Harnessing the Immune System To Combat Antimicrobial Resistance

Centauri is a Series A biotech based at Alderley Park in the UK, with current funding from investors Boehringer Ingelheim Venture Fund, the Novo REPAIR Fund, and Evotec, alongside key non-dilutive funders and partners CARB-X and PACE. We are focused on developing immune therapies as anti-infectives to treat infections in the most vulnerable patients. While our platform has significant readthrough into other therapeutic areas such as oncology, we are currently tackling Gram-negative bacterial infections as our first indication. Our technology is designed to engage the immune system as a potent component of the bifunctional antibacterial activity of our lead molecule. We believe that by actively engaging the immune system, we will be able to effectively treat infections in people who do not respond well to traditional antibiotics.

The Centauri platform is based on recruiting pre-existing, ubiquitous, anti-glycan antibodies. With our technology, we can recruit these antibodies to a chosen target (such as a pathogen), which further engages the immune system to clear the infection.

These antibodies are polyclonal and very hard to suppress. Therefore, we believe there may be an opportunity to treat infections in individuals who may also have comorbidities or are on immune suppressive agents. The antibodies our technology engages as well as the associated immune repertoire, are known to be present in most individuals. Our current research efforts are now focused on understanding which populations are likely to respond best to our therapies.

Traditional antibiotics focus specifically on the direct killing of bacteria. However, these traditional agents also rely on the patient’s own immune system to clear their infection completely. Therefore, for patients who aren’t otherwise healthy, the traditional antibiotic does its job of reducing bacterial burden, but the infection may not fully resolve because the patient’s immune system is unable to do the rest of the cleanup.

We believe that by actively engaging the immune system through our technology and bringing multiple components of the immune system together, we have the opportunity to treat infections that otherwise go untreated. At Centauri, we are eager to understand how effective our candidate may be in patients who are immunosuppressed, have cancer, are elderly or have any number of other co-morbidities as we know these are the individuals who are most at risk of developing serious infections, including the development of drug-resistant infections. 

Antibiotic resistance is the tip of the iceberg in terms of the unmet medical need that exists in this field. It is well documented that untreatable infections include both antibiotic-resistant pathogens as well as traditionally sensitive pathogens that are not effectively treated due to a variety of host factors that impact the ability of a patient to clear an infection.

The novel peptide in our molecule provides broad-spectrum antibacterial activity against multidrug-resistant (MDR) and extremely drug-resistant (XDR) Gram-negative bacteria. This intrinsic antibiotic effect occurs when the peptide binds to the bacterial surface in sufficient concentration and for sufficient time to disrupt and destroy the bacterial membranes. On the other end of our molecule is a glycan effector moiety, which engages natural anti-glycan antibodies and mediates immune-driven bacterial clearance. This requires binding at lower drug concentrations for a shorter time, providing rapid immune clearance at sub-bactericidal concentrations. This opens up the possibility of treating patients who have hard-to-treat infections that are less susceptible to traditional antibiotic modalities, as well as MDR and XDR strains.

By effectively treating infections in all patients, including those who are most vulnerable, Alphamer technology may be able to prevent the emergence of resistance as well as treat classically resistant infections.

Our lead molecule has several differentiating properties that could make it a good fit to complement current treatment paradigms and move toward personalized treatments based on the needs of the patient.

Its broad-spectrum activity and effectiveness against MDR and XDR strains mean it could be a good option for first-line treatment for serious acute Gram-negative bacterial infections, providing antibiotic cover whilst the microbiology lab is identifying the bacterial strain and antibiotic sensitivities.

Unlike Colistin and Polymyxin B (currently the only licensed antimicrobial peptides), our compound has good lung exposure and tolerability (in pre-clinical infection models), therefore having great potential to become the new standard of care for hard-to-treat lung infections.

Its immune-therapeutic mechanism of action could synergize well with other classes of antibiotics, especially in biofilm infections where antibody-mediated immune clearance has been shown to be effective.

The underlying immune mechanism employed by ABX01 is well-known, universal and shown to be highly potent, even in severely immune-compromised patients. Thus, the ability of our molecule to leverage the immune response and focus it on the site of infection may also be beneficial in the treatment of at-risk and vulnerable patients who have significantly impaired immune activity.