Prokarium’s vision is to create a new class of programmable therapeutics for equitable access. This class, Prokarium calls ‘living cures’ due to the fact that they are made of living bacteria which can be delivered to an exact location in the body.
The company’s foundational technology is ZH9, a live bacterial immunotherapy based on Salmonella Typhi. Prokarium have modified the Salmonella bacterium with two very specific attenuated deletions so that it does not cause typhoid fever. The bacterium is designed to stimulate the immune system to help treat cancer and induces a strong innate immune reaction. ZH9 naturally targets tumours, has oncolytic activity, and induces trained immunity – all important features for mounting an effective anti-tumour response.
The therapy is currently under clinical investigation for the treatment of non-muscle invasive bladder cancer (NMIBC), a very common form of the disease. Bladder cancer has the highest recurrence rate of any known cancer, which makes it a risk and a burden for both patients and health systems.
The current standard of care for NMIBC is Bacillus Calmette-Guérin (BCG), a live bacterium, and that has been used for over 40 years. Prokarium’s ZH9 leverages this proven mechanism but with a better ease of use and lower treatment burden. Rather than the standard 27 doses of treatment needed over 2 to 3 years, ZH9 reduces this number to 15.
Prokarium uses scalable manufacturing for ZH9 to meet the global demand, important in the current context of BCG facing a world-wide shortage. Batches can be manufactured in one week as opposed to the three months that BCG needs.
Preclinical data indicates ZH9 elicits a stronger and more durable immune response compared to BCG, enhancing immune cell recruitment necessary for preventing cancer recurrence. The ongoing PARADIGM 1 trial aims to assess the effectiveness of ZH9 in a new treatment paradigm for bladder cancer, focusing on durability of response.
Now, Prokarium are pushing their pipeline further. They want to use a synthetic biology toolkit to integrate biological logic gating and programmability into their immunotherapies. The goal is to make their bacteria programmable, targeted, off-the-shelf, and at a low cost.
Prokarium’s Living Cures Platform uses this technology for the targeted delivery of therapeutic payloads in cancer treatment. By inserting logic gate circuits into programmable genomic integration sites, they can engineer proteins, such as cytokines, to be delivered by ZH9 ensuring stability and function in the tumor environment. Prokarium envisions ZH9 and its programmable capabilities to become a new pillar in cancer treatment, addressing the limitations of current therapies.
