Vertex Pharmaceuticals has always championed a culture of innovation, one that empowers its employees to tackle tough problems, pivot toward novel solutions, and tap creative resources in order to help patients. While the company, headquartered in Boston with research sites in San Diego and Oxford, United Kingdom, has numerous projects underway, its main mission for the last several years has been to treat cystic fibrosis (CF), a genetic disease that affects the lungs, liver, gastrointestinal tract, pancreas, sinuses, sweat glands, and reproductive tract. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and inflammation, often resulting in progressive lung damage and eventually leading to death. According to the Cystic Fibrosis Foundation Patient Registry, there are more than 30,000 people in the United States living with CF (and more than 70,000 worldwide), and approximately 1,000 new cases of CF are diagnosed each year.But CF is only one of several serious diseases that Vertex

is working on. And by investing in science and going after the root cause of disease, the company empowers its diverse teams to “make the impossible possible,” says Reshma Kewalramani, Vertex’s chief executive officer and president. “We go after some of the most difficult scientific problems, knowing that our unique approach to drug discovery, coupled with the perseverance and commitment of our team, will get us to solutions that ultimately help patients.”

It starts with picking the right problemAcross all of its R&D programs, Vertex has championed an

innovative approach to drug discovery. “It starts with picking the right problems to go after,” says David Altshuler, Vertex’s chief scientific officer. “We only work on diseases where we have a deep understanding of the underlying human biology, validated targets, and biomarkers that translate well from the lab into people. We select diseases for which we believe we can have a transformative impact for patients, not just an incremental benefit. Then we research and develop therapeutic approaches that are most likely to succeed. Rather than looking for problems we can solve with only the tools we’ve used before, we figure out the problems that need to be solved for the diseases we’re going after and invent the tools to fix them.” PH

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VERTEX PHARMACEUTICALS PROVES DRUG DISCOVERY IS THE ULTIMATE TEAM SPORT

There is no “I” in “team.” Vertex is proud of its collaborative, corporate culture.

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This strategy is central to Vertex and has fundamentally shaped the company’s pipeline of R&D programs. It starts with a scientific problem waiting to be solved. “We first ‘crack the biology’ of a disease, meaning we ensure our biological target plays a causal role in the disease. Then we ‘pour on the chemistry or technology’ to find potential treatments,” says Kewalramani. “We spend a lot of time and effort validating our laboratory assays and clinical biomarkers upfront, which gives us higher confidence that a potential therapy will succeed when we investigate it in the clinic.”Investing in scientific research is clearly where the

company is focused. In 2019, 73% of the company’s operating expenses were dedicated to R&D, a disproportionately large amount when compared to the average biotech and pharma companies in the industry. In addition, three out of five employees work in R&D, which Altshuler credits as the most important aspect of drug discovery. “Discovering potential new medicines is the

ultimate team sport,” says Altshuler. “It takes hundreds of scientists and researchers working together to bring a new medicine to patients who are waiting.”

Team Impossible is on the caseIndeed, “I often refer to our teams as ‘Team

Impossible,’ because no matter how big the challenge, they always find solutions that seem to defy what’s possible,” says Kewalramani. “This sense of urgency is incredibly important to the people living with serious diseases.” Vertex spearheads novel systems and processes

to foster this velocity and tenacity. For example, in 2015, Vertex became one of the first companies to implement drug product continuous manufacturing (CM) technology in the development and production of its investigational and commercial medicines. With CM, raw materials are added into one continuously running system, and quality control takes place throughout the production process. “Continuous manufacturing results in faster, more streamlined manufacturing process development and scale-up,” says Stuart Arbuckle, Vertex’s chief commercial officer. “We’ve successfully integrated this technology into our process development, clinical and commercial supply production processes.”Another way Vertex reduces development timelines

is by doing clinical studies and other development activities in parallel, where possible, instead of one at a time. “We’re always looking for ways we can do multiple things at the same time, because having these faster timelines gives us the potential to get

medicines to patients quicker, and the sooner we can get medicines to patients the better,” explains Carmen Bozic, Vertex’s chief medical officer.Vertex’s innovations aren’t just happening in the

lab or in clinical studies. Nia Tatsis, Vertex’s chief regulatory officer, views the company’s partnerships with regulators as a critical piece of the puzzle. “Part of my goal is to ensure regulations are keeping pace with scientific innovation,” she says. “Our science is evolving rapidly, and we need strong working relationships and trust with regulators to achieve our shared goal of bringing new medicines to patients who need them.”None of these advancements would be possible

if not for the enterprise’s prime directive: “We have developed a very special, inclusive culture at Vertex,” Kewalramani shares. “More than half of our global employees are women and five out of 10 of our directors are diverse on a gender or ethnic basis—and it’s that diversity of thought and experience that ensures we make the best decisions for patients and our business.”

To infinity and beyond: Tackling the next set of disease targets“Our mission is to use scientific innovation to bring

treatment options to people with serious diseases. So we’re applying what we’ve learned in CF to a number of other serious diseases in which we understand the causal human biology and have validated targets and biomarkers with high fidelity from bench to bedside, such as sickle cell disease, alpha-1 antitrypsin deficiency, and Duchenne muscular dystrophy,” says Kewalramani. “We’re leveraging multiple therapeutic modalities such as cell therapies, gene editing, and mRNA [messenger RNA] therapies.” Vertex continuously asks the following questions:

What else can we do to advance medicines? Where else can we apply our research in helping patients? How can we bring medicines to patients faster? By using the power of biology, chemistry, emerging technologies, creativity, and teamwork to address serious diseases, Vertex will continue to pioneer advances in science and medicine in the service of patients who are waiting for them.

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