Interview: Carme Almansa


Who is Carme Almansa and what is your professional area?

Born in Vall d’Aran I arrived at Barcelona with 6 years old and always liked to read and study. I was fond of almost every subject, from Literature to Mathematics, but I finally decided to study Chemistry.  I liked its broad application and the fact that it could help me understand the nature of many fundamental phenomena. I think that it was a good choice as I enjoyed most of the chemical disciplines, and again, having to choose, I chose Organic Chemistry, which was the basis of my transition to Medicinal Chemistry, that after my PhD became my lifelong dedication. Chemistry brought me also a lot in my personal life, as I married a classmate, an Organic Chemist too, and we have a son and a daughter, that are now living independently. Together we have done many trips and we have enjoyed our main hobbies, such as walking, skiing, playing paddle, dancing and going to the cinema and theater.

Can you tell us about your background and what inspired you to pursue your career?

After my MS in Organic Chemistry, I was offered the possibility of doing a PhD in Synthetic Chemistry at the University of Barcelona under the direction of Prof Felix Serratosa, a pioneer in the field. His passion for building beautiful and complex molecules from simple pieces became also mine and when I finished my thesis on the synthesis of triquinacenes it was clear to me that I wanted to continue solving this type of challenges.

When I was about to initiate a postdoc in the US, I was made aware of a position as a medicinal chemist in Grupo Uriach, a local pharmaceutical company. The industrial world, as opposed to following an academic career, was attractive to me as I thought it could have a more direct application. Also at that time, it was quite difficult to have this type of job in Barcelona, as only a handful of pharmaceutical companies had solid R&D groups, and believe or not, being a woman was still a drawback. So, after doing a quite intensive selection process I was given the job and, not without doubts, I decided to stay in Barcelona.

Medicinal Chemistry was not taught at the University and in fact it is quite a unique discipline, both an art and a science, mastered in Pharmaceutical Companies, so I began a path of continuous and never-ending learning, as the field is always under huge progress.  Being a Medicinal Chemist is an exciting job, having a central role in the discovery of new molecules and requiring interaction with many different disciplines. I enjoyed my 22 years at Uriach, where I led several projects that ended up in clinical candidates and marketed drugs.

In 2011 Esteve Pharmaceuticals offered me to join their team as Chemistry Director, where I led a group of medicinal, synthetic and analytical chemists as well as the compound management unit. I participated quite directly in the design of compounds in the sigma-1 receptor platform, including the development of EST-73502, a dual compound that completed phase I clinical trials for the treatment of pain and in the development of Seglentis, a cocrystal approved in 2021 by the FDA for the treatment of pain.

In 2020 Esteve transferred us, the Drug Discovery team, to LEITAT, creating Welab, where we continued the development of our sigma platform. After 3.5 years, 6 patents filed and 3 candidates selected, the unit was closed in March 2024. A disastrous management left 68 people jobless.

Any current research projects that you want to share?

As said in question 2, our working unit was recently closed. I cannot share anything of the work done from 2020 at Welab, except that published in two recent papers (J. Med. Chem.  2023, 66, 12499-12519; J. Med. Chem.  2024, 67, doi.org/10.1021/acs.jmedchem.4c00288).

The work of these last years at Esteve and Welab can be summarized as a dedication to unraveling the therapeutic role of the sigma-1 receptor, a chaperone potentially involved in several neurological diseases and pain states. Also, to the development of dual compounds combining sigma-1 with other potentially synergistic targets. This work led to the filing of more than 80 patents describing a wide variety of frameworks that fulfilled the desired primary activity and drug-like filters. One compound (E82562) reached phase II clinical trials and a dual compound (EST-73502) completed phase I clinical trials for the treatment of pain, but they were discontinued, and no other compound reached the clinic, despite showing attractive enough profiles.

Can you share a particularly exciting discovery or achievement from your work?

I must say that I have enjoyed every step of the way but if I had to choose I would select one of the early projects, where I was still learning the principles of the art of Medicinal Chemistry, and learning to integrate its main “stakeholders”: design, including the incipient molecular modeling tools, synthesis, pharmacology, pharmacokinetics, toxicology, IP, CMC, market access, regulatory requirements, etc.

As a Medicinal Chemistry Team Leader at Grupo Uriach I was responsible for the discovery of cimicoxib, a selective COX-2 inhibitor initially intended for human use. However, the problems encountered by Merck with the first-in-class rofecoxib, that was withdrawn from the market, put a question mark on the approach versus the traditional non-selective (COX-1 & COX-2) NSAIDs. Uriach was quite agile in finding a way out, and after a joint development, a licensing agreement was made with Vetoquinol, a veterinarian company that marketed cimicoxib for the treatment of inflammatory pain in animals under the brand name Cimalgex.

Another interesting project from that time is the discovery of UR-13870, a p38 MAP kinase inhibitor that was quite outstanding in its drug-like profile and was out-licensed to the Dutch company Organon, soon to be acquired by Schering Plough. Going to Organon to present the project and participate in the meetings of a much bigger pharmaceutical company was really stimulating. Unfortunately, the project only reached phase II clinical trials as it was deprioritized when Merck acquired Schering Plough, an acquisition that, later on, led to the complete shutdown of the site in Oss. It is curious that we started with an Uriach-Organon collaboration and we ended up with a Palau Pharma-Merck collaboration, involving several compound name changes!

What advice would you give to aspiring scientists interested in pursuing a career in biotech and biochemistry?

Show your value: Propose ideas, be constructive, and speak up.

Dare:  If you do not do it somebody else will. Why not you?

Continuous formation: Ending the University is only the beginning of learning. Never stop to be updated, to read a lot about your field and related matters.

Adaptation to change: As Darwin said the only constant is change. Do not be afraid of change, it is always an opportunity. Never lose the capacity to think outside the box.

Resilience: Always necessary, accept what you cannot change.