ENDO 2021 Conference LUM-201 Elicits Greater GH Response Than Standard GH Secretagogues in Pediatric Growth Hormone Deficiency March 20-23, 2021 Abstract #7102 George M Bright MD; Roy G Smith PhD; Michael O Thorner MB, BS, DSc Lumos Pharma, Inc, Austin, TX USA Objective GHSR1a Methods Table 1 Baseline Characteristics Hypothalamus To compare GH responses to an oral GH secretagogue, LUM-201 LUM-201 (ibutamoren, formerly MK-0677) and standard GH stimulation tests used for SST GHRH • GH responses measured to a single, oral 0.8 GH diagnosis of pediatric growth hormone deficiency (PGHD) Bone HT- Pretreatment mg/kg dose of LUM-201 and to two standard GH Age Stimulatio IGF-1 GHSR1a Age SDS Height Velocity stimulation tests (arginine, clonidine, glucagon, (years) n Tests (ng/mL) Introduction (years) (cm) (cm/year) Pituitary insulin, L-Dopa) (ng/mL) LUM-201 is an orally administered agonist of the growth hormone • 68 subJects (40 M, 28 F) had GH responses secretagogue receptor (GHSR1a). A clinical study is underway measured to a single, oral 0.8 mg/kg dose of (NCT04614337) to determine if LUM-201 is a safe and effective alternative to GH LUM-201 and to two standard GH stimulation Median 9.2 6.0 -3.3 4.0 5.4 51 inJections of recombinant human growth hormone (rhGH) in PGHD. Background tests (arginine, clonidine, glucagon, insulin, L- Dopa) LUM-201 is an agonist of the growth hormone secretagogue receptor SST = somatostatin GHRH = growth hormone releasing hormone • Median (interquartile range) values for patient -4.5, (GHSR1a) in the hypothalamus that diminishes inhibitory signals via GHSR1a = growth hormone secretagogue receptor 1a IQR 7.2, 10.8 4.5, 7.9 3.2, 4.6 1.8, 7.6 24, 111 GH = growth hormone characteristics are shown in Table 1 -2.5 somatostatin and increases stimulatory signals via GHRH to augment IGF-1 IGF-1 = insulin-like growth factor 1 endogenous GH pulsatility (Fig 1). Figure 1 Mechanism of Action of LUM-201, an orally administered GHSR1a agonist The null hypothesis of no difference in GH responses to LUM-201 and standard GH stimulation tests was Summary and Conclusion rejected (p < 0.00001). In prepubertal subjects diagnosed with Pediatric The median (IQR) response to LUM-201 was 15.0 (3.5,49) and to two standard GH stimulation tests was 5.4 (1.8, 7.6). 75.00 Fig 3. The subJect-level data are shown below in Figure 2. 50.00 Dependence of Growth Hormone Deficiency differential GH - GH responses to single, oral doses of 25.00 response on baseline IGF-I LUM-201 are substantially higher than Results 7.50 concentration observed in two standard GH stimulation Fig 2. Comparison of GH Responses to LUM-201 and to two standard GH stimulations test 5.00 tests. (Note both parameters are displayed on logarithmic scales) 2.50 (Note the differential - The difference in GH responses response is increases with higher baseline 0.75 displayed on a The differential GH responses, shown Differential GH Response 0.50 concentrations of IGF-I and higher GH LUM-201 - Standard Standard - LUM-201 (ng/mL) logarithmic in Fig 3 and Fig 4, is defined as the scale) stimulation test results. difference between GH response to a 0 30 60 90 120 150 180 210 240 - A differential response between LUM-201 single oral dose of LUM-201 and the Baseline IGF-I Concentration (ng/mL) GH response to two standard GH and standard GH stimulation tests is more stimulation tests. likely in patients with more moderate Fig 4. forms of PGHD. 75.00 Dependence of In a forward stepwise model of the 50.00 differential response as dependent differential GH variable and including age, height SD 25.00 response on References and weight as potential covariates, standard GH Smith RG, Development of Growth Hormone standard stimulated GH 7.50 stimulation test Secretagogues, Endocrine Reviews, 2005; 26: 346-360 5.00 results (p = 0.036) and baseline IGF-I Bright, GB, Development of a Predictive Enrichment (p < 0.000001) were most strongly 2.50 Marker for the Oral GH Secretagogue LUM-201 in (Note the correlated (model r-square = 0.736). Pediatric Growth Hormone Deficiency, J Endocrine differential Society, 2021, doi/10.1210 Differential GH Response 0.75 0.50 response is LUM-201 LUM-201 - Standard (ng/mL) displayed on a Disclosures 0 2 4 6 8 10 12 logarithmic The authors are consultants to Lumos Pharma, Inc. GH Response to Standard GH Stimulation scale) Dr Thorner has equity in Lumos Pharma, Inc. Tests (ng/mL).