Public-Private Partnerships

Madam Therapeutics and LUMC join forces on new antibiotic treatment

Experiences of an SME on the Top Sector’s funding opportunities

Do you have a small or medium-sized enterprise (SME) in the life sciences and health sector? Are you working together with an academic partner and searching for R&D funding opportunities? The PPP Allowance might be the way to go! We asked Remko van Leeuwen, CEO of Madam Therapeutics, how the PPP Allowance has contributed to opportunities for his company.

Antimicrobial resistance (AMR) is an emerging problem worldwide due to excessive use of traditional antibiotics. In addition, development of new treatment strategies against bacterial infections has been a great challenge since 1970, because the obvious targets have already been tackled. If the current trend of excessive use of antibiotics progresses, by 2050 more people will die from infections than from other diseases. In close collaboration with University Medical Centres, the Dutch biotech company Madam Therapeutics is seeking to combat AMR through a fundamentally different class of antibiotic treatment. We spoke with the CEO of Madam Therapeutics, Remko van Leeuwen, about his ambitions and the way the Top Sector’s PPP Allowance helped him realising his goals.

Public private collaboration on sticky peptides

Madam Therapeutics is an SME with two employees that develops Synthetic Antimicrobial and Antibiofilm Peptides (SAAPs). These SAAPs are able to attack microbes by making little holes in the cell membrane. By this non-specific targeting, SAAPs seem to work against both resistant and non-resistant bacterial strains and, therefore, are very valuable next to traditional antibiotics. From the moment of establishment in 2011, Madam Therapeutics has been working closely together with the Leiden University Medical Centre (LUMC). During this intensive collaboration, both organisations continuously looked for opportunities to fund their research lines. This resulted in a granted PPP Allowance project in 2015: ‘Sticky’ peptides to fight antimicrobial resistance.

During the execution of the project, the preclinical dossier has been completed. Three major clinical indications with high infection risks will be further investigated: diabetic foot ulcers, burns and MRSA carriage. Madam Therapeutics is now preparing clinical trials together with the LUMC.

PPP Allowance fitted for every SME?

Van Leeuwen emphasises how the PPP Allowance strengthens his existing collaboration with the LUMC during the fundamental stages of their research. It can be challenging for a company to be involved in the research at such an early time point, as commercialisation prospects are still far away. The PPP Allowance provides the extra support for such collaboration. In fact, Van Leeuwen believes it can be very helpful for parties to initiate first contact between a company and a research organisation before jointly starting an R&D project.

For a small SME like Madam Therapeutics, intellectual property (IP) is the core of the business. Protection of IP prior to the start of the PPP project is very valuable for an SME. Van Leeuwen had already gained patent rights for the working compound of their SAAP approach before the start of the PPP project. With this background IP, he could safely investigate possible applications of the compound together with the academic partner based on this earlier agreement. Such an early understanding may help avoid difficult patent licensing discussions with the Technology Transfer Office (TTO) at the end of the project. Early and intensive contact between all stakeholders in a PPP project is vitally important.

If you are an SME in search of funding or need help in the application process then do not hesitate to contact Health~Holland. Interested in current funded PPP projects? Look at our project page!

Deciphering cellular proteins and pathways involved in virus replication and in suspension growth of Vero cells

Despite the critical role for vaccines in public health, there are issues with costs and manufacturing that prevent a significant portion of the world’s population from accessing vaccines.

The aim of this project is to make the production of viral vaccines less expensive. To achieve this, Intravacc aims at the identification of cellular pathways that are important in virus replication and suspension growth in Vero cells. By permanent modification of the identified host factors, Vero cell lines can be constructed that are better suited for the production of viral vaccines. The industrial partner, Applikon, is aiming at developing disposable, single use bioreactors, which offer flexibility and require less investment in infrastructure compared to conventional bioreactors. Combining these strategies in this partnership will ultimately result in the development of vaccines in less time at lower costs.

This innovative project will lead to more fundamental knowledge on proteins and intracellular pathways important for viral replication by doing siRNA screens. This knowledge will be used to develop new Vero cell lines with modulated host genes using CRISPR-CAS9 that can significantly enhance virus production at reduced costs, thereby promoting global introduction of affordable vaccines. Also, we aim to use the knowledge obtained from the screens to design Vero cells that are capable of growing in suspension, which is a great advantage for easier scale-up and less expensive production of vaccines. The last aim is  to develop single-use, disposable bioreactors, that will eliminate the costs in the vaccine production process associated with disassembly, cleaning and reassembly of conventional bioreactors. This offers flexibility in vaccine development, and in change-over from one vaccine manufacturing process to another. In the last phase of this project, the modified Vero cells will be cultured at lab-scale in the disposable bioreactors developed by Applikon.

'Sticky' peptides to fight antimicrobial resistance

PharmAMPs: Pharmaceutical development of antimicrobial peptides for the prevention and treatment of infections against (multi)-drug resistant bacteria.

Antimicrobial peptides (AMPs) are inspired by naturally occurring antimicrobial proteins and peptides, that are produced by all living organisms and can combat bacterial infections, including resistant infections. AMPs are typically small, cationic peptides (“sticky peptides”) that exhibit a broad range of antimicrobial activities, and often also possess immunomodulatory properties. Moreover, intrinsically, they are also more robust towards resistance development than traditional antibiotics. In the recent O’Niell report on solutions to fight AMR, AMPs and their derivatives are ranked amongst the most promising alternatives to traditional antibiotics.

The concept of using AMPs for therapeutic purposes has been around for some time. Unfortunately, the 1st generation AMPs had limitations that prevented further development, especially with regard to their (limited) potency and high cost of goods, resulting in poor commercial perspectives. Several peptides have been tested in clinical studies against a range of topical infections, but their development was halted for these reasons.

A new public private partnership was formed between the Leiden University Medical Centre (LUMC) and Madam Therapeutics with the intent to work on 2nd generation peptides with improved characteristics. Madam Therapeutics, is a near clinical stage biotech company that is developing a new generation of AMPs specifically to combat resistant bacterial infections and to prevent and treat infections that are currently left untreated due to the risk of resistance development with current antibiotics. The new peptides are based on technology from LUMC with whom Madam Therapeutics has been working closely over the recent years to develop the most optimal peptides, which we are now converting into powerful antibacterial products.

Within this PPP, we have established that the lead peptide (SAAP-148) indeed has significant advantages over traditional antibiotics. SAAP-148 was found to be a very effective, broad-spectrum anti-microbial peptide which possesses very rapid bactericidal activity. SAAP-148 has shown in this project to be very effective against bacteria residing in biofilms whereas traditional antibiotics are not. SAAP-148 is also very effective in the killing of (multi-) resistant bacteria and is very robust against resistance formation itself. Finally, we established that SAAP-148 has also shown significantly more potency than 1st generation AMPs in in-vitro comparison studies; in fact we demonstrated that SAAP-148 is one of the first in its class to be active at a sub-micromolar range.

As a follow-up to this project, Madam Therapeutics and LUMC are now preparing the first clinical proof of concept studies with the lead product SAAP-148 formulated as a gel for topical treatment of bacterial infections in chronic wounds, burns and in a nose gel to treat nasal MRSA carriers. In addition, we are also investing possible novel PPPs for collaborative (academic) research efforts and continuous pre-clinical development of other AMP-based products for other indications and other formulations.