Madam Therapeutics

News Archive

Can SAAPs help fighting a flesh eating bug that is on rise in Australia?

The Medical Journal of Australia and news agency AAP report on a flesh-eating bug that is on the rise in Australia, and says that researchers don’t know how it’s spreading.

Experts are calling for urgent government funding so they can figure out how to contain the bacteria, which causes an infectious disease called Buruli ulcer. Most commonly found in west or central Africa and usually associated with stagnant water, it can have devastating impacts on sufferers, including long- term disability and deformity.

The cases are also becoming more severe and occurring in new areas, but efforts to control the outbreak have been thwarted, because it’s not known how humans are infected, a new study published in the Medical Journal of Australia says.

Madam Therapeutics is working along with international partners on the BURULICARE project. The project aims to improve the treatment options for patients with Buruli Ulcers. The consortium is currently looking for funding.

Remko van Leeuwen, CEO of Madam Therapeutics, elected as board member of the BEAM Alliance

Paris, April 12th 2018.

 

The BEAM Alliance announced today that Remko van Leeuwen, CEO of Madam Therapeutics, has been elected as a new board member of the BEAM Alliance. BEAM (Biotech companies in Europe combating AntiMicrobial Resistance) represents European small and medium-sized biopharmaceutical companies involved in developing innovative products to tackle antimicrobial resistance BEAM gives its members a unique voice to propose and support policies and incentives in antimicrobial research and development in Europe. BEAM recommends bold incentives that warrant action by policymakers to stimulate much needed innovation.

“I am excited to have received the trust of the members of BEAM by electing me as board member of BEAM”, say Remko van Leeuwen. “I anticipate taking an active role in the BEAM Alliance efforts, and help to increase the impact of the initiative, giving us what we need to battle superbugs”.

 

 

LUMC infectiologist Mark de Boer interviewed by the Volkskrant on shortage of antibiotics

In the past few months, seven types of antibiotics were temporarily or permanently unavailable in the Netherlands. Due to the increasing shortage, doctors are more likely to resort to broader antibiotics that are still available. However, these are more expensive and have more side effects. “The patient is the victim of this. When using heavy artillery, the resistance risk is higher”, says Mark de Boer, internist infectiologist at the LUMC, in an interview in the Dutch Newspaper de Volkskrant. The interview can be read here (In Dutch, subscription may be required).

Madam Therapeutics is working closely with Mark de Boer and other specialist of the LUMC on the development of SAAP-148 and other compounds.

More info on the recent concerns about increasing shortages of antibiotics in The Netherlands on the site AMR-insights from Maarten van Dongen (in English, free of charge).

A recent example of the clinical challenges that physicians face on a daily basis is that mupirocine nasal ointment is not available in the coming period in the Netherlands.
Mupirocine nasal ointment is used for decolonization of MRSA carriers and decolonization of S. aureus in dialysis and around the operation. As far as the Dutch antibiotic working group is concerned, there are no proven effective alternative available at the moment.

Madam Therapeutics is working on a nose cream for nasal MRSA carriers. Market introduction is still a number of years away, as clinical trials need to be completed first.

Looking back at an successful Bio Europe Spring Conference

Last week, BIO-Europe Spring took place in Amsterdam. Over 2500 life sciences professionals gathered in our country’s capital city to engage in three full days of partnering meetings, educational sessions and networking. The conference convincingly presented the Netherlands as Europe’s most attractive and innovative biopharmaceutical environment.

The conference is one of Europe’s largest and most successful partnering conferences for the biotech and pharmaceutical industry, and was again very helpful for Madam Therapeutics in meeting many interesting new people in this 3-day pressure cooker event.  We are exited about the many new opportunities that were created during this meeting…

 

 

 

 

SAAP-148 featured in news show on Dutch National TV

SAAP-148, which Madam Therapeutics anticipates to bring into clinical studies later this year, was highlighted in the Newsshow “EenVandaag” on Dutch National TV.

EenVandaag is a newsshow from Dutch broadcaster AVROTROS, which analyzes news developments in a clear way, “close to the people”. In addition to general subjects from home and abroad, special attention is given to politics, economy, safety, health and culture. EenVandaag reaches more than a million people daily on TV, radio and online.

SAAP-148 is also highlighted on the EenVandaag Website. The site describes that “humanity faces a gigantic problem: existing antibiotics regularly fail to function properly because bacteria become increasingly resistant”. They continue that if this trend continues, “simple infections such as a bladder infection or an infected wound, but also medical interventions such as transplants, the placement of prostheses and other surgeries will soon become life-threatening”.

The effects of SAAP-148 are described as a new generation of antibiotics from Leiden could make a difference worldwide in the treatment of these infections. But whether it works is by no means certain…..Once the researchers find out in which combinations and dosage forms the peptide works best, they can make the next step to testing in patients. Nibbering hopes that this step can be taken at the end of 2018″.

 

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.