Hypothesis II: f508d heterozygotes will benefit as much, if not more, from 809/770 Combo
Right. The drugs facilitate the rescue dynamics. Generally, misfolded proteins such as CFTR with F508del will be degraded by lysosomal enzymes. Any hypothetical defect in the degradation process can rescue misfolded CFTR. It is possible that VX-809 patches up missing F (phenylalanine) just well enough to enhance the trafficking to the cell membrane. There are many possibilities with varied degrees of rescue, resulting in diverse drug response. So, your Hypothesis 1 can be explained in terms of more mechanistic terms.