Gregory Bell, CMO at Attralus Shares Insights from its License Agreement with Ossianix to Use Ossianix’s Brain Shuttle Technology

Shots:

Gregory initially spoke about the Attralus licensing agreement with Ossianix’s brain shuttle technology to enhance the targeted delivery of novel pan-amyloid removal candidates for use in neurodegenerative disorders such as Alzheimer’s Disease
He also talked about how Ossianix VNAR antibody-based brain shuttle TXP1 will help Attralus to deliver AT-04, its developmental PAR therapeutic candidate, across the BBB to the brain.
The interview shows Attralus’ efforts to develop novel PAR therapeutics to improve the lives of patients

Smriti: Can you please tell us about the license agreement between Attralus and Ossianix?

Gregory Bell: Under the terms of the agreement, Attralus will use Ossianix’s single-domain antibody platform (VNARs) to deliver AT-04 across the blood-brain barrier to the brain. This joint program will be titled AT-07. The initial research collaboration will focus on developing a preclinical package.

Smriti: Highlight the characteristics of Ossianix’s TXP1 Brain Shuttle technology.

Gregory Bell: Ossianix’s 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.

Smriti: Please tell our readers the details (MOA, ROA, formulation, etc) of AT-04.

Gregory Bell: AT-04, a peptibody, is a fusion of our pan-amyloid removal (PAR) peptide with the fragment crystallizable region (Fc) component of an immunoglobulin G1 (IgG1) antibody. The PAR peptide mediates binding to all types of amyloid, as well as Aß, tau, and α-synuclein fibrils in neurodegenerative disorders, and the Fc stimulates the immune system with the potential to serve as an opsonin for the removal of amyloid by the action of astrocytes and microglia. This interaction can induce phagocytosis, which is anticipated to lead to clearance from the body.

Smriti: How will the combination of TXP1 brain shuttle and AT-04 prove to be a potential treatment option for neurodegenerative disorders?

Gregory Bell: Extracellular aggregates of Aß amyloid and phosphorylated tau are common pathologic deposits in the brains of patients with Alzheimer’s disease. The removal of Aß amyloid plaques is an intensively pursued therapeutic target for the treatment of AD, with one FDA approved therapeutic currently. 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. AT-04 has demonstrated potent binding to Aß, tau, and α-synuclein fibrils. With this binding, in combination with Ossianix’s patented VNAR antibody-based brain shuttle TXP1, we anticipate targeted delivery of AT-04 to the central nervous system utilizing the transferrin receptor, thus stimulating the immune system and potentially removing the amyloid deposits. The combination of AT-04 with Ossianix VNAR will be titled AT-07.

Smriti: Can you elaborate on how AT-04 will stand out differently from its competitors?

Gregory Bell: As part of our pan-amyloid portfolio, AT-04 is unique from competitors in that it is not limited to a single type of amyloid. AT-04 has demonstrated binding with Aß, tau, and α-synuclein, as well as ATTR and AL amyloid. While most therapies in development for neurodegenerative amyloid pathologies target individual forms of amyloid, such as Aβ, tau, or α-synuclein, there is an opportunity for therapeutic differentiation with AT-04 by targeting multiple misfolded proteins and amyloid types, which can be present in the same patient, with one pan-amyloid therapy. AT-04 is the smallest of our therapeutic products and adding a blood-brain barrier (BBB) shuttle has the potential to further improve penetration, efficacy, dosing, and side effects relative to AT-04 alone.

Smriti: Are you looking forward to other such collaboration(s) in neurology or any other indication(s)?

Gregory Bell: We have multiple therapeutic and diagnostic products in our development pipeline for systemic amyloidosis and neurodegenerative disease and we are open to collaborations.

Image source: Canva

About the Author:

Gregory Bell is the Chief Medical Officer at Attralus. In 1996, he joined Merck & Co., Inc and contributed to several products that received regulatory approval including Vioxx, Etoricoxib, and Cancidas. Prior to joining Attralus, Greg was SVP of Development at Global Blood Therapeutics. He earned his medical degree from Cornell University Medical College and completed his training in Internal Medicine and Rheumatology at Brown University and the University of California, San Francisco (UCSF), respectively. Dr. Bell is an Assistant Clinical Professor of Medicine at UCSF and is a member of the American College of Rheumatology.