REJIO SALONEN: A CHARIZMATIC LEADER AND SCIENTIST, WHO WANTS TO HELP EACH PATIENT INDIVIDUALLY…

Particle Analytical Blog

We have an interview that was conducted by our very own Anna Shevchenko. Anna interviewed the renowned Rejio Salonen!

Reijo Salonen took some time away from his summer cottage quality time with his daughter and granddaughter to chat with us. I know him since 2006 when he came back from New York City to his cold “kotimaa” (homeland) Finland to take a Senior Vice President position in Orion Corporation and lead the Research and Development organization. At that time, Reijo Salonen had already made a brilliant international career (several Vice President positions in GlaxoSmithKline and Pfizer), but Finland meant a lot to him. I will never forget his first talk about our future Research and Development organization that will become THE BEST IN THE WORLD! Guess what? He did it! He had succeeded in making people to deliver the best they could to make each of us feel “I AM IMPORTANT, I AM THE BEST” and my organization is THE BEST IN THE WORLD.

Now, in 2021, Reijo Salonen (RS) is enjoying his life, watching his grandchildren grow, and at the same time being a member of director boards of several technological and consulting companies. Very recently, in 2021, he received a visiting professor position in the frame of the InFLAMES Flagship research project at his Alma Mater (University of Turku, Finland). The goal of the Flagship is to integrate the immunological and immunology-related research activities to develop and exploit new diagnostic and therapeutic tools for personalized medicine.

…….

How do you see the Future of Pharmaceutical Industry?

RS:  I expect the Pharmaceutical Industry to be as successful in the future as it is now despite of the increasing pressure on drug prices. There will always be need for pharmaceutical products to treat a wide range of diseases. Pharmaceutical Industry will always be in demand. I cannot imagine what social shifts can happen in modern societies to change this situation.

Then Reijo explained his point of view in more detail. In his opinion, new technologies will continuously appear in Pharmaceutical Industry, and in the near future, such technologies as molecular diagnostics using biomarkers, genetic technologies like CRISPSR, personalised medicine, and novel digital tools, such as machine learning and artificial intelligence, will become more and more important. These technologies will make it possible to faster and easier find the causes and mechanisms of diseases, select multiple lead drug candidates, reveal, and confirm the ways of their action against the target, and investigate optimal conditions for new drug production.  As a result, the proof-of-concept phase of drug discovery and further development stages will become more efficient.

We are now evidencing the increased attention of the Pharmaceutical Industry towards big molecules. What is the future of small molecules in drug discovery?

Small molecules can have some drawbacks, such as difficulty to synthesise, low solubility, low permeability, instability, toxicity, variability in efficacy, etc. However, with the development of new technologies, we will be able to overcome some of these drawbacks. Oral small molecule will be a preferred choice for many targets also in the future. Pharma is, however, also ready for large molecules, gene therapies and cell therapies.

RS: By new technologies I mean the advanced formulation technologies, such as nanotechnology, solubility enhancement, and other novel drug formulation and drug delivery approaches. It is also important to understand and appreciate the commercial value and need for personalised medicine.

What are the key points of the concept of personalised medicine? Is it all about the genes?

RS: Not only. In addition to genetic, the sociological, psychological, behavioural, geographical, gender, and other biological and environmental factors can affect the mechanism of a disease and the efficacy of a treatment. Ideally, the medicine should be tailored and prescribed for each person individually, but this is still in most cases unrealistic (CAR-T cell therapies are exceptions). On the way there, we should be able to stratify patients’ populations into smaller biologically relevant groups where efficacy is higher and adverse events less common and/or less severe.

Right now, when diseases are defined by inadequate understanding of the basic etiology and pathogenesisone group of patients has a high response, the second group responds well, but have some side effects, and the third group does not show any response to the same medicine. The reasons can be many, depending on the case. Recently, FDA have approved the Aduhelm (aducanumab) to treat patients with Alzheimer’s disease using the Accelerated Approval pathway. The drug is proven to reduce the presence of amyloid beta plaques in the brain. However, only the patients with early symptoms responded well to the treatment and the drug, unfortunately, is not efficient in the whole population of patients with this diagnosis. This is an example of a very small step forward in patient stratification

What the new InFLAMES Flagship program is about? Is it also about the personalised medicine?

RS: The Flagship programs are founded by the Finnish government and the Academy of Finland. The programs support top quality research and increases the societal impact emerging from the research. The Flagships represent a mix of close cooperation with business and society.

We learned that the InFLAMES Flagship aims to identify new neuroimmulogical drug development targets and develop new medicines together with biotechnology and pharmaceutical companies. The Flagship also seeks breakthroughs in diagnostics and personalized medicine.

RS: The personalized medicine will develop diagnostics so that targeted therapies could be designed for individual patients. International collaboration is an integral part of the Flagships’ activities.

The Academy promotes international cooperation in flagship fields through special actions together with its American partners. Read more about the Finnish Academy’s cooperation with the United States.

Naturally, the scientific and commercial networking competence of Reijo Salonen in addition to his neuroimmunology background are of critical value for the program.

Despite the visible enhancement of investments into the discovery and development of biologics followed by growing numbers of such drugs, we still do not see the breaking through numbers of the approved new biologics on the market. What are the main challenges in the discovery and development of the large molecules?

RSAs you know, the country where you work now (Denmark) has a large Pharma company that is concentrating on large molecules almost entirely.

Reijo is convinced that the nearest future is in a balance between small molecules and biologics and thinks that the pharmaceutical companies in general are increasing research focused on biologics. He explains that with biologics, their structural characterisation is more complicated than with small molecules.

RSYou must be sure that you are working with the same structure – molecule – from the very beginning to the end of the drug discovery and development. This means that you should work with the final product from the very beginning. It is important that all stages of the drug discovery and development are going on in harmony and preferably in the same place. In those cases where outsourcing is needed, it might be better to oursource the whole chain. On the other hand, this makes it difficult for biosimilars (generic copies of the proved biologicals) to get on the market, as to prove “similarity” requires a lot more work than with traditional generics. Biologics have also clear advantages over small molecules and e.g. off-target toxicity is generally not a problem. When you come to later stages, the clinical and non-clinical trials targeting to prove the safety and efficacy are conducted and designed in a similar way for both big and small molecules.

The big molecules being unstable in intestine and having low membrane permeability are normally injected intravenously or subcutaneously. Have you heard about the pioneering oral biologics with semaglutide (peptide) for treatment of type 2 diabetes by Novo Nordisk? It has been formulated using a permeability enhancing excipient salcaprozate sodium SNAC (sodium-N-(8(2-hydroxybenzoyl) amino) caprylate).

RSVery interesting… Why not, if there are not any side effects induced by such permeability enhancer?

This is a new excipient approved by FDA. According to the studies, cell membranes recover safely after exposure. I was so proud to hear that also Finnish experts and innovators are involved in the formulation development.

Nanomedicine is a fast-growing research area. What do you think about this, about the market and potential applications?

RS: For nanomedicine, the objective is to produce a nanosized particulate of a pure drug or a drug product (formulation) containing nanosized particles. Such materials are expected to enhance the bioavailability of a drug.

He told that he really trusts in the nanomedicine approach to enhance bioavailability of low soluble molecules having the dissolution limited absorption. However, he was a bit skeptical about the commercial attractiveness of the idea to re-formulate old drugs in nanosized particulate to decrease the needed dosage.

Can the nanomedicine be used for the dry inhalation formulations?

RS: Interesting question. There is a common opinion that the particle size of an active pharmaceutical ingredient in the dry inhalation product should be small but not too small: a micron-, not a nano-sized particle. I am afraid that too small particles can end up deeper in the lungs to the places where they should not go. And what is your opinion?

I was thinking that introducing too small particles on the surfaces of a carrier should affect the cohesive-adhesive balance. It seems to me that the cohesive forces might be too high. This might lead to the nano particles of the drug sticking to each other and forming agglomerates. The result of such new formulation cannot be predicted, but this would be interesting to test.

What is your opinion about possible use of nanomedicine for overcoming the blood-brain barrier that is a major obstacle on the way of any molecules larger than 600 Da restricting up to 98 % of small molecules and all biologics?

RS: I know people claim that it is possible. But does it really work? I would like to see the facts, more studies, and more evidence.

The field of Artificial Intelligence (AI) is growing fast. What opportunities the AI opens for Pharma?

RSThere is so much data already generated by numerous studies performed in the pharmaceutical industry and academia research, but we are not yet good in using it.

RS does not have any doubts that, already in the near future, implementation and use of AI will speed up and make it easier many processes in Pharmaceutical Industry, from analytical and clinical study results evaluation to assistance in the decision-making processes. AI can help to solve challenging problems, for example, of the synthesizability of the molecules that have previously not ended up as hits due to too complex structures.

What are your most important goals in next 2 years?

RS: My most important project for the future is watching my grandchildren grow. Me and my wife, we have three, and one more is coming soon… In addition, I participate as a board member in few small companies. Consulting and giving advice.

If you had to start now your own business, what would you do?

RS: I am not any more interested in leading large departments in big or middle Pharmaceutical companies, but I continue to be excited in advising enthusiastic new scientists and companies as they try to find their way in the world. I need to believe that their idea is great, and this will motivate me. By the way, what are you doing in Denmark? Can you tell me?

I work for Particle Analytical, a privately owned CRO company having over 20 years of expertise in the field of solid-state characterization and physical analysis of pharmaceutical powders and products. We are offering our services for pharmaceutical companies. We are offering both single analysis and broader service packages and can help with our expertise at all phases of drug discovery and development. For instance, last year we were busy with particle size analysis of the COVID-19 vaccine product.

My work is to develop new business areas, search for new methods and technologies to conduct solid-state form screenings, and analyse the results of our new studies. So, here I am in Denmark looking for and implementing the Great Ideas J. I think there are many opportunities here in Denmark for a pharmaceutical scientists. Thank you for asking.

Imagine you are looking for an outsourcing organization, what are your criteria?

RS briefly listed them in priority order from the most critical to less critical criteria:

(1) Expertise; it is not supposed to be so that we must teach the outsourcing company how to do things

(2) Quality of work

(3) Meeting the timelines

(4) The CRO must have competitive, reasonable prices even though the prices are not so critical. You should not price yourself out.

We spent some more time discussing the effect of the COVID-19 pandemic on Pharmaceutical Industry. His scenario of the further development of the pandemic is turning the aggressive young virus after numerous mutations into less aggressive forms. RS: Now with the vaccine, we will eventually be OK.

RS sees no harm to the industry brought by the pandemic, but vice-versa, only positive developments, since in his opinion, the society’s trust in pharmaceutical industry has been considerably enforced. A lot will depend on how the pricing and access to vaccinations is handled in the coming years.

At this optimistic point, our time had come to the end and I have heard a sound of washing dishes…

So warm, so comforting, so HYGGE background sound of the New Normal Time under the COVID-19 restrictions….

We wished each other to be healthy and wealthy. The world is small and maybe we will meet again…. Don’t know how, don’t know where… But now, having over 30 years of working experience, I know that all of us who used to work in the WORLD BEST R@D will never forget those times.

Blog Expert Profile – Anna Shevchenko