Table 2.
MYO‐029 PD parameters estimates for mouse and monkey
| Species | Parameter | Units | Estimate | CV% | |
|---|---|---|---|---|---|
| Mouse | EDL | Emax | % | 29.9 | 5 |
| E0 | Gram | 16.7 | 1 | ||
| AUC50 | ug*h/mL | 1,152.6 | 21 | ||
| Cave50 a | nM | 47.2 | NA | ||
| Gastro | Emax | % | 23.2 | 13 | |
| E0 | Gram | 0.24 | 2 | ||
| AUC50 | ug*h/mL | 1,560.5 | 50 | ||
| Cave50 a | nM | 63.9 | NA | ||
| Quad | Emax | % | 27.2 | 15 | |
| E0 | Gram | 0.34 | 3 | ||
| AUC50 | ug*h/mL | 1,762.6 | 54 | ||
| Cave50 a | nM | 72.2 | NA | ||
| Monkey | Female quad‐L (135d) | Emax | % | 274.1 | 57 |
| E0 | % | 4.1 | 40 | ||
| AUC50 | ug*h/mL | 32,092 | 98 | ||
| Cave50 a | nM | 1,313.8 | NA | ||
| Female quad‐L (271d) | Emax | % | 200.5 | 2 | |
| E0 | % | 6.1 | 1 | ||
| AUC50 | ug*h/mL | 32428 | 4 | ||
| Cave50 a | nM | 1,327.5 | NA |
CV, coefficient of variation; EDL, extensor digitorum longus; Gastro, gastrocnemius; NA, not applicable; PD, pharmacodynamic; Quad, quadriceps.
a
Cave50(nM) = AUC50/1,000/168/145.4; MYO‐029 MW: 145.4 kDa.
Direct effect Emax model was used to describe effect of steady‐state exposures (AUC0–168h) on % increase in muscle mass over baseline in mouse, and rate of growth in muscle circumference in monkeys. Parameters are defined as: maximum % change over vehicle (Emax), vehicle baseline (E0), steady‐state area under the curve to achieve 50% effect (AUC50), steady‐state average concentration to achieve 50% effect (Cave50).