Businesswire) - "AriBio...announces approval of the Investigational New Drug (IND) application by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the initiation of the Phase 3 Polaris-AD trial in China of AR1001 in early Alzheimer’s Disease (AD) on May 11th, 2024. The Phase 3 clinical trial will enroll early AD patients at up to 20 clinical trial centers in China with consistent eligibility criteria compared to other countries that are also enrolling patients....Looking ahead, AriBio is poised to commence the Phase 3 clinical trial in China in Q3 2024."

Trial status • Alzheimer's Disease

AriBio Receives EMA Phase 3 Clinical Trial Authorisation for AR1001 in Treatment of Alzheimer’s Disease (POLARIS-AD) (Businesswire) - "AriBio...announced authorisation from the European Medicines Agency (EMA) for POLARIS-AD (AR1001-ADP3-US01), a global, phase 3, early Alzheimer’s disease clinical trial. EMA now aligns with the U.S. Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) on the Clinical Trial Authorisation of POLARIS-AD. The final decision from EMA was completed on April 24th with clinical trial approvals in the following member states: Czech Republic, Denmark, France, Germany, Italy, Spain and The Netherlands. Currently, 1,150 participants are expected to be randomized into the Phase 3 clinical trial across 200 sites globally. POLARIS-AD is a double-blind, randomized, placebo-controlled, multi-center registration trial evaluating the efficacy and safety of AR1001 (Mirodenafil) in treatment of patients with early Alzheimer’s disease (AD) with confirmed amyloid pathology."

Trial status • Alzheimer's Disease

AriBio Licenses Exclusive Marketing Rights for AR1001 for Alzheimer’s Disease in China for $770 Million USD (Businesswire) - "AriBio Co., Ltd. (AriBio), announces signing of exclusive marketing rights for AR1001, an investigational drug for early Alzheimer’s disease, in China for up to $770 million USD. The term consists of a non-refundable upfront payment of 120 billion KRW (approximately 90 million USD), with the total deal summing up to 5.59 billion RMB (approximately 770 million USD) inclusive of milestone payments with additional royalties. The upfront payment will be paid starting from mid-2024."

Licensing / partnership • Alzheimer's Disease

MHRA Issues Notice of Acceptance for POLARIS-AD, a Phase 3 Early Alzheimer’s Disease Trial Sponsored by AriBio Co., Ltd. (Businesswire) - "AriBio...receives Notice of Acceptance for POLARIS-AD, a Phase 3 early Alzheimer’s disease clinical trial from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom (UK). The MHRA completed their review on the 21 of February and confirmed a favorable ethical opinion, the Company expects to initiate the clinical trial before the end of Q1’2024 in the UK. POLARIS-AD is a double-blind, randomized, placebo-controlled, multi-center registration trial to evaluate the efficacy and safety of AR1001 (Mirodenafil) over 52 weeks of treatment in patients with early Alzheimer’s disease."

Trial status • Alzheimer's Disease

THERAPEUTIC EFFECTS OF AR1001, A PHOSPHODIESTERASE 5 INHIBITOR, IN THE MIDDLE CEREBRAL ARTERY OCCLUSION MODEL OF STROKE IN RATS (ADPD 2024) - "AR1001 demonstrated protective effects in MCAO-induced mild and severe stroke rate models."

Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • CASP3

AriBio sets up drug marketing network with Vietnamese state enterprise (Korea Biomedical Review) - "AriBio has entered into a comprehensive collaboration with Vietnam's state-owned Central Pharmaceutical Joint Stock Company (CPC1) to sell and distribute AR1001, an oral dementia treatment candidate....Under the agreement, AriBio will develop a highly efficient extraction method for special active ingredients that support neurological stabilization and immune-related balance and transfer the technology to Vietnam three to five years after the development."

Licensing / partnership • Alzheimer's Disease • CNS Disorders • Dementia