Ultragenyx Pharmaceutical Inc.

Ladies and gentlemen, thank you for standing by and welcome to the fourth quarter 2021 financial results and corporate update conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you only press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your host today, Joshua Higa. Sir, please go ahead.

Good afternoon, and welcome to the Ultragenyx Pharmaceutical Financial Results and Corporate Update Conference Call for the fourth quarter and full year 2021. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. I am Joshua Higa, Senior Director of Investor Relations. Joining me on this call are Emil Kakas, Chief Executive Officer and President, Camille Bedrosian, Chief Medical Officer, Eric Harris, Chief Commercial Officer, and Marty Deer, Chief Financial Officer. I would like to remind investors that this call will include forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to the types of statements identified as forward-looking in our annual, quarterly, and periodic reports filed with the SEC, which are all available in the investor section on our website. These forward-looking statements represent our views only as of the time of this call. It involves substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those projected in any forward-looking statement. For a further description of the risks and uncertainties that could cause actual results to differ materially from those expressed in the forward-looking statements, as well as risks related to our business, see our periodic reports filed with the SEC. I'll now turn the call over to Emil.

Thanks, Josh, and good afternoon, everyone. We've had an exciting start to the year. We concluded a strategic rare disease deal with Regeneron to license global commercial rights outside of the U.S. for both EFKISA and the potential for a second rare disease therapy, Coridizumab. We also released with our partner, Genetics, a clinical update on the ANHRN program showing positive clinical activity and no lower extremity weakness events observed. We finished 2021 in a strong financial position, exceeding expectations of the performance of our commercial products. And finally, we've made good progress with our broad late-stage pipeline, where we've initiated enrollment in three of four pivotal programs that will be ongoing this year. Along the way, and despite the challenges presented by the COVID pandemic, we also successfully completed manufacturing technology transfer to our partner, Daiichi Senkyo. I'll let Eric, Marty, and Camille provide more details on these accomplishments later on this call. I do want to spend a few minutes to discuss the deal with Regeneron on the commercialization of Evkisa for the treatment of homozygous familial hypercholesterolemia, or HOFH, outside of the U.S. The deal also includes our exclusive right to negotiate a separate ex-U.S. agreement for their investigational antibody for fibrodysplasia ossificans progressiva, or FOP. This deal establishes a strategic partnership with a leader in high-quality antibody drug discovery and development. It also enables us to both scale and leverage our global commercial capabilities in commercial medical affairs and regulatory functions. Efkisa is a potent approved product with a novel treatment mechanism that strengthens our portfolio with another commercial stage, traditional biologic that targets the underlying cause of HOFH. This disease occurs when two copies of the familial hypercholesterolemia-causing genes are inherited, one from each parent, resulting in very low or absent LDL receptors on the liver and lead to dangerously high levels of LDL-C. Patients with HFH are at risk for premature atherosclerotic disease and severe cardiac events. Despite all the studies and all the work that's been done in this disease over many years, True homozygous null patients still don't have a great treatment approved, and aparesis to remove lipid from the blood every single week is very difficult to tolerate and very cumbersome. FKESA targets and binds to ANG-PTL3, which is a protein that plays a broad role in cholesterol regulation and atherosclerosis. In patients whose LDL receptors are not present, to direct appropriate liver uptake, EFKES instead enables an alternative pathway by which VLDL are converted into VLDL remnants that are rapidly cleared by the liver through an alternative set of receptors. Taking advantage of this novel mechanism significantly reduces the level of LDL cholesterol in these severe patients despite the lack of working LDL receptors. The clinical value of blocking angPTL3 is supported by data showing that that natural genetic mutations also protect patients from atherosclerotic disease, and treating LDL receptor-deficient mice with an angPTL3 blocker does reduce atherosclerosis. In Regeneron's pivotal clinical program for epikesis, the drug demonstrated significant improvement over standard of care with consistent 49% reduction in LDL-C in a 24-week study in 65 patients with HOFH on top of all existing LDL-lowering treatments. The study also showed that treatment reduced the LDL-C by 72 percent in the most severe patients with less than 2 percent of LDL receptor activity, and that triglycerides were also reduced by 50 percent across study participants. FKESOS also has a good safety profile and has been well-tolerated across all study populations. Evkisa is approved by the FDA and EMA for patients 12 and older. Regeneron is currently marking the treatment as Evkisa in the U.S., and we will lead its launch and commercialization all around other countries and regions, including Europe, Latin America, and Asia. We may also expand our collaboration with Adreneron to include another antibody in Phase II-III development called FOP. That license will include the same commercial rice, excluding the U.S., FOP is an ultra-rare, devastating genetic ectopic bone disease that affects approximately 1,400 patients in these territories. In patients with FOP, abnormal bone formation occurs in soft tissue like muscles, leading to freezing of movement and difficulties in eating, walking, and breathing, and leads to premature death by patients in their 50s. I met my first patient with FOP while training in Los Angeles, and recently presented a keynote at the IFOPA meeting, so I'm familiar with this oral disease. Seeing patients frozen in terrible positions waiting for someone to save them or to freeze completely is not a sight you readily forget. I'll now hand the call over to Eric, who will talk about the commercial team's performance last year and what his teaming is doing to launch FKESA.