Vertex Pharmaceuticals Incorporated

Good evening. Welcome to the Vertex full year and fourth quarter 2019 financial results conference call. This is Michael Partridge, Senior Vice President of Investor Relations for Vertex. Making prepared remarks on the call tonight, we have Dr. Jeff Lydon, Chairman and CEO, Dr. Reshma Kewalramani, Chief Medical Officer, Stuart Arbuckle, Chief Commercial Officer, and Charlie Wagner, Chief Financial Officer. We recommend that you access the webcast slides on our website as you listen to this call. This conference call is being recorded, and a replay will be available on our website. We will make forward-looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and our filings with the Securities and Exchange Commission. These statements, including without limitation, those regarding Vertex's marketed CF medicines, our pipeline, and Vertex's future financial performance, are based on management's current assumptions. Actual outcomes and events could differ materially. I will now turn the call over to Dr. Jeff Lydon.

Thanks, Michael. Good evening, everyone. We saw many investors and analysts at the J.P. Morgan Conference two weeks ago, so I'll spend just a few moments highlighting our 2019 achievements and what we believe sets Vertex apart for the future. 2019 was a truly remarkable year for Vertex. all parts of our business met or exceeded the goals we set at the start of the year. And as a result, we are very well positioned to bring our CF medicines to many more people and to advance our broad pipeline in additional diseases in 2020. In cystic fibrosis, the U.S. approval of Trikafta for patients 12 and older in October, five months ahead of our PDUFA date, was the most significant milestone to date in our efforts to bring new CF medicines to all people with this disease. Trikafta is a remarkable medicine that holds the potential to treat up to 90% of all people with CF. As you'll hear from Stuart, the U.S. launch of Trikafta in patients ages 12 and older is off to a very strong start. There's clear interest in Trikafta across all groups of eligible patients, and the early feedback from both patients and doctors is highly positive. Outside the U.S. in 2019, we reached a number of key reimbursement agreements for our CF medicines that will allow many thousands of new patients to begin treatment with our CFTR modulators in countries including England, France, Spain, Australia, and many others throughout 2020. We are also making excellent progress advancing and broadening our pipeline beyond CF. As we enter 2020, we are now in the clinic with multiple new medicines and five diseases outside of CF. We continue to implement our strategy of advancing a portfolio of medicines into clinical development for each of the disease areas. Key programs include Alpha-1 antitrypsin deficiency, our AAT program, where we have multiple small molecule correctors in the clinic aimed at addressing the underlying cause of disease in both the liver and the lung. These include VX814, which has recently entered Phase II clinical development. Beta thalassemia and sickle cell disease, where we announced clinical data for two patients treated with CTX001, a one-time CRISPR-Cas9 ex vivo gene editing therapy, which suggests that we may be able to functionally cure these diseases. FSGS, where our first small molecule aimed at halting the progression of the disease will move into phase two development in 2020. And type 1 diabetes, where we are developing an autologous islet transplantation therapy with cells alone, and a second with a combination of cells and a device to correct eyelid cell function and potentially transform the treatment of this disease. Importantly, these pipeline programs now span multiple modalities, including small molecules, where Vertex has excelled in the past, but also new approaches such as cell and genetic therapy. For these new modalities, we've acquired or partnered with leading companies who have the best teams and unique expertise to manufacture and deliver transformational therapies for diseases that fit our strategy. And in business development, we completed more transactions in 2019 than in the four prior years, including our acquisitions of SEMA, with a leading cell therapy approach for type 1 diabetes, and Exonix, the leader in gene editing for DMD and DM1. In summary, 2019 was the culmination of almost a decade of focused execution against our strategy of discovering and developing transformative medicines for serious diseases in specialty areas by focusing on validated targets and predictive biomarkers that will improve the probability of clinical success. Our strategy is playing out exactly as we had planned and will position us for continued short-term and long-term growth. The company has never been stronger or better positioned for future success in CF and beyond. Let me now turn the call over to Reshma, who will talk in more detail about the year ahead.

Thanks, Jeff. Our 2019 progress has positioned us for continued growth in 2020 and for many years to come. We are focused on bringing our CF medicines to more people, advancing our pipeline, and building financial strength to support continued investment in internal and external innovation. In 2020, we expect to gain approval for the triple combination in Europe in patients 12 years and older and to submit Trikafta for approval in the U.S. for children ages 6 to 11. Beyond CF, we are advancing multiple molecules in our pipeline through late preclinical and early clinical development and are now entering a period of multiple proof-of-concept data readouts and clinical advances with potentially transformative medicines. With our AAT program, we recently initiated a Phase II proof-of-concept study of the small molecule corrector VX814 in patients with two copies of the Z mutation and expect data from the study in 2020. In APOL1-mediated FSGS, we completed a Phase I study of VX147 in late 2019 and expect to initiate an open-label Phase II proof-of-concept study in 2020. to evaluate the reduction in protein levels in the urine with VX147. In pain, having established proof of concept data from NAV1.8 inhibition with VX150 in multiple Phase II studies, our focus is now to find the optimal molecule or molecules to advance into mid- and late-stage studies. We are continuing to advance a portfolio of medicines into clinical development and will be advancing an additional molecule into phase one development in the first half of 2020. We have discontinued phase one development of VX961 because it did not display an optimal PK and tolerability profile. Beyond our small molecule programs, we've made significant progress in building and progressing a portfolio of cell and genetic therapies in line with our research strategy. primarily through our business development activities. We are highly encouraged by our recent clinical data for our CRISPR-Cas9 ex vivo gene editing treatment CTX001 for beta thalassemia and sickle cell disease. Both studies continue to enroll, and we expect to provide additional data for this program in 2020. I'd also like to highlight our cell therapy approach for type 1 diabetes. This program comes to us from our acquisition of Sematherapeutics in October of 2019. The team of scientists at SEMA have cracked the biology on both the production and scale-up of fully mature islet cells and has developed a novel implantable device to protect these cells from the immune system while preserving cell health and function. We have set an ambitious goal to progress this program into clinical development in late 2020 or early 2021. In summary, We've made outstanding progress in CF and multiple other diseases in 2019, and I look forward to updating you on our progress over the coming months and years. I'll now turn the call over to Stuart.