Scientists have made great progress in the last few years developing new treatments for serious diseases along with new methods of delivering them, thanks to advances in everything from genetics to antibodies. Yet when it comes to cancer, researchers are just beginning to discover the most promising ways to attack what is the second leading cause of death globally.
“There’s a major unmet need that exists in oncology, Cancer is an incredibly prevalent disease. Roughly half of us will develop cancer sometime in our lives. So, the need is very acute and relevant to all of us.” - John Reed, MD, PhD, Global Head of Research & Development
Even though significant progress has been made in the standard of care, with more and more therapies available that target specific kinds of tumors, the greatest successes have been limited to only a few types of cancers. For some of the most prevalent and dangerous cancers – breast, colon, and prostate, which together affect more than five million people, according to the World Health Organization – therapies have not advanced nearly as rapidly.
To address those unmet needs, Sanofi has been making significant investments in research into oncology. The result: A significant increase in both budget and staffing for cancer R&D in the past year, plus some key acquisitions and partnerships that offer new technologies and tools for developing novel cancer treatments.
Building a Bigger Toolbox
This increased focus on cancer R&D comes at a time when the science “has gotten a lot richer,” Reed notes, making the work done today markedly different from work being done only a decade ago. Greater knowledge of the genetics of various cancers, the emergence of “checkpoint inhibitors” that can help the immune system defeat a tumor’s defense mechanism, and major advances in delivery mechanisms have vastly expanded the options for researchers.
“We continue to build a richer toolbox of weapons to fight cancer, from small molecules to next generation antibodies to cytokines (small proteins that affect the immune system),” he said. “We’re looking for new ways to attack targets as well as other modalities, like oncolytic viruses, that could be a way to stimulate an immune system response to tumor.”
Attacking Cancer Inside and Out
Cancer research at Sanofi is divided into two main areas: Work in the field of immuno-oncology, focusing on engaging the body’s own immune system to locate and attack cancers; and in molecular oncology, where scientists are developing medicines that can be delivered directly to specific tumors or target receptors on them.
In molecular oncology the focus is on precision medicine, identifying the genetic mutations in a tumor so that researchers can match the medicine to the mutation. Armed with ever-increasing knowledge about the human genome, scientists are looking for the most informative biomarkers that identify those mutations, as well as new techniques for repairing them.
In immuno-oncology, much of the excitement involves PD-1 and PD-L1 checkpoint inhibitors, a class of medicines designed to defuse a tumor’s attempt to hijack the body’s immune system. Many tumors produce an excessive number of these checkpoint receptors, which essentially “turn off” an immune system attack. Checkpoint inhibitors work by blocking these receptors so the immune system can go about its job.
A New Era for Antibody Cancer Treatment
An important development is the creation of bi-specific and tri-specific antibodies, proteins that are capable of delivering treatments to multiple targets at once. Because cancers are complex and have multiple defenses, single-target treatments often have a limited and temporary effect. The ability to address multiple targets offers scientists a much better chance of successfully eliminating the cancer.
Another exciting development in antibodies is the discovery of “nanobodies,” which are a tenth of the size of conventional antibodies. Because they are so small, it’s possible to link them, like beads on a string, and facilitate their penetration into the tumor microenvironment, where ordinary antibodies are too large to reach. Sanofi acquired the technology last year when it purchased Ablynx, the company that first developed them.
By combining checkpoint inhibitor-based solutions with advances in the development of antibodies, scientists should be able not only to create more effective cancer treatments but also to control their application more effectively.
“Within five or ten years, I think we’ll start to see the next wave in cancer immunotherapy, beyond what we are currently able to achieve with checkpoint inhibitors,“ he said. “We’ll find ways to drive immune cells into the tumors so when you take the brakes off the immune system you have some fuel in the tank. We’ll see patients responding in a more durable way to their cancer care.”
Sharing data at #ASCO 2019
Reed expects to see a lot of discussion about the next generation of antibodies and checkpoint inhibitors at the upcoming American Society of Clinical Oncology annual meeting in Chicago at the end of May. He’s anticipating presentations about combination therapies that build on PD-1 or PD-L1 inhibitors in an effort to improve response rates, which today hover between 20-30%.
At the meeting, Sanofi will be sharing the first data of the pivotal Phase III trials of a combination therapy involving its anti-CD38 antibody treatment in development which has shown promising clinical results when used in combination with standard care of multiple myeloma patients who were unresponsive to first-line treatment. Sanofi also will present abstracts on novel oral treatments for metastatic breast cancer as well as an anti-CEACAM-5 approach for fighting non-squamous non-small cell lung cancer.
Partnering to Improve Pipeline Potential
The renewed efforts in both areas of oncology R&D are working their way through the laboratory and into studies as Sanofi builds on its existing foundation of therapies and technologies. Work on nanobodies is ongoing, as are efforts directed specifically at hematological indications, myeloma, lung cancers, as well as an in-house oral estrogen receptor therapy for use in breast cancer. Bi-specific and tri-specific antibodies are already a key platform in the lab, and work continues on developing nanobody technology.
One of the keys to advancing the research is working with partners, where work is focused on finding ways to make checkpoint inhibitors more effective in groups of patients who today don’t respond well to them. There also is work on how to make T-cells – one of the immune systems main defenders – more effective against tumors that have created barriers against them.
“Even with the resources a company like Sanofi can bring, partnerships are very important, especially because multi-pronged combination therapies are often needed to fighting cancer,” he said. As cancer cells mutate, they can become resistant to one treatment or another, the goal is to “complement your own molecules, without creating overlapping toxicities, in the same way that viral diseases did and are tamed with combination therapies.”
This release was first published 23 May 2019 by Sanofi.
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