HMI-203 also led to significant changes in skeletal deformities compared with vehicle. We expect to initiate a Phase 1/2 dose-escalation clinical trial with HMI-103 in 2021. 8226; Control manufacturing through our in-house capabilities. In vivo gene editing proof-of-concept at the murine F8 locus. These findings were published in Human Gene Therapy Clinical Development in March 2018. PKU results from mutations in PAH that render its enzymatic activity deficient. Worldwide sales of Kuvan were $458 million in 2020. These data were presented at WORLDSymposium™ in February 2021. We may terminate the agreement for convenience. These so-called Phase 4 studies may also be made a condition to approval of the BLA. PDUFA also imposes an annual program fee for marketed products. Additionally, a product may be eligible for accelerated approval. The FDA does not regulate the behavior of physicians in their choice of treatments. Other national and European Union-wide regulatory requirements may also apply. As of December 31, 2020, we had an accumulated deficit of approximately $328.4 million. We were established and began operations in 2015. We may not be successful in such a transition. Moreover, none of those trials has involved our nuclease-free gene editing technology. The same principles are valid for the EU as well. Further, the CPRA was also recently voted into law by California residents. As a result, increasingly high barriers are being erected to the entry of new products. We also do not have long-term supply agreements with any of our component suppliers. It is not clear what, if any, impact the AIA will have on the operation of our business. We currently in-license certain intellectual property from COH and Caltech. The COVID-19 pandemic continues to rapidly evolve. Item 1B. Unresolved Staff Comments.
