Our company, Adnexus, has developed a unique and innovative approach to producing antibodies that target specific sites on viruses. This process involves using Artificial Intelligence to identify conserved and immutable targets, which we can then analyze for linearity, accessibility by antibodies, neutralizability, and the effect of mutations.
A Monoclonal Antibody Platform for producing antibodies that target immutable, conserved sites on viruses to avoid ineffectiveness due to virus mutation. The resulting antibodies are Fully Human, Universal, Durable, broadly neutralizing, and unaffected by mutations.
Adnexus has a unique Monoclonal Antibody Platform that permits the production of antibodies that target conserved immutable sites identified by Artificial Intelligence. This technology allows the Company to build 3D Models of all the conserved targets such that they may be analyzed for linearity, accessible by antibodies, neutralizable, and effect of mutations.
The Company then uses its proprietary methodology to create Fully Human Monoclonal Antibodies. This methodology starts with human “immune-B cells,” obtained from convalescent individuals who have recovered from the target virus. The primary distinction of this innovative process for creating fully human monoclonals is the starting point – from human “immune-B cells” obtained from humans who have successfully survived a “natural” infection. From these human “immune-B cells,” the company then produces antibodies that target conserved immutable sites (neutralizable epitopes) on the virus’ surface envelope proteins – which will thereby avoid “virus escape.”
Our antibodies retain the original natural antibody affinity and specificity and have a lower risk of immunogenicity when used as a therapeutic.
Adnexus is pursuing a comprehensive solution for both preventing and curing HIV. Two Monoclonal Antibodies being developed for HIV, Clone-3 and Clone-7
At the outset of the AIDS epidemic in the early to mid 1980’s, the founder of BioClonetics, Dr. Joseph Cotropia, M.D., treated numerous HIV positive patients in his medical practice. In treating these patients, he recognized that some, while having the virus, did not progress to frank AIDS but rather were able to naturally fend off the virus.
Dr. Cotropia theorized and later confirmed that these patients were a small subset of HIV patients (today called “long-term non-progressors”) who naturally produce antibodies that control the virus. Using what is now a company proprietary technique invented by Dr. Cotropia, he cloned the repertoire of B cells of these patients and isolated several clones that were producing antibodies that would bind to the virus.
These antibodies were then tested against HIV isolates (strains of the virus) and one antibody was found to remarkably neutralize 41 of 43 strains of the virus against which it was tested. Dr. Cotropia also identified the location on the virus to which the antibody binds and found that that location is immutable (never changing) in over 98% of more than 5,000 different global strains of HIV. This means that Dr. Cotropia had discovered an antibody that neutralizes the virus by binding to a conserved epitope on the gp41 transmembrane protein. The binding of the antibody to the virus at this location results in the virus not being able to bind to and infect the human CD4+ cells. The immutability of the target site on the virus surface envelope, provides the basis on which a vaccine can be produced for HIV prevention world-wide.
Clone 3 Antibody targets 98% of all HIV viral strains worldwide, via epitope KLIC
- Exact match [KLIC] on viral target: 78%
- Conservative match on viral target: 20%
Mismatch: 2%
RED = DEAD HIV
Utilizing AI, Adnexus analyzed 87500 HIV isolates and confirmed 8 conserved epitopes. This analysis confirmed the conserved nature of the Clone 3 Monoclonal Antibody. The initial epitope(identified 30 years ago) remains conserved, as confirmed by the Los Alamos database. The Company’s primary anti-HIV monoclonal Antibody targets one conserved site on HIV, the site is 98% conserved.
The In-Vitro neutralization tests of primary anti-HIV monoclonal Antibody showed over 95% of the HIV viruses tested to be neutralized. The Clone 3 fully human antibody neutralized HIV in all clades and groups found worldwide, as demonstrated by five independent global labs.
The potency of neutralization of the recombinant has increased 16-fold. Specifically, the Recombinant Antibody IC90 neutralization is 0.05 ug/m while the parent mAb IC90 was measured at 0.8ug/ml – a 16-fold improvement. In addition, while our Recombinant Antibody has an IC90 of only 0.05 ug/ml, in comparison, the mAb VRC01, now being tested by the Vaccine Research Center at the National Institutes of Health (NIH), has an IC90 neutralization of 2.49 ug/ml (a 50-fold difference).
Samsung Biologics is our partner for the large-scale production and distribution of monoclonal antibodies. We are proceeding with primate studies and IND enabling studies.
HIV’s mutation potential is 4 times more than SARS-CoV-2 and HIV patients tend to have multiple mutations circulating in blood. Hence it is essential to target sites that remain unchanged. Our Monoclonal Antibody for HIV is 50 times more potent than the closest Monoclonal Ab being developed by VRC.
We are currently planning animal studies to demonstrate In-Vivo efficacy to meet the milestones required by pharmaceutical companies.
We are continuing to produce both IgG and IgA HIV Monoclonal Antibodies.
We are producing Fully Human Monoclonal antibodies targeting the other 7 conserved sites identified by AI analysis.
We are currently producing two HIV monoclonal Antibodies (Clone-3 and Clone-7) that will be used in combination for therapeutics.
- Clone 3 is a broadly neutralizing human monoclonal antibody (mAb) derived from a long-term non-progressor patient
- Clone 3 mAb is protective; binds to a conserved linear amino acid sequence (KLIC) on the gp41 HIV envelop and neutralizes (kills) the virus
- The Clone 3 mAb has therapeutic potential to prevent HIV viral infectivity from individual to individual
- The Clone 3 Vaccine, KLIC epitope on gp41 viral envelop used as an immunogen
- Mini-antibody, a small peptide molecule that is a subset of the Clone 3 antibody
- A competitive binding entry-fusion inhibitor made from the amino acid sequence (KLIC) epitope
Samsung Biologics is our CDMO partner for large scale production of these Monoclonal Antibodies.
We are also developing monoclonal antibodies for SARS-CoV-2. Adnexus Artificial Intelligence Analysis the number of SARS-CoV-2 isolates that have (thus far) been analyzed: = 2,800,000
Using artificial intelligence identified conserved linear epitopes within the transmembrane S 1 and S 2 spike protein of covid virus
The variants of concern have shown the same conserved sequences
Targeting these conserved sites allows the production of therapy that will not become ineffective due to mutation of the virus.
An extensive AI analysis of 2.8 million SARSCOV2 isolates confirmed these 19 immutable sites to be conserved in all Variants of Concern and Variants of Interest.
Furthermore, most of the conserved sites were confirmed to be 100% conserved in the Omicron variant.
The Company’s Artificial Intelligence platform has been used to build 3D Models of all the 19 conserved targets. The analysis of the SARS-CoV-2 spike protein revealed that all epitopes identified by the Company are linear on the spike proteins, accessible by antibodies, neutralizable, and unaffected by mutations.
AI enabled 19 conserved sites identified as targets for Adnexus’ Anti-SARS-CoV2 Monoclonal Antibodies.
All these conserved sites are confirmed as conserved in ALL variants of concern including Omicron Variant (12/02/21).
Adnexus Monoclonal Antibodies are Universal, Durable and Broadly Neutralizing not affected mutations.
We are developing both IgG and IgA Monoclonal antibodies. To efficiently block COVID-19 infections and transmission, we need to get high levels of secretory IgA, reflecting mucosal immunity.
These antibodies, Human-19G and Human-19A have disruptive potential. In addition, we recognize the role of IgA antibodies in the immune function of mucous membranes and are working on harnessing their potential for powerful, efficient Immunotherapeutics.
Human-19A will be offered as an intranasal spray that can be easily applied to achieve long-term protection.
Capsid inhibitors interfere with assembly and disassembly of capsid proteins and inhibit viral replication.
- STC-CI-01 is a peptide designed to target specific components of the HIV capsid.
- It interacts with the capsid protein, disrupting viral replication and assembly.
- The University of Missouri’s research team has made significant strides in understanding its mechanism of action.
HIV Capsid Inhibitors:
- Capsid inhibitors are a class of antiretroviral drugs that specifically target the HIV capsid.
- By disrupting the capsid’s function, these inhibitors hinder viral replication and assembly.
- STC-CI-01 is a promising addition to this class, offering a novel approach to managing HIV.
Screening
The assembly reaction was initiated by mixing 125 μl of 5 M NaCl with 125 μl of 88 μM purified CA proteins at RT.
After the addition of NaCl, the increase in optical density at 350 nm was monitored every 10s.
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