On February 8, 2018 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the fourth quarter and full year 2017 and highlighted recent progress in advancing its pipeline (Press release, Alnylam, FEB 8, 2018, View Source [SID1234523814]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"2017 was a defining inflection point in Alnylam’s history, with positive results from the APOLLO Phase 3 study culminating in regulatory filings for patisiran, a first-ever milestone for RNAi, with the potential to bring a whole new class of innovative therapeutics to the forefront of medicine. With newly acquired rest-of-world rights, we anticipate making patisiran available to hATTR amyloidosis patients around the world starting with the U.S. in mid-2018, followed by European countries in late 2018, and then Japan and other countries shortly thereafter. To this end, we have initiated a staged build of global medical and commercial capabilities to expand our reach and ensure that patients and physicians are educated about this rare disease and the safety and efficacy profile of patisiran, upon market approval," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "Beyond patisiran, we advanced our late-stage pipeline with three additional RNAi therapeutics in Phase 3 development, including givosiran for acute hepatic porphyrias in our ENVISION Phase 3 study, with topline interim analysis results expected in mid-2018. Also, together with our partners Sanofi and The Medicines Company, we restarted fitusiran in the ATLAS Phase 3 study and advanced inclisiran in the ORION-9, -10, and -11 Phase 3 studies, respectively, with results expected for both programs in 2019. In sum, we believe our efforts position the Company to achieve its Alnylam 2020 goals of building a multi-product, commercial-stage company with a deep clinical-stage pipeline and robust product engine by the end of 2020, a profile rarely achieved in biotech history."
Fourth Quarter 2017 and Recent Significant Corporate Highlights
Advanced patisiran, an investigational RNAi therapeutic for the treatment of patients with hereditary ATTR amyloidosis.
Presented positive, final results from the APOLLO Phase 3 pivotal study.
Completed the rolling submission of a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) and submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA), with the agencies recently accepting both applications.
Received Breakthrough Therapy Designation and Priority Review status from the FDA, and expansion of patisiran’s Orphan Drug Designation to the "treatment of transthyretin-mediated amyloidosis (ATTR amyloidosis)." In addition, patisiran received Accelerated Assessment status from the EMA, and has been designated as a Promising Innovative Medicine (PIM) by the Medicines and Healthcare Products Regulatory Agency (MHRA) in the U.K.
In response to the urgent need for treatment of patients living with hATTR amyloidosis, the Company is fulfilling requests from treating physicians for early access or compassionate use of patisiran; the Company announces today that, to date, more than 100 eligible patients have begun treatment with patisiran under these programs in the U.S. and EU.
Advanced ALN-TTRsc02, a once-quarterly, subcutaneously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis.
Reaffirmed guidance to initiate a comprehensive Phase 3 program for ALN-TTRsc02 in late 2018.
Advanced givosiran, an investigational RNAi therapeutic in development for the treatment of acute hepatic porphyrias (AHPs), with initiation of the ENVISION Phase 3 study.
The Company reached alignment with global regulatory authorities on the design of the ENVISION study, including with the FDA on an interim analysis based on reduction of urinary aminolevulinic acid (ALA), a biomarker that the FDA considers reasonably likely to predict clinical benefit.
The Company announces today that the interim analysis is also designed to conduct a blinded assessment of the porphyria attack rate for the purpose of a study sample size adjustment from approximately 75 patients to up to approximately 94 patients.
The Company has guided that it expects interim analysis results in mid-2018 and, pending FDA review of the program at the time of interim analysis and assuming positive results, it expects to submit an NDA at or around year-end 2018.
Advanced fitusiran, an investigational RNAi therapeutic in development for the treatment of hemophilia A and B with or without inhibitors, and reached alignment with the FDA on safety measures and a risk mitigation strategy resulting in a lift of the temporary hold on clinical studies.
Alnylam’s partner, The Medicines Company, initiated the ORION-9, -10, and -11 Phase 3 clinical studies for inclisiran in patients with heterozygous familial hypercholesterolemia (HeFH), atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents, and completed enrollment in the approximately 1,500 patient ORION-11 study ahead of schedule.
Advanced lumasiran (formerly known as ALN-GO1), an investigational RNAi therapeutic in development for the treatment of primary hyperoxaluria type 1 (PH1), with new positive data from the Phase 1/2 study presented at the American Society of Nephrology Kidney Week 2017 Annual Meeting.
Announced a strategic restructuring of the Company’s rare disease alliance with Sanofi, originally formed in 2014, with Alnylam obtaining global rights to its ATTR amyloidosis programs – patisiran and ALN-TTRsc02 – and Sanofi obtaining global rights to fitusiran.
Joined a research consortium with the UK Biobank, Regeneron, and four major pharmaceutical companies aimed at generating 500,000 human exome sequences linked to medical records by the end of 2019.
Announced a licensing agreement with Vir Biotechnology for the development and commercialization of RNAi therapeutics for infectious diseases, including HBV.
Upcoming Events in Early 2018
Alnylam announces today that it will present additional data from the APOLLO Phase 3 study of patisiran at the International Symposium on Amyloidosis (ISA), being held March 26-29, 2018 in Kumamoto, Japan.
The Company also announces that it will present additional data from the Phase 1 and Phase 2 OLE studies of givosiran at the European Association for the Study of the Liver (EASL) 53rd Annual International Liver Congress, being held April 11-15, 2018 in Paris, France, in an oral presentation on Saturday, April 14 at 10:00 am Central European Time (4:00 am ET).
The Medicines Company has guided its intention to complete enrollment in the ORION-9 and -10 pivotal studies of inclisiran in early 2018.
Alnylam and Sanofi expect to enroll patients in the ATLAS Phase 3 program of fitusiran in patients with hemophilia A or B with and without inhibitors throughout the year, with resumption of dosing expected in early 2018.
Financial results for the quarter and year ended December 31, 2017
"Alnylam’s robust balance sheet and overall financial position allow for the staged build of commercial capabilities and the execution of anticipated product launches in the U.S. and Europe during 2018, assuming regulatory approvals," said Manmeet Soni, Chief Financial Officer of Alnylam. "We also continue to invest in our broad pipeline of investigational RNAi therapeutics, advancing our Phase 3 development programs in addition to several other programs in early- to mid-stage clinical development."
Cash and Investments
At December 31, 2017, Alnylam had cash, cash equivalents and fixed income marketable securities, and restricted investments of $1.73 billion, as compared to $1.09 billion at December 31, 2016.
In November 2017, Alnylam sold an aggregate of 6,440,000 shares of its common stock through an underwritten public offering at a price to the public of $125.00 per share. As a result of the offering, which included the full exercise of the underwriters’ option to purchase additional shares, Alnylam received aggregate net proceeds of $784.5 million.
Credit Agreements
In December 2017, Alnylam repaid $120.0 million under its term loan agreements outstanding. The obligations under its remaining term loan agreement are secured by cash collateral equal to the principal amount of the terms loan outstanding. As a result, in connection with this repayment, Alnylam’s restricted investments decreased by $120.0 million in December 2017.
GAAP and Non-GAAP Net Loss
The net loss according to accounting principles generally accepted in the U.S. (GAAP) for the fourth quarter of 2017 was $142.2 million, or $1.48 per share on both a basic and diluted basis, as compared to a net loss of $112.9 million, or $1.32 per share on both a basic and diluted basis, for the same period in the previous year. For the year ended December 31, 2017, the net loss was $490.9 million, or $5.42 per share on both a basic and diluted basis, as compared to a net loss of $410.1 million, or $4.79 per share on both a basic and diluted basis, for prior year.
The non-GAAP net loss for the fourth quarter of 2017 was $115.1 million, or $1.20 per share on both a basic and diluted basis, as compared to a non-GAAP net loss of $92.3 million, or $1.08 per share on both a basic and diluted basis for the same period in the previous year. The non-GAAP net loss for the year ended December 31, 2017 was $398.1 million, or $4.40 per share on both a basic and diluted basis, as compared to a non-GAAP net loss of $334.6 million, or $3.91 per share on both a basic and diluted basis, for prior year.
The non-GAAP net loss excludes stock-based compensation expense. See "Use of Non-GAAP Financial Measures" below for a description of non-GAAP financial measures and a reconciliation between GAAP and non-GAAP net loss appearing later in this press release.
Revenues
Revenues were $37.9 million in the fourth quarter of 2017, as compared to $17.5 million in the fourth quarter of 2016. Revenues for the fourth quarter of 2017 included $20.1 million from the Company’s alliance with The Medicines Company, $13.4 million from the Company’s alliance with Sanofi Genzyme, and $4.4 million from other sources. Revenues were $89.9 million in the year ended December 31, 2017, as compared to $47.2 million in the year ended December 31, 2016. Revenues for the year ended December 31, 2017 included $54.6 million from the Company’s alliance with Sanofi Genzyme, $30.2 million from the Company’s alliance with The Medicines Company, and $5.1 million from other sources.
GAAP and Non-GAAP Research and Development Expenses
GAAP research and development (R&D) expenses were $117.8 million in the fourth quarter of 2017 as compared to $105.0 million in the fourth quarter of 2016. GAAP R&D expenses were $390.6 million in the year ended December 31, 2017 as compared to $382.4 million for the prior year.
Non-GAAP R&D expenses were $102.9 million in the fourth quarter of 2017 as compared to $95.0 million in the fourth quarter of 2016. Non-GAAP R&D expenses were $338.8 million in the year ended December 31, 2017 as compared to $339.4 million for the prior year. Non-GAAP R&D expenses exclude stock-based compensation expense. A reconciliation between GAAP and non-GAAP R&D expenses appears later in this press release.
GAAP and Non-GAAP General and Administrative Expenses
GAAP general and administrative (G&A) expenses were $67.5 million in the fourth quarter of 2017 as compared to $27.9 million in the fourth quarter of 2016. GAAP G&A expenses were $199.4 million in the year ended December 31, 2017 as compared to $89.4 million for the prior year.
Non-GAAP G&A expenses were $55.2 million in the fourth quarter of 2017 as compared to $17.2 million in the fourth quarter of 2016. Non-GAAP G&A expenses were $158.4 million in the year ended December 31, 2017 as compared to $56.8 million for the prior year. Non-GAAP G&A expenses exclude stock-based compensation expense. A reconciliation between GAAP and non-GAAP G&A expenses appears later in this press release.
2018 Financial Guidance
Alnylam expects that its cash, cash equivalents and fixed income marketable securities, restricted cash and restricted investments balance will be approximately $1.0 billion at December 31, 2018.
The Company expects its 2018 annual Non-GAAP R&D expenses to be in the range of $400 to $440 million and Non-GAAP selling, general and administrative (SG&A) expenses to be in the range of $280 to $320 million. Both Non-GAAP R&D and SG&A expenses exclude stock-based compensation expenses.
Use of Non-GAAP Financial Measures
This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.
The item included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in the press release is stock-based compensation expense. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards.
The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between GAAP and non-GAAP measures is provided later in this press release.
Conference Call Information
Management will provide an update on the Company and discuss fourth quarter and year end 2017 results as well as expectations for the future via conference call on Thursday, February 8, 2018 at 8:30 a.m. ET. To access the call, please dial 877-312-7507 (domestic) or 631-813-4828 (international) five minutes prior to the start time and refer to conference ID 9496435. A replay of the call will be available beginning at 11:30 a.m. ET on the day of the call. To access the replay, please dial 855-859-2056 (domestic) or 404-537-3406 (international), and refer to conference ID 9496435.
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.
Alnylam – Sanofi Genzyme Alliance
In January 2014, Alnylam and Sanofi Genzyme, the specialty care global business unit of Sanofi, formed an alliance to accelerate the advancement of RNAi therapeutics as a potential new class of innovative medicines for patients around the world with rare genetic diseases. The alliance enables Sanofi Genzyme to expand its rare disease pipeline with Alnylam’s novel RNAi technology and provides access to Alnylam’s R&D engine, while Alnylam benefits from Sanofi Genzyme’s proven global capabilities to advance late-stage development and, upon commercialization, accelerate market access for these promising genetic medicine products. In January 2018, Alnylam and Sanofi Genzyme restructured their alliance, providing Alnylam with global rights to develop and commercialize products for the treatment of ATTR amyloidosis, including patisiran and ALN-TTRsc02, and Sanofi Genzyme with global rights to develop and commercialize fitusiran for the treatment of hemophilia and other rare bleeding disorders. Sanofi Genzyme continues to have the right to opt into other Alnylam rare genetic disease programs for development and commercialization in territories outside of the United States, Canada and Western Europe, as well as one right to a global license.