Alnylam Pharmaceuticals Reports Second Quarter 2019 Financial Results and Highlights Recent Period Activity Achieved Second Quarter 2019 ONPATTRO Global Net Product Revenues of $38.2 Million with More Than 500 Patients o

Achieved Second Quarter 2019 ONPATTRO Global Net Product Revenues of $38.2 Million with More Than 500 Patients on Commercial Product Worldwide -

Reported Positive Results from ENVISION Phase 3 Study of Givosiran, Submitted Regulatory Filings in the U.S. and EU, and Received Priority Review from FDA -

- Completed Enrollment in ILLUMINATE-A Phase 3 Study of Lumasiran and Advanced Multiple Additional Late-Stage Pipeline Programs -

Formed Broad Collaboration with Regeneron to Discover, Develop and Commercialize RNAi Therapeutics Focused on Ocular and Central Nervous System (CNS) Diseases -

Strengthened Balance Sheet and Ended Second Quarter with Approximately $2.0 Billion in Cash; Lowers 2019 Non-GAAP R&D and Non-GAAP SG&A Expense Guidance -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--August 6, 2019--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today reported its consolidated financial results for the second quarter 2019 and reviewed recent business

"Over the past quarter, we're pleased with the continued strong progress in the global launch of ONPATTRO. We believe that continued commercial execution with ONPATTRO and expected upcoming launches of other products puts us on a path toward

attaining self-sustainability in our business, delivering on the promise of RNAi therapeutics for patients around the world," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "During this period we also achieved several key

milestones with our late and earlier stage pipeline, including positive Phase 3 results with givosiran. We expect this track record of commercial and R&D execution to continue well into the future. Specifically, as we turn to the second

half of 2019, we look forward to pivotal data readouts from two programs - inclisiran and lumasiran - and additional Phase 3 initiations, namely APOLLO-B with patisiran, HELIOS-B with vutrisiran, and ILLUMINATE-C with lumasiran. Each of these

planned milestones will bring us closer to achieving our Alnylam 2020 vision of building a multi-product, global biopharmaceutical company that includes a deep clinical pipeline to fuel continued growth and a robust product engine for

sustainable and organic innovation for the future, a profile rarely achieved in the biopharmaceutical industry."

"As we approach the one year anniversary of the ONPATTRO approval, we couldn't be more proud of our commercial execution. We finished the quarter with over 500 patients on commercial therapy, and we expect continued and steady growth in the

years to come driven by new patient finding, global expansion, and additional evidence generation in our ATTR amyloidosis franchise," said Barry Greene, President of Alnylam. "We are committed to decreasing the time to diagnosis and treatment

for the benefit of patients with hATTR amyloidosis with polyneuropathy, and we see increased utilization of diagnostic programs such as Alnylam Act. With recent approvals in Japan and Canada, and multiple pricing or reimbursement approvals

enabling commercial sales in over ten countries across the CEMEA region, we are expanding our global footprint, bringing ONPATTRO to patients internationally and laying the groundwork for planned future launches of other RNAi therapeutics.

Finally, we believe that evidence generation for ONPATTRO will continue to demonstrate the potential benefits and differentiated profile of ONPATTRO."

Second Quarter 2019 and Recent Significant Corporate Highlights

Commercial Performance in Second Quarter 2019

Achieved global ONPATTRO net product revenues for the second quarter of 2019 of $38.2 million.

Attained more than 500 patients worldwide on commercial ONPATTRO treatment as of June 30, 2019.

Received marketing authorization approvals for ONPATTRO in Japan and Canada.

Continued progress with market access efforts across the CEMEA region (Canada, Europe, Middle East, and Africa).

Achieved recent reimbursement approvals and favorable ratings from health technology assessment agencies in England, Scotland, Germany, France, Canada, and Sweden, with significant progress in several additional markets.

Advanced patisiran (the non-branded name for ONPATTRO), an intravenously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis, with plans to initiate the APOLLO-B Phase 3 study in ATTR

amyloidosis with cardiomyopathy in mid-2019.

Presented positive 12-month data from the Global Open-Label Extension (OLE) study, as well as new analyses from the APOLLO Phase 3 study in patients previously treated with tafamidis and results from an indirect treatment comparison of

patisiran versus inotersen in hATTR amyloidosis patients with polyneuropathy.

Advanced vutrisiran (ALN-TTRsc02), a subcutaneously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis.

Continued enrollment in the HELIOS-A Phase 3 study of vutrisiran in hereditary ATTR amyloidosis patients with polyneuropathy.

The Company announces today that it has obtained regulatory alignment on the design of HELIOS-B - a Phase 3 study of vutrisiran in patients with both hereditary and wild-type ATTR amyloidosis cardiomyopathy - which it expects to start

Advanced givosiran, an investigational RNAi therapeutic in development for the treatment of acute hepatic porphyria (AHP).

Presented positive results from the ENVISION Phase 3 study.

Completed submissions of a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) and a Marketing Authorisation Application (MAA) with the European Medicines Agency (EMA); both agencies have accepted the

applications for filing. The FDA also granted the Company's request for Priority Review and has set an action date of February 4, 2020, under the Prescription Drug User Fee Act (PDUFA). At this time, the FDA is not planning to hold an

advisory committee meeting to discuss this application.

Alnylam announces today that it has inititated an Expanded Access Program for givosiran to support requests by Health Care Providers for pre-approval access for AHP patients.

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

Completed enrollment in the ILLUMINATE-A Phase 3 study of lumasiran in PH1 patients six years of age or older with mild-to-moderate renal impairment, and remain on track to report results by year-end 2019.

Presented complete positive results from the Phase 1/2 clinical study and positive results from the ongoing Phase 2 open-label extension (OLE) study of lumasiran.

Initiated ILLUMINATE-B, a global Phase 3 pediatric study of lumasiran in PH1 patients under six years of age.

Alnylam's partner, The Medicines Company, reported new results for inclisiran, an investigational RNAi therapeutic in development for the treatment of hypercholesterolemia.

New data included interim results from the ongoing ORION-3 OLE study in patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents and results from the ORION-2 and -7 studies in patients with homozygous

familial hypercholesterolemia (HoFH) and in patients with renal impairment, respectively.

In addition, The Medicines Company announced that the Independent Data Monitoring Committee for ongoing inclisiran Phase 3 clinical trials (ORION 9, 10, and 11) completed its seventh planned review of safety and efficacy data from the

ORION trials and recommended that the trials continue without modification. The safety database for inclisiran now provides more than 3,500 patient-years of exposure to an RNAi therapeutic, representing the industry's most comprehensive

body of safety data for an RNA therapeutic.

Alnylam's partner, Sanofi, reported new results from the Phase 2 OLE study of fitusiran, an investigational RNAi therapeutic in development for the treatment of hemophilia.

Advanced early- and mid-stage RNAi clinical pipeline.

Initiated a Phase 1 study of ALN-AGT, an investigational RNAi therapeutic targeting angiotensinogen (AGT) for the treatment of hypertension in high unmet need populations, including patients with resistant or refractory hypertension,

chronic kidney disease or heart failure.

Announced new platform advances, including preclinical results demonstrating oral delivery of GalNAc-conjugated small interfering RNAs (siRNAs) directed to a liver target. Oral delivery could broaden the clinical and commercial

opportunities for RNAi therapeutics, which are currently administered with intravenous or subcutaneous dose administration.

Additional Business Highlights

Formed a broad collaboration with Regeneron Pharmaceuticals, Inc. (Regeneron) to discover, develop, and commercialize RNAi therapeutics focused on ocular and CNS diseases.

Concluded the research and option phase of the Company's 2014 collaboration with Sanofi focused on advancing RNAi therapeutics for rare genetic diseases.

Entered into a collaboration with 23andMe to support the addition of a new Genetic Health Risk report for Hereditary Amyloidosis (TTR-related). Read more about the report here.

Announced senior leadership changes, including the appointment of Kelley Boucher as the Company's Senior Vice President, Chief Human Resources Officer; and Jeff Poulton as Executive Vice President, Chief Financial Officer, effective August

In the second half of 2019, Alnylam intends to:

Initiate the APOLLO-B Phase 3 study of patisiran in ATTR amyloidosis patients with cardiomyopathy in mid-2019.

Launch ONPATTRO in Japan, England, Switzerland, and multiple other countries.

Initiate the HELIOS-B Phase 3 study of vutrisiran in ATTR amyloidosis patients with cardiomyopathy.

Initiate the ILLUMINATE-C Phase 3 study of lumasiran in PH1 patients with severe renal impairment.

Report topline results from the ILLUMINATE-A Phase 3 study of lumasiran in PH1 patients six years of age or older.

In addition, The Medicines Company intends to report initial topline results from the ORION-9, 10, and 11 Phase 3 studies of inclisiran, and assuming positive results, to file an NDA.

Financial Results for the Quarter Ended June 30, 2019

"Alnylam had strong financial performance in the second quarter. We ended with cash and cash equivalents on our balance sheet of approximately $2.0 billion, bolstered by robust ONPATTRO sales as well as $800 million in additional cash

received from our recently announced collaboration with Regeneron," said Manmeet Soni, outgoing Chief Financial Officer of Alnylam. "I have thoroughly enjoyed my time as part of the Alnylam team and am confident that the foundation created over

the past few years will serve the Company well."

"I am thrilled to be joining an organization with great near- and long-term growth prospects driven by advancing innovative therapies with the potential to transform patients' lives," said Jeff Poulton, recently appointed Executive Vice

President, Chief Financial Officer of Alnylam, effective August 13. "Having supported the profitable globalization of Shire's business during my tenure there, I look forward to partnering with the business team at Alnylam to develop a roadmap

toward financial self-sustainability."

Cash and Investments

At June 30, 2019, Alnylam had cash, cash equivalents and marketable debt securities, and restricted investments, excluding equity securities, of $1.97 billion, as compared to $1.13 billion at December 31, 2018.

In May 2019, Alnylam received an upfront collaboration payment from Regeneron of $400 million. In addition, Regeneron purchased $400 million of Alnylam equity at a price per share of $90.00 (4.44 million common shares).

GAAP and Non-GAAP Net Loss

The net loss according to accounting principles generally accepted in the U.S. (GAAP) for the second quarter of 2019 was $219.5 million, or $2.02 per share on both a basic and diluted basis, as compared to a net loss of $163.6 million, or

$1.63 per share on both a basic and diluted basis, for the same period in the previous year.

The non-GAAP net loss for the second quarter of 2019 was $198.3 million, or $1.83 per share on both a basic and diluted basis, as compared to a non-GAAP net loss of $161.9 million, or $1.61 per share on both a basic and diluted basis for the

same period in the previous year.

Reconciling items between GAAP and non-GAAP net loss include stock-based compensation expense, a gain on the change in fair value of a liability obligation related to the sale of common stock to Regeneron, and a gain on a litigation

settlement. 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.

ONPATTRO Revenues, Net

Net product revenues from sales of ONPATTRO were $38.2 million in the second quarter of 2019.

Net Revenues from Collaborators

Net revenues from collaborators were $6.5 million in the second quarter of 2019 as compared to $29.9 million in the second quarter of 2018.

GAAP and Non-GAAP Research and Development Expenses

GAAP research and development (R&D) expenses were $163.9 million in the second quarter of 2019 as compared to $137.6 million in the second quarter of 2018.

Non-GAAP R&D expenses were $148.6 million in the second quarter of 2019 as compared to $126.0 million in the second quarter of 2018. 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 Selling, General and Administrative Expenses

GAAP selling, general and administrative (SG&A) expenses were $112.8 million in the second quarter of 2019 as compared to $84.7 million in the second quarter of 2018.

Non-GAAP SG&A expenses were $97.4 million in the second quarter of 2019 as compared to $74.1 million in the second quarter of 2018. Non-GAAP SG&A expenses exclude stock-based compensation expense. A reconciliation between GAAP and

non-GAAP SG&A expenses appears later in this press release.

2019 Updated Financial Guidance

Alnylam is updating its 2019 annual non-GAAP R&D expenses to be in the range of $550 to $575 million (previously $550 to $590 million) and non-GAAP SG&A expenses to be in the range of $390 to $400 million (previously $390 million to

$410 million). Both non-GAAP R&D and non-GAAP SG&A expenses exclude stock-based compensation expenses.

The Company expects its current cash, cash equivalents, and marketable debt securities will support company operations for multiple years based upon its current operating plan.

Use of Non-GAAP Financial Measures