** Cash balance includes cash, cash equivalents and short and long term investmentsAnticipated Upcoming Milestones
|2Q 2013: Initiation of Phase 3 trial for PEG-PAL for PKU|
|2Q 2013: Presentation on Phase 1/2 BMN-673 solid tumor data at ASCO meeting|
|Mid 2013: Initiation of Phase 2 trial for BMN-111 for achondroplasia|
|Mid 2013: Initiation of Phase 1/2 trial for BMN-190 for Batten disease|
|4Q 2013: Initiation of Phase 3 trial for BMN-673|
|4Q 2013: Potential FDA approval of Vimizim for MPS IVA|
|4Q 2013: Initiation of Phase 2/3 switching trial for BMN-701 for Pompe disease|
- Vimizim for MPS IVA: The company submitted the BLA for Vimizim at the end of the first quarter of 2013 and the market authorization application filing in the EU earlier this week. Vimizim has received accelerated review status from the EMA.
- PEG-PAL for PKU: The company plans to initiate a pivotal Phase 3 study in the second quarter of 2013. The Phase 3 design includes (1) an open-label study to evaluate safety and blood Phe levels in naïve patients and (2) a randomized controlled study of the Phase 2 extension study patients and patients from the open label trial to evaluate blood Phe levels and neurocognitive endpoints. The FDA indicated the possibility for an accelerated approval based on demonstrating sustained reduction in Phe levels, though full approval may require demonstration of neurocognitive improvement.
- BMN-701 for Pompe Disease: The company plans to initiate a Phase 2/3 switching trial by the end of 2013 in late-onset Pompe patients who have previously been treated with alglucosidase alfa. Subject to discussions with health authorities, the proposed study design is a single arm trial, with treatment at 20 mg/kg administered every other week for 24 weeks. The company intends to use the respiratory parameter MIP as the primary endpoint. Secondary objectives include MEP and six-minute walk test, as well as safety. The study will be conducted with full scale material from a revised manufacturing process, which has improved process robustness and increased productivity.
- BMN-673 (PARP inhibitor): An update on the Phase 1/2 study in solid tumors is expected at the ASCO Annual Meeting in June 2013.
- BMN-111 for Achondroplasia: The company plans to initiate a Phase 2 trial in patients in mid 2013. The primary objective of the clinical proof of concept study in pediatric patients will be to evaluate the safety and tolerability of daily subcutaneous (sc) injections of BMN-111 administered for six months. Secondary objectives of the study will be to assess changes in annualized growth velocity, changes in absolute growth and changes in body proportions. Other exploratory objectives will also be assessed.
- BMN-190 for LINCL (Batten disease): BioMarin filed a CTA in the first quarter of 2013 and expects to begin enrolling the study in mid 2013. Orphan drug designation has been granted in both the U.S. and EU.
- Other early stage programs: BioMarin is working on multiple additional early development opportunities, including two new lead optimization programs gained through the acquisition of Zacharon Pharmaceuticals: inhibition of heparan sulfate synthesis for MPS III and inhibition of ganglioside synthesis for diseases such as Tay Sachs and Sandhoff. The company also has an ongoing Factor VIII gene therapy research program for Hemophilia A from University College London and St. Jude Children's Research Hospital.