5 Questions with Josep Tabernero

Dr. Tabernero served as the European Society for Medical Oncology (ESMO) President from 2018 – 2019, including its Executive Board. As the Head of the Medical Oncology Department at the Vall d'Hebron Barcelona Hospital Campus and Director of the Vall d'Hebron Institute of Oncology (VHIO), Dr. Tabernero has been Principal Investigator of several Phase I pharmacodynamic studies and translational projects with tumor-directed targeted therapies and immune therapies.

We spoke with Josep recently to learn more about his background, what he sees as new opportunities in cancer therapies, and his new role on Totus’s Scientific Advisory Board (SAB).

Can you tell us more about your background, and share what inspired you to join Totus’s Scientific Advisory Board?

I'm a medical oncologist and MD/PhD by training, and have dedicated my life to treating patients with solid tumors, as well as creating early drug development programs that advance their treatment options. Part of my work includes years of experience with PIK3?, which is what inspired me to work with Totus Medicines - the assets they have in this field are potentially game-changing. I’m also honored to be on this board especially because I’m surrounded by people that I deeply admire and respect. Dr. Kevan Shokat and Dr. Stephen P. Hale in particular are just two of the esteemed colleagues who I have the pleasure to work alongside here.?

What specifically is Totus doing that relates to your work, or that you find inspiring?

Throughout my career, I’ve both witnessed and participated in a continuous effort to develop cancer drug programs that would breach preclinical and propel translational medicine into clinical research. What I’ve learned is that the only way to move forward successfully is to care about all the complexities of a study, not just the clinically important aspects like safety and efficacy. That means needing to get back to pharmacodynamic readouts and trying to understand why the drugs work when they do, or why they don't. Totus Medicines understands the importance, and their scientists clearly take a multidimensional approach. I think that lends itself to a very unique opportunity for an efficient, successful clinical development process.

What do you think makes Totus unique in the broader drug discovery field?

With other companies, and even within academia, people are either extremely focused on the chemical aspects of drug development, or fixated on the platform. At Totus, they do both, and they do it well. Recently they’ve been discussing complex chemistry, like how to circumvent some of the mechanisms of secondary resistance with kinase inhibitors and precisely in this case with PIK3? inhibitors, while understanding the unique opportunity with the platform. It’s how they brought their first candidate, TOS-358, to the clinic so quickly, in fact. So, in a way, it’s like Totus is a perfect consolidation of a researcher’s dreams.

What do you wish more people knew about TOS-358?

The fact that this compound is a covalent inhibitor that targets the mutation alpha - but also the wild type - poses tremendous opportunities compared to reversible compounds. A compound like this continues to be highly selective for the alpha-isoform of PIK3? and with this irreversible approach you can favor that there is sustained inhibition of the target over time. This creates maximum opportunities for tumor cell death. We know that there is reactivation of the wild type of PIK3?. Because TOS-358 targets not only the mutants but also the wild type, it could possibly prevent the reactivation of the cancer in non-mutated cells when the mutant forms are inhibited. It is incredibly fascinating.

Finally, when you think about the future of drug discovery, what would you like to see?

I can only hope that we have stronger cooperation between the biotech industry and academic institutions in trying to promote and accelerate the clinical development of compounds in a more holistic way. With more of these kinds of collaborations, it will be possible to tackle the vast complexities of creating new treatments and bringing them into the clinical setting.?