It could become the first drug worldwide to treat a disease that currently lacks a specific treatment. It was formulated by Immunalgia Therapeutics, a biotechnology start-up incubated at the Institute for Translational Medicine Research (IIMT) of the Universidad Austral-CONICET and at the César Milstein Institute of Science and Technology. In November, trials will begin on healthy volunteers – approved by ANMAT – and, if successful, permission will be requested for trials on patients with Complex Regional Pain Syndrome.

Buenos Aires, November, 2023

Pain is an alert mechanism; it warns us that the body is suffering some kind of damage. What for most people is usually temporary and reverses once the cause is treated, for about 30% of the world's population becomes chronic pain, of moderate to severe intensity, which worsens over the months or with age, affecting family, social, and work life, and even becoming disabling for one in three people.

A group of 15 researchers, made up of biologists, biochemists, technicians and doctors from the Institute of Translational Medicine Research (CONICET-Faculty of Biomedical Sciences of the Universidad Austral) and the César Milstein Institute of Science and Technology (CONICET-Cassará Foundation), designed a new drug to treat chronic pain of neuropathic and inflammatory origin.

To advance this development, they created Immunalgia Therapeutics, a biotechnology start-up through which they aspire to bring this disruptive technology to market. The team—led by Drs. Alejandro Montaner, Pablo Brumovsky, Marcelo Villar, and economist Gustavo Alvarez—identified a DNA sequence (called IMT504) that, when injected, sends an alert to the immune system, prompting the body to mount an analgesic and anti-inflammatory response to repair the damage.

“When there is loose DNA in the body (whether due to cell damage, viral infection, radiation, etc.), the immune system is prepared to respond to that attack. What we achieved with this synthetic DNA sequence that we patented was to mimic that damage signal and enhance the natural response that every patient already has programmed in their body. In other words, it is the patient's own cells, and not the drug itself, that are responsible for resolving the problem,” stated Alejandro Montaner, General Director and Project Manager of Immunalgia Therapeutics.

Pre-clinical and clinical stage

The drug was tested in experimental models (pre-clinical phase) and showed effectiveness in treating chronic pain of neuropathic and inflammatory origin.

Neuropathic pain, with common examples such as sciatica or post-amputation pain, is caused by direct injury to the central or peripheral nervous system, manifesting as burning, stinging, itching, and/or electric shock sensations. It is a very difficult pain to treat, affecting 10% of the world's population. “General analgesics (opioids, non-steroidal anti-inflammatory drugs) and several drugs originally designed to treat diseases such as epilepsy (for example, gabapentin) or depression (tricyclic antidepressants) have limited use and are not without adverse effects that frequently lead to treatment discontinuation. Our drug, on the other hand, acts directly on pain-related mechanisms and has demonstrated a high safety profile in pre-clinical trials,” stated Dr. Pablo Brumovsky, Scientific Director of Immunalgia Therapeutics and Deputy Director of the Institute for Translational Medicine Research.

“In the case of inflammatory pain (such as osteoarthritis, arthritis and lower back pain, etc.) although there are anti-inflammatories on the market, their effectiveness is limited in time and their prolonged use can generate adverse effects such as gastric ulcers,” said Dr. Villar.

In both cases, pre-clinical trials showed that even a single dose of IMT504 produces an analgesic effect lasting between 35 and 42 days. The next stage—which has already been approved by ANMAT—is to test the drug's safety in healthy volunteers, a process that will begin at the end of November and will take six months. "What is being evaluated in this stage is the highest dose that can be administered without causing severe adverse effects, and the pharmacokinetics and biodistribution of the molecule," Brumovsky emphasized.

“According to market estimates, it is calculated that of every 10.000 projects conceived in the laboratory, only 10 reach this Clinical stage (Phase 1), where we are today. And of these 10, only one reaches the market,” Montaner explained, demonstrating the achievement reached with this development.

The characterization of the new drug "required an approximate investment of $500 in the initial and pre-clinical phase, to which an additional $350 from various public and private sources will be added for clinical testing," said Mr. Alvarez.

The goal: to relieve pain

Once the Phase 1 results are obtained, Immunalgia Therapeutics will request authorization from ANMAT (Argentina's National Administration of Drugs, Food and Medical Technology) to proceed with trials in patients with pain. The chosen pathology will be Complex Regional Pain Syndrome (CRPS), an orphan disease that affects the upper or lower limbs and usually appears after a traumatic injury or elective surgery, although it can also arise without an apparent cause. It is also known as allodystrophy, causalgia, or reflex sympathetic dystrophy.

“The pain these patients experience is similar to the pain a woman feels during childbirth and is highly debilitating. Furthermore, the available treatments for these patients are often complex, multifactorial (medications, interventional approaches, physical therapy), and have a difficult prognosis,” Brumovsky emphasized.

If Phase 2 clinical trials demonstrate the safety and effectiveness of the new drug, it would become the first treatment developed entirely in the country for Complex Regional Pain Syndrome. Based on the time required for the clinical trial phase and regulatory approvals, Immunalgia Therapeutics estimates that the drug could be available on the market in approximately four years.

“This development is an example of capacity building because it involves two Research Institutes, one associated with a pharmaceutical laboratory (Cassará) and the other linked to the Faculty of Biomedical Sciences of the Universidad Austral which, together with the Austral University Hospital, forms the Academic Health Center. “This synergy allows us to integrate, on the one hand, pharmaceutical development, regulatory aspects, production under quality standards, etc.; and on the other hand, therapeutic needs and medical-scientific aspects,” Montaner stated. “Furthermore, it highlights the value of scientific evidence as a foundation for impactful projects in a critically needed area of ​​health such as the treatment of chronic pain,” added Dr. Brumovsky.

For more information: www.immunalgia.com 

You can also read the article at La Nación.