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Press Release / Jun 06, 2003

Ivan Villax, 1925-2003

Ivan Villax was fond of saying he had left his country aged 23 with a toothbrush in one pocket, a chemical engineering diploma in the other and the Russians at his heels.

Born in 1925 in Magyaóvár, a small town in Hungary just East of Vienna, his mother was of Austro-Hungarian landowner stock and his father a Hungarian scientist. In 1948, while the family was in a displaced persons camp in Salzburg, a letter from Professor Victoria Pires, then Secretary of State for Agriculture in the Portuguese government, invited Ivan's father to come to Portugal. Ödon Villax was to help establish an agronomy research center into plant genetics in Portugal such as those he had run in Hungary. Ivan arrived in Lisbon a little later to join his family after working at the Centre de Recherches Agronomiques de Clermont-Ferrand in France.

He knew then that antibiotics were to be his future and while in France he had isolated from soil samples some tetracycline producing strains that he later named Streptomyces lusitanus. He joined the Instituto Pasteur de Lisboa in 1952, then one of the leading pharmaceutical laboratories in the country.

His first inventions were in the area of chloramphenicol preparation and tetracycline and penicillin fermentation. During this period he made good use of Prof. Maia Loureiro’s equipment, the inventor of submerged aerobic fermentation. This Portuguese technology had been instrumental in solving the industrial challenges of penicillin fermentation during World War 2.

In 1958 he wed Diane Du Boulay; and together with two other Hungarians, Nicholas de Horthy and Andrew Onody, they founded Hovione in 1959. During the first 10 years the company was a research laboratory located in the basement of the family house in Lisbon, not far from the American and British embassies. As Ivan made chemistry in test tubes, Diane typed out invoices and for the next 45 years they made an amazing team.

A close collaboration developed with Fermentfarma Spa, Milan - a company also run by Hungarian refugees - Villax became the technical director and a minority shareholder. Technology for the fermentation and isolation of tetracyclines was licensed to Imperial Chemical Industries of the UK, National Fermentation of South Africa, and to International rectifier of El Segundo, California among others. In 1967 Rachelle Laboratories bought out Fermentfarma and the proceeds of Ivan Villax’s share were used to build the first Hovione plant in Loures, just outside Lisbon.

Growing tired of the unpredictability of fermentation processes, he directed his research efforts to chemical synthesis. In the Loures plant he developed and industrialized an 18 consecutive step process to produce betamethasone and its derivatives, and throughout the 70s Hovione enjoyed a privileged position in Japan, thanks to Villax's independent process patents. As the business grew, and Portugal went through some troubled times after the 1974 revolution, Ivan sent his children to finish their studies in England and started looking for a location for further expansion. A Hong Kong office was established in 1978, and in the same year Hovione's first purchasing visit to the Canton fair took place. One after the other his four children spent a few years working in the Far East; it was all part of giving them the best possible education.

By 1982 the Loures plant had expanded and got organised to supply the US generic market with semi-synthetic antibiotics; the Macau plant went on stream in 1985 to provide additional capacity. This was prior to the Roche-Bolar amendment, and at FDA for several years people remembered how samples of doxycycline were provided at 9am at their Fishers Lane Rockville, Maryland offices, and not a minute too early, or too late, before the innovator’s patent expired. In Europe this product generated extensive patent litigation with Pfizer suing a number of Hovione customers in 8 different countries. True to his beliefs, Villax volunteered as co-defendant in every suit. His tenaciousness in the face of such adversity meant he did not give up and eventually the matter was settled out of court in 1992. This dispute diverted Villax’s efforts from following other creative pursuits much to his disappointment; though throughout this time the industry recognized in Hovione a fighting spirit that was a characteristic of its founder. Today the generic industry worldwide benefits from Hovione's efficient processes in the production of many other active ingredients: minocycline, roxithromycin, are products where Hovione retains a leading role in several countries.

Ivan Villax was always grateful to the country that welcomed him and allowed him to make a new life. He was happy that in providing generic contrast media Hovione was somehow celebrating Prof. Egas Moniz, a Portuguese Nobel Laureate, the father of angiography.

After the fall of the Berlin wall he made frequent visits to Hungary. The Technical University of Budapest, his Alma Mater, awarded him a PhD in recognition for his 40 years of work in pharmaceutical chemistry and he was made a member of the University's Senate. By then he had authored over 100 patents and scientific articles.

In 1995 his health started to weaken and he made arrangements for an organised hand-over of his responsibilities. With the business in the hands of a professional management team led by his son Guy, Ivan Villax still came to the Loures plant on a daily basis, keen on being kept informed on the new chemistries and on the performance of the business, and quick to point out any slack in the rigour, discipline or housekeeping in either the labs or the manufacturing facilities. Every year, together with Diane, he visited the Macau plant keen to encourage the younger generation and to acknowledge the service of long-standing staff.

In his last years he saw Hovione becoming an important producer of HIV protease inhibitors, a key medicine in the fight against AIDS, and taking an active role in many drug development projects as the provider of the active ingredient. In 2002 Hovione established a pilot plant in New Jersey, not far from Rahway where in the 50s Villax had turned down an offer for a position at Merck's research laboratories. He and Diane traveled the world, whereby he was able to satisfy one of his other passions, collecting plants from exotic locations, planting and nurturing them in his quinta outside Lisbon.

This May, after a severe deterioration of his lung condition, Ivan, ever the fighter, ever determined to control his own fate, realized that hospitals and science could do no more for him and asked to be taken home. At his quinta in Manique surrounded by his flowers and his trees, with his children, grand-children and his wife Diane, his life-long partner, he lived another two happy weeks - he died on Friday June 6th.

Church services will be celebrated at the Igreja Matriz of Loures at noon, and at the Basilica da Estrela, in Lisbon, at 7pm on June 12th.

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The podcast "The Next Discovery" is a six-episode series created by Observador, a leading portuguese digital newspaper and radio station, in partnership with Hovione. And what if some of the scientific discoveries that can improve the lives of millions of people were happening right now in Portugal? The Next Discovery. Listen to the first episode of the podcast here, featuring Diane Villax, co-founder of Hovione. [English transcription] Welcome to The Next Discovery. This is a series of conversations, created in partnership between Observador Lab and Hovione, an international pharmaceutical company of Portuguese origin, that will open the doors to its world and share real stories of science, innovation and global impact. Over six episodes, we will meet the people behind technologies that help develop and manufacture innovative medicines for the world’s largest pharmaceutical companies that improve the lives of more than 80 million patients every year. I am Nelson Ferreira and, in this first episode, we will discover how an unlikely story, which began in a basement in Lisbon, became a story of global leadership. To talk about this legacy, I have the honour of welcoming Diane Villax, co-founder and non-executive board member of Hovione, who at the age of 91 remains a living witness to this journey. Nelson Ferreira (NF): Welcome, Mrs Diane Villax. Let us begin our conversation in 1959. Hovione was born in an unlikely way, in a basement in Lisbon, founded by your husband, Ivan Villax, by you and by two other partners. How did you manage family life and, at the same time, the birth of a pharmaceutical company, all in the same space? I imagine that created some interesting logistical challenges. Diane Villax (DV): From the beginning, we decided that we would manufacture raw materials for the pharmaceutical industry, that is, the active ingredients of medicines. We had no money, so it had to start from our home, which was in a residential neighborhood in Lisbon. Right from the start, we divided the tasks. My husband, a brilliant Hungarian chemical engineer, would be the inventor, the producer and the salesman, while I would take care of all the administrative side: imports, exports, accounting and banks. I kept those responsibilities for at least 30 years. At the same time, we also thought about the values that would guide us over this long period: transparency, innovation, the pursuit of excellence and great consideration for everyone who would come to work with us over the years. NF: Very early on, your husband made it clear that Hovione would not compete on low price, but rather on quality and on solving complex problems. What was it like to apply this principle of rigour when resources were still scarce? Especially because, from day one, it always seems to me that your objective was global. The world would be your market. DV: From the beginning, we felt that Portugal, with a population of 10 million people, would not be a very significant market, and that the world would be ours. Perhaps we were a little naïve, because we were entering a global market that was already quite sophisticated. But the decision was made and we moved forward. We moved forward and were fortunate that Japan discovered us quite quickly. They came knocking on our door, because of course we did not have the means to knock on theirs. At that time, they did not manufacture; they only formulated, so they needed to buy raw materials. My husband had invention patents for independent processes and there were long discussions. They felt that our technology was good, our IP was very robust and our quality was excellent. This led to a cooperation that lasted 10 or 15 years and was very profitable for both sides, I believe. NF: In the 1980s and 1990s, Hovione took a more significant leap forward. What were the decisions, the technological bets or even the moments of greatest courage that allowed this small Portuguese company to become a leading multinational? DV: In 1982, after a successful inspection by the FDA, the regulatory authority in the United States of America, we entered the American market with our generic doxycycline antibiotic. The inventor’s patent had already expired and we had an independent manufacturing process. It was a huge, demanding and competitive market, but one that respects good service and quality. And it was indeed a major leap, because the market was so large that we had no real sense of what it would mean, and demand was much greater than what we were able to produce. I remember, it must have been the summer of 1983, many people probably had to postpone their holidays to the autumn or winter, because missing delivery deadlines was not an option. Later, in the 1990s, we entered a new business area: services. We realized that large American pharmaceutical companies, as well as small biotechs, were increasingly inclined to outsource the development work for new molecules. This is a very long period, which can take four, six or even 10 years — the development process for new molecules before they are approved by regulators and become commercial products. So we began to offer this development service, and it went very well. From there, we developed new technologies, such as spray drying, for poorly soluble molecules, because this could greatly increase their bioavailability. Today, this services area is our largest business segment. NF: Hovione today works with 19 of the world’s 20 largest pharmaceutical companies. How do you maintain the agile, pioneering spirit that was born in that basement, when today the company has 2,600 employees, more than 300 scientists, and has even become the largest private employer of PhDs in Portugal? DV: Agility has to be maintained. For example, during the pandemic, we suddenly received large, unexpected orders to manufacture a component of Remdesivir, which was the product authorized to help Covid patients. So agility has to be maintained, and we always maintain our quality. Today, with more than 60 years of history, clients come to us because they know they can count on our quality and on our responsibility to produce and deliver on time what they order. NF: There is another impressive figure here. Your products reach 80 million people every year and Hovione participates in up to 10% of the new medicines approved annually by the FDA in the United States. When you look at this impact, do you feel that the dream of 1959 has been fully achieved? DV: I think it has been far exceeded. When we founded Hovione, my husband, who was a scientist, simply wanted to have his own laboratory. But he never imagined that we would develop in such a way that, today, we are sought out by major international pharmaceutical companies, which frequently come to us. NF: This is a series about science, but it is also about people. And the rigour, ethics and long-term vision that Diane always brought to management are still present at Hovione. What message would you leave to the scientists who join Hovione today with the mission of finding the next discovery? From what I understand, Diane makes a point of welcoming them whenever they join the company. DV: Yes. Four times a year, twice in English and twice in Portuguese, I speak to the newcomers at Hovione, giving them a very brief account of our journey, our values, our objectives, our dreams, the challenges we faced and how we overcame them to get to where we are today. And I always recommend that anyone who joins this company must work with passion. They must work with passion and always remember that our work is to produce medicines for those who need them. We have the privilege of serving patients. We are a company that works for society. I think “In it for life”, which is our motto, has a lot to do with us, because we have been here for 67 years as a family company, and that is how we intend to continue for many good years to come. Above all, in the healthcare sector, there is a great advantage, because we can look at the long term. We do not have to think about stock market results every quarter, as public companies do. And, on the other hand, we are here precisely to give life to those who need it. “In it for life.” NF: At the age of 91, how does Diane herself maintain this passion and continue to make long-term plans? DV: Because I was a founder of this company. I see it progressing and developing successfully, so it is a joy for me. And I have a large family coming after me. I have six grandchildren and seven great-grandchildren, and I hope to leave the company to them so that they can continue it as I managed it. NF: That is truly inspiring. Mrs Diane Villax, thank you very much for sharing the memories and inspiration of this legacy, which remains very much alive. It was a privilege. This was the first chapter of The Next Discovery. In the coming weeks, we will continue to open the doors of Hovione to discover how Portuguese talent is leading the world, from complex chemistry to particle engineering, from respiratory therapies to next-generation biological medicines.   You can listen to the next episodes on observador.pt and on your usual podcast platform.    

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Hovione is bringing momentum to the intranasal field after announcing that its lead single-use nasal dry powder device, developed in collaboration with Industrial Design Consultancy Ltd (IDC), is now available for commercial partnerships. The milestone marks the transition from prototype to a fully integrated intranasal drug delivery platform that spans Hovione’s end-to-end partnership capabilities–from API synthesis through advanced formulation and particle engineering to drug product manufacturing, including device supply and advanced analytical tools for nasal performance characterization. The platform’s single-use device is designed to be manufacturable at scale and to leverage existing advanced particle engineering and drug product manufacturing capabilities, a practical advantage that can shorten timelines to clinic and commercialization while reducing development risk and cost. The device’s patented mechanism supports targeted nasal deposition, including access to the upper olfactory region. This enables rapid systemic absorption and potential nose-to-brain delivery pathways that are increasingly important for CNS and emergency-use indications. Beyond the single-use format, Hovione and IDC are advancing a multi-dose variant to broaden applicability across dosing regimens and therapeutic areas. The collaboration is backed by an intellectual property portfolio and initial patent grants, positioning the platform as a turnkey option for pharma partners seeking a single integrated supplier for both drug substance and device. This development arrives as intranasal delivery gains traction for systemic, CNS and rapid-onset therapies. This is precisely the focus of the upcoming 4th Nasal Formulation & Delivery Summit, for which Hovione is a key sponsor. The annual summit unites formulation, delivery and product development leaders to tackle drug-device compatibility, translational preclinical models, and strategies for scalable, regulatory-ready intranasal programs. Hovione’s recent progress will be highly relevant to attendees looking to de-risk nose-to-brain and systemic intranasal programs. Read the full article at News-Medical.net    

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