Pipeline
Pipeline Overview
Madam Therapeutics is developing a portfolio of highly effective antibiotic compounds for a variety of indications by bringing the most promising SAAPs up to proof of concept (phase II) clinical trials in humans. These compounds will then be out licensed to large industrial players (pharmaceutical companies) that will complete the later stages of clinical development and commercialization.
Madam Therapeutics intends to out-license the P10 variants for veterinary use at an earlier (pre-clinical) stage to veterinary pharmaceutical companies as veterinary development is not Madam’s core competence.
Together with LUMC (Leiden University Medical Center) and AMC (Amsterdam Medical Center), Madam Therapeutics has shown the value and potential of our peptide library by the general pre-clinical proof of concept (efficacy and safety) of the two lead compounds SAAP-148 and P10.
During the artificial intelligence screening and the lead development stage, several alternative SAAPs are now being identified for various infectious diseases. Madam Therapeutics intends to develop several of them until clinical proof of concept (phase II) and is open to out-license other spin-off variants to other companies.
Diabetic Foot Ulcers
Diabetic foot ulcer (DFU) is an open sore or wound that has a high chance of becoming infected and a major complication of diabetes mellitus (DM). Globally, 422 million people suffer from diabetes, of which 25% develop a DFU. Due to the chronic nature of these wounds, they are associated with high rates of antimicrobial resistance (AMR) – with an average rate of 20% in DFU specifically.
AMR and its related deterioration and infection of DFU leads to severe complications including hospitalization, amputation or even death. Moreover, the economic consequences are enormous as they exceed €10 billion yearly in Europe alone.
Current antibiotics are ineffective in treating DFU infections due to the high rates of resistance and their lack of anti-biofilm activity, resulting in a difficulty killing a majority of the bacteria. Additionally, traditional antibiotics administered orally or intravenously, do not reach the location of the infection due to the typically poor blood supply of the infected wounds.
Therefore, there is a strong unmet need for novel, locally applicable, effective, preventive and sustainable antibiotic strategies that can be applied in DFU infections and combat resistant infections in this setting.
Acne
The Global Burden of Disease Study found that acne vulgaris is the eight most common skin disease, with an estimated global prevalence (for all ages) of 9.38%.
Colonization with the bacteria Cutibacterium acnes (previously called Propionibacterium acnes) plays an important role in establishing this disease. These bacteria with their immunologic consequences form the essential factor in the production of inflammation in acne.
However, the question remains whether a commensal like Cutibacterium acnes is capable of initiating inflammation in the sebaceous gland. In other words, what triggers Cutibacterium acnes to play its part in acne? Recent literature suggests that the answer to this question may very well be found in biofilms that are produced by Cutibacterium acnes.
The SAAPs from Madam Therapeutics are a novel group of therapeutics that addresses the problems of biofilms to acne, a problem that is not addressed with current therapies. Moreover, our novel SAAP based therapeutics address the issue of antimicrobial resistance (AMR).
These 2 factors are currently limiting the use of antibiotic therapy for acne. We therefore believe that our SAAPs provide a promising novel therapeutic approach.
Systemic Infections
The problem faced by Madam Therapeutics and other manufacturers of these new peptide-based antibiotics is the method of administration. Peptides are small molecules that are broken down quickly or stick to other components when they enter the body.
They will not survive a stay in the stomach anyway. Hence, such antibiotics almost always have to be injected, which greatly limits their use. This is where our collaboration with PharmaCytics comes into play.
The company has developed the Nutrient Drug Conjugate technology (NDCt), which allows to disguise all kinds of medicines as food. The technique from PharmaCytics links a food group to the peptides, causing the digestive tract to think it is related to nutrients.
Due to this disguise, they are excellently absorbed by the intestines into the bloodstream. The greater uptake – bioavailability – may even allow for a lower dosage. Once in the bloodstream, the link is broken and the peptides can exert their antibacterial effect.
With this technique we go from local administration or injection to a pill. Using this technology, we aim to expand our portfolio for systemic infections such as sepsis, urinary tract infections, respiratory infections and Lyme disease.
Animal Health
Several recent trends have a negative impact on the treatment options for infections in animals. Regulators across the globe are becoming stricter on the principle that new antibiotics as well as some antibiotics currently used in veterinary medicine are restricted to use in humans only.
Most biotech companies do not really care about this too much, as they have an exclusive focus on human health where most of perceived unmet medical need is situated, and where most of the current funding instruments are focused on (activity against critical pathogens in humans determines eligibility).
In practical terms, the fall-out of these trends is that new antimicrobial compounds are less and less available for use in animals. But treatment options for animals are equally compromised, and anti-microbial resistance is rising, for animals as they are for humans. The ultimate risk is that we leave animals without any effective treatment option when they develop (severely resistant) infections.
We exploit the diversity of our antimicrobial platform specifically for the use in animals, without the inherent risk to compromise the effectiveness of such a new class of antimicrobials in humans.
Our dedicated program for the development of antimicrobial peptides intended for use in animals (livestock and companion) is based on a cluster of peptides that is far removed from the amino-acid composition of our human peptides. We believe that our proposition is genuinely unique, in the sense that we are one of the few dedicated biotech companies with an antimicrobial development program targeted towards human health as well as, and by simultaneously, focusing on veterinary health.
Our peptides for veterinary use are derived from the prototype peptide P10, of which we have many variants. Since both the human and veterinary compounds are so called alpha-helical peptides, we believe that many of the positive characters of our human peptides as outlined above can therefore be translated to our veterinary antibiotics as well.
