WHAT IS NMIBC
Non-Muscle Invasive Bladder Cancer (NMIBC) is a form of bladder cancer that remains confined to the bladder’s inner layers, without invading the muscle layer.
NMIBC accounts for approximately 75% of all bladder cancer cases (1). It is categorized into two grades: low-grade, which makes up about 70% of NMIBC cases (2), and high-grade, which accounts for the remaining 30% (2).
NMIBC is most common among elderly men, affecting men 3.3 times more often than women (3), with the average age at diagnosis being 73 (4). Globally, more than 4 million people currently suffer from NMIBC, and around 460,000 new cases are diagnosed each year (5).
THE MARKET NEED
The gold standard for high-grade NMIBC treatment over the last 30 years has significant limitations: efficacy, product availability, and side effects.
For those unresponsive to this standard, alternative solutions are often very expensive and inaccessible. Low-grade NMIBC is treated with intravesical chemotherapy, which also has its drawbacks. Therefore, there is an urgent need for a new and better therapy for NMIBC.
OVERVIEW OF UPEC-Fim-ON
Introduction to UPEC-FimON
UPEC-FimON is Hopec Pharma’s innovative immunotherapy for NMIBC, utilizing a genetically engineered strain of microbiome based Uropathogenic E. coli (UPEC). By targeting cancer cells and activating a robust immune response, UPEC-FimON offers a better alternative to conventional therapies.
The Science Behind UPEC-FimON
UPEC-FimON is a genetically engineered bacteria that is constantly expressing the type 1 fimbria allowing them to bind specifically to mannosylated receptors, which are more abundant on cancer cells. Once attached, UPEC-FimON triggers a strong T and NK-cells - mediated immune response against the tumor. To ensure safety, the bacteria are inactivated with formaldehyde, retaining their binding ability while eliminating infection risk and unable to kill the recruited immune cells.
In preclinical models, UPEC-FimON has shown superior efficacy compared to existing treatments, with fewer side effects and easier production and scalability. This makes UPEC-FimON a promising candidate for improving NMIBC treatment outcomes.
MECHANISM OF ACTION
UPEC-FimON is an innovative immunotherapy for NMIBC, utilizing a genetically modified UPEC strain engineered to express type 1 fimbriae. This modification enables UPEC-FimON to bind selectively to mannosylated receptors on bladder cancer cells, triggering a potent immune response involving both T cells and Natural Killer (NK) cells.
Preclinical studies have shown UPEC-FimON’s superior efficacy in tumor elimination compared to the current standard treatment, BCG. Remarkably, UPEC-FimON remains effective even with depleted NK cells, underscoring its strong T cell-mediated response.
Safety is enhanced through the use of a hemolysin A-deficient UPEC mutant and formaldehyde inactivation, preserving its binding capability while reducing infection risks. In a rat model, UPEC-FimON exhibited fewer adverse effects, as evidenced by stable body weight in treated animals and higher survival rate.
Ongoing research, led by experts like Prof. Chamutal Gur and Prof. Gilad Bachrach, continues to investigate the immune mechanisms and potential combination therapies to further boost efficacy.
These findings support UPEC-FimON's potential as a safer and more effective treatment option for NMIBC.
(1) Matulewicz RS, Steinberg GD. Non–muscle-invasive bladder cancer: Overview and contemporary treatment landscape of neoadjuvant
chemoablative therapies. Reviews in Urology. 2020;22(2):43–51. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393683/
(2) Grabe-Heyne K, Henne C, Mariappan P, Geiges G, Pöhlmann J, Pollock RF. Intermediate and high-risk non-muscle-invasive bladder cancer:
an overview of epidemiology, burden, and unmet needs. Front Pharmacol. 2023;14.
Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272547/
(3) International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today. Data visualization tools for exploring global cancer statistics.
Available at: https://gco.iarc.fr/today/en/dataviz/tables?mode=population&cancers=30&types=0&sexes=2
(4) Patient Power. Bladder Cancer Survival Rates by Age. Available at: https://www.patientpower.info/bladder-cancer/survival-rates-by-age
(5) World Cancer Research Fund. Bladder Cancer Statistics. Available at: https://www.wcrf.org/cancer-trends/bladder-cancer-statistics/