ProCase (AB002) / Aronora, Xoma - LARVOL DELTA

Unraveling the Immune Puzzle: Role of Immunomodulation in Alzheimer's Disease. (PubMed, J Neuroimmune Pharmacol) - "Preclinical studies of immunomodulatory agents, including salidroside, festidinol, astragalin, sulforaphane, BM-MSC, simvastatin, Ab-T1, hTREM2, and XENP345, demonstrate promising effects. Additionally, clinical investigations of drugs such as simufilam, AL002, TB006, VGL101, DNL919, XPro1595, astragalus, and IBC-Ab002 underscore the therapeutic potential of targeting immune pathways in AD. This review emphasizes how neuroinflammation, microglial activation, and peripheral immune responses contribute to disease progression. By exploring immunomodulatory mechanisms, the article sheds light on potential therapeutic targets that could help mitigate AD pathology which may pave the way for novel interventions preventing neurodegeneration in AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Immunology • Oncology • CTNNB1 • TNFA

A First in Human Study of IBC-Ab002 in Persons With Early Alzheimer's Disease (AD) (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Immunobrain Checkpoint | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • APOE

Harnessing Peripheral Immunity in Early Alzheimer's Disease: Safety and Tolerability of IBC-Ab002 in a Phase 1b Clinical Trial (CTAD 2024) - No abstract available

Clinical • P1 data • Alzheimer's Disease • CNS Disorders

AB002. DNA methylation-regulated genes contribute to temozolomide (TMZ) resistance by scaffolding paraspeckle proteins. (PubMed, Chin Clin Oncol) - "Our results reveal that HSD52 in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy."

Epigenetic controller • Journal • Ataxia • Brain Cancer • CNS Disorders • CNS Tumor • Genetic Disorders • Glioblastoma • Glioma • Immunology • Mental Retardation • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • Targeted Protein Degradation • ATRX • DNMT1 • TCF12 • USP7

Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial. (PubMed, Commun Med (Lond)) - P2 | "As far as we are aware, this proof-of-concept study is the first clinical trial assessing the therapeutic potential of protein C activation. The results herein support additional investigation of AB002 to safely prevent and treat thrombosis in at-risk populations."

Clinical • Journal • P2 data • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Renal Disease • Thrombosis

A First in Human Study of IBC-Ab002 in Persons With Early Alzheimer's Disease (AD) (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Immunobrain Checkpoint | Trial completion date: Dec 2024 ➔ Nov 2025 | Trial primary completion date: Oct 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • APOE

HARNESSING PERIPHERAL IMMUNITY: EARLY INSIGHTS FROM IBC-01-01 PHASE I TRIAL DEVELOPING A NOVEL IMMUNE-BASED THERAPY IN ALZHEIMER'S DISEASE. (ADPD 2024) - "Unlike conventional treatments that directly target brain pathology, this trial assesses the safety, pharmacokinetics, and preliminary efficacy of a new anti-PD-L1 antibody, IBC-Ab002. IBC-01-01 adopts an innovative approach in AD treatment, employing for the first time an immune checkpoint inhibitor for the treatment of dementia. Initial findings suggest a promising pharmacological and safety profile, with evidence of intended peripheral target engagement and immune activation. These insights could mark the beginning of a paradigm shift in AD immunotherapy, supporting the contention of the systemic immune system's role in managing neurodegenerative diseases."

IO biomarker • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Oncology

Endogenous Protein C Activation with AB002 Improves Outcomes in a Rat Model of Acute Ischemic Stroke (ASH 2023) - P2 | "8 to 9-week-old male rats (275-377 g) were anesthetized under isoflurane and a small laser-Doppler probe was affixed to the skull to monitor cortical perfusion and verify vascular occlusion and reperfusion. Treatment with AB002 during ischemia reduced infarct volume and improved outcomes in the rat experimental stroke model. Considering its neuroprotective and antithrombotic properties, we propose that early treatment with AB002 may confer outcome benefit for patients experiencing acute thrombotic emergencies."

Preclinical • Anesthesia • Cardiovascular • Hematological Disorders • Ischemic stroke • Myocardial Ischemia • Reperfusion Injury • Thrombosis

Cytoprotective E-WE thrombin reduces disease severity in a murine model of relapsing-remitting multiple sclerosis. (PubMed, Am J Physiol Cell Physiol) - "Both methylprednisolone and E-WE thrombin reduced demyelination and immune cell recruitment. These results provide rationale for considering engineered forms of thrombin biased toward anticoagulant and cytoprotective activity as a therapeutic strategy and perhaps effective alternative to high-dose methylprednisolone for management of acute relapsing MS attacks."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis

IBC-Ab002 Fc modifications for fast clearance are associated with advantageous safety profile (AAIC 2023) - "We demonstrate that the clearance rate of the antibody inversely-relates to the probability of developing an adverse immune response, and that no delayed long-term irAEs are expected once full clearance of the antibody was achieved. Overall, these findings suggest that shortening the half-life of anti-PD-L1 antibodies in treatments that do not necessitate continuous exposure can considerably increase the safety profile."

Clinical • Alzheimer's Disease • CNS Disorders • Diabetes • Immune Modulation • Immunology • Metabolic Disorders • Oncology • Type 1 Diabetes Mellitus

Concept Mapping with Black Men: Barriers to Prostate Cancer Screening and Solutions. (PubMed, J Cancer Educ) - "The mean age of respondents was 52 (±10), 50% were rural, 37% were college-educated, 56% with income <$44,500, and 22% with PROCASE Knowledge Index ≤5...Our study identified specific barriers to PCS among AA with diverse sociodemographic backgrounds. Culturally sensitive interventions delivered by trained healthcare professionals, peers, and relatable role models, can potentially increase PCS among AA men."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Generation of two human induced pluripotent stem cell lines (ABi001-A and ABi002-A) from cone dystrophy with supernormal rod response patients caused by KCNV2 mutation. (PubMed, Stem Cell Res) - "PBMCs from donors have been reprogrammed into iPSC lines. Derived clones were characterized with mutation sequencing, analysis of common pluripotency-associated markers at the protein levels, and in vitro differentiation studies."

Journal • Preclinical • Achromatopsia • Retinal Disorders

A Phase 2 Trial of the Protein C Activator AB002 in End-Stage Renal Disease Patients on Chronic Hemodialysis (ASH 2021) - P2 | "In a preclinical baboon thrombosis model, AB002 rapidly interrupted thrombus development with no observable hemostasis impairment, and was similar in antithrombotic efficacy to high-dose enoxaparin while appearing superior to interventional tissue-plasminogen activator. In ESRD patients undergoing heparin-free hemodialysis, AB002 was well-tolerated and reduced thrombus accumulation in the hemodialysis circuit without observable hemostasis impairment. The results of this study support further clinical evaluation of AB002 as a novel drug candidate to limit thrombus development or device-initiated clotting in patients with elevated bleeding risk, including ESRD patients on chronic heparin-free hemodialysis."

Clinical • P2 data • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • Thrombosis

A First in Human Study of IBC-Ab002 in Persons With Early Alzheimer's Disease (AD) (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Immunobrain Checkpoint | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2022 ➔ Feb 2023

Enrollment open • Trial initiation date • Alzheimer's Disease • CNS Disorders • APOE

FIRST-IN-HUMAN CLINICAL TRIAL OF IBC-AB002, A PROPRIETARY HUMAN ANTI-PD-L1 ANTIBODY, IN PERSONS WITH EARLY ALZHEIMER’S DISEASE: TRIAL DESIGN AND OBJECTIVES. (CTAD 2022) - "Immune checkpoint blockade via inhibition of the PD-1/PD-L1 pathway is a novel and promising potential approach for modulating the adaptive immune system to treat AD, and perhaps other neurodegenerative conditions as well."

Clinical • IO biomarker • P1 data • Alzheimer's Disease • CNS Disorders • Immune Modulation • Immunology • Inflammation • Solid Tumor

A First in Human Study of IBC-Ab002 in Persons With Early Alzheimer's Disease (AD) (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Immunobrain Checkpoint

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

A Phase 2 Trial Evaluating the Safety and Antithrombotic Efficacy of AB002, a First-in-class Protein C Activator in End-stage Renal Disease Patients on Heparin-free Hemodialysis (ISTH 2022) - P2 | "AB002 demonstrated a favorable safety profile, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient, and AB002 did not affect time to hemostasis at the vascular access site. Drug exposure was confirmed by a transient, dose-dependent elevation of APC-PCI."

Clinical • P2 data • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • Thrombosis

The antithrombotic protein C activator thrombin mutant W215A/E217A (AB002, E-WE) is slowly inhibited by the endogenous thrombin inhibitors antithrombin, protein C inhibitor, and heparin cofactor II (ISTH 2022) - P1 | "AB002-inhibitor complexes were not detected within 90 min of AB002 addition to plasma without addition of heparin or thrombomodulin (Figure 1). In buffer, the addition of either antithrombin or HCII to AB002 did not produce observable complex formation within 20 min, compared to PCI, which formed complexes within minutes. Thrombin rapidly complexed with all inhibitors."

Immunology

Social Media Engagement and Influenza Vaccination: a Survey During the COVID-19 Pandemic. (PubMed, J Med Internet Res) - "Using social media is negatively linked to compliance with seasonal influenza vaccination in this study. A high proportion of non-compliant individuals can lead to increased consumption of healthcare and therefore overload the health services. This is particularly crucial with a concomitant outbreak, such as COVID-19. Healthcare professionals should use improved and targeted health communication campaigns with the aid of experts in social media. Targeted communication, based on socio-demographic factors and personalized social media usage, might increase influenza vaccination rates and compliance with other vaccines as well."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and Efficacy Study of AB002 (E-WE Thrombin) in End Stage Renal Disease Patients on Chronic Hemodialysis (clinicaltrials.gov) - P2; N=36; Completed; Sponsor: Aronora, Inc.; Recruiting ➔ Completed

Clinical • Trial completion • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • Thrombosis

[VIRTUAL] TRANSLATIONAL PHARMACOLOGY OF IBC- AB002, A NOVEL FULLY HUMAN ANTI-PD-L1 ANTIBODY, FOR TREATING ALZHEIMER’S DISEASE (CTAD 2020) - "IBC-Ab002 antibody, a novel engineered antibody that was selected for clinical development for treating AD, has a superior safety profile in terms of immune-related adverse events. We developed a predictive model that simulates PK/PD and efficacy in human and informs our Phase 1 clinical trial design. A first-in-human study of IBC-Ab002 in AD patients is planned for the second half of 2021."

IO Biomarker • Alzheimer's Disease • Amyloidosis • CNS Disorders • Dementia • Diabetes • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Oncology

Protein C activator AB002 rapidly interrupts thrombus development in baboons and appears safe in a first-in-human trial. (PubMed, Blood) - P1, P2 | "We also describe its safety and activity in a phase 1 first-in-human clinical trial (www.clinicaltrials.gov; NCT03453060). Together, these results support further clinical evaluation of AB002 as a potentially safe and effective new approach for treating or preventing acute thrombotic and thromboembolic conditions."

Journal • P1 data • Thrombosis

Dual mechanisms of novel CD73-targeted antibody and antibody-drug conjugate in inhibiting lung tumor growth and promoting antitumor immune-effector function. (PubMed, Mol Cancer Ther) - "We developed two novel series of CD73 antibody Ab001/Ab002 and humanized version Hu001/Hu0002, which demonstrated high CD73 binding affinity, potent enzyme inhibition and efficiently protected effector T lymphocyte function from adenosine/cancer-imposed toxicity. Studies with human PBMC-derived systems confirmed CD73-ADC as fully functional in protecting effector T cells and stimulating DCs thus providing dual benefits in killing CD73-high tumors and improving cancer immunity response. These results warrant clinical investigation of CD73-targeted antibody and ADC for treating advanced lung cancer."

IO Biomarker • Journal • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD73 • EGFR • EML4

[VIRTUAL] IBC-Ab002, an anti-PD-L1 monoclonal antibody tailored for treating Alzheimers disease (AAIC 2020) - "IBC-Ab002 antibody was selected for clinical development based on its unique characteristics, tailored for the mechanism of action intended for treating AD, and superior safety profile in terms of immune-related adverse events. We are currently planning the first-in-human study of IBC-Ab002 in AD patients."

IO Biomarker • Alzheimer's Disease • CNS Disorders • Dementia • Diabetes • Immunology • Metabolic Disorders