Technology
Metaba Platform
Metabolomics
Metaba Analysis Platform
Metaba PGNN Computation
Metabolomics
In recent years metabolomic studies have demonstrated that in addition to their involvement in cellular homeostasis and energy production, metabolites derived from multiple metabolic pathways, play important roles in regulation of cellular behavior, proliferation, apoptosis, signaling, and gene expression, both in physiological and pathological contexts. Dysregulation of cellular metabolism and changes in tissue and blood metabolites occur in many human diseases, including viral and bacterial infections such as tuberculosis (TB), HIV and HBV infections, cancers such as pancreatic and lung cancers, lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and cystic fibrosis (CF), liver diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and drug induced liver injury (DILI), kidney disorders such as diabetic chronic kidney disease (CKD), and cardiovascular diseases including atherosclerosis and stroke, and metabolic diseases such as obesity and diabetes, to name a few. Metabolomics provides a comprehensive understanding of metabolic pathways in biological systems. Using advanced analytical techniques and metabolomics, scientists have been able to identify diagnostic as well as therapeutic targets in multiple diseases, and identify novel drug targets while elucidating their mechanism of action and developing personalized treatment strategies. In that front, Metaba’s scientists identified a novel druggable, bacteria-specific, target for intervention in TB using metabolomic analysis, and have started collaborations with several national and international research institutes and biopharmaceutical companies to apply metabolomic analysis to investigate molecular mechanisms underlying therapeutic effects of novel drug candidates for NASH and IPF, and to investigate diagnostic metabolic changes in these diseases that are crucial for assessing therapeutic efficacy and disease prognosis. Metaba will continue to expand its reach in discovering therapies using its expertise in metabolomics and novel platform technology.
Our Therapeutic Strategies for TB
Adjunctive Therapeutics
In 2021, there were 1.6 million deaths in 120 countries from all forms of tuberculosis (TB), resulting in $580.1 billion in total losses, an average loss of $407,821 per TB death. The direct treatment costs of non-drug resistant TB are estimated to be around $20,000 per patient in the U.S. with treatment duration lasting for as long as 12 months. The direct treatment costs increase significantly for multidrug resistant TB (MDR-TB) and extensively-drug resistant TB (XDR-TB), amounting to $182,000 per patient with 20-26 month duration and $586,000 per patient with 32 month duration, respectively. Current treatment of active TB requires the use of a combination of standard of care (SOC) antibiotics for a minimum of 4-9 months. This lengthy treatment period which may result in the formation of drug resistant strains of bacteria, together with the adverse effects of chronic use of antibiotics that contributes to nonadherence, has highlighted the urgent need for enhancing the bactericidal activity of SOC antibiotics to reduce treatment duration that would lead to increased adherence and improved patient outcomes. Through the use of metabolomic studies, Metaba’s scientists identified a previously untargeted, bacteria-specific enzyme (trehalose synthase), that is involved in the ability of the microorganism to evade the full killing force of SOC antibiotics and survive. Inhibition of this enzyme was shown to enhance the therapeutic effect of SOC antibiotics while reducing the rate of formation of drug resistant mycobacteria. This strategy of employing adjuvant therapies together with antibiotics holds significant promise for safer and more effective TB treatment. Through the use of Artificial Intelligence (AI)-guided hit identification and lead optimization and machine learning methods employed by its platform technology, Metaba is poised to bring novel adjunctive therapies to address the global pandemic of TB especially in underserved populations in underdeveloped countries.
Host-Directed Therapeutics
Mycobacterium tuberculosis (Mtb), the causative agent of TB, like many other infectious agents including herpes viruses, chicken pox, and HIV, can survive and remain dormant (latent) in the human body for a prolonged period, often in the host immune cells, and is responsible for chronic and recurrent infections, especially among immunocompromised TB patients. Unfortunately, the most susceptible segment of the population to TB is the elderly whose innate immune system, the first line of defense against Mtb, often-times has been weakened due to aging-associated immunosenescence and inflammaging. Immunosenescence involves aging-associated changes to the immune system, both adaptive and innate immune systems, that tend to lose efficacy over time, leading to difficulties mounting immune responses against pathogens, including Mtb. Hence, in addition to therapies with direct bactericidal activity, identification and development of immune enhancers that are safe and effective for use in the elderly and the immunocompromised is of utmost importance in better management of these individuals. In collaboration with MAX BioPharma Inc, Metaba’s scientists have identified novel orally-bioavailable small molecule oxysterols that enhance the ability of host immune cells, for example macrophages, to clear microorganisms by producing anti-microbial factors. Using its metabolomic platform technology in synergy with other omic methodologies, including genomics, proteomics, and lipidomics, Metaba is evaluating the immune enhancing effects of oxysterol-based drug candidates that would mimic the activities of naturally occurring immune oxysterols in a safer and more robust manner to target Mtb and other infectious agents.
Novel Chemical Class of Antibiotics
In collaboration with our partners at MAX BioPharma, we have identified novel small molecule oxysterols with significant bactericidal activity when applied directly to mycobacteria tuberculosis (Mtb) or administered to innate immune cells (macrophages) infected with Mtb. We propose that oxysterol-based antibiotics may provide a novel class of anti-Mtb antibiotics with a different mechanism of action from classic, standard of care (SOC) antibiotics such as Rifampicin. This approach is complementary to our strategy of developing novel adjunctive therapies that work by enhancing the efficacy of SOC antibiotics.
Adjunctive Therapeutics
In 2021, there were 1.6 million deaths in 120 countries from all forms of tuberculosis (TB), resulting in $580.1 billion in total losses, an average loss of $407,821 per TB death. The direct treatment costs of non-drug resistant TB are estimated to be around $20,000 per patient in the U.S. with treatment duration lasting for as long as 12 months. The direct treatment costs increase significantly for multidrug resistant TB (MDR-TB) and extensively-drug resistant TB (XDR-TB), amounting to $182,000 per patient with 20-26 month duration and $586,000 per patient with 32 month duration, respectively. Current treatment of active TB requires the use of a combination of standard of care (SOC) antibiotics for a minimum of 4-9 months. This lengthy treatment period which may result in the formation of drug resistant strains of bacteria, together with the adverse effects of chronic use of antibiotics that contributes to nonadherence, has highlighted the urgent need for enhancing the bactericidal activity of SOC antibiotics to reduce treatment duration that would lead to increased adherence and improved patient outcomes. Through the use of metabolomic studies, Metaba’s scientists identified a previously untargeted, bacteria-specific enzyme (trehalose synthase), that is involved in the ability of the microorganism to evade the full killing force of SOC antibiotics and survive. Inhibition of this enzyme was shown to enhance the therapeutic effect of SOC antibiotics while reducing the rate of formation of drug resistant mycobacteria. This strategy of employing adjuvant therapies together with antibiotics holds significant promise for safer and more effective TB treatment. Through the use of Artificial Intelligence (AI)-guided hit identification and lead optimization and machine learning methods employed by its platform technology, Metaba is poised to bring novel adjunctive therapies to address the global pandemic of TB especially in underserved populations in underdeveloped countries.
Host-Directed Therapeutics
Mycobacterium tuberculosis (Mtb), the causative agent of TB, like many other infectious agents including herpes viruses, chicken pox, and HIV, can survive and remain dormant (latent) in the human body for a prolonged period, often in the host immune cells, and is responsible for chronic and recurrent infections, especially among immunocompromised TB patients. Unfortunately, the most susceptible segment of the population to TB is the elderly whose innate immune system, the first line of defense against Mtb, often-times has been weakened due to aging-associated immunosenescence and inflammaging. Immunosenescence involves aging-associated changes to the immune system, both adaptive and innate immune systems, that tend to lose efficacy over time, leading to difficulties mounting immune responses against pathogens, including Mtb. Hence, in addition to therapies with direct bactericidal activity, identification and development of immune enhancers that are safe and effective for use in the elderly and the immunocompromised is of utmost importance in better management of these individuals. In collaboration with MAX BioPharma Inc, Metaba’s scientists have identified novel orally-bioavailable small molecule oxysterols that enhance the ability of host immune cells, for example macrophages, to clear microorganisms by producing anti-microbial factors. Using its metabolomic platform technology in synergy with other omic methodologies, including genomics, proteomics, and lipidomics, Metaba is evaluating the immune enhancing effects of oxysterol-based drug candidates that would mimic the activities of naturally occurring immune oxysterols in a safer and more robust manner to target Mtb and other infectious agents.
Novel Chemical Class of Antibiotics
In collaboration with our partners at MAX BioPharma, we have identified novel small molecule oxysterols with significant bactericidal activity when applied directly to mycobacteria tuberculosis (Mtb) or administered to innate immune cells (macrophages) infected with Mtb. We propose that oxysterol-based antibiotics may provide a novel class of anti-Mtb antibiotics with a different mechanism of action from classic, standard of care (SOC) antibiotics such as Rifampicin. This approach is complementary to our strategy of developing novel adjunctive therapies that work by enhancing the efficacy of SOC antibiotics.
