Pulmonary fibrosis is a chronic, life-threatening disease that occurs when lung tissue becomes damaged and scarred, impairing lung function and resulting in daily symptoms such as chronic cough, extreme breathlessness and severe fatigue often experienced after exercise, household activities or social activities. Currently approved therapies can slow the decline in lung function, but unmet needs remain. Hear Bruce Ellsworth, PhD, scientific executive director, Medicinal Chemistry, and Aryeh Fischer, MD, Lung Fibrosis clinical development lead, discuss how Bristol Myers Squibb is leveraging its deep expertise in drug discovery and disease biology to research potential treatments for pulmonary fibrosis.
Urgent unmet needs in pulmonary fibrosis
Q: As a physician who has treated patients with pulmonary fibrosis, can you explain how the disease impacts a person’s quality of life?
Aryeh: Pulmonary fibrosis is often a devastating illness. Living with the disease may include daily symptoms such as coughing, labored breathing and fatigue. Many people are physically impaired and have difficulty performing simple activities due to breathlessness.
Many patients or their loved ones have never heard of the disease. As they learn more about the condition, the shock and weight of the diagnosis can be life-altering, not unlike that seen in patients diagnosed with cancer. The realization that their lives will be forever changed as they care for their health, with potentially only a few years left to live, often leads to fear, depression, isolation and hopelessness.
Q: Why is there such a pressing unmet need for new pulmonary fibrosis treatments?
Aryeh: While the introduction of approved therapies for idiopathic pulmonary fibrosis (IPF) in 2014 was a breakthrough, unmet needs remain. Patients often still experience daily symptoms, and their condition may continue to worsen. There remains an unmet need for more tolerable medicines that can stop the progression of pulmonary fibrosis.
Innovating the next generation of pulmonary fibrosis treatments starts with drug discovery
Q: How does Bristol Myers Squibb approach the drug discovery process to address critical unmet needs in diseases like pulmonary fibrosis?
Bruce: Large cross-functional groups of our scientists work in lockstep to solve complex biological problems. The discovery process starts when our team identifies a pressing unmet medical need. My team of chemists build hypotheses for the most promising compounds and they synthesize these molecules. Then, together with biologists, drug metabolism and pharmacokinetics (DMPK) scientists and other researchers, we pinpoint the most promising molecules that may change and improve how the disease in question is treated. Our colleagues in development and commercialization then carry forward our findings to evaluate the most promising molecule in clinical trials, with the ultimate goal of gaining approval for medicines that address unmet patient needs.
In the case of pulmonary fibrosis, previous research told us that blocking lysophosphatidic acid receptor 1 (LPA1) receptors may have the potential to benefit patients with lung injury and fibrosis.
Learn more about Bristol Myers Squibb's commitment to developing new treatments for immune-mediated diseases with our research on the LPA1 receptor and its role in idiopathic pulmonary fibrosis and progressive pulmonary fibrosis.
Q: For pulmonary fibrosis, the team has advanced “back-up” molecules because a prior molecule was halted. What did you learn and how do back-up molecules fit into the drug discovery process at Bristol Myers Squibb?
Bruce: In drug development, there are always many hurdles. When there is great patient need, developing back-up molecules increases the chances of success. For example, you need the medicine to be effective, but you also need to make sure it’s safe to use, so if there is a safety issue with the lead molecule, scientists may take learnings from that original molecule and move a back-up molecule forward in clinical trials.
In pulmonary fibrosis, there is a great need for treatments that not only work, but that patients can tolerate. For these reasons, we’re building on prior learnings and working with back-up molecules to address that need. We want to make sure no stone goes unturned in developing potential new treatments for this community.
New advances, new hope
Q: What is unique about how Bristol Myers Squibb is approaching new treatments for pulmonary fibrosis?
Aryeh: We have a great appreciation for the heterogeneity in pulmonary fibrosis. We are studying not only IPF, but also progressive pulmonary fibrosis (PPF) — a group of diseases with similar features but diverse geneses, including rheumatoid-related lung fibrosis, scleroderma-related lung fibrosis and environmental lung fibrosis. The study of these diseases is critical because it addresses the broader spectrum of lung fibrosis and patients with these autoimmune and environmental types of lung fibrosis are often considerably younger and from a more diverse population than IPF patients.
Q: Why is LPA1 antagonism such a promising target for the treatment of pulmonary fibrosis?
Bruce: Fibrosis is a part of the natural wound-healing process gone awry. Our goal is to reset that balance. Lung injury stimulates LPA production and causes scarring (fibrosis), so we're trying to stop LPA over-activation.
Aryeh: There may be the potential to use LPA1 antagonists in combination with established pulmonary fibrosis therapies, and it is also possible they could be taken alongside immunosuppressive medications for other conditions. This is what we’re researching: a therapy with the potential to meet the diverse unmet needs of pulmonary fibrosis patients. That’s our ultimate goal, and that’s what drives us.
At Bristol Myers Squibb, we are pursuing pathbreaking science in Immunology to deliver transformational solutions that address unmet needs for patients. Fueled by our passion to support more people living with immune-mediated diseases, scientists like Bruce and Aryeh are driven to deliver the right treatments, at the right time, to the right patients — helping to relieve the burdens of conditions like pulmonary fibrosis.
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