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Neuroendocrinology and Pituitary

SUN-045 - Pharmacodynamic Serum Biomarker for JUV-161 - an Insulin-Like Growth Factor 2 Fusion Protein Therapeutic Treatment

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Vengadeshprabhu Karuppagounder, Ph.D: No financial relationships to disclose
The signaling pathway of insulin-like growth factors (IGFs) has been studied extensively due to its crucial role in development, growth, and repair. However, most of the studies were performed under the context of in vitro cell cultures and pathological diseases in vivo, owing to the short half-life of IGFs and phosphorylation events in vivo. We assessed the effects following administration of an engineered version of a long-lasting IGF2, JUV-161, and determined that an unique serum biomarker is up-regulated in response to IGF signaling.

Following the administration of JUV-161 and vehicle in mouse animal studies, serum was collected at multiple timepoints and analyzed for both JUV-161 and the novel biomarker. The serum concentration of the biomarker was measured by MSD and compared to the vehicle mice. With a n = 10, there was a statistically significant 4.5x fold increase in the biomarker following administration of JUV-161 compared to vehicle mice, with a P-value < 0.05. JUV-161 pharmacokinetic profile was generated using the available timepoints and compared to the measured concentration of the biomarker. Upon integration of the pharmacokinetic data of JUV-161 to the dynamic response of biomarker, it is revealed that the concentration of the biomarker strongly correlates to the concentration of JUV-161 in serum.

Given the difference in IGF signaling between murine animal models and primates, similar experiments were performed in non-human primates and with healthy human volunteers. Following subcutaneous administration of JUV-161 in cynomolgus macaque (n = 10/group), serum biomarker was measured by an ELISA specific to the human and primate version of the biomarker. There was a ~4x fold increase in the biomarker compared to the baseline and showed the same correlation to JUV-161. Following repeated weekly subcutaneous administration of JUV-161 in healthy normal human volunteers (n = 6/group), there was a ~5x fold increase in the biomarker compared to the baseline. A strong Pearson correlation between the measured JUV-161 and the biomarker, with an r-value of 0.86 and p-value of < 0.0001 was observed.

The direct signaling of IGF2 in vivo can be difficult to measure directly due to the short half-life of cascading phosphorylation events. The increase in the biomarker serves as a downstream readout of IGF2 activation given its role in the IGF2 complex formation, as well as directing IGF2 towards the ECM for receptor activation. The biomarker is also distinct from other serum-based biomarkers in that it is more readily expressed in muscle tissues as compared to the liver. The strong correlation between the pharmacodynamic response of the biomarker to the pharmacokinetics of JUV-161 make it a promising candidate for measuring IGF2 signal in vivo.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*