Challenges antibiotic resistance06/10/16
QureTech Bio AB develops a new class of anti-infective agents with the unique ability to disarm bacteria to avoid or reverse antibiotic resistance. Antibiotic resistance is a serious and accelerating problem. Infections with multidrug-resistant bacteria cause around 25,000 deaths annually in the EU alone, and the accompanying economic burden is immense. Without adequate tools to control bacterial infections, modern healthcare will collapse to the point that oncological treatments and advanced surgery that make patients highly susceptible to infections will become difficult or impossible to perform. There is an urgent need for new remedies against bacterial infections. Regulatory bodies offer a fast track for novel treatments of bacterial infections and in the US an extra five years’ market exclusivity is awarded once an antibacterial drug is approved.
QureTech Bio is developing a revolutionary new class of antibacterial agents, virulence blockers, which block the bacteria’s ability to cause disease. These agents selectively disarm the pathogenic properties of the bacteria and may be used alone or in combination with antibiotics.
Tuberculosis (TB) is the most deadly infectious disease with 1.5 million deaths yearly. The current standard treatment is long – six to nine months – the drug dose burden is high and this combination gives rise to significant side effects. Compliance is of utmost importance to avoid development of drug resistance. However, compliance is challenged by the long duration and the side effects. Lack of compliance has caused spread of
multidrug-resistant TB (MDR-TB). MDR-TB is steadily increasing and has a mortality of around 50% even after two to three years’ treatment. By 2050 MDR-TB threatens to kill 75 million people and cost USD 16.7 trillion (~€15.1tr) according to the Centers for Disease Prevention and Control (CDC).
QureTech Bio has developed virulence blockers that prevent Mycobacteria tuberculosis (Mtb) from going into persistent state and tolerating antibiotic treatment. Hence, the bacteria are rendered defenceless against key antibiotic Isoniazid (INH). These mycobacterial tolerance inhibitors (MTIs) represent a fundamentally new approach to the treatment of tuberculosis.
- MTI, developed by QureTech Bio, blocks the stress response of Mtb and in that way prevents the establishment of persistent bacteria that cause the long treatment time;
- By combining the MTI with INH, treatment time can be shortened significantly as persistence is inhibited and the efficacy of the antibiotic treatment is dramatically increased;
- Resistance to INH is outmanoeuvred, enabling the treatment of MDR-TB based on restored efficacy of this well-known drug;
- Shortening the treatment time to a month will greatly improve side effect profile, compliance, patient quality of life and in the end treatment outcome;
- Shortening the treatment time for TB to a month will save 75% of current drug costs. This creates a value of $5bn on drug costs alone. In addition, savings in the healthcare system will be in the range of billions of euros in Europe alone, and will make this attractive for payers; and
- The MTIs may also be used for prophylactic treatment against tuberculosis by maintaining Mtb sensitive to the immune response of the host.
QureTech Bio is ready to start full validation of the treatment of active Mtb infection and prevention of the reactivation of disease in animal models. Besides acute treatment, absence of relapses will be the main readout parameters in this study.
The chemical series is well-suited for drug development with good potency and tractable properties, including PK. QureTech Bio has secured intellectual property (IP) for these findings.
Partnership and collaboration sought
The company firstly seeks funding for the proof of concept study and to secure further IP rights. To achieve this $500k is needed over 18 months. Further development to a candidate drug and clinical phase 1 trial is estimated to require $10m over 3.5 years. QureTech Bio also seeks partners to help progress this project into the clinic. Besides capital that will require competence within CMC, safety assessment, regulatory and clinical.
Chlamydia trachomatis is the most common sexually transmitted infection with 100 million cases continuously. These infections are associated with a large economic burden. The direct medical cost was estimated at €3bn in the EU (2009) and similar in the US. Moreover, Chlamydia is the main cause of pelvic inflammatory disease (PID), a main cause of female infertility, accounting for healthcare costs of another $10bn annually. Current treatment is based on broad spectrum antibiotics. However, these drugs become less and less preferable for none acute infections like Chlamydia as they affect the natural gut flora and favour drug-resistant pathogens, which are becoming more and more common in society. New treatment for Chlamydia will be required to meet the ongoing spread of antibiotic-resistant Chlamydia, which is now seen in 8% of cases.
QureTech Bio has developed highly Chlamydia selective small molecules that are non-toxic to human cell lines and well tolerated in mice. Proof of concept studies in an animal disease model are ongoing with excellent preliminary readouts.
- QureTech Bio’s new class of compounds – virulence blockers – stop the infection by specifically blocking the pathogenic properties of Chlamydia, while final clearance is handled by the immune system;
- Remaining immune system capability directed against Chlamydia will be followed up on in the in vivo validation study to trace any vaccine effect;
- The compounds are selective and target a pathogenic process rather than bacterial survival. This reduces the risk of drug resistance development. The compounds will most likely also be effective against Chlamydia strains that are resistant to antibiotics used today;
- Virulence blockers are selective for Chlamydia and have no negative effect on the normal bacterial flora. That in itself serves as a very good barrier against pathogens; and
- The virulence blockers are aimed as front line treatment of Chlamydia and present a solution to the ‘antibiotic dilemma’. With minimal risk for drug resistance development the sales should not be affected by the restrictions of use that limit the market value of new antibiotics.
Initial proof of concept animal studies with a positive outcome have been carried out for Chlamydia and the complete readout is expected during 2016. The chemical lead series is attractive with good potency and tractable properties based on a stable chemical platform. To identify a candidate drug 18 months of lead optimisation and profiling are required. QureTech Bio has full ownership of a recent PCT (Patent Cooperation Treaty) application covering the Chlamydia trachomatis indication.
Partnership and collaboration sought
QureTech Bio needs $5m over a three-year period to make the Chlamydia project ready for clinical trials. A combined clinical phase 1 and 2 based on around 100 patients will require an additional $4m for completion.
QureTech Bio AB develops a new class of anti-infective agents with the unique ability to selectively prevent the disease-causing properties of certain bacteria without disrupting the normal bacterial flora. Therefore, the risk for resistance development is significantly reduced. The company was founded as a drug development company in 2010 to commercialise world-leading research from groups based at Umeå University, Sweden, and Washington University, St Louis, MO, USA.
QureTech Bio AB