‘Progress does not happen overnight’: Sanofi on evolution of medicine

A global pharmaceutical company is not likely to remain a significant player if they don’t continue to pursue and encourage innovation. Frank Nestle, global head of research and chief scientific officer with Sanofi, discussed how the company is harnessing unique disease insights and emerging technologies to achieve notable advancements in research.

OSP: Technology has always been a key driver in the evolution of medicine. Could you please share your thoughts on what kinds of factors tend to have the biggest influence? What makes a tool or technique more likely than others to have an impact?​

FN: At Sanofi, we are going beyond incremental therapeutic improvements building on the wealth of molecular disease insights combined with novel and proprietary technology platforms to discover and deliver transformative medicines. Progress does not happen overnight — we've been carefully building out our portfolio of innovative biomolecular platforms over several years, to empower our scientists and drug hunters with the tools they need to engineer sophisticated solutions to seemingly intractable medical problems.

One technology I’m especially excited about is our natural killer (NK) cell platform. NK cells have the innate ability to detect and destroy cancer cells and help trigger a broader adaptive and protective anti-cancer immune response, all without attacking the body's own healthy cells. This has major implications for minimizing toxicity associated with many of the currently available cancer cell therapies.

Sanofi's proprietary NK-cell platform expands and activates NK cells derived from a unique universal donor pool using our PM21 particle technology. It enables our teams to move on from costly individualized cell therapies and develop "off-the-shelf" immunotherapies that provide potential future access to a wider range of cancer patients.

OSP: What types of technologies have been emerging and transforming the life sciences in recent years?​

FN: Sanofi’s Expanded Genetic Alphabet technology adds two letters to the existing four letters of the genetic alphabet, allowing our scientists to engineer new proteins with highly specific attributes. This empowers our teams to overcome long-standing challenges in drug design and fills important gaps in protein-based therapeutics for cancer and immune-mediated diseases.

This platform has already yielded an immuno-oncology drug candidate, SAR 245/THOR-707, which addresses a well-known limitation of the cytokine drug IL-2. Introducing a novel amino acid into the IL-2 protein and attaching a PEG at a specific site has made it possible for this investigational therapy to increase the numbers of tumor-killing T effector cells and Natural Killer (NK) cells in cancer patients – without significant expansion of potentially immunosuppressive regulatory T cells.

SAR245 is just a first example of a whole new generation of sophisticated and highly engineered protein therapeutics that exploits progress in synthetic biology to design medicines with unprecedented efficacy and safety features.

OSP: In your position with Sanofi, you have a unique and informed perspective on what specific technologies stand to transform the field. Could you please share your thoughts on perhaps a handful of those technologies/platforms, and what makes them potentially transformative?​

FN: Sanofi’s NANOBODY technology is a next-generation single domain antibody technology that facilitates binding to multiple targets at once.

Nanobody proteins are approximately 1/10 of the size of a normal antibody, highly modular, and bind with high affinity to their targets. Through the creation of a “string of pearls” of Nanobody proteins, we can target multiple disease components with a single medicine. Nanobody proteins can also be engineered as bi-specific binders to connect a tumor and a T cell or NK cell for instance.

Our Nanobody technology allows us to develop single, multi-action medicines that could one day replace complex combination treatment regimens and improve treatment outcomes and quality of life for patients. The first approved Nanobody drug that targets von Willebrand factor is a first-in-class treatment for acquired thrombotic thrombocytopenic purpura, making a difference for patients suffering from this acute and potentially life-threatening disease.

OSP: Tech companies are constantly working on new tools and platforms that stand to elevate life-science operations. What are some of the areas of need/interest you might recommend such tech brains focus on if they hope to come out with solutions that stand the greatest hope of capturing the attention of drug research and development firms?​

FN: Sanofi's toolkit of proprietary technology platforms brings our teams several steps closer to developing transformative medicines for patients with difficult-to-treat diseases. Our goal is to offer a whole new class of treatments that could make patients' lives better and fundamentally change how clinicians approach cancer and immune disorders.

OSP: Do you have anything to add?​

FN: A few other exciting technologies in our pipeline include:

• In vivo immune cell reprogramming using mRNA, which helps the body to make its own killer CAR-T cells.
• Chimeric antigen receptor (CAR) T cell therapy has emerged as a powerful cancer treatment, but its impact has been limited by a complex treatment procedure: patient cells must be extracted from each individual patient, amplified in the laboratory, genetically reprogrammed, and then re-infused. As demonstrated in pre-clinical experiments, our scientists use proprietary nanoparticle technology to deliver therapeutic mRNA directly to a patient's immune cells where it can reprogram those cells into CAR T cells in the patient’s body to detect and destroy cancer cells more effectively. This approach may be a gateway to expanding Sanofi's capabilities in both immuno-oncology and inflammatory diseases.
• IntelliSelect Transgenics: An advanced human-antibody generation platform.
• Sanofi’s proprietary IntelliSelect Transgenics platform is one of the most advanced human-antibody generation platforms. It applies advanced single-cell technology and bioinformatics to help our teams generate fully human monoclonal antibodies that are highly specific to their target and minimizes untoward immune reactions against antibody-based medicines. One therapeutic candidate that has already been produced using this technology binds to a protein called OX40-ligand, a key inflammatory master regulator expressed on immune cells, making it a promising target for treating a range of immune-mediated diseases and inflammatory disorders.