SAT-186 Higher Order Time Series Interactions Within The Growth Hormone (GH) Secretion Profile Mark Growth Responsiveness Induced By The Oral Growth Hormone Secretagogue Lum-201

Abstract Disclosure: A. Roslan: None. T. Garner: None. E. Brincks: Lumos Pharma, Inc. J.C. McKew: Lumos Pharma, Inc. P. Pitukcheewanont: Lumos Pharma, Inc. M. Thorner: Lumos Pharma, Inc. F. Cassorla: Lumos Pharma, Inc. P. Clayton: Lumos Pharma, Inc. A. Stevens: Lumos Pharma, Inc.. Background: Both patterns as well as amounts of GH secretion influence stature and growth rate in normal children1. We have shown the investigational oral GH secretagogue, LUM-201 restores normal GH secretion in GH deficient (GHD) children and alters the pattern of variation within growth hormone secretion profiles2. We have now explored the use of higher order interactions (HOI) in the GH secretion profiles induced by LUM-201 defining the relationships between all points within the time series. Objective: To assess HOIs impacted by LUM-201 treatment with a hypergraph model on a matrix of the whole time series with coordination quantified using a random walk (RW) to measure the probability of a relationship between time points in GHD children between baseline and 6m. Methods: Pulsatile GH secretion was assessed at baseline and after 6 months on LUM-201 (1.6 and 3.2mg/kg/day) in 12-hour (08.00-20.00) profiles with 10minute sampling (n=73) in moderate pediatric GHD (n=22). As GH secretion was not different between LUM-201 doses, the 22 subjects were studied together. Responsiveness was defined at 6m by annualised height velocity (AHV), in tertiles: High [8.9], Medium [7.7] and Low [6.7] [mean cm/year]. Hypergraphs were generated from points in the series (in a 73 x 73 matrix) above median GH-secretion. RWs3 derived from the hypergraphs were used to measure the probabilities for each point in the matrix. Fisher’s exact test was used to generate odds ratios (OR) and confidence intervals (CI) in the early and late time points in the series. Results: Comparison of the RWs at baseline and 6m revealed a shift of HOI coordination in response to LUM-201 in the AHV tertiles: early time points [0-240 mins] High response increase 36.5% OR 6.4 [CI 3.2-14.1] p<0.001; Low response increase 45.5% OR 11.7 [CI 5.2-29.5] p<0.001; later time points [490-720mins] High response decrease 43.0% OR 7.7 [CI 3.8-16.5] p<0.001; Low response decrease 29.5% OR 3.6 [CI 1.9-7.0] p<0.001. The magnitude of these changes are different between High and Low responders to LUM-201 (p<0.001) indicating the pattern of time series coordination is a biomarker of response. Conclusions: In response to LUM-201, there are distinct shifts in the pattern of GH secretion which are related to AHV tertiles. This implies that there is signalling information in all parts of the GH time series. 1. Gill et al. (2001), JCEM, p.5860 2. Clayton et al. ESPE (2024), FC15.2 3. Carletti et al 2020.Physical review E, p.022308 Presentation: Saturday, July 12, 2025