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SAN FRANCISCO, PHILADELPHIA – Nov. 17, 2022 – Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with amyloidosis, and Ossianix, an antibody engineering company developing a single domain antibody platform (VNARs) to deliver molecules across the blood-brain barrier (BBB), announced today that they have entered into a definitive agreement using Ossianix' brain shuttle technology to enhance the targeted delivery of novel pan-amyloid removal candidates for use in neurodegenerative disorders such as Alzheimer’s Disease.
Under the terms of the agreement, Attralus will use the patented VNAR antibody developed by Ossianix to help deliver AT-04, its developmental pan-amyloid removal (PAR) therapeutic candidate, across the BBB to the brain.
"Encouraging preclinical data for AT-04 indicates that it potently binds to all types of amyloid, including synthetic fibrils composed of Ab, tau, and a-synuclein, pathologic aggregates common to neurodegenerative disorders such as Alzheimer's," said Gregory Bell, MD, Chief Medical Officer at Attralus. "The addition of the TXP1 brain shuttle has the potential to significantly improve CNS penetration and efficacy. While most therapies in development target individual pathologies, such as Ab, tau or a-synuclein, AT-04 can target all amyloid pathologies in each patient and has the potential to transform the lives of patients living with neurodegenerative disorders."
AT-04, a peptibody, is a fusion of the Company's PAR-peptide technology with the fragment crystallizable region (Fc) component of an immunoglobulin G1 (IgG1) antibody. The latest preclinical data for AT-04 demonstrate potent binding to multiple types of amyloid, as well as Ab, tau, and a-synuclein fibrils in neurodegenerative disorders. This interaction can induce phagocytosis, which is anticipated to lead to clearance from the body.
"We are very excited to be working with Attralus and combining Ossianix' patented VNAR antibody-based brain shuttle TXP1, which is capable of delivering high levels of therapeutic products to the central nervous system utilizing the transferrin receptor, with their novel pan-amyloid removal technology," said Dr. Frank Walsh, CEO of Ossianix. "We look forward to developing a successful collaborative relationship with Attralus.”
About AT-04 PAR Therapeutic
AT-04 is a fusion of our pan amyloid removal (PAR) peptide technology with the Fc component of a human IgG1 antibody. The PAR-peptide mediates binding to all types of amyloid as well as Aß, tau, and α-synuclein fibrils. The Fc stimulates the immune system to remove amyloid.
About the TXP1 Brain Shuttle
Ossianix’ brain shuttle platform is based on single domain VNAR antibodies and TXP1 is the most advanced brain shuttle ready for clinical translation. TXP1 was developed to be paired with CNS drug candidates to improve their brain penetration and therapeutic efficacy, while also potentially reducing dosing and side effects.
About Neurodegenerative Disease
Extracellular aggregates of Ab amyloid and phosphorylated tau are common pathologic deposits in the brains of patients with Alzheimer’s disease (AD). The removal of Ab amyloid plaques is an intensively pursued therapeutic target for the treatment of AD, with one FDA approved therapeutic. Preventing the accumulation of hyperphosphorylated tau, and perhaps removal of the aggregates, may prevent progression of AD and may potentially reverse cognitive decline. In addition, α-synuclein is believed to play a role in Parkinson’s disease, Dementia, and Lewy Body diseases.
About Attralus
Attralus is a clinical stage biopharmaceutical company focused on creating transformative medicines to improve the lives of patients with systemic amyloidosis. The company’s proprietary pan-amyloid removal (PAR) therapeutics are designed to directly bind to and remove toxic amyloid in organs and tissues. By targeting the universal disease-causing pathology in systemic amyloidosis diseases, PAR therapeutics have the potential to treat and reverse disease in patients with all types and stages of systemic amyloidosis. Attralus was founded by scientific experts in the field of amyloidosis and the company is headquartered in San Francisco.
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-Results to be Presented at Protein & Antibody Engineering Summit - Europe
Stevenage, UK, November 9, 2020 – Ossianix, an antibody engineering company, today announced the results of a non-human primate study demonstrating best-in-class blood-brain barrier (BBB) delivery by single domain antibodies. The Ossianix proprietary VNAR shuttle TXP1 showed efficient transfer into all six regions of the brain examined, with the hippocampus showing an over 30-fold increase in levels of the molecule compared to the control. The TXP1 shuttle was administered at a dose of 1.35 mg/kg by intravenous injection and reached a concentration of 4 nM in the brain after 20 hours. These data will be presented at the Virtual PEGS Summit Europe meeting on November 11 at 15:40 GMT.
Poor brain delivery is a major barrier in the development of biological therapeutics for neurologic diseases because they are too large to cross the BBB. Developing efficient shuttles that target key transporters such as the transferrin receptor is a necessary step in delivering therapeutic levels of biologic drugs. The VNAR shuttle is a single domain antibody derived from sharks that is significantly smaller than monoclonal antibodies used today as therapeutics.
Previous preclinical studies demonstrated that the TXB2 shuttle, which targets the transferrin receptor, transferred a variety of protein cargoes including antibodies at low therapeutic doses to the central nervous system (CNS) by crossing the BBB, producing high levels in the brain with no safety issues in the mouse model. The observed long plasma pharmacokinetics and lack of side effects such as reticulocyte depletion are differentiating features of the VNAR shuttles.
“These latest results of our VNAR antibody BBB delivery are a truly exciting advancement in our quest to overcome the blood-brain barrier for CNS therapies,” said Ossianix CEO Frank S. Walsh, PhD. “Our first-generation TXB2 shuttle showed the ability of VNAR for high level CNS delivery, and the TXP1 shuttle allows efficient translation to primates, enabling a fast route to human clinical trials. This versatile TXP1 shuttle is indeed best-in-class as it operates at the dosing range of biologics in humans.” New paragraph
Of the 23 projects, $6.8 million was awarded to 12 vaccine projects, nearly $1.2 million was awarded to five therapy projects, nearly $1.6 million was awarded to five treatment projects, and $430,000 was awarded to a project that will support the build out of physical infrastructure, advancing the development of leading edge innovations in the fight against SARS-CoV-2.
The current COVID-19 pandemic is a healthcare catastrophe of global proportion. There are no treatments for the disease and a vaccine will take time to develop. Therefore, additional novel immunological approaches need to be considered for therapeutic development. Passive immunization via antibodies that target and neutralize the virus are attractive options. There are already early reports of antibodies cloned from B cells of infected individuals, as well as monoclonal antibodies developed from humanized mice.
A novel approach being pioneered at Ossianix uses its patented VNAR phage display libraries to identify single domain antibodies with high affinity and specificity against the COVID-19 spike protein. The spike protein is the site of attachment of the virus with its cellular receptor ACE-2 and blockade at that site will neutralize its activity.
Single domain VNAR antibodies have large CDR3 binding domains that preferentially bind cavities and buried epitopes in proteins. These are often the sites of protein-protein interactions. It is thus highly likely that screening of the multi-isoform and [HKC1] highly complex VNAR libraries will identify hits that will be different from those isolated from human B cells. Once identified, VNAR single domain antibodies can then be developed to block these sites. Certain VNAR antibodies that bind to the transferrin receptor have also shown the capability to specifically target the lung in rodents and non-human primates. These VNARs can be fused to antibodies or other therapeutics creating bispecific biologics for targeted delivery.
The screening campaign against the COVID-19 spike protein at Ossianix is advancing rapidly and we hope to announce the results to the scientific community over the coming weeks.
Ossianix wishes to partner after this screening stage with interested parties in government, academia or biotech and pharma companies to develop the virus blocking VNAR antibodies and move the project to a therapeutic reality in the shortest possible time.
Ossianix contact: Dr Frank S Walsh CEO (walsh@ossianix.com).
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