VNAR antibodies / Ossianix - LARVOL DELTA

ASSESSMENT OF THE ABILITY OF TRANSFERRIN RECEPTOR-TARGETED ANTIBODIES TO CROSS THE BLOOD-BRAIN BARRIER IN VITRO AND IN VIVO (ADPD 2026) - "We examined BBB transport of the bispecific VNAR antibody TXB4-PD-L1 and BapineuzumabFab8D3 (Babi-Fab8D3) and compared it to the high-affinity anti-TfR antibody Ri7. In spite, being internalized by mBECs and neurons, TXB4-PD-L1 seems to enter the brain by a mechanism unrelated to BBB-mediated transcytosis. As expected, the Ri7 antibody did not pass the BBB in vitro nor in vivo."

Preclinical • CNS Disorders

CDR3 Variants of the TXB2 Shuttle with Increased TfR1 Association Rate and Enhanced Brain Penetration. (PubMed, Pharmaceutics) - "As we have previously shown, efficient and selective brain delivery was achieved with TXB2, a cross-species reactive, anti-TfR1 VNAR antibody...We also showed that fusion of TXB4 to four therapeutic antibodies (anti-CD20, anti-EGFRvIII, anti-PD-L1 and anti-BACE1) improved their brain exposure between 14- to 30-fold. In summary, we enhanced the potency of parental TXB2 brain shuttle and gained a critical mechanistic understanding of brain delivery mediated by the VNAR anti-TfR1 antibody."

Journal • TFRC

CHARACTERIZATION OF BRAIN SHUTTLE ENABLED TRKB NEUROTROPHIN RECEPTOR AGONIST ANTIBODIES - TRANSLATION TO NON-HUMAN PRIMATES (ADPD 2023) - "Aims: We previously reported on the TXB4 transferrin receptor 1 VNAR antibody that can transport a TrkB agonist antibody to the CN S and provided full neuroprotection in a mouse model of Parkinson's Disease... TXP1 is a high -capacity shuttle for delivery of antibodies and other products to the CNS. The shuttle should allow the delivery of TrkB agonist antibodies in NHPs and lead to clinical trials in neurodegenerative diseases."

CNS Disorders • Movement Disorders • Parkinson's Disease • NTRK2 • TFRC

Single domain shark VNAR antibodies neutralize SARS-CoV-2 infection in vitro. (PubMed, FASEB J) - "The viral neutralizing potential of the VNAR clones was also confirmed for the 10 antibodies tested using live Wuhan variant virus in in vitro cell infectivity assays. Single domain VNAR antibodies, due to their low complexity, small size, unique epitope recognition, and formatting flexibility, should be a useful adjunct to existing antibody approaches to treat COVID-19."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

[VIRTUAL] BRAIN PENETRANT TRKB NEUROTROPHIN RECEPTOR AGONIST ANTIBODIES - TRANSLATION TO NON HUMAN PRIMATES (ADPD 2021) - "Aims: We previously reported on TXB4 a transferrin receptor (TfR) single domain VNAR antibody that can transport TrkB agonist antibodies to the CNS at therapeutic concentrations and are active in PD mouse models... TXP1 is a high-capacity shuttle for delivery of antibodies and other products to the CNS. The shuttle will allow the delivery of TrkB agonist antibodies in NHPs and lead to clinical trials in neurodegenerative diseases."

CNS Disorders • NTRK2