function isPangram(str) {
  if (str.length < 26) return false
  let known = 0  
  for (let i = 0; i < str.length; i++) {
    const char = str.charCodeAt(i)
    const delta = char >= 97 && char < 123 ? 97 : 65
    const n = char - delta    
    if (n >= 0 && n < 26) {
      const shift = 1 << n;
      known |= shift      
      if (known === 67108863) {
        return true
      } 
    }
  }
  return false
}

Orig: len=6, count=1000000: 5.318ms
Alt: len=6, count=1000000: 4.567ms
Orig: len=44, count=1000000: 330.504ms
Alt: len=44, count=1000000: 162.405ms
Orig: len=26, count=1000000: 279.974ms
Alt: len=26, count=1000000: 89.065ms
Orig: len=20000, count=1000: 146.068ms
Alt: len=20000, count=1000: 143.111ms
Orig: len=94778, count=1000: 2.673ms
Alt: len=94778, count=1000: 1.468ms
Orig: len=9475857, count=10: 0.097ms
Alt: len=9475857, count=10: 0.051ms