First in Human: Needle-free vaccine for COVID variants; Fabry disease therapy

This is a recurring column on clinical research in the early stages of development, which is referred to as phase 1. These are treatments being used for the first time in a small number of human patients to determine safety, dosing and general pharmacological activity.

British biotech Scancell Holdings PLC is embarking on a phase 1 trial of two next-generation vaccine candidates against COVID-19, which may not only improve protection against new variants of the virus but also provide an option for anyone afraid of needles.

The candidates, called SCOV1 and SCOV2, are based on Scancell's ImmunoBody DNA vaccine technology and have a dual mechanism of action targeting both the virus's highly conserved nucleocapsid N antigen and its more variable spike protein. Delivered via different needle-free options, the vaccines are designed to elicit a high level of virus-neutralizing antibodies that can cross-react against a range of COVID-19 variants of concern, including the Beta variant first identified in South Africa.

Due to the rapid rollout of the U.K. vaccination program, the first part of the clinical trial will take place in South Africa at the University of Cape Town Lung Institute, where it will be easier to recruit a pool of healthy adult volunteers who are still unvaccinated. The second part of the trial — intended to take place in the U.K. — will see SCOV2 administered to healthy volunteers who have already received two doses of an approved vaccine.

The immune responses from the second part of the study will allow Oxford, U.K.-based Scancell to see if SCOV2 can boost the immune response against current and potential future strains of COVID-19 in pre-vaccinated individuals.

"There is a significant threat from future mutations of the SARS-CoV-2 virus, as we have seen with the rapid transmission of the Delta variant," Scancell CEO Cliff Holloway said in a statement. "Our next-generation COVID-19 vaccine has the potential to work alongside currently approved vaccines by protecting the population against new variants of SARS-CoV-2."

Gene therapy for Fabry disease

Another U.K.-based biotech, Freeline Therapeutics Holdings PLC, has launched a phase 1 trial of its gene therapy for Fabry disease.

Fabry disease is a genetic condition estimated to affect 1 in 40,000 people. It is characterized by the absence of a key enzyme needed to break down lipids and fats, leading to an increased risk of heart attack, stroke and kidney failure.

Nasdaq-listed Freeline began a phase 1/2 trial of its therapy, called FLT190, to examine the drug's safety and efficacy across four dose levels in approximately 10 male patients with classic Fabry disease, who will be monitored for nine months. Data from the drug, which is administered by intravenous infusion, will be presented later this year.

Healthcare investment fund Syncona Ltd. has a 47% shareholding in Freeline, and the Stevenage, U.K.-based biotech also has ongoing clinical programs targeting hemophilia B and Gaucher disease type 1 — another genetic disorder characterized by a missing enzyme needed to break down lipids — as well as a preclinical program in hemophilia A.

"Dosing the second patient in the MARVEL-1 study is an important milestone for Freeline and evidence of progress in our Fabry program," Freeline CEO Theresa Heggie said in a statement.

"Easing of COVID-19 restrictions, together with geographic expansion of study sites, should enable continued enrollment as we work to make FLT190 available to the Fabry disease patient community," Heggie added. "With dosing complete in our first cohort, we look forward to advancing through the next cohorts in our dose-finding study."

Hope for cystic fibrosis?

Brighton, U.K.-based Enterprise Therapeutics Ltd. has dosed the first subjects in a safety study of ETD001, an inhaled therapy for cystic fibrosis that has already demonstrated a long duration of action in the lung.

Cystic fibrosis causes a buildup of sticky mucus in the lungs, resulting in breathing problems and an increased risk of lung infections. Over time, the lungs may stop working properly, and the mucus also clogs the pancreas, preventing enzymes from reaching food in the gut. Some 83,000 people worldwide have the condition, which carries an average life expectancy of 40 years.

ETD001 targets the ENaC epithelial sodium ion channel, which controls fluid volume and mucus clearance from the airways. By increasing the amount of airway fluid available to hydrate mucus, the therapy addresses the underlying mechanisms of mucus congestion with the aim of restoring lung function, reducing the frequency of lung infections and improving patients' quality of life, Enterprise said.

This mode of action means the drug could be used for all patients with cystic fibrosis and potentially even those with other lung diseases, the company added.

"We are excited to be entering the clinic with ETD001. This ENaC blocker has best-in-class potential due to its long duration of action in the lung and favorable pre-clinical safety profile," Enterprise CEO John Ford said in a statement.

"ETD001 could significantly improve quality of life for people living with cystic fibrosis and other respiratory diseases linked to mucus obstruction," Ford added.