We develop products using a technology platform based on engineered bacteria, proven safe in 10 adult and paediatric clinical trials in the US, UK and Vietnam. Using our expertise in engineering biology and immunology we apply our platform to prevent infectious diseases (Vaxonella®) and to treat solid tumours (Onconella™). Our safe, engineered bacteria retain their natural ability to survive transiently inside of human cells after being ingested, and we can use this to deliver and produce medicines from inside of the body’s own cells. This has many advantages including oral delivery and stimulation of strong, protective mucosal, antibody-based and cellular immunity.
Bacteria are ingested, pass through the stomach and then traverse the lining of the small intestine via microfold cells (M cells) into lymphatic nodules called Peyer’s patches. There they are phagocytosed by antigen-presenting cells (APCs) such as macrophages and express the antigen genes. The antigens are processed and presented by the APCs to stimulate cellular and humoral immune responses, including mucosal responses.
In this adaption of our platform technologies, we leverage proprietary genetic engineering interventions to build on the natural ability of our bacterial strains to seek out and colonise solid tumours. We have developed attenuated strains capable of targeting tumours without causing pathology in normal tissues. These Onconella™ strains are also capable of delivering specific immunostimulatory cargo aimed at activating the patient’s immune system to destroy tumours.
Enteric fever, a preventable illness caused by Salmonella enterica serovars Typhi and Paratyphi A, is the most common bacterial bloodstream infection in South Asia. Despite progress made in controlling enteric fever in several parts of the world, it remains an important public health burden in South Asia and Africa. It has been estimated to cause >15 million illnesses and nearly 153,000 deaths worldwide annually and the incidence is estimated to be over 100 per 100,000 population.
Prokarium is developing Entervax™, a novel, oral bivalent vaccine for the prevention of enteric fever in at-risk populations. Entervax™ is based on the Vaxonella® platform and is the combination of our proprietary strain ZH9 (Salmonella enterica serovar Typhi ZH9), which has been safely administered to 351 individuals, plus a novel strain modified to express antigens specific to S. Paratyphi A. Entervax™ will be entering the clinic in 2H2019.
Chlamydia trachomatis, a Gram-negative obligate intracellular pathogen, is one of the most common sexually transmitted infections (STIs) that occurs in humans. Genital Chlamydia infection is of worldwide importance and concern. There were 203,000 diagnoses of Chlamydia related STI in 2017 in England (PHE) and 131 million new cases worldwide; 20% of the STIs occurring annually (WHO).
Even though infection is easily diagnosed, many infections are asymptomatic (50% of men and 90% of women) so a large proportion of cases remain undiagnosed. Infection with C. trachomatis can lead to long-term health problems, such as pelvic inflammatory disease (PID) that can cause permanent damage to the female reproductive system. Associated complications can include chronic pelvic pain, ectopic pregnancy and tubal factor infertility. Furthermore, in developing countries infection from C. trachomatis can lead to blindness in infants due to trachoma.
Prokarium aims to be the first to develop an effective Chlamydia vaccine that could prevent PID and infertility and at the same time reduce antibiotic use and save on costs for national healthcare systems.
Prokarium is currently working with the UK Defence Science and Technology Laboratory (DSTL) to develop a plague vaccine, based on its recombinant live attenuated Salmonella strains expressing two plasmid-encoded Yersinia pestis antigens. Plague is recognised by WHO as a re-emerging disease. From 2010 to 2015, over 3000 cases were reported worldwide, including 584 deaths. In 2015, 16 human cases of plague were reported in the US, resulting in 4 deaths and a large outbreak of the disease occurred in Madagascar in late 2017, with over 2000 cases confirmed, including 202 deaths (WHO Target Product Profile for PlagueVaccines, April 2018). In March 2018, a plague outbreak on Uganda’s border with the Democratic Republic of Congo also resulted in multiple fatalities. The recrudescence of plague outbreaks together with the increasing concern of multiple antibiotic resistance Yersinia pestis strains, and its potential as an aerosol-delivered biological warfare agent, justify a renewed interest in the development of a plague vaccine.
We are currently exploring the application of Onconella™ in several solid tumour indications.
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