Follow up Protocol to the Open Label Phase I/II Study OPN-305-106: A Prospective, Open Label Phase I/II Study to Assess the Safety and Efficacy of Cycles of Intravenously Infused Doses of OPN-305 in Second-line and Third-line Lower (Low and Intermediate-1) Risk Myelodysplastic Syndrome (MDS)

This protocol is a follow-up for patients receiving continuation of OPN-305 monotherapy treatment or combination treatment with azacitidine after completion of the dose confirming, dose expansion and HMA naïve parts of the main study OPN-305-106.

Start Date27 Feb 2018

Sponsor / Collaborator

Opsona Therapeutics Ltd.

[+3]

NCT02363491

/ CompletedPhase 1/2

A Prospective, Open Label Phase I/II Study to Assess the Safety and Efficacy of Cycles of Intravenously Infused Doses of OPN-305 in Second-line or Third-line Lower (Low and Intermediate-1) Risk Myelodysplastic Syndrome (MDS)

The dose-confirming part of this study, comprising at least 10 patients is designed as a single center, prospective, single arm, open label in patients who have failed or are unresponsive to Azacitidine (AZA) or Decitabine (they may also have additionally failed an Erythropoiesis Stimulating Agent (ESA) followed by a dose expansion part with at least 44 patients; the objective of the whole study being to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of intravenously infused multiple doses of OPN-305 in low and intermediate-1 risk myelodysplastic syndrome (second and third line Lower risk MDS).

Start Date01 Jan 2015

Sponsor / Collaborator

Opsona Therapeutics Ltd.

[+3]

EUCTR2012-005767-27-AT

/ Not yet recruitingPhase 2

Follow-up Protocol to the Double-Blind Parts A and B of the Phase II Opsona Study OPN305-102 (A Three-Part, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Sequential Adaptive, Phase II Study to Evaluate the Safety, Tolerability and Efficacy of OPN-305, a Humanised Monoclonal Antibody that Blocks Toll-Like Receptor 2, in Renal Transplant Patients at High Risk of Delayed Graft Function)

Start Date19 Feb 2014

Sponsor / Collaborator

Opsona Therapeutics Ltd.

100 Clinical Results associated with Tomaralimab(Opsona Therapeutics Ltd.)

100 Translational Medicine associated with Tomaralimab(Opsona Therapeutics Ltd.)

100 Patents (Medical) associated with Tomaralimab(Opsona Therapeutics Ltd.)

Literatures (Medical) associated with Tomaralimab(Opsona Therapeutics Ltd.)

01 Dec 2024·Biochemical and Biophysical Research Communications

TLR2–EGR1 signaling axis modulates TGFβ1-induced differentiation of fibroblasts into myofibroblasts in pulmonary fibrosis

Article

Author: Han, Junekyu ; Jung, Euitaek ; Shin, Soon Young ; Kim, Tae Yoon ; Lee, Kye Young

Pulmonary fibrosis is a progressive lung condition characterized by the excessive activation of myofibroblasts. Transforming growth factor beta 1 (TGFβ1) plays a crucial role in the differentiation of fibroblasts into myofibroblasts. In addition, toll-like receptor 2 (TLR2), known for its role in immune responses, contributes to pulmonary fibrosis by promoting myofibroblast differentiation. However, the interplay between TGFβ1 and TLR2 signaling pathways in myofibroblast differentiation has remained elusive. In the present study, we investigated the involvement of TLR2 in TGFβ1-induced fibroblast differentiation into myofibroblasts using IMR-90 human pulmonary fibroblasts as a model cell line. We found that TLR2 activation induced myofibroblast differentiation by enhancing the expression of early growth response 1 (EGR1) via the mitogen-activated protein kinase (MAPK) signaling pathway. Elevated EGR1 levels were detected in the lung tissues of a bleomycin (BLM)-induced mouse model of pulmonary fibrosis. Moreover, the administration of tomaralimab, an antagonistic anti-TLR2 antibody, reduced the EGR1 expression and collagen deposition. Altogether, targeting the TLR2-EGR1 pathway could be a promising therapeutic approach for pulmonary fibrosis by blocking TGFβ1-induced myofibroblast differentiation.

01 Oct 2024·Brain, Behavior, and Immunity

TLR2 immunotherapy suppresses neuroinflammation, tau spread, and memory loss in rTg4510 mice

Article

Author: Ryu, Shin-Hyeon ; Cho, Young-Sin ; Kim, Youbin ; Hyun, Junho ; Jung, Yong-Keun

In Alzheimer's disease, chronic neuroinflammation is accompanied by amyloid and tau pathologies. Especially, aberrant microglial activation is known to precede the regional tau pathology development, but the mechanisms how microglia affect tau spread remain largely unknown. Here, we found that toll-like receptor 2 (TLR2) in microglia recognizes oligomeric tau as a pathogenic ligand and induces inflammatory responses. Knockout of TLR2 reduced tau pathology and microglial activation in rTg4510 tau transgenic mice. Treatment of oligomeric tau induced TLR2 activation and increased inflammatory responses in microglial cells. TLR2 further mediated the tau-induced microglial activation and promoted tau uptake into neurons in neuron-microglia co-culture system and in mouse hippocampus after intracranial tau injection. Importantly, treatment with anti-TLR2 monoclonal antibody Tomaralimab blocked TLR2 activation and inflammatory responses in a dose-dependent manner, and significantly reduced tau spread and memory loss in rTg4510 mice. These results suggest that TLR2 plays a crucial role in tau spread by causing aberrant microglial activation in response to pathological tau, and blocking TLR2 with immunotherapy may ameliorate tau pathogenesis in Alzheimer's disease.

16 Aug 2022·ACS Omega

Unraveling the Tomaralimab Epitope on the Toll-like Receptor 2 via Molecular Dynamics and Deep Learning

Article

Author: Ahmad, Bilal ; Choi, Sangdun

Tomaralimab (OPN-305) is the first humanized immunoglobulin G4 monoclonal antibody against TLR2 and is designed to prevent inflammation that is driven by inappropriate or excessive activation of innate immune pathways. Here, we constructed a homology model of Tomaralimab and its complex with TLR2 at different mapped epitopes and unraveled their behavior at the atomistic level. Furthermore, we predicted a novel epitope (leucine-rich region 9-12) near the lipopeptide-binding site that can be targeted and studied for the utility of therapeutic antibodies. A geometric deep learning algorithm was used to envisage Tomaralimab binding affinity changes upon mutation. There was a significant difference in binding affinity for Tomaralimab following epitope-mutated alanine substitutions of Val266, Pro294, Arg295, Asn319, Pro326, and His372. Using deep learning-based ΔΔG prediction, we computationally contrasted human TLR2-TLR2, TLR2-TLR1, and TLR2-TLR6 dimerization. These results reveal the mechanism that underlies Tomaralimab binding to TLR2 and should help to design structure-based mimics or bispecific antibodies that can be used to inhibit both lipopeptide-binding and TLR2 dimerization.

News (Medical) associated with Tomaralimab(Opsona Therapeutics Ltd.)

01 Mar 2024

·www.globenewswire.com

BioVie’s NE3107 Demonstrates Potential Improvements in Motor and Non-motor Symptoms for Parkinson’s Disease Patients and May Be Realigning Physiological Processes for Alzheimer’s Patients in Data to be Presented at the International Conference on Alzheimer’s and Parkinson’s Diseases 2024

Data from Phase 2a trial in Parkinson’s Disease suggest patients treated with NE3107 experienced significant improvements in non-motor symptoms and motor control while placebo-treated patients worsened Data from Phase 3 trial in mild to moderate Alzheimer’s Disease suggest NE3107 may have the potential to realign physiological processes in patients consistent with decreased neurocognitive decline and diseases of aging CARSON CITY, Nev., March 01, 2024 (GLOBE NEWSWIRE) -- BioVie Inc., (NASDAQ: BIVI) (“BioVie” or the “Company”) a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease, today announced two upcoming presentations at the International Conference on Alzheimer’s and Parkinson’s Diseases 2024 (AD/PD™ 2024) to be held March 5-9, 2024 in Lisbon, Portugal. Improvements in non-motor symptoms correlated with improvements in motor symptoms for Parkinson’s Disease patients The presentation Improvement of Non-Motor Symptoms with NE3107 Adjunctive to Carbidopa/Levodopa in Patients with Parkinson’s Disease: A Phase 2A, Placebo-Controlled Study will be presented at 15:10 GMT on March 9, 2024 and suggest improvements of NE3107-treated patients with non-motor symptoms. These findings complement previously reported improvement in motor symptoms in patients treated with NE3107 and demonstrate potential intrinsic, levodopa-enhancing activity of NE3107 that is consistent with data from animal models. NE3107-treated patients experienced a significant improvement of -2.4 points for the sleep/fatigue domain of the Non-Motor Symptom Scale (NMSS) in Parkinson’s Disease, whereas placebo patients experienced a worsening of +1.0 points (p=0.0159). Sleep/fatigue domain improvements correlated with motor score improvements (r=0.51; p=0.0259). More patients on NE3107 had improvements in the NMSS sleep/fatigue domain, while more patients on placebo worsened. NMSS changes for NE3107-treated patients were driven by improvements of -0.87 in fatigue/lack of energy (p= 0.0005) and improvement of -2.91 on the urge to move legs/restlessness in legs (p=0.0036). Placebo patients saw no significant change of -0.39 on fatigue (p=0.1242) and -0.71 on leg restlessness (p=0.5141). The new data on non-motor improvements complements previously presented data1 showing NE3107-treated patients saw a 3+ points advantage compared to placebo on the Part 3 (motor) score of the Motor Disease Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). In patients younger than 70 years old, the advantage was over 6 points. Furthermore, 26% of NE3107-treated patients experienced improvement in their ability to move, having Part 3 scores prior to their first morning dose of carbidopa/levodopa that were equal to or better than Part 3 scores associated with their being in the “on” state after carbidopa/levodopa treatment at the start of the study, whereas none of the placebo patients had the similarly improved morning Part 3 scores. The difference was statistically significant (p=0.046). “These data suggest that NE3107 as adjunct therapy to levodopa may hold promise in ameliorating specific non-motor symptoms of Parkinson’s Disease, particularly in sleep/fatigue and restlessness of the legs,” stated Joseph Palumbo, BioVie’s Chief Medical Officer. “These findings extend previously reported improvement in motor symptoms with NE3107 and demonstrate potential intrinsic and levodopa-enhancing activity of NE3107 that is consistent with data from animal models and support further clinical investigation of NE3107 in late-phase trials.” Possible physiological realignment in Alzheimer’s Disease The presentation Clinical Outcomes from a Phase 3, Randomized, Placebo-Controlled Trial of NE3107 in Subjects with Mild to Moderate Probable Alzheimer’s Disease will be presented at 14:50 GMT on March 8, 2024 reconfirms topline cognitive and functional data previously presented and will provide additional biomarker data and analyses. The NM101 Trial enrolled 439 patients through 39 sites. The Company previously reported that upon trial completion, significant deviation from protocol and Good Clinical Practice violations were found at 15 sites, causing the Company to exclude all patients from these sites. After these exclusions and other exclusions per the statistical analysis plan, 57 patients in the Per-Protocol population were verified to have taken study drug from pharmacokinetics data and completed the full duration of the trial. Baseline and completion data were available for 50 subjects (NE3107, n=24 and placebo, n=26; 7 subjects randomized to placebo discontinued before day 150), and DNA methylation data were available for 33 subjects in this cohort. Due to the exclusion of data from so many sites the trial missed statistical significance but showed promising directional data on cognitive and functional measures. NE3107-treated patients saw an advantage compared to placebo of -0.95 (68% slowing of decline) on CDR-SB, -0.94 (26%) on ADAS-COG-12, -0.43 (139%) on ADAS-CGIC, -0.03 (27%) on ADCOMS, +1.02 (40%) on MMSE, and +3.08 (47%) on ADCS-ADL.2 Significant improvements for NE3107-treated patients vs. placebo were observed for biological age deceleration (-3.87 years, p=0.012), fasting glucose levels (-8.5 mg/dL, p=0.036), cholesterol (-15 mg/dL, p=0.049), HOMA2 beta cell function (+12.4%, p=0.040), HOMA2 Insulin Sensitivity (+1.95%, p=0.018), and MCP1 (-90.5 pg/mL, p=0.007). Trending improvements in HOMA2 Insulin Resistance of -0.020 (p=0.0.063) were also observed. A statistical technique called Principal Component Analysis3 identified neurological assessments and biological age deceleration as the two “principal components” that maximally explained the data across the large set of variables collected. Among NE3107-treated patients, correlations of neurological assessments and biological age deceleration with improved metabolic and glycemic control, improved neuropsychiatric indices, and levels of chemokines associated with microglial attraction to and digestion of Aβ plaques. Among placebo patients, neurological assessments and biological age deceleration were correlated with increased metabolic inflammatory measures, M1 to M2 transition, and plaque phagocytosis. “We previously reported that NE3107 appeared to decrease metabolic inflammation-driven systems dysregulation,” stated Chris Reading, BioVie’s Senior Vice President of Alzheimer’s Disease Programs. “Principal component analyses, divergent correlations, and epigenetic analysis suggest that metabolic inflammation may be a driver of biological aging and AD, and that NE3107 might have the potential to realign physiological processes consistent with decreased neurocognitive decline and diseases of aging.” “The data being presented reinforce our confidence in the potential of NE3107 to have a meaningful impact on core symptoms of both Alzheimer's disease and Parkinson's disease,” stated Cuong Do, BioVie's President and CEO. “These findings add to the growing body of evidence supporting our hypothesis that by selectively modulating inflammation and enhancing insulin sensitivity in the brain, NE3107 could offer benefits in slowing disease progression and improving the lives of patients living with these devastating conditions.” About BioVie BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate NE3107 inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of Alzheimer’s and Parkinson’s diseases. The Company conducted and reported efficacy data from its randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate NE3107 in patients who have mild to moderate Alzheimer's disease (NCT04669028). Results of a Phase 2 investigator-initiated trial (NCT05227820) showing NE3107-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trial in Alzheimer’s Disease (CTAD) annual conference in December 2022. An estimated six million Americans suffer from Alzheimer’s. A Phase 2 study of NE3107 in Parkinson’s disease (NCT05083260) has completed, and data presented at the International Conference on Alzheimer's and Parkinson's Disease and Related Neurological Disorders conference in Gothenburg, Sweden in March 2023 showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of NE3107 and levodopa vs. patients treated with levodopa alone, and no drug-related adverse events. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with U.S. Food and Drug Administration (FDA) Fast Track status, is being evaluated and discussed with guidance received from the FDA regarding the design of Phase 3 clinical testing of BIV201 for the treatment of ascites due to chronic liver cirrhosis. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. For more information, visit http://www.bioviepharma.com/. Forward-Looking Statements This press release contains forward-looking statements, which may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. In this press release, forward-looking statements include, but are not limited to, the potential impact of NE3107 on cognition and function among study participants and topline data from the NE3107 trial. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due to the Company's ability to successfully raise sufficient capital on reasonable terms or at all, available cash on hand and contractual and statutory limitations that could impair our ability to pay future dividends, our ability to complete our pre-clinical or clinical studies and to obtain approval for our product candidates, our ability to successfully defend potential future litigation, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law. For Investor Relations Inquiries: Contact:Bruce MackleManaging DirectorLifeSci Advisors, LLCbmackle@lifesciadvisors.com For Media InquiresMelyssa WeibleManaging Partner, Elixir Health Public Relations Ph: +1 201-723-5705mweible@elixirhealthpr.com _________________________1 A Randomized, Phase 2a, Double-Blind, Placebo-Controlled Clinical Trial With NE3107 Adjunctive to Carbidopa/Levodopa in Patients With Parkinson’s Disease. Presented at the 2023 International Congress of Parkinson’s Disease and Movement Disorders, August 27-31, 2023 in Copenhagen, Denmark2 ADAS-Cog12 = 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (lower is improvement); ADCOMS = Alzheimer’s Disease Composite Score (lower is improvement); ADCS-ADL = Alzheimer’s Disease Cooperative Study-Activities of Daily Living (higher is improvement); ADCS-CGIC = Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (lower is improvement); CDR-SB = Clinical Dementia Rating, Sum of Boxes (lower is improvement), MMSE = Mini Mental State Examination (higher is improvement).3 Principal component analysis is a statistical method for identifying/combining separate variables to a few “principal components” that maximally explain the variance of all the underlying variables. In the process, the method provides an approximation of the original data represented by the many individual variables using only a few major components.

Clinical ResultPhase 2Orphan DrugFast Track

20 Dec 2023

·www.biospace.com

Terran Biosciences Receives FDA Clearance for NM-101, the industry’s first software for the analysis of neuromelanin-sensitive MRI

MIAMI--(BUSINESS WIRE)-- Terran Biosciences, Inc. ("Terran"), a biotech platform company developing therapeutics and technologies for patients with neuropsychiatric illnesses, has received FDA clearance to market NM-101, a cloud-based software platform to analyze neuromelanin-sensitive MRI scans. Currently, there is no other FDA-cleared software indicated for the analysis of neuromelanin MRI on the market, making Terran’s technology the world’s first. NM-101 is a cloud-based analysis platform that is able to seamlessly integrate into existing workflows at hospitals and imaging centers. The device allows doctors to send neuromelanin MRI images to Terran directly through the hospital picture archiving and communication system (PACS) and receive a full report back in under an hour. When interpreted by a neuroradiologist, NM-101 can provide information useful in determining neuromelanin association as an adjunct to diagnosis. “This is a big moment for us and our collaborators and we’re thrilled to bring this new tool to doctors where it can begin benefiting patients,” said Terran Biosciences Founder and CEO Sam Clark, MD, PhD. “We were excited to partner with leading researchers in the field and conduct the key development steps necessary to bring it through to FDA clearance. We believe this technology could become very important in the clinical workflow of patients with neurological and psychiatric disorders.” Neuromelanin is a molecule associated with certain cell populations in the brain. While neuromelanin was first described in the 19th century, researchers have elucidated its possible role as a biomarker for neurological disorders such as Parkinson’s disease in the last two decades. Studies show that neuromelanin MRI may provide useful adjunctive information to aid in the evaluation of Parkinson’s disease, and avoids the disadvantages of current adjunctive imaging modalities such as DaT-SPECT, which requires a five-hour procedure, intravenous radiation exposure, and can cost well over $3,000 [1-6]. A recent meta-analysis of 12 clinical neuromelanin MRI studies comprising 403 patients with Parkinson’s disease and 298 control participants concluded that neuromelanin MRI provided a “favorable diagnostic performance in discriminating patients with Parkinson’s disease from healthy controls” [7]. The benefits of neuromelanin MRI include: Fast scan time (less than 10 min of additional time in the scanner) No injections No exposure to radiation Cost-effective; can be added to the MRI that most patients already receive as part of their initial workup Potential to provide adjunctive information in indications beyond Parkinson’s disease, such as Alzheimer’s disease and schizophrenia [6,7,9-12] David Sulzer, PhD, professor of neurobiology at Columbia University Vagelos College of Physicians and Surgeons and co-author of multiple studies using neuromelanin MRI, commented, “The research suggests that neuromelanin MRI is a promising approach with the potential to become part of the standard of care for the workup of all patients suspected of Parkinson’s and related diseases.” One of the first researchers to study neuromelanin, Luigi Zecca, MD, PhD, head of the Brain Aging and Neurodegeneration Unit at the Institute of Biomedical Technologies-CNR in Milan, commented on the news, “After many years of hard work to show neuromelanin MRI could be a powerful tool, it’s exciting to see this technology finally become available to physicians and patients.” Despite these benefits, there have been no FDA-approved devices capable of providing clinicians with analysis of neuromelanin MRI due to a lack of automation and standardization that has prevented its clinical use. Historically, the standardization of neuromelanin measurement has been difficult due to variability in results among MRI scanners, even those from the same manufacturer and model [7,8]. NM-101 contains algorithms that enabled for the first time the fully automated analysis and the cross-scanner harmonization of neuromelanin MRI scans [8-10,12,13]. Guillermo Horga, MD, PhD, Associate Professor of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons, and Clifford Cassidy, PhD, now Assistant Professor of Cellular and Molecular Medicine at the University of Ottawa, were pioneers of the original algorithms and authors of studies using neuromelanin MRI in neuropsychiatric disorders including schizophrenia [9,12]. “It’s great to see neuromelanin MRI become more accessible in clinical settings,” said Dr. Horga. “We hope this opens the door for the adoption of neuromelanin MRI into the clinical workflow for patients with neuropsychiatric disorders.” “Now that we’re able to access measurements of neuromelanin-associated signal in both the substantia nigra and locus coeruleus,” added Dr. Cassidy, “it allows us to obtain potentially useful adjunctive information about many other diseases such as Alzheimer’s disease, and PTSD.” Disclosures Terran Biosciences has an exclusive license to the CNS biomarker software platform and related patents co-owned by Columbia University and Research Foundation for Mental Hygiene. Dr. Horga will receive a portion of the royalties paid to Columbia University for sales of the product. ABOUT TERRAN BIOSCIENCES Terran Biosciences is a biotech platform company developing a portfolio of therapeutics and technologies for patients with neurological and psychiatric diseases. Terran has built a CNS-focused, tech-enabled drug development platform, and is rapidly advancing a number of late-stage assets, which includes a neuroimaging software platform (now FDA cleared), a late-stage therapeutic for schizophrenia, and a drug design engine that has generated first-in-class and best-in-class psychedelic-based therapeutics. Follow us on LinkedIn and X. Learn more about NM-101 at . Citations Okuzumi, A., et al. "Neuromelanin or DaT‐SPECT: which is the better marker for discriminating advanced Parkinson's disease?" European journal of neurology 26.11 (2019): 1408-1416. Pavese, Nicola. "Is neuromelanin the imaging biomarker for the early diagnosis of Parkinson's disease that we were looking for?" Parkinsonism & Related Disorders 58 (2019): 1-2. Prasad, Shweta, et al. "Motor asymmetry and neuromelanin imaging: Concordance in Parkinson's disease." Parkinsonism & Related Disorders 53 (2018): 28-32. Liu, Yu, et al. "Optimizing neuromelanin contrast in the substantia nigra and locus coeruleus using a magnetization transfer contrast prepared 3D gradient recalled echo sequence." Neuroimage 218 (2020): 116935. Wang, Xiangming, et al. "The diagnostic value of SNpc using NM-MRI in Parkinson’s disease: meta-analysis." Neurological Sciences 40 (2019): 2479-2489. Sulzer, David, et al. "Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson’s disease." NPJ Parkinson's disease 4.1 (2018): 11. Cho, Se Jin, et al. "Diagnostic performance of neuromelanin-sensitive magnetic resonance imaging for patients with Parkinson’s disease and factor analysis for its heterogeneity: a systematic review and meta-analysis." European radiology 31 (2021): 1268-1280. Wengler, Kenneth, et al. "Cross‐scanner harmonization of neuromelanin‐sensitive MRI for multisite studies." Journal of Magnetic Resonance Imaging 54.4 (2021): 1189-1199. Cassidy, Clifford M., et al. "Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain." Proceedings of the National Academy of Sciences 116.11 (2019): 5108-5117. Cassidy, Clifford M., et al. "Association of locus coeruleus integrity with Braak stage and neuropsychiatric symptom severity in Alzheimer’s disease." Neuropsychopharmacology 47.5 (2022): 1128-1136. Horga, Guillermo, Kenneth Wengler, and Clifford M. Cassidy. "Neuromelanin-sensitive magnetic resonance imaging as a proxy marker for catecholamine function in psychiatry." JAMA psychiatry 78.7 (2021): 788-789. Wengler, Kenneth, et al. "Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals." JAMA psychiatry (2023). Al Haddad, Rami, et al. "Normative Values of Neuromelanin‐Sensitive MRI Signal in Older Adults Obtained Using a Turbo Spin Echo Sequence." Journal of Magnetic Resonance Imaging 58.1 (2023): 294-300.

License out/in

28 Aug 2023

·www.globenewswire.com

BioVie Presents Data for NE3107 at 2023 International Congress of Parkinson’s Disease and Movement Disorders

New preclinical data characterizing NE3107 mechanism of action featured in oral presentationPhamacokinetic data from Phase 2a study supports potential co-administration of NE3107 with carbidopa/levodopaSeparate analysis of Phase 2a study data shows evidence of motor effects of NE3107 independent of levo-dopa/ carbidopa, supporting further investigation of NE3107 as first line therapy in Parkinson’s Disease CARSON CITY, Nev., Aug. 28, 2023 (GLOBE NEWSWIRE) -- BioVie Inc., (NASDAQ: BIVI) (“BioVie” or the “Company”) a clinical-stage company developing innovative drug therapies for the treatment of advanced liver disease and neurological and neurodegenerative disorders, today announced details of three presentations given from studies of NE3107 in the treatment of Parkinson’s Disease (PD) at the 2023 International Congress of Parkinson’s Disease and Movement Disorders (MDS), being held in Copenhagen, Denmark August 27-31, 2023. “The results and analysis we are presenting at the MDS this week add to the growing body of data for NE3107 that support our core understanding of this molecule and its potential in diseases such as PD,” said Cuong Do, President and CEO of BioVie. “The presentations include new pre-clinical data that support the relationship between neuroinflammation and insulin resistance in diseases like PD, and new analyses from our Phase 2a clinical trial that further characterize the pharmacokinetics of NE3107 and its potential as an adjunctive or first-line therapy. We are pleased to see these results highlighted at the MDS Congress this week, which provide confidence in the potential of this asset as we look ahead to topline data readout from our Phase 3 Alzheimer’s trial later this fall.” Details of the three presentations are as follows: Effects of NE3107 Anti-Inflammatory Treatment on Motor Activity and Neurodegenerative Features of Parkinson’s Disease in a Marmoset Monkey Model (Ingrid H.C.H.M. Philoippens, Clarence Ahlem, Christopher L Reading) – presented as a poster and oral presentation on Wednesday, 30 August 2023 13:00 CEST Objectives of this pre-clinical study were to evaluate the safety, tolerability, and the extent of anti-inflammatory effects of NE3107 treatment, specifically on the major features of PD in marmosets with Parkinson’s-like disease.Results showed that mean immobility scores with NE3107 monotherapy (during weeks 8 and 9 on therapy) were significantly lower, indicating improved mobility, than comparison treatment with amantadine HCl or vehicle only. These improvements within 24 hours of initiating NE3107 monotherapy, suggesting a direct influence on neuro-motor signaling, as opposed to an effect that increased with time of treatment, which might imply a link to neuroprotection.Investigators concluded that the findings corroborate the involvement of chronic neuroinflammation and insulin resistance in PD clinical symptoms, in addition to neurodegenerative pathways, support the continued investigation of therapies like NE3107 nondopaminergic therapies. Safety and Pharmacokinetics of Anti-Inflammatory NE3107 Treatment in Carbidopa/Levodopa-TreatedPatients with Parkinson’s Disease: A Phase 2a, Double-Blind, Placebo-Controlled Study (Jason Aldred, Ramon Rodriguez, et al) – presented as a poster Monday, 28 August 2023 at 13:00 – 15:00 CEST The objectives of this clinical trial were to evaluate the safety, tolerability, and exploratory effects of anti-inflammatory NE3107 treatment adjunctive to concomitantly administered carbidopa/levodopa (C/L) in patients with PD and examine its effects on the pharmacokinetics (PK) of levodopa.Results showed that in comparison of Day 1 and Day 14 of treatment, PK parameters demonstrated that NE3107 administration did not affect the PK profile of levodopa: In patients who received NE3107 + C/L, levodopa AUC was 4243.08 (±1913.81) ng·h/mL and 4127.41 (±1568.47) ng·h/mL on day 1 and day 14, respectively.In patients who received placebo + C/L, levodopa AUC was 3175.55 (±2526.68) ng·h/mL and 3093.19 (±1919.73) ng·h/mL on day 1 and day 14, respectively.PK analysis on day 14 showed that levodopa reached a maximum serum concentration (Cmax) of 2089.15 (±973.08) ng/mL and 3093.19 (±1919.73) ng/mL in patients treated with NE3107 + C/L and placebo + C/L, respectively. Investigators concluded that the findings of the NM201 study, together with the results of the marmoset pre-clinical study, suggest that through its anti-inflammatory and insulin-sensitizing properties, NE3107 may possess intrinsic pro-motoric and potentially levodopa-enhancing activities, while having a favorable safety profile, and support further investigation of the safety and clinical benefit of nondopaminergic therapies in late-phase clinical trials. A Randomized, Phase 2a, Double-Blind, Placebo-Controlled Clinical Trial with NE3107 Adjunctive to Carbidopa/Levodopa in Patients with Parkinson’s Disease (Jason Aldred, Ramon Rodriguez, et al) -presented as a poster Monday, 28 August 2023 at 13:00 – 15:00 CEST This separate analysis of the Phase 2a trial examined the exploratory efficacy of NE3107, specifically improvement of motor function, in C/L-treated patients with PD.Clinical efficacy was assessed by evaluating changes in motor control as assessed by MDS-UPDRS scores, between visit 1 and visits 2, 5, and 6, and between visit 2 and visits 5 and 6.Results showed that on day 28, patients treated with NE3107 + C/L demonstrated a lower (3+ points) MDS-UPDRS Part III (motor) score than patients treated with placebo + C/L at the 2- and 3-hour marks, indicating improved motor control. Patients who received NE3107 + C/L had a lower Part III disease score at time 0 (before medication administration) compared to patients treated with placebo + C/L On day 28, patients <70 years old treated with NE3107 + C/L experienced improvements that were ~6 points better than those who received placebo + C/L at the 2- and 3-hour marks NE3107 +C/L-treated patients <70 years old had lower morning OFF state MDS-UPDRS Part III scores prior to medication administration (t=0) compared to those treated with placebo + C/L. 80% of NE3107 + C/L-treated patients and 88.9% of NE3107 + C/L-treated patients <70 years of age demonstrated >30% improvement in their MDS-UPDRS Part III scores 2 hours post administration from baseline, compared with 63.6% and 66.7% of all patients and patients <70 years of age, respectively, treated with placebo + C/L.Investigators concluded that the NE3107 + C/L combination treatment was associated with clinically meaningful and superior improvements (3+ points) on the motor examination part (Part III) of the MDS-UPDRS, and demonstrate the potential intrinsic and levodopa-enhancing, pro-motoric activity of NE3107 that is consistent with data from pre-clinical trials and support further clinical investigation of nondopaminergic therapies in late-phase clinical trials. About BioVie BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate NE3107 inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of Alzheimer’s and Parkinson’s diseases. The Company is conducting a potentially pivotal Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate NE3107 in patients who have mild to moderate probable Alzheimer's disease (NCT04669028). Results of a Phase 2 investigator-initiated trial (NCT05227820) showing NE3107-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trial in Alzheimer’s Disease (CTAD) annual conference in December 2022. An estimated six million Americans suffer from Alzheimer’s. A Phase 2 study of NE3107 in Parkinson’s disease (NCT05083260) has completed, and data presented at the International Conference on Alzheimer's and Parkinson's Disease and Related Neurological Disorders conference in Gothenburg, Sweden in March 2023 showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of NE3107 and levodopa vs. patients treated with levodopa alone, and no drug-related adverse events. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with FDA Fast Track status, is being evaluated in a US Phase 2b study for the treatment of refractory ascites due to liver cirrhosis. BIV201 is administered as a patent-pending liquid formulation. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. For more information, visit http://www.bioviepharma.com/. Forward-Looking Statements This press release contains forward-looking statements, including statements regarding the Company’s strategy, plans and objectives, such as statements regarding the Company’s anticipated timeline for announcing topline data readout for our NM101 product candidate. Forward-looking statements may generally be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due risks associated with conducting and completing clinical trials, including our reliance on third parties to conduct our clinical trials, to successfully defend potential future litigation, our ability to raise capital when needed on reasonable terms, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law.  For Public/Press Relations Inquiries:Contact: Anna Marie David630-550-7510annamarie@quantum-corp.com For Investor Relations Inquiries:Contact: Bruce Mackle Managing Director LifeSci Advisors, LLC bmackle@lifesciadvisors.com

Phase 2Clinical ResultFast TrackOrphan Drug

100 Deals associated with Tomaralimab(Opsona Therapeutics Ltd.)

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D11503	-	-	DB15415

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Indication	Highest Phase	Country/Location	Organization	Date
Delayed Graft Function	Discovery	United Kingdom	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	France	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	Poland	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	Switzerland	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	Spain	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	Belgium	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	Netherlands	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	Austria	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	Germany	Opsona Therapeutics Ltd.	01 Oct 2012
Delayed Graft Function	Discovery	United States	Opsona Therapeutics Ltd.	01 Oct 2012

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


OPN-305 (EHA2017)	Phase 1/2	Myelodysplastic Syndromes	31	OPN-305 5mg/kg	(beixmuwgvs) = There is no evidence of treatment related anti-drug antibodies zybmmtwdyn (ayfbpbahea ) View more	Positive	18 May 2017

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