At Blueprint Medicines, we’re driven by our goal to address important medical problems for people with serious diseases, exploring previously untapped approaches to pioneer treatment advances and improve patient outcomes. Leveraging our proven track record in systemic mastocytosis (SM), we have a unique foundation to scale our impact and bring our innovation to more people affected by mast cell disorders. To achieve our lofty goals, we must first leverage our deep expertise in mast cell biology, a crucial yet underappreciated area of research with the potential to fundamentally shift the treatment of many allergic and inflammatory diseases.
Understanding the biology of mast cell disorders
Mast cells are found throughout the body, residing in border tissues such as the skin, respiratory system and gastrointestinal tract.1-3 These cells can become activated by external stimuli such as allergens or bacteria, triggering the process of degranulation and the release of mediators.1,3,4 The heterogeneity of symptoms may make certain diseases, including SM, difficult to diagnose.5 For example, one person’s reaction to an allergen or trigger might cause brain fog, diarrhea and flushing, whereas another person’s response could include fatigue, bone pain and shortness of breath.6
KIT, a tyrosine kinase receptor, is a key regulator of mast cell proliferation, maturation and survival and is universally expressed across tissue types.7 Targeting the KIT receptor offers an approach to potentially improve outcomes in diseases driven by mast cell activation and the release of mediators, which ultimately trigger type 2 inflammation.7
The mediators released during degranulation – such as cytokines, proteases, histamines or prostaglandins – can activate other cells that perpetuate inflammatory responses. These responses can lead to long-term effects, such as tissue remodeling, which contribute to chronic disease.1,3 While targeting specific mediators has shown clinical benefit, we believe that targeting KIT, a primary regulator of the mast cell, has the potential to block the overproduction of abnormal and hyperactive mast cells that contribute to symptoms.7
Innovating with patient impact in mind
Building on our SM expertise, we aim to overcome treatment challenges in additional diseases where mast cells play a core role. We believe our investigational oral, small-molecule wild-type KIT inhibitor offers broad therapeutic potential, with sub-nanomolar potency and high selectivity across the kinome. Additionally, we aim to enable flexible dosing regimens to achieve disease-specific outcomes, and we continue to evaluate its profile for optimization of benefit-risk across a range of diseases.
As we progress the development of this investigational therapy, we plan to initiate multiple proof-of-concept studies this year, moving rapidly into currently de-risked areas and exploring other biology across organ systems to unlock broader potential. We’re continuously utilizing our learnings and successes in SM to advance our mast cell franchise and potentially transform future treatment paradigms, focusing on the important role of the mast cell and our commitment to making the greatest patient impact possible.
References
1. Rossignol, J. F1000 Research. 2019;8:F1000 Faculty Rev-1961.
2. Hartmann, K. J Allergy Clin Immunol. 2016;137(1):35-45.
3. Gülen, T. J Intern Med. 2016;279(3):211-228.
4. Theoharides, T. et al. N Engl J Med. 2015;373(2):163-172
5. Ungerstedt, J. Cancers. 2022;14(16):3942
6. Jennings, S. Immunol Allergy Clin N Am. 2018;38(3):505-525.
7. Pardanani, A. Am J Hematol. 2023;98(7):1097-1116.
More posts and webinars