Consistently, and especially in the last 2 years, Healthcare & Life Sciences Limited has expanded its development programs to include clinical-stage programs in Coronavirus (COVID-19) and immuno-oncology, adding to ongoing preclinical programs in hemorrhagic fever viruses (Ebola, Lassa Fever, Marburg, Sudan), Zika, and malaria. The breadth of vaccines in development and the nimbleness in providing solutions to emerging threats speaks to the ability and broad utility of our technology platform. 

COVID-19 Vaccine for Immunocompromised Patients (COH04S1) – In November 2021, we announced a license agreement with City of Hope (“COH”), granting Healthcare & Life Sciences Limited exclusive rights to further develop and commercialize COH04S1, a synthetic attenuated modified vaccinia Ankara (sMVA) vector expressing spike and nucleocapsid antigens of the SARS-CoV-2 virus. In a placebo-controlled Phase 1 clinical trial of healthy adults, COH04S1 was shown to be safe and immunogenic. A Phase 2 clinical trial to evaluate the safety and immunogenicity of the COH04S1 investigational vaccine, compared to the Pfizer mRNA-based vaccine, in patients who have previously received either an allogeneic hematopoietic cell transplant, an autologous hematopoietic cell transplant or chimeric antigen receptor (CAR) T cell therapy is currently underway. The trial is also the first to compare an investigational multi-antigenic COVID-19 vaccine to the current Food and Drug Administration (FDA)-approved mRNA vaccine from Pfizer/BioNTech in people who are immunocompromised. Such patients have often shown a weak antibody response after receiving currently available COVID-19 vaccines. The ongoing Phase 2 trial is designed to evaluate COH04S1 in immunocompromised patients.

 

COVID-19 Booster Vaccine (COH04S1) – In December 2021, we began an additional Phase 2 trial to evaluate COH04S1 as a universal booster to current FDA-approved. The Phase 1 portion of the trial, which was fully enrolled, was designed as dose-escalation safety study in healthy individuals, 18-55 years of age that had not been previously infected with SARS-CoV-2. The primary objectives were to evaluate the safety, tolerability and immunogenicity of COH04S1 vaccine in healthy volunteers administered vaccine at three different dose levels by intramuscular (IM) injection. Follow-up studies of the volunteers are continuing to better assess duration of immune responses and scientific presentations and publications are planned for early 2022.

 

The Phase 2 booster study, which is currently enrolling, will include 60 healthy individuals, 18 years of age or older, that were previously vaccinated with one of the approved SARS-CoV-2 mRNA vaccines. The study is designed as a dose-escalation trial to specifically evaluate the safety profile and immunogenicity of COH04S1 as a booster shot. The immunological responses measured throughout the study will include both the level of SARS-CoV-2 neutralizing antibodies and specific T-cell responses.

 

Pan Coronavirus Vaccine (GEO-CM02) – We are developing our vaccine candidate, GEO-CM02 as a universal vaccine to address evolving SARS-CoV-2 variants. First-generation SARS-CoV-2 vaccines were rapidly developed and have proven highly efficacious in the human population and were designed to encode the prefusion stabilized Spike protein (S) with the goal of inducing high levels of neutralizing antibodies. However, potential limitations of narrowly focusing on S are becoming apparent with emerging variants that partially escape neutralization by vaccine-induced antibodies. Thus, the effectiveness of these vaccines against new SARS-CoV-2 variants and future coronavirus spillover events remains in question.

Using our GV-MVA-VLP^TM platform, we have developed a design strategy for vaccines expected to induce broader immunity through the inclusion of multiple, genetically conserved structural proteins from the target pathogen. The GV-MVA-VLP^TM platform is known to induce a balanced humoral (antibody) and cellular (T-cells) response against the multiple encoded immunogens, potentially limiting immune escape against emerging variants. Expression of the SARS-CoV-2 spike, membrane, and envelope proteins by MVA supports the in vivo formation of virus-like particles, or VLPs, which induce both antibody and T-cell responses. The incorporation of sequence-conserved structural and nonstructural proteins can provide targets for T-cell responses to increase the breadth and function of vaccine-induced immune responses. This strategy provides the basis for generating a universal vaccine with the augmented potential to alleviate the burden of disease caused by circulating coronaviruses.

Ebola and Other Filoviruses

Ebola, Sudan, and Marburg viruses are the most virulent species of the Filoviridae family.  They can cause up to a 90% fatality rate in humans and are epizootic in Central and West Africa with 29 outbreaks since 1976.  The 2013-16 Ebola outbreak caused 28,616 cases and 11,310 deaths (40% fatal).

We have demonstrated 100% single-dose protection in preclinical lethal challenge models for our Ebola vaccine and are developing vaccines against Sudan and Marburg which also have pandemic potential.  Our Ebola vaccine has completed efficacy testing in non-human primates and is ready for GMP manufacture and phase 1 human trials.

Lassa Fever

Lassa fever virus, a member of the Arenaviridae family, causes severe and often fatal hemorrhagic illnesses in an overlapping region with Ebola. In contrast to the unpredictable epidemics of filoviruses, the Lassa virus is endemic in West Africa with an annual incidence of >300,000 infections, resulting in 5,000-10,000 deaths.  Data from a recent independent study suggest that the number of annual Lassa Fever cases may be much higher, reaching three million infections and 67,000 deaths, putting as many as 200 million persons at risk.

Our initial preclinical studies in rodents for our Lassa Fever vaccine candidate have shown 100% single-dose protection against a lethal challenge composed of multiple strains of Lassa delivered directly into the brain.  The study was conducted at the Institute of Human Virology at the University of Maryland School of Medicine in Baltimore. We are currently progressing with advanced preclinical testing and GMP manufacturing for our Lassa fever vaccine in preparation for human clinical trials; this work is being funded by a grant from the U.S. Department of Defense and is being performed in collaboration with USAMRIID, the Geneva Foundation, and IDT Biologika.

Zika Virus

Zika virus infection has been linked to an increase in microcephaly in infants and Guillain-Barre syndrome (a neurodegenerative disease) in adults. Zika is a member of the Flaviviridae family, which includes medically important pathogens such as dengue fever, yellow fever, Japanese encephalitis, tick-borne encephalitis, and West Nile viruses

We have achieved 100% protection of mice when vaccinated with a single dose of our Zika vaccine and exposed to a lethal challenge injected directly into the brain. Our Zika vaccine is based on the NS1 protein of Zika which is not associated with Antibody Dependent Enhancement (ADE) of infection, a safety concern for other Zika vaccines under development. Moreover, an NS1-based vaccine has the potential advantage of blocking transmission of Zika from humans to its mosquito vectors. Our Zika vaccine has completed efficacy testing in non-human primates and is ready for GMP manufacture and Phase 1 clinical trials. 

Malaria

Globally, malaria causes 228 million infections and 405,000 deaths annually. Despite decades of vaccine research, vaccine candidates have failed to induce substantial protection (e.g. >50%). Most of these vaccines are based on truncated proteins or VLP proteins targeting a limited number of antigens derived from only one stage of the malaria parasite’s life cycle. Our MVA-VLP multi-antigen malaria vaccine candidates are designed to induce a Th1 biased immune response with durable functional antibodies (IgG1 and IgG3) and CD4+ and CD8+ T cell responses, all hallmarks of an ideal malaria vaccine.  

We have collaborated with the Burnet Institute, a leading infectious disease research institute in Australia, as well as with Leidos, Inc. (under a contract from USAID Malaria Vaccine Development Program) for the development of a vaccine to prevent both malaria infection and transmission by targeting antigens derived from multiple stages of the parasite’s life cycle..