There is a story that began less than 5 years ago in Milan, in a spin-off of the State University, and which from now on will continue in Germany, precisely in Ingelheim am Rhein. It is the story of a scientific discovery that aims to change the fight against cancer once again. And it is also the story of an entrepreneurial adventure quite rare for our country.
Research: one euro invested in a clinical study generates almost three
by Irma D’Aria
Let’s start from the beginning, namely from the intuition of two Italian researchers, the molecular biologist expert in oncology Massimiliano Pagani and the immunologist Sergio Abrignani, both full professors of the Milanese university. The intuition is this: to develop a highly selective immunotherapy, which ‘awakens’ the immune system only and exclusively within the tumour, that is, where it is needed.
The immunotherapy revolution and the autoimmunity problem
In the last 12 years, immunotherapy has revolutionized the treatment of tumors, so much so that in 2018 it was worth the Nobel Prize for Medicine and Physiology to those who had discovered the mechanism on which it is based, James P. Allison and Tasuku Honjo. The principle is simple: our immune system would naturally be able to recognize cancer cells as something foreign, and to destroy them. This probably occurs in the majority of us, but when the disease develops it means that the tumor is able to hide and go unnoticed, activating a ‘brake’ mechanism of the immune system itself. Well, immunotherapy allows you to unlock this brake and recover the immune response. “This approach has allowed an important clinical improvement in many patients, although not in all, with an efficacy ranging from 30% to 50% of the patients treated, depending on the type of tumors – explains Abrignani to Oncoline – Unfortunately, however, the vast majority of treated patients develop autoimmune side effects, including pneumonia, hepatitis and colitis. This happens because immunotherapy acts on all regulatory T lymphocytes (which suppress the immune response, ed.), even on those that are found outside the tumor and which have the function of helping us tolerate ourselves. The consequence is that at least 10% of patients suffer from severe autoimmunity and are forced to interrupt the immunotherapy which for many of them would be of great benefit”.
Oncological research: what are the critical issues to overcome in Italy?
by Irma D’Aria
The research, the discovery and the patent
Hence the idea: to act selectively only on regulatory T lymphocytes that infiltrate the tumor tissue. “The research was born in the ‘Romeo ed Enrica Invernizzi’ National Institute of Molecular Genetics (INGM), realized thanks to what is probably the largest single philanthropic donation ever made by a private citizen in Italy, of 20 million euros – continues Abrignani, who directs it – We began by isolating intratumoral T lymphocytes, sequencing their RNA and comparing it with that of the lymphocytes of the corresponding healthy tissues and peripheral blood, until we identified surface molecules present in a very selective way only on T lymphocytes tumor infiltrating regulators. We patented the discovery in 2016 and published the data from the study shortly after Immunity”.
Pancreatic cancer, discovered a new way to fight it
by Simone Valesini
The spin-off is born
The results were so promising that they bet on a start-up. So in 2018 it was born Checkmabwhich sees among the founding partners, in addition to Pagani and Abrignani, also INGM and the University of Milan, and an investment fund, Xyence Capital SGR, which contributed 6 million euros: “That loan – says Abrignani – was invested on 7 researchers, including Renata Grifantini, Scientific Director of Checkmab, who have dedicated body and soul to the project. We have thus come to develop two monoclonal antibodies that have been shown to have an anti-tumor immunotherapeutic effect both in vitro and in animal models”.
Towards a “made in Italy” gene therapy against cancer
by Tiziana Moriconi
The agreement with Boehringer Ingelheim
A new type of ‘targeted’ immunotherapy could derive from these monoclonal antibodies. And here the bet was made by a Big Pharma company: Checkmab has in fact concluded an agreement with Boehringer Ingelheim in which it grants, under an exclusive worldwide license, the molecules identified, in exchange for a total consideration of 240 million euros ( which includes an upfront payment and a variety of other payments tied to the achievement of clinical development goals). Following an initial period of joint research between the two companies, Boehringer Ingelheim will assume all development and commercial responsibilities. “We are planning the phase 1 clinical study – says Abrignani – and if the drugs developed will reach the market, Checkmab will receive an additional percentage of sales”. In the world of university spin-offs, an agreement with these numbers is not common in Italy: “No – he concludes – but I think it is a good example of how it is possible to ground the research that is generated in the academic field, even in our country, it can give confidence to many other companies like ours and attract other investments. In our case, the equation worked well: the philanthropy of the Invernizzi Foundation combined with the academic research of the State University and the entrepreneurship of the researchers. We continue to do translational research, not only in oncology, but also in autoimmune diseases”.