Madam Therapeutics

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Madam Therapeutics newest member of HollandBIO

Madam Therapeutics is proud to announce that it become member of HollandBIO today.
HollandBIO is the Dutch biotech industry association. They actively look after the sector’s interests and support a strong, national and international network.
HollandBIO’s activities include advocacy, networking, national and international representation, as well as our HollandBIO Business Solutions: a range of services dedicated to supporting start-ups and SMEs.

Dr Kim Lewis calls SAAP-148 “an important piece to the puzzle of creating a perfect antibiotic” in an editorial comment on the website of Science.

Press Release
Leiden, 17 January 2018

How do you cure bacterial infections that can not be controlled with antibiotics?
This is possible with peptides: short chains of amino acids, the building blocks of proteins.

The Leiden University spin-off Madam Therapeutics reports that researchers from the Leiden University Medical Center (LUMC), Academic Medical Center (AMC) and the Association of Dutch Burn Centers have published on this subject in the scientific journal Science Translational Medicine.

As part of a European research consortium ”Biofilm alliance” (BALI), they have tweaked a naturally occurring peptide found in the human body. By doing so, the researchers have designed a drug that could wipe out obstinate microbes resistant to available antibiotics.

In an editorial comment on the website of the scientific journal Science, Dr Kim Lewis, a microbiologist at the Northeastern University in Boston who was not involved in the work says that the candidate adds “an important piece … to the puzzle of creating a perfect antibiotic”.

When a small subset of bacteria survives antibiotic treatment an infection can get out of control fast. As these resilient microbes thrive, they can group together on a surface—like a wound or a medical device—and encase themselves in a slimy protective layer known as a biofilm. Such biofilms are hard for drugs to penetrate, and they harbor dormant cells called persisters that toleratean antibiotic assault only to come roaring back later. Such infections “can be horrible for patients,” says immunologist Dr Peter Nibbering at Leiden University Medical Center in the Netherlands.

The team of Dutch collaborators are trying to combat these biofilm-associated infections by improving on a human peptide called LL-37, which play multiple roles in the body’s immune response. LL-37 displays bacteria-killing abilities, and the researchers previously shortened the peptide to make a more powerful variant, consisting of 24 of the 37 original amino acids. In the new work, they optimized this peptide by making a series of random replacements to its building blocks without disrupting its overall tertiary structure.

One variation, dubbed SAAP-148, proved a powerful weapon, the team reports in Science Translational Medicine. Whereas most traditional antibiotics target specific groups of bacteria and kill by disrupting key mechanisms of those microbes, SAAP-148 is more of a generalist. It kills by damaging most any bacterium’s plasma membrane, causing it to spill its contents and deflate.

SAAP-148 eradicated drug-resistant Staphylococcus aureus and Acinetobacter baumannii biofilms successfully —two leading causes of hospital-acquired infections that often defy available treatments — from human skin samples and infected wounds on the backs of mice.
It also managed to knock out persister cells in a bacterial biofilm that had already been treated with the antibiotic rifampicin, often used to fight persistent infections at the site of prostheses.

“This is the first published demonstration of the killing of such persisters”, notes Prof Bob Hancock, a microbiologist at the University of British Columbia in Vancouver, Canada, in the  editorial comment on the website of Science.

SAAP-148 also appears to overcome what Hancock calls “one of the big bedevilments” of antibiotic candidates: The environment of the human body inhibits the activity of many such molecules because they stick to proteins and lipids in the blood. SAAP-148 looks to be one of the few known peptides that kills bacteria efficiently without also binding to these circulating obstacles in serum, he notes.

Nibbering and colleagues also report that bacteria didn’t manage to develop resistance to SAAP-148 after repeated exposures. That’s surprising, says Dr Tim Tolker-Nielsen, a microbiologist at the University of Copenhagen’s biofilm research center in the editorial comment, though he notes that resistance could still develop under different conditions.

In partnership with the researchers, Madam Therapeutics is pursuing SAAP-148 to treat amongst others, skin wound infections, bladder infections, or infections at the site of prostheses. To administer the drug systemically, the team is also working on the design of an injectable formulation that protects the peptide from breaking down in the body, makes it more selective, and directs it to the site of infection inside the body.

Madam Therapeutics expects to test SAAP-148 in clinical trials soon—first to disinfect lesions from the inflammatory skin disease atopic dermatitis, then to treat patients suffering from diabetic foot ulcers as well as burn patients.

About Madam Therapeutics

Madam Therapeutics is a privately held company from the Netherlands that is developing Synthetic Anti-Microbial and Anti-Biofilm Peptides (SAAPs) to combat resistant bacterial infections. Our SAAPs combine two characteristics essential for such new strategies: powerful killing of bacteria and limited likelihood of emerging resistance. To date, Madam Therapeutics and her academic partners have raised over 9 million Euro’s non-dilutive funding for the development of a platform of SAAP based products. To enable this first clinical trials in patients Madam Therapeutics is currently actively fundraising through private equity.

For more information, please contact:
Remko van Leeuwen
CEO
+31 71 2040 105 Extension 103
press@madam-therapeutics.com
@RemkovanLeeuwen

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Investor relations:
investors@madam-therapeutics.com

Scientific article published today on SAAP-148 in Science Translational Medicine: New way to keep bacteria at bay.

The first major scientific article on the antimicrobial peptide SAAP-148 appeared today in Science Translational Medicine.

In this paper, scientists from LUMC, AMC and the Association of Dutch Burn Centers tested SAAP-148 in bacterial cultures in the lab and models of injured skin. The results were positive: all bacteria were eliminated, including bacteria that were resistant to antibiotics and even bacteria that had formed a protective layer around them called biofilms.

Additionally, the scientists observed that it is much harder for bacteria to become resistant to the peptides in contrast to traditional antibiotics. The peptides kill the bacteria from the outside by disrupting the cell membranes, within minutes.

The prestigious journal writes: “Antibiotic resistance is a major threat to public health. To develop a new type of weapon in the arms race against bacteria, de Breij et al. generated a panel of synthetic peptides based on the human antimicrobial peptide LL-37. The lead candidate from this panel, SAAP-148, can kill dangerous antibiotic-resistant pathogens in many contexts, including on ex vivo human skin and in biofilms. Long-term exposure to SAAP-148 did not induce bacterial resistance. Topical application of SAAP-148 could one day be used in hospitals to help patients combat bacteria resistant to traditional antibiotics”.

Science Translational Medicine calls the new peptide a new way to keep bacteria at bay

In a press-release, the scientists emphasize that bacteria often form biofilms that attach to catheters, infusion lines and prostheses. “As a result, bacterial infections of, for example, an artificial hip or knee are difficult to combat with antibiotics ” Dr Peter Nibbering of the LUMC and Dr. Bas Zaat of the AMC say in this press release. “It is expected that it will succeed with these peptides.”

SAAP-148 is the lead product of Madam Therapeutics, and is anticipated to enter the first clinical trials in humans in 2018, for which we are currently fundraising.

SAAP-148 development gets boost via grant from NWO

Close to fifty scientists and twenty companies, funds and foundations are going to work on the development of new accessible and affordable antibiotics, and https://www.lumc.nl/alternatives to antibiotic use.

This is done in eight research projects that have received the green light today from the NWO domain Applied and Technical Sciences (TTW). Jointly NWO and the Ministry of Health, Welfare and Sport (VWS), invests almost 7 million euros in this research program entitled NECTAR.

Madam Therapeutics is part of one of the 8 consortia that have received an award in this NECTAR program. 

The project is entitled next stage development of the novel synthetic antimicrobial peptide SAAP-148 (NESDAP). In this project we will develop chemical modifications to increase our peptide’s ability to penetrate cells. Several strategies, e.g. nanoparticles and PLGA microspheres, to optimize the delivery of SAAP-148 deep into wounds with a controlled release over time will be developed in parallel. Efficacy of combinations of optimal formulations and SAAP-148 will be investigated in animal models for chronic wound infections. The NESDAP program is coordinated by Dr. Peter Nibbering from the department of Infectious Diseases of the LUMC in Leiden. Other project partners include AMC, VUmc, Association of Dutch Burn Centres, the Dutch Burns Foundation, the Diabetes Fund and the formulation company Avivia. The project budget is 880,000 EUR.

Madam Therapeutics is proud to be part of the industrial partners which contributed over one million euros to NACTAR projects, financially or in the form of knowledge or equipment.  The eight funded research projects involved a total of twelve knowledge institutes, as well as fifteen (pharmaceutical) companies and five health funds and foundations.

UK statistics office: life expectancy drops because of antibiotic resistance

Antibiotic resistance has caused a fall in life expectancy for the first time, the UK Office for National Statistics has said. Life expectancy in future years has been revised down after the statistics authority said that “less optimistic views” about the future had to be taken into account.

Opinions on “improvements in medical science” had declined, it said, and fears of the “re-emergence of existing diseases and increases in anti-microbial resistance” meant people would not live as long as was previously expected.

The ONS uses predictions about how medicine and science will improve to model how life expectancy will change. Under the projection made in 2010, a baby girl born in 2016 could expect to live 83.7 years. This has now been revised down to 82.9.

Life expectancy for babies born in 2060, the latest year which appears in both models, is now two years shorter than it was in the 2010 data. Baby girls born in that year were previously expected to live to 90.1 – this has now fallen to 88.3.

Baby boys are also set to live less long, with children born in 2016 expected to live to 79.2, instead of 79.9, and those born in 2060 expected to live to 85.7 instead of 86.8. The expectancies have been revised down before but this is the first time the ONS has said it believes resistance plays a part.

Experts have repeatedly warned of the dangers of antibiotic resistance, which could cause hundreds of diseases which are currently easily curable to become killers.

Anti-microbial resistance also includes the issue of viruses and funguses becoming resistance to antiviral and antifungal medication.

An increasing number of people with HIV have a version of the condition which is resistant to antiretroviral medication.

The NHS has previously warned that too many people are taking antibiotics for inappropriate conditions such as viruses, leading to greater resistance.

The World Health Organisation has said that the phenomenon is “one of the biggest threats to global health”.

Earlier this month it told farmers and the food industry to stop giving the medicines to healthy animals.

BEAM Alliance: more financial support needed for Europe’s 40 top innovator companies in antimicrobial drug development

Taking advantage of the World Antibiotic Awareness Week (WHO), the European BEAM alliance, representing 40 ‘Biopharmaceutical companies from Europe innovating in AntiMicrobial resistance’ research including Madam Therapeutics, released a position paper to acknowledge these efforts and to highlight the important role that small and medium-sized enterprises (SMEs) are playing as innovators.

The document lists ten (10) guidelines as to how antibacterial R&D could be revived and proposes specific support for SME-driven innovation in the AMR field. The alliance particularly demands that policymakers understand the specific nature and needs of SMEs to design effective PUSH and PULL mechanisms.

  1. Adequately-shaped incentive mechanisms that ultimately rewards R&D evidence
  2. Health Technology Assessment recognising the true value of SME innovation
  3. Dedicated regulatory pathways to support the specific needs of AMR projects and act as pre-qualification criteria to some PUSH/PULL incentive mechanisms
  4. PUSH incentives and funding mechanisms that are directed to SMEs, calibrated and accessible for SMEs in practice
  5. Calibrated Market Entry Rewards (MER) to ensure continuous and sustainable innovation from academics to biotech companies and to large pharma players
  6. R&D prizes and phase entry rewards as effective PULL mechanisms for SMEs to incentivise the most underserved indications in AMR
  7. Targeted tax incentives specifically addressing SMEs to incentivise private investments into AMR-focused companies and/or avoid de-prioritization
  8. Going beyond to exploit all possibilities for AMR from SMEs
  9. Support education to strengthen attractiveness of the field for R&D professionals/scientists
  10. Long term thinking and wisely usage of AMR innovations combined with appropriate diagnostics development

World Antibiotic Awareness Week, 13-19 November 2017

Every year, the WHO organised the World Antibiotic Awareness Week, This year’s theme: Seek advice from a qualified healthcare professional before taking antibiotics. Antibiotics are a precious resource, so it is important to get the right advice before taking them.

The WHO asks all stakeholders to spread the word and start planning now by:

  • Organizing events or activities in your workplace, community, school, university.
  • Spreading the word – you can find lots of information from last year’s campaign on the WAAW website, and more social media materials will be available soon. Get active on your social media accounts and get your networks involved.
  • Reaching out to your local government representatives, local leaders or influencers and encouraging them to take action on antibiotic resistance.
  • Leading by example: ensure you only take antibiotics if prescribed by a qualified healthcare professional, practice good hand hygiene, and never share or use leftover antibiotics.

We at Madam Therapeutics are highly supportive of this initiative. Awareness is absolutely critical to guarantee the sustainability of antibiotics. We will use our Twitter account to raise awareness for this campaign and trust this will help people with seeking advice from a qualified healthcare professional before taking antibiotics.

 

Madam Therapeutics has become member of the BEAM Alliance

The BEAM Alliance represents biopharmaceutical companies from Europe innovating in Anti-Microbial resistance research. BEAM works to improve the regulatory, investment, and commercial environments in Europe for research, development, approval and market viability of new products combating antimicrobial resistance.

 

Feature Article on Madam Therapeutics and LUMC partnership in the Health~Holland Update September 2017

In an interview in the September issues of the Health~Holland Update, Remko Van Leeuwen, CEO of Madam Therapeutics tells about how the PPP Allowance from the Dutch government has strengthened the collaboration with the LUMC during the fundamental stages of their collaborative research. While describing that it can be challenging for a company to be involved in the research at such an early time point, this PPP allowance mechanism provides the extra support for such collaboration. In fact, Van Leeuwen explains that he 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.

The full interview can be viewed here

CEO Madam Therapeutics interviewed on Dutch Radio Show

On September 1st, Remko van Leeuwen CEO of Madam Therapeutics, gave a pitch and was interviewed on the “Zaken doen met” radioshow on the Dutch Radio Station BNR. “Zaken doen met” is advertised as the most entrepreneurial radioshow of the Netherlands. During the interview, Remko van Leeuwen explains the urgent need for new antimicrobial agents, and talks about the opportunities and difficulties he experiences as entrepreneur of a small biotech company. A replay of the interview can be listened to (in Dutch) via https://www.bnr.nl/player/archief/20170901113300360