Recordati S.p.A [BIT: REC]

Stefano Biondi epitomizes the pinnacle of pharmaceutical leadership, boasting an impressive profile as an innovative entrepreneur with a wealth of global experience. His extensive knowledge base and multifaceted expertise have been instrumental in spearheading and nurturing diverse projects and enterprises within the pharmaceutical and biotech domains. Stefano's forte lies in his exceptional ability to swiftly assimilate new information, adapt adeptly, and make resolute, impactful decisions.

Widely acknowledged as a luminary in his field, Stefano effortlessly engages with Key Opinion Leaders (KOLs), industry titans, and stakeholders at the highest echelons. His international renown as an expert is a testament to his acumen and influence.

As a fervent and zealous senior figure in Pharma R&D, Stefano boasts a stellar track record marked by triumphant achievements. His proficiency extends to conceiving and cultivating groundbreaking products spanning a diverse spectrum of therapeutic areas. Notably, his approach is characterized by a judicious blend of pragmatism and an unwavering commitment to delivering tangible outcomes.

Please share with our readers your career journey and current roles and responsibilities.

I have been working as Head of Pre-Clinical at Recordati S.p.A. since 2021. My professional journey spans over three decades, commencing with my graduation in Chemistry from the esteemed University of Bologna in Italy. Throughout my career, I have navigated through diverse roles in research and development across small and large companies. I have worked for over 15 years in GSK. From there my professional footprint extended across Europe, with substantial work undertaken in France, Switzerland, and Italy. This wealth of experience positioned me as a seasoned professional in the realm of drug discovery and development as well as several therapeutic areas including anti-infectives, metabolic disease, central nervous system, and ophthalmology.

Can you share some of the challenges you notice in the industry?

The challenges in both drug discovery and drug development vary. In the realm of drug discovery, I have been involved in various projects undertaking various approaches and techniques to identify drug development candidates. This includes high-throughput screenings for lead compound identification, ensuring drug-like properties for optimization, the scientifically driven, hypothesis-based endeavors where a select few molecules are synthesized based on literature investigation, analytical data, or three-dimensional target structures. I have also dealt with problems tied to developing products derived from natural sources, particularly derivatives of natural products. I believe that the crucial aspect lies in the judicious selection of tools and framing the right questions during both drug discovery and development phases. Establishing a target product profile from the outset is paramount. This guides the properties a molecule must have to evolve into a development candidate. Characterizing drugs is not only important for potency assessment. It is also important to understand metabolic stability, selectivity, and potential toxic liabilities. While my primary focus has been on small molecules within classical medicinal chemistry, I've also delved into larger molecules, encompassing small peptides and antisense drugs. In the latter case, a meticulous approach involves synthesizing only a select few analogs, tailoring them to mitigate potential liabilities before committing to full development.

What are some of the best practices you employ to manage a diverse portfolio of drugs?

In evaluating each drug, the cornerstone lies in characterizing it against a predefined target product profile, akin to what some refer to as a screening cascade—a series of tests functioning as filters to select  potential candidates. The crux of this process is to run these assays in parallel, accumulating comprehensive knowledge for the majority of products under evaluation. This entails assessing relative potency, seeking selectivity, and delving into drug metabolism or stability in diverse biological environments like blood plasma and liver homogenate, tailored to the specific therapeutic area. Also having an idea about solubility, LogP characteristics, protein binding, potential cytotoxicity, and, depending on the target, measuring cell permeability is also important. A pivotal aspect, in my perspective, is initiating in vivo testing as soon as a lead compound exhibits a sufficient profile to indicate potential in vivo activity. This early in vivo assessment serves as a benchmark, facilitating further optimization of the product series or potential future candidates for drug development. So in my experirece, I believe introducing in vivo testing alongside the screening cascade, even if the molecule may not progress to development, provides a crucial benchmark and a valuable reference point for ongoing optimization while identifying potential liabilities within the compound class.

In the realm of drug discovery, a guiding principle I advocate is to commence projects with a clear target product profile in mind.

How do you envision the future of this industry?

Predicting the trajectory ahead is challenging due to the myriad possibilities ahead. The role of small molecules is undergoing a shift, constituting less than 50 percent of the overall drug being in development. Despite this, I anticipate a potential resurgence, particularly in the intermediate future, as small molecules could serve as substitutes for certain large molecules, like proteins and monoclonal antibodies. The monoclonal antibody and proteins weights around 20,000 to over a hundred thousand kilodaltons where only a small portion—around 1 percent—is actively involved in target interaction. The rest may carry liabilities like immunogenicity responses. So some of the trends we may notice is substituting  large molecules with compounds presenting only the active site for interaction which streamlines efficacy and mitigate risks. And another significant trend is the emphasis on targeted drug delivery, especially prevalent in oncology. The idea is to administer drugs specifically where needed, enhancing efficacy, reducing required doses, and minimizing the risk of adverse events due to unintended interactions in other organs. This targeted approach is applicable beyond oncology, addressing diverse therapeutic areas.  Advancements in gene therapy are on the horizon. While gene therapy shows promise, optimization is essential before widespread adoption. This optimization aims to overcome existing drawbacks and enhance the therapy's overall effectiveness. Another trend we notice is the popularity of antibody-drug conjugates, particularly in oncology. These conjugates utilize antibodies as carriers for cytotoxic drugs or radioligands, ensuring selective targeting of tumors without widespread cytotoxic effects. In addition to this there is a growing trend improvements in drug formulation. Innovations in administering drugs intravenously, especially those unsuitable for oral or alternative routes, play a pivotal role in expanding treatment options.

What is your piece of advice to your fellow peers?

In the realm of drug discovery, a guiding principle I advocate is to commence projects with a clear target product profile in mind. It's akin to envisioning what will be inscribed in the prescription of the drug and detailed in the product leaflet—the very essence of what you aim to bring to market. By establishing this blueprint early on, it significantly enhances the trajectory of drug discovery and development.