Alnylam Pharmaceuticals, Inc.

Good morning. I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam. With me today on the phone are John Merriganori, Chief Executive Officer, Andy Orth, Senior Vice President and Head of the U.S. Business, Akshay Vaishnav, President of R&D, Jeff Poulton, Chief Financial Officer, and Yvonne Greenstreet, President and Chief Operating Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the events section of the investors page of our website. During today's call, as outlined in slide two, John will provide some introductory remarks and provide some general context. Andy will provide an update on our global commercial progress. Akshay will review recent clinical and preclinical updates. Jeff will review our financials. And Yvonne will provide a brief summary of upcoming milestones before opening the call to your questions. I would like to remind you that this call will contain certain remarks concerning O'Neill's future expectations, plans, and prospects, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual and quarterly reports and APAs on file with the SEC. In addition, any forward-looking statement represent our views only as the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'd like to turn the call over to John.

Thanks, Christine, and thank you, everyone, for joining the call today. We believe the third quarter and recent period highlight the tremendous progress El Nilem has made as a global commercial organization with a highly productive R&D platform. Starting with our commercial execution, we saw strong Onpatro and Giblari performance in Q3, which Andy Orth will review momentarily. We have continued confidence for the rest of this year with another upward revision of our Onpatro revenue guidance range for 2020 and another beat for Giblari relative to estimates. Akshay will review our recent R&D progress shortly, but the highlight in the recent period is the positive CHMP opinions recommending approval of Oxlumo, or Lumaceran, and Lecvio, or Inclisiran, which set us up with the potential to achieve four RNAi therapeutic approvals and launches in less than three years, a truly remarkable achievement. You'll also hear from Jeff on our financial performance and our progress toward achieving a self-sustainable financial profile. We believe we're on our way. Indeed, at Almilum, we're focused on continued global commercial execution on potentially transformational medicines, excellence in productivity from our organic R&D efforts, while maintaining a clear line of sight toward financial self-sustainability. In fact, this is what we envisioned when we established our Alnylam 2020 goals back in 2015, that we'd be a multi-product, global company with a deep clinical pipeline for future growth and an organic product engine for sustainable innovation. That moment is now upon us, and we couldn't be prouder of our achievements toward those very bold goals, which we're on track to actually exceed, and we couldn't be more excited for the next phase of Alnylam's evolution, We will lay out our multi-year vision soon, and we look forward to delivering on our potential as a top-tier biopharmaceutical company focused on advancing medicines with transformative potential to patients around the world. Now, before I hand it over to Andy, I'd like to mention that we plan to host a virtual R&D Day event on the mornings of December 15th and 16th, where we'll be reviewing progress across our pipeline of investigational RNAi therapeutics. We hope you'll be able to join us online. So with that, let's now turn to a review of our commercial and medical affairs progress. Andy?

Thanks, John, and good morning, everyone. I'll begin by reviewing our commercial performance in this third quarter, as well as our medical affairs progress. For OnPatro, we achieved $82.5 million in global net product revenue, delivering 24% growth versus Q2, primarily driven by increased patient demand. As of September 30th, over 1,150 patients were on commercial on-patro treatment worldwide. Turning to the U.S., we saw notable increases in demand and new patients starting therapy. Also, with many patients now having successfully transitioned to alternate sites of care, including home care, we benefited from strong patient compliance, which also contributed to the rebound in revenues. We continue to see progress with new prescribers in the U.S., with cardiologists making up more than half of new prescribing physicians. In the United States, we also continue to see a steady rate of concomitant use of Onpatro with TTR stabilizers and expect this trend to continue to grow. Turning to the rest of the world, we made very encouraging progress with Onpatro in the third quarter with $43.5 million in revenues from ex-U.S. markets. As noted last quarter, We have secured access in all priority markets in Western Europe, including Portugal, following our Q3 launch. We are also pleased with the continued growth in Japan, a country of strength for Onpatro. An important dynamic observed in XUS is patients switching to Onpatro from stabilizers for the potential to halt or reverse disease progression in HATTR patients with polyneuropathy. This dynamic represents greater than 50% of new Onpatro patients outside the U.S., Our medical affairs team also remains committed to addressing the challenge of raising disease awareness and improving diagnosis rates of HATTR amyloidosis, including with Alnylam Act, our third-party genetic screening initiative in the U.S., Canada, and Brazil. As of October, greater than 30,000 samples have been submitted, out of which approximately 1,800 have tested positive for a pathogenic TTR mutation. We are encouraged by the recovery in L-Nylomac genetic testing volumes we've seen in recent months, and we believe these volumes will continue into the fourth quarter. We've also seen continued recovery in the number of PYP scans conducted for detection of cardiac amyloid. As you know, HATTR amyloidosis is a multisystemic disease, and in the U.S., detection of cardiac amyloid is often the first step in an overall diagnosis of the disease, as many of these patients also have polyneuropathy. Untatro continues to be recognized as a breakthrough for patients with HATTR amyloidosis with polyneuropathy, and we're honored to have received the highly prestigious Pre-Galien USA Award just last week. Moving on to Givlari, we achieved $16.7 million in global net product revenues in the quarter, with over 150 patients now on commercial drugs. Our progress with patient access in the U.S. has been strong, having now finalized 10 value-based agreements, or VBAs, with U.S. payers. We currently have confirmed access for over 90% of covered U.S. lives. We've not experienced any payer headwinds with Giblari to date, and we're pleased to see the majority of plans adopt medical policies without restrictions to the number of baseline attacks. The Samia region saw great progress as well. with a successful ongoing GIVLARI launch in Germany and name patient sales in other countries, including France. We're off to a very strong start for market access in Samia. In France, GIVLARI received an improvement of medical benefit, or ASMR, score of two, concluding it offers significant additional therapeutic value. Additionally, GIVLARI obtained a considerable added benefit rating in Germany, with only 15% of all orphan drugs achieving such a high rating. And we secured a strong HCA rating in Italy. We're also excited to soon get our launch underway in Canada, following the recent approval, and look forward to the completion of the ongoing review of our NDA in Japan, which was submitted in September. Finally, our commercial affairs teams are prepared for the upcoming launch of Oxlumo, the brand name for Domaceran. With a positive CHMP opinion in hand in the EU, and an FDA PDUFA date just weeks away on December 3rd, we look forward to soon bringing our third RNAi therapeutic to patients around the world. We are well-prepared with our Oxlugal supply chain and are ready to deploy our trained U.S. field team upon approval to help get this important medicine to the underserved primary hyperoxaluria type 1, or PH1, community. As with our other launches and guided by our patient access philosophy, we are hard at work making sure the patients who need Oxlumo are able to access it. Constructive conversations are ongoing with payers regarding VBA arrangements, and we look forward to updating you further upon launch. In conclusion, the third quarter highlighted the broad capabilities of our commercial and medical affairs operations, including the continued growth of OnPatro, the continued launch of GiveLawry, and the preparation for the launch of Oxlumo. And we'll be watching with excitement as Novartis prepares to launch Lecvio or Inclisiran, which will mark the entry of RNAi therapeutics into a highly prevalent chronic disease indication. With that, I will now turn it over to Akshay to review our recent R&D and pipeline progress.