PREP-ing for Future Pandemics and AMR


As the Covid-19 pandemic rages, worries about rising antimicrobial resistance are increasing too. One company is preparing for future pandemics and antimicrobial resistance.

The intentions of AiCuris as a company are unequivocal and can be determined simply by breaking down the company name: Ai = anti-infective and Curis refers to finding a cure.

Holger Zimmermann, AiCuris
Holger Zimmermann, CEO of AiCuris

Emphasizing this tenet, while speaking about the current pandemic, Holger Zimmermann, Chief Executive Officer of AiCuris, said: “In times like these, biotech and pharmaceutical companies have a great societal responsibility. We must ask ourselves how we can best help in such a situation.

To this end – preparation for future pandemics and antimicrobial resistance – AiCuris, a leading company in anti-infective drug development, recently launched the Pandemic and Resistance Emergency Preparedness (PREP) initiative. 

In light of Covid-19, the need for global preparations for an antimicrobial-resistant/superbug emergency cannot be overstated. For instance, the US Centers for Disease Control and Prevention’s Antibiotic Resistance Threats 2019 report stated that over 2.8 million antibiotic-resistant infections occur in the US each year and more than 35,000 people die as a result. Furthermore, over 70% of the bacteria that cause these infections are resistant to at least one of the antibiotics commonly used to treat them.

While PREP comprises four pillars, the initiative has two main thrusts: the development of a novel biological immunomodulator, AIC649, and the establishment of an incubator known as AiCubator.

Pillar 1: Develop AIC649 as a broad-acting first-line therapy against corona and other viruses with pandemic potential

AIC646, AiCuris, against pandemics, immunotherapy
AIC649 boosts the immune system against viral infections and might have potential as a broad-acting, first-line pandemic therapy

AiCuris discovered a novel biological immunomodulator, AIC649, a proprietary inactivated parapoxvirus particle preparation, which has the ability to boost the immune system against unrelated viruses. Consequently, the compound has the potential to act as a broad, first-line therapy for current and future pandemics.

Given its potential, AiCuris is preparing a clinical pilot trial to test AIC649 versus placebo in SARS-CoV-2 patients with asymptomatic infections. The company will try to have the first patients in the trial as soon as possible.

AiCuris’ hopes for AIC649 were bolstered following the successful completion of a clinical phase I trial in patients with chronic hepatitis B. The study showed the compound’s safety and provided preliminary evidence that a patient’s immune system could be stimulated already by a single dose of AIC649. 

Mode of action

The basis for the potent and broad antiviral activity of AIC649 is the induction of a natural, regulated, and self-limiting immune response that leads to the release of physiologically significant amounts of different cytokines with antiviral potential.

Pillar 2: Innovative approaches to fight antimicrobial resistance

antimicrobial resistance

AiCuris is at the vanguard in the field of fighting antimicrobial resistance and tirelessly innovates and seeks partners to explore new channels. 

Partnership 1

For instance, in July 2019, AiCuris entered into a relationship with Lysando AG. The two companies collaborate to develop and optimize Artilysin®-based drug candidates for various anti-bacterial indications, including bloodstream infections caused by Gram-negative pathogens.

The novel mode of action of these drug candidates can be used against multi-drug-resistant germs, in cases where antibiotics are no longer effective. The interaction of Artilysin®-based drugs with peptidoglycans destabilizes and degrades the bacteria cell envelope, which causes the cell to quickly burst from the high osmotic pressure. 

Partnership 2

Another exciting avenue of exploratory teamwork is to identify novel compounds together with the prestigious Max Planck Institute (MPI) of Molecular Physiology in Dortmund, Germany

Under the terms of a collaboration agreement, AiCuris has access to a proprietary collection of natural product inspired substances from the MPI. With such a resource at researchers’ disposal, AiCuris intends to optimize initial hits to lead compounds and eventually to clinical candidates.

Partnership 3

An equally impressive partnership is with Cyclenium Pharma Inc., an emerging Canadian pharmaceutical company that specializes in the discovery of novel therapeutics based on its proprietary CMRT™ macrocyclic chemistry technology. 

Cyclenium performs synthetic and medicinal chemistry activities to generate and optimize new macrocyclic molecules effective against specific anti-infective targets chosen by AiCuris. AiCuris performs the pharmacological characterization, further compound optimization, pharmaceutical profiling, and development of these new chemical entities. 

Pillar 3: The AiCubator to strengthen and support novel approaches in anti-infective research

AiCubator, anti-infection, Aicuris

This scheme is a new way to collaborate in the anti-infective field and support novel research approaches. The program will offer young academic researchers and start-ups insights into preclinical and clinical drug development and provide them with a firm grasp of the pharmaceutical industry. 

The main focus in the antibiotics field is on gram-negative resistance-breaking solutions; antiviral projects should be focused on the treatment of herpes viruses, adenoviruses, hepatitis B virus, and respiratory viruses. The following are welcome to apply:

  • Academic scientific groups or recently formed biotech start-ups with early-stage projects in the antiviral or antibacterial field.
  • Inventors of a new breakthrough mechanism of action with supporting data.
  • Organizations that wish to transform data into reality.
  • Fledgling firms that require support and guidance that will help them take flight.

Submitted projects will be evaluated by AiCuris experts and up to three projects per year will be awarded the AiCubator Resident Status. Over a period of up to three years, the winning projects will mainly benefit from expert scientific and business support to advance their ideas and approaches.

The proposal deadline is October 31, 2020. Successful pitches will be announced mid-December and will kick off January 1, 2021.

Pillar 4: AiCuris’ success driven by an active licensing strategy and partnering

Since spinning off from Bayer in 2006, AiCuris’ strong internal expertise and mutually beneficial collaborations, as seen above, has resulted in considerable success.

For example, AiCuris granted to MSD an exclusive worldwide license for Letermovir, a first-in-class non-nucleoside cytomegalovirus (CMV) inhibitor acting via a novel mechanism. In 2017, Letermovir was approved in the US for the prevention of CMV infections in adult recipients of an allogeneic hematopoietic stem cell transplant, which was followed by approvals in the EU, Switzerland, Canada, and Japan.

While its licensing focus is on projects after the clinical proof-of-concept, AiCuris is open for exploratory discussions at an earlier stage e.g. interest in co-development of a given project or in joining efforts to develop compounds.

Four pillars support a platform for innovative anti-infective drug development

Covid-19 has reiterated and reinforced the absolute necessity for robust measures to counter any future epidemics or pandemics. Indeed, several sources have stated that up to 10 million deaths per year worldwide could occur by 2050 if the current trajectory continues.

AiCuris’ position is that fighting Covid-19 alone is not enough because another large threat, antimicrobial resistance, hidden behind the current SARS-CoV-2 outbreak, also kills hundreds of thousands of people around the world.

It is for these reasons that AiCuris has launched the PREP initiative, to ensure that global healthcare systems can be properly PREP-ared for future pandemics and antimicrobial resistance.

Author: Andy McCulloch, Freelance Writer and Senior Editor

Images via AiCuris and