Our current focus is to leverage the dual hapten payload, developed to treat influenza, across other acute respiratory viruses like RSV and COVID-19.  For RSV, we have identified a ligand that binds with high affinity to the F protein found on both the RSV virus and infected cell.  We are currently in the process of optimizing the molecule.  Our goal is to closely follow the development of our influenza drug with the development of our RSV solution.

For COVID-19, we have identified several potential targeting ligands.  Work is being done to identify the ligand that binds to a conserved region of the spike protein to address as many strains of the virus as possible.

Regarding the second option, we have similarly shown that Zan-folate can completely cure mice injected with a lethal dose of influenza virus. The advantage of this approach is that it does not require the patient to have anti-DNP antibodies (even though the vast majority of people do have these antibodies). 

In like manner we have tested various forms of the Fc fragment linked to Zanamivir in an influenza mice model.  In a recent study comparing the efficacy of the current immunological ligands described, one of the Fc fragment variants had superior performance and like the others, better than Xofluza. 

Leveraging our toolkit of targeting ligands and immune cell-recruiting payloads (i.e., the dual hapten and others under development), there is an opportunity to address indications beyond acute respiratory viruses to include other infectious diseases and cancer.

HBV: We can deliver immune agonists specifically into the hepatocytes of chronic hepatitis B (CHB) patients to aid their functionally impaired immune system. Liver-targeted delivery will ensure the selective activation of the immune system without causing any systemic immune-related adverse events and will help in achieving a functional cure for CHB by suppressing the viral replication and causing a persistent reduction in the titer of HBV surface antigen in the bloodstream.

Cancer: The Low lab has identified multiple ligands that target specific cancers.  The folate receptor, for example, is expressed on the majority of ovarian, renal, triple negative breast, colorectal and non-small cell lung cancers.  We have conjugated folate to our dual hapten payload and conducted mice studies in several of these cancers both as a monotherapy and in combination with current standard of care.  In many cases, the monotherapy showed efficacy and the combination therapy did better than the standard of care. 

Post organ transplant infection: Clinicians face a very tricky balance between suppressing the immune system to prevent organ transplant rejection and avoiding an opportunistic infection that exploits the suppressed immune system.  We can target the immune system solely to the infected cells, therefore systemic activation of the immune system is not required to eradicate the virus, thereby avoiding this delicate balancing problem.

Other diseases:  We can address any disease or condition where killing an aberrant cell or pathogen is desired.  Some examples include:

·         Fibrosis producing cells

·         Bacteria infected cells and free bacteria

·         Fungal infections

·         Misbehaving immune cells (e.g., MDSCs)

·         Adipocytes

·         Endometriosis tissue

·         Thyroid tissue in Graves’ disease

We use targeted small molecules or antibody fragments that diffuse through solid tissues much more rapidly and thoroughly than antibodies. Our smaller targeted molecules also have much lower toxicities, are more stable, and cost much less to produce than antibodies.

Our technology is unique and the IP playing field is less crowded for the treatment of infectious diseases and cancer than it is for full-sized antibody technologies.

We leverage two mechanisms to treat respiratory viruses.  We both inhibit viral replication and recruit involvement of the immune system. In addition, only a few proteins have to be tagged with our drug for the immune system to respond. As mentioned earlier, this process can be quickly and effectively stopped in the unlikely case of a cytokine storm by independently dosing the cell targeting ligand (e.g., zanamivir for flu). However, our recent data in influenza-infected mice suggest that our drug does not lead to any significant increase in cytokines upon treatment suggesting that the development of cytokine storm is highly unlikely.

We can target a highly conserved site on the chosen viral protein whether or not the site is involved in viral entry or another critical function. In addition, if an escape mutation were to emerge, our technology lends itself to a quick remedy, whereas a neutralizing antibody could require extensive screening to respond to the mutation.

We have a robust intellectual property portfolio covering both components of our bispecific technology. The IP covers different immune cell ligands (i.e. payloads that recruit NK cells, T cells, and macrophages) and a breadth of ligands for targeting respiratory viruses including influenza, RSV, and COVID-19. The portfolio further protects IP on targeting other viruses such as acute and chronic HBV and latent HIV.  We also have IP on using our technology in cancer.