Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2019 Financial Results and Highlights Recent Period Activity Achieved Fourth Quarter and Full Year 2019 ONPATTRO (patisiran) Global Net Product Revenues of $55

Achieved Fourth Quarter and Full Year 2019 ONPATTRO (patisiran) Global Net Product Revenues of $55.8 Million and $166.4 Million, Respectively -

As of Year-End 2019, Over 750 Patients Worldwide Receiving Commercial ONPATTRO, with Over 1,000 Total Patients Worldwide Being Treated with Patisiran -

- Observed Strong Initial Demand for GIVLAARI (givosiran) in the U.S., with 13 Start Forms Received in First Six Weeks after FDA Approval -

Reported Third Positive 2019 Phase 3 Result with Lumasiran and Initiated Rolling Submission of New Drug Application (NDA) with U.S. Food and Drug Administration (FDA) -

- Initiated HELIOS-B Phase 3 Study of Vutrisiran for the Treatment of Hereditary and Wild-Type ATTR Amyloidosis with Cardiomyopathy -

- Maintained Strong Balance Sheet with Year-End Cash and Investments Balance of $1.55 Billion -

Provides 2020 ONPATTRO Revenue Guidance and Operating Expense Guidance -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--February 6, 2020--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today reported its consolidated financial results for the fourth quarter and full year ended December

31, 2019 and reviewed recent business highlights.

"In 2019 we saw continued and steady growth of patients on ONPATTRO, and we expect growth to continue in 2020, driven by new patient finding, geographic expansion, and evidence-generating activities. We also believe that our ongoing

APOLLO-B Phase 3 study, if positive, can potentially enable future label expansion for patisiran to treat the cardiomyopathy of hereditary and wild-type ATTR amyloidosis. With the early U.S. approval of GIVLAARI in the fourth quarter, Alnylam

became a multi-product commercial company, and we are pleased with the strong initial interest from patients, physicians, and payers in the short period since the drug's approval by the FDA," said John Maraganore, Ph.D., Chief Executive

Officer of Alnylam. "Also in the fourth quarter, we reported positive topline Phase 3 results with lumasiran, Alnylam's third program in 2019 to achieve positive Phase 3 results, and we've initiated the rolling submission of an NDA, setting

us up for a potential approval later this year. In addition, in 2020 we look forward to advancing additional late-stage programs closer to the market, namely vutrisiran - with the HELIOS-A and -B studies in ATTR amyloidosis - and, inclisiran

and fitusiran with our partners at Novartis and Sanofi, respectively. With continued execution across these and other programs we are confident that by year-end we'll achieve our Alnylam 2020 goals of building a multi-product, global

biopharma company with a deep clinical pipeline to fuel future growth and a robust product engine for sustainable and organic innovation, a profile rarely achieved in our industry."

Fourth Quarter 2019 and Recent Significant Corporate Highlights

Commercial Performance

Achieved global net product revenues for the fourth quarter and full year 2019 of $55.8 million and $166.4 million, respectively.

As of year-end 2019, over 750 patients worldwide were receiving commercial ONPATTRO, and over 1,000 total patients worldwide were being treated with patisiran, when also including those patients in clinical studies and in the Company's

global Expanded Access Program (EAP).

Significant ONPATTRO new patient growth in the fourth quarter was seen in the U.S. and EU, along with a strong launch in Japan.

In the U.S., 44% of Start Forms submitted in 2019 came from cardiologists, 38% from neurologists, and 18% from other physician specialties.

In the U.S., Alnylam has now completed definitive value-based agreements (VBAs) with 15 commercial payers, including each of the top 5 commercial payers and 8 of the top 10, with signed VBAs now covering over 130 million U.S. lives in

Continued progress with market access efforts across the Canada, Europe, Middle East, and Africa (CEMEA) region, with a recent launch in the United Kingdom and reimbursement approvals in Belgium, Israel, and Italy.

A total of 13 Start Forms were submitted for the period following approval of GIVLAARI in the U.S. on November 20, 2019 through year-end 2019.

Net product revenues for the fourth quarter of 2019 were $0.2 million representing initial channel stocking.

The Company has made significant progress toward establishing VBAs, including a Prevalence-Based Adjustment feature, with multiple ongoing discussions with payers.

Continued to apply for marketing authorization of patisiran (the non-proprietary name for ONPATTRO) in additional countries for the treatment of hATTR amyloidosis patients with polyneuropathy and to advance the development of

patisiran for the potential treatment of the cardiomyopathy of both hereditary and wild type ATTR amyloidosis.

Continued enrollment in the APOLLO-B Phase 3 study in ATTR amyloidosis patients with cardiomyopathy.

Filed a marketing authorization application with the Brazilian Health Regulatory Agency (ANVISA) for patisiran for the treatment of hATTR amyloidosis patients with polyneuropathy.

Achieved the second-ever regulatory approval of an RNAi therapeutic with the approval of GIVLAARI (givosiran) in the U.S.

Received FDA approval of GIVLAARI for the treatment of adults with AHP.

Received a positive opinion for givosiran for the treatment of AHP in adolescents and adults from the Committee for Medicinal Products for Human Use (CHMP) in the EU.

Filed a marketing authorization application for givosiran with the Brazilian Health Regulatory Agency (ANVISA).

Advanced lumasiran, an investigational RNAi therapeutic in development for the treatment of primary hyperoxaluria type 1 (PH1).

Reported positive topline results from ILLUMINATE-A Phase 3 study of lumasiran for the treatment of PH1.

Initiated NDA rolling submission to the FDA, with remaining sections expected to be submitted in early 2020.

The Company announces today that it has completed enrollment in the ILLUMINATE-B Phase 3 study of lumasiran in PH1 patients less than six years of age with preserved renal function, and remains on track to report topline results in

Initiated the ILLUMINATE-C Phase 3 study of lumasiran for the treatment of advanced PH1 in patients of all ages with advanced renal disease.

Received a pediatric rare disease designation from the FDA for lumasiran for the treatment of PH1.

Announced positive efficacy results from the ongoing Phase 2 open-label extension (OLE) study of lumasiran at the American Society of Nephrology (ASN) 2019 Annual Meeting.

Advanced vutrisiran, a subcutaneously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis.

Initiated the HELIOS-B Phase 3 study in patients with hereditary and wild-type ATTR amyloidosis with cardiomyopathy.

Continued enrollment in the HELIOS-A Phase 3 study in hereditary ATTR amyloidosis with polyneuropathy, with the study over 85% enrolled.

Alnylam's partner, The Medicines Company, acquired by Novartis in January 2020, advanced inclisiran, an investigational RNAi therapeutic in development for the treatment of hypercholesterolemia.

Reported positive complete results from the ORION-9 and -10 Phase 3 studies of inclisiran in patients with heterozygous familial hypercholesterolemia (HeFH) and atherosclerotic cardiovascular disease (ASCVD).

Submitted an NDA and an MAA for inclisiran to the FDA and the EMA, respectively.

Novartis announced a groundbreaking agreement with the UK National Health Service (NHS) to study inclisiran in UK patients as part of a large-scale NHS clinical trial expected to start later this year. As part of the agreement,

inclisiran is also expected to be available to UK patients through a population-level agreement, if approved and reimbursed.

Alnylam's partner, Sanofi, continues enrollment in the ATLAS Phase 3 program for fitusiran in patients with hemophilia A or B with and without inhibitors.

Advanced early-stage RNAi pipeline programs.

Announced initial positive clinical results with ALN-AAT02 and ALN-HBV02 (VIR-2218), providing initial human proof of concept for "Enhanced Stabilization Chemistry Plus" (ESC+) GalNAc conjugate delivery technology.

Presented initial positive clinical results, namely knockdown of serum angiotensinogen levels, from Phase 1 trial of ALN-AGT, an investigational RNAi therapeutic for hypertension, expanding potential opportunities for RNAi

therapeutics in highly prevalent chronic diseases.

Reported strong progress in CNS and ocular delivery of RNAi therapeutics with seven initial programs selected as part of Regeneron collaboration, including ALN-APP, in development for the treatment of cerebral amyloid

angiopathy and potentially other neurodegenerative diseases, and ALN-HTT, in development for the treatment of Huntington's disease.

Additional Business Updates

Alnylam announces today that it ranked #3 in gender parity and #1 in fair representation for Women of Color at the leadership level among the top 25 employers in Massachusetts by the Eos Foundation's inaugural Women's Power Gap in

Corporate Massachusetts Survey and Rankings.

Received recognition as the world's #1 biopharma employer from Science magazine based on more than 7,500 responses to its annual survey of the biotech and pharmaceutical industry.

Alnylam announces today that it intends to present multiple new study results with patisiran at the XVII International Symposium on Amyloidosis on March 1-5, 2020 in Tarragona, Spain.

The Company also intends to report full results from the ILLUMINATE-A Phase 3 study of lumasiran at the OxalEurope International Congress on March 31, 2020 in Amsterdam.

In addition, in early 2020, Alnylam intends to:

Continue global commercialization of ONPATTRO.

Continue global launch of GIVLAARI, including launch in Europe following expected approval from the European Medicines Agency (EMA).

Complete enrollment in the HELIOS-A Phase 3 study of vutrisiran.

Complete rolling submission of the lumasiran NDA and file MAA with the EMA.

Financial Results for the Quarter and Year Ended December 31, 2019

"We believe our fourth quarter and full year 2019 results reflect strong ONPATTRO patient demand and excellent execution by our commercial teams around the world. Notably, we saw significant ONPATTRO new patient growth in the U.S. and EU,

and strong initial demand in Japan, together resulting in over 20 percent quarter-on-quarter growth in net product revenues. We expect growth to continue in 2020 and are guiding that we expect to achieve between $285 million and $315 million

in ONPATTRO net product revenues for the year. We also look forward to now leveraging our global commercial capabilities for the launch of GIVLAARI," said Jeff Poulton, Chief Financial Officer of Alnylam. "Our balance sheet remains strong

with $1.55B in cash and investments at year-end, enabling continued investments in R&D and commercial execution. Looking forward, we are now focused on achieving a self-sustainable financial profile. The key elements of this transition

include top line revenue growth from currently two marketed products - and in the not-too-distant future, potentially up to six marketed products - as well as disciplined investment in our operations."

Net Product Revenues

Net product revenues were $55.9 million in the fourth quarter 2019 representing 21% growth from the third quarter 2019 primarily driven by the addition of new patients on therapy and expansion into new markets.

Net product revenues grew from $12.5 million in 2018 to $166.5 million in 2019 primarily driven by the continued global launch of ONPATTRO during its first full-year on the market.

Net Revenues from Collaborators

Net revenues from collaborators were $15.7 million in the fourth quarter 2019, an increase from $9.0 million in the fourth quarter 2018 primarily due to revenues from the Regeneron collaboration.

Net revenues from collaborators were $53.2 million in 2019, a decrease from $62.4 million in 2018 primarily due to a decline in reimbursable activities from the Sanofi Genzyme collaboration, offset by revenues from the Regeneron

Research & Development (R&D) and Selling, General & Administrative (SG&A) Expenses

R&D expenses increased in the fourth quarter and full year 2019 compared to the same periods in 2018 on a GAAP and non-GAAP basis primarily due to increased activity related to the advancement of the Company's late stage programs.

SG&A expenses increased in the fourth quarter and full year 2019 compared to the same periods in 2018 on a GAAP and non-GAAP basis primarily due to increases in commercial and medical affairs activities supporting continued

investment in the ongoing ONPATTRO launch and the launch of GIVLAARI in late 2019.

R&D and SG&A expenses on a GAAP basis also increased in the fourth quarter 2019 compared to the same period in 2018 due to an increase in stock-based compensation primarily due to the probability of or achievement of certain

performance-based vesting events under outstanding equity awards.

Cash and Investments

Cash and investments were $1.55 billion at the end of 2019 compared to $1.13 billion at the end of 2018. The increase was due to proceeds received under the Company's equity offering in the first quarter of 2019 and proceeds received

under the collaboration and equity agreements with Regeneron offset by cash used in the Company's operations.

A reconciliation of GAAP to non-GAAP results is included in the tables of this press release.

2020 Financial Guidance

Full year 2020 financial guidance consists of the following:

ONPATTRO net product revenues of $285 million - $315 million

Net revenues from collaborators of $100 million - $150 million

GAAP R&D and SG&A expenses of $1,180 million - $1,300 million

Non-GAAP R&D and SG&A expenses of $1,025 million - $1,125 million*

The Company expects that its current cash, cash equivalents, and marketable debt and equity securities will support company operations for multiple years based on its current operating plans.