Home About the Company Our Team Contact Us

Our Research

The selectin inhibitor program is supported by discoveries made by our co-founding scientists who leveraged decades of continuous funding from the National Heart Lung and Blood Institute at the NIH to define and characterize selectin/receptor-mediated cell adhesion and its roll in inflammatory diseases. But this is only part of the story. Work at research institutions around the globe built on these early discoveries continues to further our understanding of these adhesion molecules and their importance in human disease. For Tetherex, this substantial body of work lays the foundation for developing new therapies with the potential for treating inflammatory diseases by blocking PSGL-1 function. Tetherex's lead clinical development program using selectin inhibition is advancing a humanized monoclonal antibody called SelK2, which targets PSGL-1 and blocks its interactions with both the selectin family of molecules and chemokines involved in unregulated inflammatory responses in inflammatory diseases. The lead indications for SelK2 are asthma, a common chronic inflammatory disease of the lungs characterized by episodes of wheezing, breathlessness, chest tightness, and cough; and chronic obstructive pulmonary disease (COPD), a disease triggered when foreign particulate matter such as that produced from cigarette smoke leads to the recruitment of inflammatory cells to the bronchial wall and lumen resulting in progressive loss of lung function.

The single-cycle adenovirus (SC-Ad) vaccine program is supported by discoveries made by Michael Barry, Ph.D., a Mayo Clinic infectious diseases researcher and co-inventor of the single-cycle adenovirus platform. Dr. Barry has worked for almost 30 years on gene and virus therapies including the development of new vaccines against infectious diseases and for cancer. The SC-Ad vector can amplify vaccine target DNA up to 10,000 times in every cell. This can produce as much as 100 times as much antigen as a replication deficient adenovirus vector. Dr. Barry has successfully tested the single-cycle adenovirus vaccine against HIV-1, influenza, Ebola virus, Zika virus and C. difficile infections. In most cases, the single-cycle vaccines are used as a single immunization and are quite effective when delivered intranasally. Most recently, Dr. Barry has applied the single-cycle adenovirus vaccine to COVID-19 which we are using to validate the platform. Since SARS-CoV-2 is a respiratory virus and enters the body through the respiratory system, intranasal administration of the COVID-19 vaccine (SC-Ad6-1) will be investigated in the initial studies.

About the Investigational Drug SelK2

SelK2 is a humanized monoclonal antibody that binds PSGL-1 with high affinity and specificity and blocks its ability to interact with P- and L-selectin as well as its ability to bind chemokines. Tetherex is currently developing SelK2 in both asthma and COPD.

Asthma and COPD

Asthma is a common chronic inflammatory disease of the lungs characterized by episodes of wheezing, breathlessness, chest tightness, and cough, and the disease is often associated with eosinophil-rich airway inflammation. Airway eosinophilia is associated with asthma exacerbations and has been shown to play a role in airway remodeling.

Chronic obstructive pulmonary disease (COPD) represents one of the leading causes of death worldwide, and there are few effective therapies. In COPD, foreign particulate matter such as that produced from cigarette smoke leads to the recruitment of inflammatory cells to the bronchial wall and lumen resulting in progressive loss of lung function. Neutrophilia is a hallmark of COPD and neutrophils are thought to be the key inflammatory cell in the pathogenesis of the disease.

Role of PSGL-1 in Asthma and COPD

The induction and maintenance of inflammation in asthma and COPD are mediated by the recruitment and extravasation of inflammatory cells including eosinophils and neutrophils from the pulmonary circulation to the airways. The initial step in this process involves the tethering and rolling of these cells on the endothelium, mediated by PSGL-1/selectin binding. Alternatively, the binding of activated platelets to PSGL-1 on eosinophils and the subsequent activation of additional adhesion molecules that participate in extravasation have also been implicated. Therefore, PSGL-1/selectin inhibition is a viable therapeutic strategy in the modulation of leukocyte extravasation into the airways in asthma and COPD. Indeed, bimosiamose, a small molecule inhibitor of PSGL-1/selectin interactions, has been shown to significantly reduce the fall in FEV1 during the late phase allergic response in a clinical study. Bimosiamose also led to an attenuation of airway inflammation including a decrease in IL-8, neutrophils and macrophages in patients with COPD. Taken together, these data provide an important proof of principle for selectin directed therapies in respiratory diseases. It is anticipated that the potent PSGL-1 inhibitor SelK2 will prevent extravasation of inflammatory cells into the airways of the lung in patients with allergic asthma and COPD.

About the Investigational Vaccine SC-Ad6-1

SC-Ad6-1 is a novel single-cycle adenovirus vector (SC-Ad) expressing the SARS-CoV-2 spike protein. The SC-Ad6-1 vector undergoes robust replication in the initial cells that it enters but lacks the genetic information to form infectious particles. Therefore, SC-Ad6-1 utilizes the potency of a replication competent adenovirus vector but does not have the capacity to cause adenovirus infections in patients and/or personnel through the formation of infectious particles. Because of this single cycle of replication, the SC-Ad vaccine platform is more potent than DNA vaccines, replication deficient adenovirus vaccines, and protein vaccines. For example, the single-cycle adenovirus vaccine engine amplifies SARS-CoV-2 spike antigen expression nearly 100-fold when compared to matched replication deficient adenoviruses.

Summary of Advantages of the Single-Cycle Adenovirus Vaccines Over Other Currently Administered Vaccines:

  • The single cycle of robust replication with SC-Ad provides 100-fold higher amounts of immunogen than benchmark replication deficient adenovirus vectors that are in use for COVID-19.
  • Increased expression of immunogen results in a marked increase in vaccine potency.
  • Increased potency per unit vaccine should enable better immune responses in aging vaccine recipients whose immune systems require stronger activation.
  • Increased potency allows the use of lower doses to generate equal vaccine effects.
  • The more robust expression per unit vaccine relative to RD-Ad enables needle-free administration of the vaccine at mucosal sites such as intranasal or oral routes.
  • Mucosal immunization against respiratory viruses (i.e., SARS-CoV-2) at the site of viral entry into the body provides a stronger mucosal barrier against the initial infection while still providing strong systemic immunity.
  • Lower doses should reduce reactogenicity that can occur with the delivery of larger numbers of adenovirus vaccine particles required with RD-Ad.
  • Lower doses should reduce off-target delivery of vaccine particles to other tissues.
  • Lower doses will allow the production of more vaccine doses per manufacturing run.
  • A needle-free vaccine can be immediately and readily available for all patients worldwide.
  • SC-Ad takes advantage of multiple levels of biological amplification to maximize protein production without the risk of causing an infection.

About SARS-CoV-2

In December 2019, a cluster of pneumonia cases were identified in Wuhan, China, which were later found to be caused by a novel coronavirus: severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Since then, nearly 184,000,000 cases have been reported worldwide resulting in approximately 4,000,000 deaths. Mortality rates in US have varied by age and range from <1% in those younger than 54 years to up to 27% in those aged 85 years.

The Benefits of SC-Ad6-1 Against SARS-CoV-2

The SC-Ad vaccine platform has demonstrated utility in several animal models when used to vaccinate by intramuscular, intranasal, sublingual, oral, and vaginal routes of delivery. Since SARS-CoV-2 is a respiratory pathogen, the nasal route of vaccine administration may offer certain advantages. Nasal vaccination can induce both mucosal as well as systemic immunity in contrast to the intramuscular vaccination which primarily induces systemic immunity. Mucosal immune responses can include IgA that may serve to neutralize SARS-CoV-2 without binding Fc receptors. Intranasal administration may also protect against infections at other mucosal sites through mucosal antibody secretion. A mucosal response allows the immune system to encounter respiratory viruses like SARS-CoV-2 at the site of entry while the viral titers are lower.

The initial Phase 1 open label study, designed to assess safety, reactogenicity and immunogenicity of the single-cycle adenovirus vaccine, is expected to recruit a total of approximately 80 healthy volunteers and includes both a single ascending dose group and a multiple dose group. Subjects will receive the vaccine via either intramuscular or intranasal administration.