Clostridium difficile infection

prevention of primary and recurrent CDI through companion probiotics

One of the ambitions of GeneCreek is to discover microbes improving our health and to lay the foundations for a second generation of a specific type of functional food additives called “probiotics”, hence addressing major public health concerns. The company does so by capitalizing on recent advances in microbiome- and data science. GeneCreek’s breakthrough RECIPE approach consists of the exploratory analysis of thousands of relevant clinical samples to discover bacteria with antagonistic activity against other, disease-causing bacteria, to design novel companion probiotics as a means to combat disease such as Clostridium difficile infection (CDI).

RECIPE

Resilience Enforcement and Competitive Intestinal Pathogen Exclusion

CDI has become the leading cause of nosocomial infections worldwide over the last decade. Control measures (hygiene and reduced use of antibiotics) in hospitals have proven capable of lowering incidence by up to 80% but insufficient to prevent CDI. GeneCreek has discovered specific bacterial species which are naturally present in the intestines of healthy subjects, protect against CDI.

CDI is essentially triggered by prescription of antibiotics. Targeted preventive use of a probiotics product for inpatients receiving antibiotics represents a latent market in the order of €100M in the EU. The design of an innovative companion probiotics product resulting from this discovery is the subject of a pending patent application with high potential to deliver broad protection. The company is working with EU food business operators (FBOs) specializing in probiotics to transform the design into a quality CDI prevention product, disrupting the market. Time-to-market is estimated at 2 years.

Colorectal cancer

prevention and improved therapeutic outcome through use of probiotics

Based on the analysis of multiple large cohorts from several continents, GeneCreek has identified one QPS/GRAS species potentially capable of preventing the formation of adenomous polyps, the precursors of CRC. Also, several probiotic species capable of modulating a frequent enterotype found in early stages of adenocarcinoma development and which procures resistance to therapy have been identified.

Epidemiology. CRC is a multi-factorial disease resulting from lifestyle, genetic, and environmental factors. Almost half of the population will develop at least one benign adenomatous colonic polyp during life, with less than 3% of those cases going on to develop CRC. Because symptoms are rare until very late stages, most cases go undetected. The 5-year survival expectation for CRC patients ranges from 93% for early stages to 8% in fully advanced stages. In the US, over 130,000 new CRC cases are declared and the annual death toll approaches 50,000 which makes it the third deadliest cancer type after lung and prostate/breast cancer.

Paediatric allergy

prevention during pregnancy and infancy though food supplements

Based on the analysis of thousands of infant microbiomes and clinical metadata, GeneCreek has found strong negative correlation between the presence of specific beneficial lactic acid bacteria in the gut in the first two years of life and the appearance of sensitization and onset of allergies, including food allergy (peanut, egg and milk). Significant insights in mechanism of action have been obtained. The discovery sets the stage for a rationally designed food supplement for pregnancy and infancy.

Epidemiology. Pediatric allergy has been rising over the last decades and food allergies in particular, for instance peanut allergy increased by 21% in the U.S. between 2010 and 2017 (source: ACAAI). The worldwide prevalence in children for hay fever is 13%, asthma 12% and eczema 8%, with 1% of children developing all three disorders. The prevalence estimates of food allergies in pre-school children, based on oral food challenge (OFC) tests, is estimated at an average 10% in western countries and 7% is Asia.

Etiology. About 30% of children with food allergies are allergic to multiple food allergens, and pediatric allergies as a whole are interrelated. A frequent sequential allergy development pattern referred to as the "allergic march" starts with infant eczema, then toddler food allergies, then school aged asthma and hay fever. Immune system maturation happens during the first two years of life and sets the stage for this march.

Economics. Familial aggregation of food allergy is important. U.S. families spend $3,500 per child and $20B annually caring for children with food allergies, whereas willingness-to-pay of parents for symptom relief of eczema was estimated at $2.6B. The food intolerance market is expected to reach $14B by 2022. The market for food supplements effective to prevent or stop the pediatric allergic march is a latent niche, since dedicated and scientifically proven products are not yet available. GeneCreek has obtained indications that a curative positioning is possible as well. The allergy immunotherapy (AIT) market is expected to reach $4.3B by 2023.

Immune checkpoint inhibition

improved response to treatment through companion probiotics

GeneCreek has developed a microbiome based PD-1 blockade response predictor based on the reanalysis of 3 published melanoma cohorts from two continents. Probiotic species antagonizing three of the 4 species correlated with nonresponse have been identified. These probiotic species do not antagonize the species correlated with response to therapy.

Checkpoint inhibitor therapy has proven effective in metastatic melanoma and a range of other tumor entities including non-small cell lung carcinoma, Hodgkin lymphoma and renal cell carcinoma. 60–70% of patients with metastatic melanoma do not respond to single agent therapy with the anti-programmed death (PD)-1 antibodies pembrolizumab or nivolumab, whereas combination therapies provoke significant side effects. Improvement of therapeutic response through modulation of the microbiome with companion probiotics could represent an important health benefit for patients.