DCN1 modulator-1

NOD.Cg-Kit^W-41 Tyr⁺ Prkdc^scid Il2rg^tm1Wjl/ThomJ (NBSGW) (human hematopoietic stem cell-reconstituted, randomized 12 weeks post-engraftment with 1-10% human cells in peripheral blood)^[1]

25 mg/kg (daily x20 days; twice daily x3 weeks); 100 mg/kg (twice daily x3 weeks)

p.o.; daily; 20 days; p.o.; twice daily; three weeks

Increased HbF protein levels 3.2-fold relative to vehicle at 25 mg/kg twice daily for three weeks.
Increased HbF protein levels 3.7-fold relative to vehicle at 100 mg/kg twice daily for three weeks.
Increased HBG1 mRNA levels in bone marrow human erythroid progenitor cells at 25 mg/kg and 100 mg/kg twice daily for three weeks.
Increased HbF% over vehicle by an average of 1.11 at 25 mg/kg daily for 20 days.
Increased HBG1 normalized to GlyA+ over vehicle at 25 mg/kg daily for 20 days.
Increased the ratio of HBG1/(HBG1+HBB) at 25 mg/kg daily for 20 days.
Exhibited statistically significant synergistic effects on HbF% with synergistic estimates of 0.86 and 1.00 when combined with hydroxyurea 75 mg/kg and 100 mg/kg, respectively.
Exhibited statistically significant synergistic effects on HBG1 normalized to GlyA+ with synergistic estimates of 619 and 751 when combined with hydroxyurea 75 mg/kg and 100 mg/kg, respectively.
Exhibited statistically significant synergistic effects on HBG1/(HBG1+HBB) with synergistic estimates of 0.054 and 0.057 when combined with hydroxyurea 75 mg/kg and 100 mg/kg, respectively.
Exhibited statistically significant synergistic effects on HBG1 with synergistic estimates of 2113 and 3268 when combined with hydroxyurea 75 mg/kg and 100 mg/kg, respectively.
Exhibited statistically significant synergistic effects on AlphaLISA counts with synergistic estimates of 35087 and 60983 when combined with hydroxyurea 75 mg/kg and 100 mg/kg, respectively.