The Heslet era
From the beginning, Reponex Pharmaceuticals, the daughter company of Pharma Equity Group, has been a pronounced patient-oriented company, which seeks to improve the treatment not only of life-threatening diseases, but also of chronic conditions that greatly impair patients’ quality of life. This can be traced back to the company’s medical co-founder, Prof. Dr. Med. Lars Heslet, pulmonary and intensive care physician by heart, who was then head of the country’s leading intensive care unit at Rigshospitalet. His practice was always strongly focused on the needs of the individual patient and he did not hold back from using innovative deviations from standard protocols for this purpose. At the same time, he achieved the highest international quality rating for his department. As a pulmonologist who was also trained as a chemical engineer, his starting point was to develop direct delivery of biological agents to the lungs in order to achieve high local concentrations and effectiveness, while minimizing systemic side effects. His recognition that organs such as the lungs formed partially independent body compartments whose defense mechanisms were only in slow equilibrium with those of the body as a whole strengthened his interest in local rather than systemic treatment in many cases, especially when poorly diffused protein biologics were to be used. Therefore, he expanded his ideas to local treatments on the skin, peritoneum and intestinal cavity. Dozens of patients whose lives had been saved by his individually tailored innovative methods attended Prof Heslet’s funeral.
In the last years of his life, Lars Heslet was severely affected by a paraneoplastic neurological disorder. This led to his old friend and colleague, Professor Lars Otto Uttenthal, being involved in the company. They had worked together on the development of the new NGAL diagnostic test for acute kidney injury, a test of utmost importance for intensive care patients, and Prof Uttenthal had also been involved in Heslet’s inhalation treatments. Uttenthal is a former researcher at the universities of Oxford, London and Madrid and was professor of biochemistry at the University of Salamanca. He has many years of experience in clinical medicine and biomedical research and also has extensive experience in research and development in the medical industry, including the conception, treatment and defense of new patents. Uttenthal’s task was to find ways and means to put Heslet’s outlined ideas into practice, while securing their patent protection and getting the necessary clinical trials done. He thus worked together with Lars Heslet in his last year and after his death took over the role of scientific and clinical director of the company.
The company’s need for proof-of-concept trials of its new treatment ideas thus led to important contacts with clinicians eager to test these ideas. The first of these contacts was with Professor Jacob Rosenberg, head of the Center for Perioperative Optimization at the Surgical Department, Herlev Hospital. It was his enthusiasm and organization that ensured the successful proof-of-concept studies of this revolutionary method of treating peritonitis. It also led to the company’s contact with his younger colleague at the time, now Professor Ismail Gögenur, head of the Center for Surgical Science at the hospital of Køge. Professor Gögenur is an internationally recognized abdominal surgeon and remains the company’s primary clinical partner.
Lars Heslets patient-centered approach and his ideas about the benefits of local treatments remain in the company’s lifeblood and are especially implemented by the strategy of finding new uses for known medicines with a strong safety profile (repositioning) and applying them by local application to the places where they are supposed to work (redirection). In this way, the therapeutic effect can be greatly enhanced using much lower doses, and systemic side effects are avoided, leading to more pleasant and fast-acting treatments. These benefits have been confirmed for the company’s innovative intraperitoneal treatment of peritonitis from ruptured appendicitis, and are also expected to be confirmed for the company’s topical preparations to promote the healing of chronic venous leg ulcers, a particularly painful and bothersome condition that affects many elderly patients. The same is also expected to apply to local treatments in the intestinal lumen for such troublesome conditions as Crohn’s disease or pouchitis, another concept that Lars Heslet first devised.