OR21-03 Dose Responsiveness Of LUM-201 As Measured By Acute GH Response And IGF-1 And Annualized Height Velocity (AHV) Measured At 6 Months In The Interim Analysis Of The OraGrowtH212 Study In Idiopathic Pediatric Growth Hormone Deficiency (iPGHD)

Disclosure: F. Cassorla: Research Investigator; Self; Lumos Pharma, Inc. Speaker; Self; Lumos Pharma, Inc. R. Román: Research Investigator; Self; Lumos Pharma, Inc. M.L. Johnson: Consulting Fee; Self; Lumos Pharma, Inc. A. Avila: Research Investigator; Self; Lumos Pharma, Inc. G. Iñiguez: Research Investigator; Self; Lumos Pharma, Inc. I. Baier: Research Investigator; Self; Lumos Pharma, Inc. D. Said: Research Investigator; Self; Lumos Pharma, Inc. A. Bruchey: Employee; Self; Lumos Pharma, Inc. Stock Owner; Self; Lumos Pharma, Inc. C. Smith: Employee; Self; Lumos Pharma, Inc. Stock Owner; Self; Lumos Pharma, Inc. E.L. Brincks: Employee; Self; Lumos Pharma, Inc. Stock Owner; Self; Lumos Pharma, Inc. J.C. McKew: None. D.B. Karpf: Employee; Self; Lumos Pharma, Inc. Stock Owner; Self; Lumos Pharma, Inc. M.O. Thorner: Consulting Fee; Self; Lumos Pharma, Inc. Stock Owner; Self; Lumos Pharma, Inc. Objective: To evaluate acute GH, IGF-1, AHV at 6 mos of treatment of iPGHD subjects. Background: LUM-201 is an investigational oral GH secretagogue (GHS) currently in 3 Phase 2 iPGHD trials. The LUM-201 predictive enrichment marker (PEM) may be used to identify patients previously diagnosed with iPGHD who are likely to respond to LUM-201. PEM positivity is defined as a baseline IGF-1 level >30 ng/mL and a peak GH of ≥5 ng/mL in response to a single 0.8 mg/kg LUM-201 dose. LUM-201, a potent, durable oral GHS agonist, acts on the GHS Receptor 1a in the hypothalamus and anterior pituitary. LUM-201 enhances the amplitude of endogenous GH pulsatile release over 24 hrs, while also acting as a functional antagonist of the somatostatin receptor. The increased IGF-1 and GH reach the growth plates and promote linear growth. Three advantages of LUM-201 as a potential therapeutic for iPGHD are that it is a small oral tablet, it enhances natural GH pulses over 24 hr, and GH release is subject to the endogenous negative feedback mechanisms, so serum IGF-1 is expected to remain within the normal range. Method: Each subject is screened with the PEM test, which includes determining the max GH concentration in the first 90 min after a single 0.8 mg/kg dose of LUM-201. Additionally, each of these PEM positive subjects was assessed for increasing doses of LUM-201 to induce further acute GH secretion on their first day of therapeutic dosing with either a 1.6 or 3.2 mg/kg dose. The first 10 subjects with 6 months of growth on LUM-201 (5 subjects on each dose) were evaluated on their IGF-1 levels and AHVs. Results: The mean (+SD, n) peak GH for the 0.8 mg/kg dose was 26.04 ng/mL (+10.6, 22), at the 1.6 mg/kg dose 35.50 ng/mL (+17.5, 9), and at a 3.2 mg/kg dose 38.34 ng/mL (+10.4, 8). Serum IGF-1 levels of the 5 subjects in each cohort were monitored at baseline and at 6 months of treatment. The mean (+ SD) serum IGF-1 levels showed a change from baseline of 84.6 ng/mL (+30.1) at 6 months for the 1.6 mg/kg cohort and 113.8 (+49.9) at the 3.2 mg/kg dose. The pretreatment HV were 4.9 (+ 0.4) at 1.6 mg/kg and 4.3 (+ 0.9) cm/year at 3.2 mg/kg respectively and the respective mean AHVs (+ SD) at 6 months were 7.14 cm/year (+0.65) and 8.60 cm/year (+1.22). The acute GH response demonstrated a dose response between the 0.8 and 1.6 mg/kg doses, but the 1.6 and 3.2 mg/kg doses produced similar GH responses. These two doses of LUM-201 induced comparable changes from baseline values of IGF-1 after 6 months of treatment. In addition to these pharmacodynamic changes, the AHVs generated from each dose also appear similar. Conclusion: LUM-201 generated the expected AHV in this naive iPGHD population. The dose-response for GH secretion after an initial dose of LUM-201 and increases from baseline of serum IGF-1 after 6 months of treatment suggest that 1.6 mg/kg/day is the optimum dose for efficacy and durability. The results from this small study are corroborated by the larger OraGrowtH210 study data. Presentation: Saturday, June 17, 2023