In partnership with GentiBio, BMS aims to harness the capabilities of engineered Treg therapies to re-establish immune tolerance and repair tissue in patients living with IBD.
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Within the next eight years, more than 3.5 million people in the United States are expected to be diagnosed with inflammatory bowel disease. With those rising numbers in mind, Bristol Myers Squibb is doubling down on treating the condition with a nearly $2 billion partnership with GentiBio to develop Treg therapies for patients with IBD.
Inflammatory bowel disease is an umbrella term for two difficult-to-treat diseases: Crohn’s disease and ulcerative colitis. Both Crohn’s and UC are characterized by chronic inflammation of the gastrointestinal (GI) tract. That inflammation ultimately damages the patient’s GI tract, which spans from the mouth to the anus.
The exact cause of inflammatory bowel disease is not entirely understood. However, it is believed to involve an interaction between the immune system, genes and environmental factors.
Pharma giant Bristol Myers Squibb, which won regulatory approval for ulcerative colitis drug Zeposia, is turning to cell therapy for potential long-lasting treatment of these diseases. In partnership with Boston-based GentiBio, BMS aims to harness the capabilities of engineered Treg therapies to re-establish immune tolerance and repair tissue in patients living with IBD.
A Potential Functional Cure
Regulatory T cells, otherwise known as Tregs, are a specialized type of T cell that can modulate both the innate and adaptive immune systems and suppress immune responses that can lead to inflammation that plays a significant role in IBD. BMS and GentiBio hope the use of Tregs will provide lasting support to patients, particularly those that have not achieved improvement from available small molecules and biologics.
Many of the current therapies aimed at types of IBD, including AbbVie’s Humira, the world’s top-selling drug, can have adverse effects outside the GI tract. They can also suppress the body’s ability to effectively respond to infections and diseases, such as COVID-19. GentiBio’s approach aims to mitigate those concerns about immune suppression. Tregs are designed to suppress multiple inflammation mechanisms and promote homeostasis within the tissue to stimulate the body’s self-repair capabilities.
GentiBio launched last year with a technology platform aimed at combining Tregs biology and antigen receptor engineering in order to develop engineered Tregs designed to provide a functional cure for autoimmune and autoinflammatory diseases. Adel Nada, co-founder and CEO of GentiBio, told BioSpace that the Tregs developed by his company can suppress inflammation in the targeted area while also repairing tissues damaged by excessive inflammation.
For IBDs, this includes repair to the mucosal lining of the intestines. By repairing that lining, Nada explained that the healing property of the Tregs will prevent the incursion of the microbiome of the intestine into the gut, which can be detrimental to patients.
“By repairing the gut/ microbiome interface… we believe we have the potential to reverse the pathology of IBD and reestablish tolerance within the body,” Nada said. “Unlike existing therapies, Tregs have the unique potential to re-establish immune tolerance in autoimmune and inflammatory diseases such as IBD.”
Nada said Tregs, which have been in development by other companies for autoimmune and inflammatory diseases, have been aimed at IBD before. However, he noted that many of those first-generation Treg-based therapeutics did not achieve the desired levels of safety and efficacy that developers had hoped for.
“It’s a challenging disease to begin with,” he said, noting the lack of success with those early Treg approaches.
As IBDs become more commonplace, Nada said they will have more opportunities to determine the best approach to treating the diseases with this modality. As the treatments improve, Nada said the manufacturing process will improve, which should help maintain cost efficiency.
A Validation of the Treg Space
Under the terms of the multi-year collaboration, GentiBio will apply its modular engineered Treg platform and scalable manufacturing process to produce stable and disease-specific engineered Tregs against multiple targets. What those targets are have not been disclosed. BMS will be eligible to develop and advance up to three of the programs from the collaboration into clinical trials.
Robert Plenge, senior vice president and head of translational medicine at BMS and head of the company’s immunology, cardiovascular and fibrosis thematic research center, touted the potential of Tregs for IBD. In other disease-based spaces, Plenge said Tregs have “demonstrated the potential to suppress inflammation and autoimmune dysfunction in a tissue-restricted manner,” which had led to the avoidance of harmful immune suppression. Plenge added that the companies will look to the promise of Tregs and explore their potential in IBD.
Nada said he not only views the collaboration with BMS as an important validation of GentiBIo’s Treg platform and approach, but he believes it will also be a validation of the Treg space “writ large.”
The partnership’s financial terms include an undisclosed cash payment made to GentiBio. As the program unfolds, GentiBio stands to make up to $1.9 billion in development and commercial milestone payments, as well as royalties on any approved therapeutics.
