Organization Description
Covalent Biosciences, Inc. was a company that developed catalytic antibodies (catabodies) as longevity therapeutics and vaccines. Conventional antibodies bind tightly to their target with the intent of either blocking its activity, pulling it away from the tissue in which it is embedded, or signaling the immune system to eliminate it. They are inefficient because one antibody can only bind to and inactivate a single target molecule.
By contrast, catabodies bind their targets with the same fidelity, but break down the targeted proteins into very small fragments instead of merely binding to them. This then leaves them free to bind to and destroy the next target molecule, and the next, in a catalytic action, giving them high efficiency and minimal perturbation of the immune system. These features make catabodies a promising tool for targeting disease-driving abnormal proteins.
The CEO of Covalent was Richard Massey; Sudhir Paul was the scientific founder and CSO.
At some point between March and August 2025, Covalent’s website announced that they had ceased operations.
Cardizyme
Cardizyme is a catabody that destroys transthyretin amyloid (misTTR). Amyloids are misfolded proteins that aggregate in harmful clumps in our tissues and fail to perform their original functions; TTR amyloid is implicated in heart failure and also contributes to spinal stenosis, and carpal tunnel syndrome. It also appears to be an important cause of death for supercentenarians, people who have lived longer than 110 years.
LRI (then SENS Research Foundation) funded the original rejuvenation research in Dr. Paul’s laboratory to develop a catabody targeting TTR amyloid. After first identifying a TTR-cleaving catabody candidate derived from patient blood, his lab optimzed this lead antibody into two potent improved versions, which break down TTR amyloid 500 times faster than the best of the patient-derived candidates. Based on the catabodies’ rapid kinetics and anticipated half-life in the blood, the researchers project that each one of these new catabodies could cleave more than 40,000 misfolded TTR molecules before they were themselves eliminated by physiological processes.
Importantly, none of these catabody candidates cleaved TTR in its healthy, normal conformation, nor did they cleave a selection of 14 other physiologically essential proteins. And the concentrations required to disintegrate 80% of a sample of TTR amyloid were many hundreds of times lower than those routinely achieved in the blood with other infused therapeutic antibodies (such as Regeneron’s monoclonal antibodies against the COVID-19 virus or antibody-based treatments for patients with autoimmune disorders).
Before Paul developed Cardizyme he discovered Alzyme, a catabody fragment specific for beta-amyloid, the protein most centrally implicated in Alzheimer’s disease. In addition to dissolving beta-amyloid ex vivo, low-dose, brief intravenous treatment with Alzyme cleared brain beta-amyloid in one mouse model of Alzheimer’s without inducing microglial activation or microhemorrhages, while delivery via gene therapy had the same effect in a second.
Tauzyme
Aberrant tau, which accumulates in the brain with age and whose spread is accelerated by beta-amyloid, is a second key driver of Alzheimer’s disease. At the 2018 Undoing Aging conference, Paul reported that he had identified natural catabodies that selectively destroy aggregated tau; subsequently, Covalent reported that they had modified these leads into prototype Tauzyme candidates for further testing.
Electrophilic Vaccines
Electrophilic vaccines harness electrophilic compounds to defeat immune-evasive superantigens used by some pathogens. Superantigens are unconventional antigens that bind to sites on immune cells or antibodies other than the ones that the body uses to recognize regular antigens. When they latch onto these exposed sites, superantigens either disable the function of an antibody or worse, crosslink them in a way that prevents them from clearing the pathogen, while firing up inflammatory signaling. Superantigen pathogens include Staphylococcus aureus, S. magnus, and HIV-1. B-cell superantigens bind to immunoglobulins on B-cells, which impairs their ability to opsonisation, IgG-mediated phagocytosis, and driving apoptosis.
By attaching to proteins, electrophilic compounds can modify their structure and create new antigens that stimulate a stronger immune response. This approach has shown promise in the development of vaccines against infectious diseases and cancer. Electrophilic vaccines have the potential to improve vaccine efficacy and provide long-lasting protection.
Covalent worked to develop the E-Vaccine Abzentek to overcome the resistance of HIV to immunization. Covalent-affiliated scientists discovered that the CLIN superantigen in HIV binds to B-cell receptors (BCRs) in a way that interferes with a necessary step in effective vaccination against HIV: the class switching of immature IgM antibodies to IgG antibodies. By designing novel E-immunogens that bound covalently to nucleophilic BCR, they were able to overcome the class-switching defect in a mouse model.. As an added bonus, the ensuing antibodies were highly effective in neutralizing the virus due to inducing catalytic and irreversible HIV-binding activities.
Team
