Nubile Biotech
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Hypertension, Uncontrolled or Resistant Hypertension

Uncontrolled or resistant hypertension is the focus of aldosterone synthase (CYP11B2) inhibitors such as baxdrostat (AstraZenica), lorundrostat (Mineralys Therapeutics), and vicadrostat (Boehringer Ingelheim). In clinical studies, baxdrostat and lorundostat have reduced placebo-controlled systolic blood pressure by approximately 10 mmHg, leaving substantial room for additional improvement.

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Interleukin-16 (IL-16) is a pro-inflammatory cytokine that plays a significant role in promoting hypertension by driving immune cell activation, exacerbating inflammation, and contributing to vascular damage. IL-16 levels correlate with increased blood pressure and target organ injury. IL-16 is elevated in hypertensive individuals, and blocking it reduces blood pressure and pathology, suggesting IL-16/CD4 axis targeting as a potential therapy for hypertension and related complications. 

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NBL101 rapidly reduces elevated IL-16 blood levels to normal ranges within days in a dose-dependent manner, thus enabling personalized oral treatment of an additional key driver of hypertension, including Uncontrolled or Resistant Hypertension, and common comorbidities of hypertensive patients.​ 

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Aldosterone promotes inflammation by increasing IL-16 expression in vascular cells and both contribute to hypertension. IL-16 exacerbates vascular damage, with Angiotensin II also boosting IL-16 and aldosterone. IL-16 is primarily produced by T-cells, and research shows a strong link between T-cells, IL-16, and an immune-mediated component in hypertension, which exacerbates blood pressure increases and organ damage.

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Common comorbidities of refractory hypertension include, sarcopenia, diabetes, and major depressive disorder (MDD) and are associated with increased IL-16. ​

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Competitive Advantage

NBL101 normalized IL-16 levels and blood pressure in a hypertensive person within days concomitant with reduction of multiple additional drivers of cardiovascular risk. In contrast to anti-IL-16 antibodies, NBL101 dosing can be personalized based on a patient's blood levels of IL-16 and initial response to oral treatment. Personalized dosing is expected to increase efficacy and safety, accelerate clinical development timelines, and also improve concomitant conditions associated with elevated IL-16. ​​​​

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Rong WW, Yang YH, Deng QW, Chen XH, Xu ZQ, Li MY, Zhao JJ, Zhai WH, Shang ZW, Gao PJ, Li XD, Wang JG. Targeting IL-16 to Protect Angiotensin II-induced Hypertension and Renal Injury. Hypertension. 2025 Nov;82(11):1975-1986. 

Fan W, Zhao Z, Wang L, Chu Q. Role of IL-16 in age-related skeletal muscle atrophy: an integrated study. BMC Musculoskelet Disord. 2025 Apr 17;26(1):379.

Niewold TB, Lehman JS, Gunnarsson I, Meves A, Oke V. Role of interleukin-16 in human diseases: a novel potential therapeutic target. Front Immunol. 2025 Jun 2;16:1524026.

Tamaki S, Mano T, Sakata Y, Ohtani T, et al. Interleukin-16 promotes cardiac fibrosis and myocardial stiffening in heart failure with preserved ejection fraction. PLoS One. 2013 Jul 19;8(7):e68893.

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Contact: al@nubilebiotech.com

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