The Future of Medicine in Massachusetts The Future of Medicine in Massachusetts

The future of medicine is being built in Boston’s backyard

What do you get when you cross the resources of a 150-year-old pharma company with the agility and innovation of a biotech startup?

Kendall Square

Mechanisms of Cancer Resistance

Discovery Biology, Translational Science, and Chemistry Research

Alewife

Devens

Cell Therapy and Biologics

Bristol Myers Squibb has been a pioneer in the Boston-area life science ecosystem for more than a decade — but progress means never being satisfied with the status quo. The company is continuing to expand its world-class science, technology, and manufacturing footprint in Cambridge and Devens, Mass., to give its scientists the best possible tools to discover and advance new treatments in cancer, immunology, cardiovascular, fibrotic diseases, and more. Read on to explore the future of medicine being created in and around Boston.

kendall square

cambridge, ma

“As we try to understand responses in different patients, both within a certain tumor type or across tumors, we're looking for commonalities,” says Emma Lees, Ph.D., senior vice president and head of the MoCR TRC. “As we build those different data sets, we suddenly now have incredibly useful information.” For years, chemotherapy was the first line of treatment against cancer. The newer approach to immunotherapy involves finding ways to activate or suppress different parts of the body’s immune system to attack tumor cells. These include checkpoint inhibitors — drugs that block the action of proteins, which normally help keep the body’s immune system in check but can hamper the cancer-fighting work of the body’s T cells. Bristol Myers Squibb pioneered the first approved immune checkpoint inhibitor, which ushered in a historic era of harnessing the immune system to treat cancer and ignited exploration into the tumor microenvironment. While checkpoint inhibitors have changed survival expectations for some patients, other patients don’t respond to them or relapse after a period of time. Bristol Myers Squibb scientists are at the forefront of research that’s trying to understand the molecular mechanisms of immunotherapy resistance. For example, they’re studying the tumor stroma (connective tissue) and suppressive stromal factors, which implicate the role of the tumor microenvironment in resistance. They’re also designing therapies to target tumor-intrinsic pathways whereby cancer cells can signal suppression of immune system proteins. The MoCR TRC has built a cross-disciplinary group where lab research and its applications for patients are efficiently intertwined. “We have discovery scientists, chemists, toxicologists, and translational medicine experts all working together on the problem and coming at it in very different ways,” Lees says. “As we use the data from our patient populations, we can take that immediately back and apply it to what we do next in discovery.”

Emma Lees Ph. D., SVP and head of the Mechanisms of Cancer Resistance Thematic Research Center in Kendall Square

We've realized the value of cross-disciplinary research and how orthogonal thinking about different data sets really comes together to enrich the solutions for the future.

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Why do some cancer treatments work at first but then become ineffective — and why do they work for some patients but not others? These questions drive the mission of the Bristol Myers Squibb Mechanisms of Cancer Resistance (MoCR) Thematic Research Center (TRC) and Translational Medicine groups in Kendall Square.

Robert Plenge, M.D., Ph.D., SVP and head of the Immunology, CV, and Fibrosis Thematic Research Center; head of Translational Medicine

It’s hard for me to imagine a better place to be than here given all the resources we have, the people we have, and the dedication and commitment to improving the lives of patients.

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The cornerstone of research at the Alewife site is studying the mechanisms behind immune-mediated diseases, including psoriasis and rheumatoid arthritis, lupus, inflammatory bowel disease, multiple sclerosis, ankylosing spondylitis, and more. Right now, researchers are studying naturally occurring inherited genetic variation in genes that cause these diseases in order to guide the development of new medicines that may one day lead to a cure. “Human genetics is a powerful starting point in a drug discovery journey,” says Robert Plenge, M.D., Ph.D., senior vice president and head of the ICF TRC and Translational Medicine. “By leveraging experiments of nature, we hope to increase the probability of success that a new idea will be turned into a medicine that can help patients with autoimmune diseases.” Because human genetics can identify new targets that are difficult to therapeutically perturb, discovery biology scientists at Alewife work closely with creative teams in small-molecule drug discovery and biotherapeutics to invent new medicines. “A clever idea cannot help patients unless our chemists and protein scientists can figure out a way to invent a molecule that can be given safely to patients,” says Plenge. These new medicines are rigorously evaluated by Alewife experts in drug metabolism and pharmacokinetics, pre-clinical toxicology, in vivo pharmacology, and pharmaceutical sciences. As a new medicine advances, translational scientists and clinical pharmacologists begin to design the best way to test safety and efficacy in a human clinical trial. “Inventing potential new medicines is a team sport at Alewife,” Plenge says.

The wide-ranging work being done at Bristol Myers Squibb’s Immunology, Cardiovascular, and Fibrosis (ICF) Thematic Research Center (TRC) has applications for improving the lives of patients with conditions ranging from lupus to heart disease. The small-molecule drug discovery, biotherapeutics, and cell therapy groups there are considered the “molecular invention engine” of Bristol Myers Squibb’s Alewife location. Based in Cambridge, these dynamic teams operate under the same roof as scientists conducting advanced work in discovery biology, in vitro and in vivo pharmacology, pre-clinical toxicology, informatics and predictive sciences, clinical pharmacology, and translational medicine, which helps scientists understand patient segments, including companion diagnostics and biomarkers for clinical trials.

cambridge, ma

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Charles G. Prescott, PMP, project manager at the cell therapy manufacturing facility in Devens

This is beyond state of the art with the level of automation, computerization, and networking all these devices together.

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In cell therapy, a patient’s cells are collected, and white blood cells (including T cells) are separated out and sent to a manufacturing facility like the one in Devens. There, the gene for a chimeric antigen receptor (CAR), which binds to a protein on the patient’s cancer cells, is added to the T cells. Then the cells, which have been reprogrammed and cultured or expanded to recognize and fight the patient’s cancer, are sent back to their treatment center and given via a one-time infusion. Autologous CAR T-cell therapies differ from small-molecule or biologic therapies because the medicines are manufactured for each individual patient using their own T cells as a starting material. The goal of the Devens expansion is to scale this process so that these individualized treatments can be manufactured in parallel for a larger number of patients. “This is beyond state of the art with the level of automation, computerization, and networking all these devices together with software that’s integrated across procurement, research, and development — you name it,” says project manager Charles G. Prescott, PMP, who’s currently overseeing building construction and installation of the vast array of specialized equipment at the cell manufacturing facility. “The goal is to have it all work seamlessly to provide top quality at a speed that’s second to none.”

Devens, ma

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Exterior of a modern-looking brick building with large glass windows, nice landscaping, and a bicycle rack out front.

The expansion is “one of Bristol Myers Squibb’s latest investments as we expand our global manufacturing footprint,” says Carolyn Kelley, human resources director for U.S. biologics. “We’ll be hiring several hundred employees over the next several years to enable a quick ramp-up.” Bristol Myers Squibb is well positioned to attract top talent in Massachusetts to support this effort. “We really combine the agility of a biotech startup with the reach and resources of an established pharmaceutical company with over 150 years of industry experience,” says Kelley. Plus, the Devens location is close enough to metro Boston to allow easy collaboration with the R&D sites at Alewife and Kendall Square in Cambridge, as well as the area’s top-ranked hospitals and universities.

Experimental research, clinical mechanisms, bioinformatics, and pathology done here are helping to expand understanding of mechanisms of resistance. Research is underway to dive deep into the tumor milieu, including the tumor stroma (connective tissue) and suppressive stromal factors, which implicate the role of the tumor microenvironment in drug resistance.

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This collaboration extends to scientists in other research fields and Bristol Myers Squibb locations around the world. Here in Cambridge, researchers at Kendall Square will join those currently at the Alewife R&D site — which focuses on immunology, cardiovascular, and fibrotic diseases — in a new facility set to open in 2023 at Cambridge Crossing. Those scientists are also working with others outside of Bristol Myers Squibb to take advantage of the Boston area’s uniquely rich academic, medical, and commercial life sciences environment. In addition to mentoring startups and working with established pharmaceutical firms, Bristol Myers Squibb has joined the Massachusetts Institute of Technology (MIT) Industrial Liaison Program, a partnership that gives scientists access to MIT’s world-class tools and resources, and is launching its own postdoctoral program next year. It’s also helping bring new talent into the industry as lead sponsor of the Massachusetts Biotechnology Education Foundation Life Sciences Apprenticeship Program. “There’s nowhere like Boston,” Lees says. “You really could not find a better place to do science, from my perspective.”

Lees describes the exhilarating work being done inside the Mechanisms of Cancer Resistance Thematic Research Center in Kendall Square.

All of this work has one overarching goal: to understand not just how to control inflammatory diseases, but how to treat and reverse their underlying mechanisms. Plenge and his team are working toward designing interventions that can treat molecular defects so future patients may be able to modify the course of their disease, rather than just treating the symptoms. Bristol Myers Squibb’s long-term strategy is to leverage the concept of sequential immunotherapy, which they believe may ultimately lead to cures for patients suffering from chronic immune-mediated diseases. The Bristol Myers Squibb team believes that there are three key steps to sequential immunotherapy. First, doctors will prescribe medicines that control inflammation to get the immune system under control. Next, medicines will be administered that reset the immune system, like you might reboot your computer. Finally, medicines will be given to promote either tissue repair or immune homeostasis. “We have a very creative, scientifically engaging, and curious culture,” Plenge says. “What I really enjoy about being at Bristol Myers Squibb is working with a group of very smart, like-minded individuals, working collaboratively towards our unifying goal of helping make patients’ lives better.”

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In Alewife, Plenge and his team are working to gain insight into the underlying causes of a host of immune-mediated, cardiovascular, and fibrotic conditions.

Prescott and Shaw-Reid give a behind-the-scenes look at what’s to come in the new cell therapy manufacturing facility.

To fill its ranks, Devens is drawing on graduates of the world-class scientific, medical, and engineering programs at Harvard, MIT, and Northeastern to the east; Worcester Polytechnic Institute (WPI) to the west; and several University of Massachusetts campuses — “all of these great places where great minds go and greater minds come out,” says Prescott, who himself is a WPI graduate and sixth-generation engineer. Bristol Myers Squibb doesn’t wait until promising candidates are out of school to nurture the next generation of talented scientists. High school, college students, and early career professionals can complete internships and apprenticeships through a variety of programs. “We’re very excited to support the MassBioEd Life Sciences Apprenticeship Program,” says Cathryn Shaw-Reid, Ph.D., vice president of global drug substance biologics operations. “[The program] will give early career staff members the opportunity to explore what the biopharmaceutical industry can offer to them for their careers.” As for current Bristol Myers Squibb employees, Kelley tends to hear positive feedback about the work and company culture. “One thing you’ll always hear about is the interesting work and doing something that matters, knowing that we’re impacting patients’ lives,” Kelley says. “It’s the belief in the current product portfolio as well as the really exciting future pipeline.”

Kelley shares how Bristol Myers Squibb attracts top scientists — and drives continued career growth.

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In cell therapy, a front-line individualized cancer treatment, the patient’s cells are collected, and white blood cells (including T cells) are separated out and sent to a manufacturing facility like the one at Devens. There, the gene for a chimeric antigen receptor (CAR), which binds to a protein on the patient’s cancer cells, is added to the T cells. Then the cells, which have been reprogrammed to recognize and fight the patient’s specific cancer, are sent back to her treatment center and given via a one-time infusion. Autologous CAR T-cell therapies differ from small-molecule or biologic therapies because the medicines are manufactured for each individual patient using their own T cells as the starting material. The goal of the Devens expansion is to scale up this process so treatments can be manufactured for a large number of patients at one time. To support this effort, BMS will be hiring several hundred new employees in the next few years — a process that’s already well underway. By summer 2021, the company hopes to bring 20-25 scientists, engineers, and other new employees on board every month. “Our human resources people are working overtime to find qualified candidates,” says project manager Charles Prescott, who’s overseeing building construction and installation of the vast array of specialized equipment.

Robert Plenge M.D., Ph.D. Head, Immunology, Cardiovascular and Fibrosis Thematic Research Center

It’s hard for me to imagine a better place to be then here given all the resources we have, the people we have, and the dedication and commitment to improving the lives of patients.

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by alice waugh

Bristol Myers Squibb’s campus in Devens, Mass., has been developing, producing, and testing clinical and commercial medicines for over a decade — and it’s about to expand. A new cell therapy manufacturing facility is under construction on the 89-acre site, a mixed-use industrial park and former Army base about 40 miles from Boston.

Kelley shares how Bristol Myers Squibb attracts top scientists — and drives continued career growth.

In Alewife, Plenge and his team are working to gain insight into the underlying causes of a host of immune-mediated, cardiovascular, and fibrotic conditions.

Woman with dark braided hair and glasses, wearing a green shirt with yellow blazer. She is smiling widely.

Cathryn Shaw-Reid, Ph.D., VP of global drug substance biologics operations

We have designed this facility to be one that can expand to suit the needs of patients....It’s designed for our current technology today, but it’s also a facility that can evolve as technology evolves in the future.

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Scientists are designing targeted therapies to reach tumor-intrinsic pathways whereby cancer cells can signal suppression of immune system proteins.

Teams are tackling the stages of drug discovery through molecular discovery technologies, discovery biologics, and discovery platform chemistry.

Click to learn more about what happens at Kendall Square

Plans for novel therapies in immune-mediated diseases are created and implemented here. The team works collaboratively across departments, including discovery biology, translational medicine, and clinical development, to progress programs through proof-of-concept clinical trials.

To develop new treatments for immune-mediated diseases such as inflammatory bowel disease, psoriasis, and rheumatoid arthritis, research in small-molecule drug discovery and biotherapeutics is being done to understand how to activate or inhibit protein targets that orchestrate a complex immune response.

Informatics and predictive science researchers are mining “big data” from population biobanks, clinical trials, and experimental systems to define causal pathways in human disease. These insights are used to inform all aspects of research and early development, from validating new drug targets to translational endpoints in clinical trials.

Click to learn more about what happens at Alewife

Click to learn more about what happens at Devens

Current campus supports process development, clinical manufacturing, and commercial manufacturing for biologics and immuno-oncology medicines.

Here, cells are grown, cultured, and harvested. Medicines are also produced through recombinant DNA technology, which allows scientists to manufacture a wide variety of proteins within cells.

Expansion is underway to include a new cell therapy manufacturing facility, where T cells from individual patients will be modified to include a gene for a chimeric antigen receptor (CAR), which is designed to bind to a protein on the patient’s cancer cells and fight the disease.

This is beyond state of the art with the level of automation, computerization, and networking all these devices together.

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Charles Prescott Project Manager - Cell Therapy Facility

To fill its ranks, Devens is drawing on graduates of the world-class scientific, medical, and engineering programs at Harvard, MIT, and Northeastern to the east, Worcester Polytechnic Institute to the west, and several UMass campuses — “all of these great places where great minds go and greater minds come out,” says Prescott, who himself is a WPI graduate and sixth-generation engineer. Bristol Myers Squibb doesn’t wait until promising candidates are out of school to nurture the next-generation of talented scientists. High school, college students, and early career professionals can complete internships and apprenticeships through a variety of programs.