TetramOX® the first-in class antibiotic to solve multi drug resistance
Antibiotics are considered one of the greatest discoveries of the 20th century and have become an integral part of healthcare and our daily lives. However, the combination of dwindling antibiotic pipelines and growing antimicrobial resistance has brought us to the brink of a post antibiotic era, as patients are dying from infections that were once treatable.
More than ten years ago Prof. Mark Moloney at the University of Oxford began to develop a new class of active compounds with the aim to avert this danger to mankind. He discovered that a 5-ring tetramate or 6-ring piperidinedione core can be used to generate libraries of small molecules which exhibit broad spectrum antibacterial activity. Since the synthesis of this compound class is simple and efficient, libraries of unique compounds can easily be created.
After optimization and pre-clinical research done by the team of Oxford Antibiotic Group the antibiotic TetramOX® is now highlighted as new hope against multidrug resistant bacteria with following characteristics:
First in-class patented compound with a new chemistry (not a “me-too” or analog) that can treat multi drug resistant bacterial infections and thus help us to prevent the post antibiotic era.
Excellent potency and broad spectrum with activity against all important bacterial pathogens, in particular:
- MRSA is a bacterium that is resistant to antibiotics normally used to treat Staphylococcus infections. The bacterium is often found on the skin, inside the nostrils and the throat. It can cause serve infections of the skin and induce sepsis if the infection spreads throughout the body
- MSSA lives harmlessly on the skin but it can cause blood poisoning if it gets into the bloodstream
- Beta-haemolytic Streptococcus, this are bacteria which can destroy red blood cells and can cause different diseases, such as Meningitis or Angina.
- Streptococcus pneumonia that causes Pneumococcal infections, which leading to inflammation of one or both lobes of the lung.
- Enterococci that cause diverse infections, such as the life-threatening Endocarditis. VRE strains are strains of Enterococci bacteria that are resistant to the antibiotic Vancomycin
- Clostridium difficile is an anaerobic gut bacterium which causes serve infections and toxin production
Innovative mode of action (UPPS), affecting the bacterial fat synthesis, with clear ID of the active center and low potential for resistance development
Excellent safety and compatibility with good therapeutic window, no genotoxicity, no phototoxicity, no cross resistance and other important positive characteristics
Superior pharmacological features such as stability, distribution and metabolism
Highly active in sepsis models showing better results than golden standard antibiotics
Good formulation features compound can be given orally and/or injected
Cost efficient and easy production allows reasonable pricing
TetramOX® outstanding activity against multi-resistant pathogens and its properties, which have been optimized over more than ten years of international research, is primarily aimed at the following medical fields of application:
Multi-drug resistant Staphylococcus aureus infections (MRSA)
MRSA is a common cause of nosocomial infections, where the bacteria is resistant to beta-lactam antibiotics such as methicillin, amoxicillin, penicillin and oxacillin. MRSA can cause a broad variety of infections. The infection can range from superficial skin eruptions to life-threatening cellulitis, blood and surgical infections, pneumonia and urinary tract infections. Hospital acquired and community-acquired MRSA are the two main types of MRSA infection.
The incidence of MRSA is gradually increasing throughout the world. The increase in cases is mainly due to the development of resistance towards antibiotics. The global methicillin-resistant Staphylococcus aureus (MRSA) drugs market is estimated to be valued at US$ 922.2 Mn in 2020 with a CAGR of 4.1%.
TetramOX® with its new mode of action and highly activity against MRSA and MSSA is an innovative strategy against life threatening infections. The compound can be used either as injection in clinical settings and as pill for the community settings. This versatility paired with the compounds high efficacy will allow TetramOX® to develop into a blockbuster and solve the resistance problem to this group of germs.
Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart by bacteria or fungi, which may include one or more heart valves, the mural endocardium, or a septal defect. Its intracardiac effects include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial abscesses. Streptococcus species (spp.), Staphylococcus spp. and Enterococci are the most common microorganism causing IE. In recent years, the unmet medical need in IE is the infection with Vancomycin resistant Enterococci (VRE). If left untreated, IE is generally fatal.
Globally, IE is associated with a significant burden and was responsible for 69,000 deaths in 2019. The mortality rate from IE is significantly high, with an in-hospital mortality rate of up to 22% and a 5-year mortality rate of 45%. The annual incidence of IE in the adult population ranges between 3-9 per 100,000 subjects per year.
Market volume is US$ 920 Mn (2019) with no specific registered drugs in market and therefore standard antibiotics are often used in an attempt to treat it. However, Off-label use of these antibiotics can cause toxic side effects during therapy. In most cases, the problem by using standard antibiotics for the treatment of IE is the liver toxicity during the long-term therapy.
The endocarditis market is one of OxAG’s main targets due to the high unmet medical need, substantial market size with increasing prevalence and awareness. TetramOX’s excellent activity against the endocarditis causing pathogens (MRSA, VRE and Streptococci) combined with the good toxic profile for extended usage and its first in class capabilities it is an excellent candidate to treat that disease.
Acute Skin and Skin Structure Infections (ABSSSI)
Skin and skin structure infections (SSSI) encompass a range of bacterial-related illnesses that can manifest in a variety of symptoms. The extent of the disease can range from mild to severe. Common skin structure infections include post-surgical wound infections, carbuncles, and traumatic wound infections. The organisms causing SSSI are typically Gram-positive bacterial pathogens, such as Staphylococcus aureus and Streptococcus pyogenes. Aside from the general complications associated with skin infections, such as the swelling and discharge common with carbunculosis, other more serious symptoms can occur, namely Acute Skin and Skin Structure Infections (ABSSSI). For example, streptococcal infections of cutaneous and soft tissue can range from localized impetigo to invasive fasciitis associated with toxic shock that can rapidly lead to death.
The global Acute Bacterial Skin and Skin Structure Infections Treatment market is projected to grow rapidly in the coming years. The market was valued at US$ 7,270.9 Mn in 2019 and is predicted to reach US$ 14,972.6 Mn by the end of 2026. The severity of acute bacterial skin and skin structure infections (ABSSSI) has led to an increasing emphasis on the identification of novel strategies to treat this disease.
TetramOX® has the potential to be an excellent new therapeutic against Skin and Skin Structure Infections (SSSI) and will allow the clinicians to fight against the resistance problem. Especially the activity of TetramOX® against new Staphylococcus aureus strains (VISA, VRSA) gives it an edge as treatment compared to existing antibiotics or me-too candidates.
Healthcare-Associated Pneumonia (HCAP)
Hospital-acquired pneumonia (HAP) or respectively the Healthcare-Associated Pneumonia (HCAP) are the most dangerous infections of the lung parenchyma that occurs during the course of hospitalization. The majority of patients with hospital-acquired pneumonia develop serious complications that include renal failure, respiratory failure and empyema due to underlying conditions and weak health conditions. Therefore, increasing incidences of hospital-acquired pneumonia will lead to a surge in the demand for pneumonia therapeutics drugs.
Healthcare-associated infections (HAIs), HCAP/ HAP in hospitals have significant economic consequences for healthcare systems. HCAP/HAP in hospitals impose significant economic consequences on the nation’s healthcare system and are a significant source of morbidity, mortality, and increased resource expenditures. According the World Health Organization (WHO), 1.6 million people die each year as a result of pneumococcal diseases. The global hospital acquired pneumonia drug market is projected to reach US$ 3.8 bn by the end of 2020 and will grow at a CAGR of 7.6% from 2020 to 2026.
Patients with HAP/HCAP are at risk of infections with drug resistant or multidrug-resistant organisms (MDRO) such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, gram-negative rods bacteria which produce extended-spectrum beta-lactamases (ESBL), and other gram-negative rods.
Compared to other antibiotics, which were not able to penetrate the lungs, TetramOXs high solubility and Vd value of 2 should allow it to easily penetrate the lungs. This, together with its excellent activity against MRSA and Streptococcus, makes it an excellent candidate to treat pulmonic infections.