Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom (Investors and Media) 617-682-4340 Josh Brodsky (Investors) 617-551-8276 Alnylam Pharmaceuticals Reports Second Quarter 2021 Financial Results and Highli

Alnylam Pharmaceuticals Reports Second Quarter 2021 Financial Results and Highlights

Recent Period Activity

Achieved Second Quarter 2021 Combined Net Product Revenues of $161 Million for

ONPATTRO , GIVLAARI , and

Advanced Vutrisiran with New Drug Application (NDA) Submission to the U.S. Food and

Drug Administration (FDA) for the Treatment of

the Polyneuropathy of Hereditary ATTR

Amyloidosis (hATTR-PN); Received FDA Acceptance of NDA

with Prescription Drug User Fee

Act (PDUFA) Date Set for April 14, 2022

Completed Enrollment in APOLLO-B Phase 3 Study of Patisiran in Transthyretin-Mediated

(ATTR) Amyloidosis Patients with Cardiomyopathy (ATTR-CM)

Initiated KARDIA Phase 2 Program with Zilebesiran (ALN-AGT) in Patients with Mild-to-

Moderate Hypertension

Increased 2021 Guidance Range for Combined Net Product Revenues from $610-$660 Million

to $640-$665 Million

CAMBRIDGE, Mass., August 3, 2021 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today reported its

consolidated financial results for the second quarter ended June 30, 2021 and reviewed recent business highlights.

Our commercial performance

in the second quarter continued to demonstrate steady and continued growth across our three wholly owned marketed products. The second quarter also marked significant progress for our TTR franchise overall, including NDA submission and acceptance

for vutrisiran based on positive HELIOS-A results, initiation of a biannual dosing study for vutrisiran, completion of enrollment in the APOLLO-B Phase 3 trial and

imminent enrollment completion for HELIOS-B, and introduction of ALN-TTRsc04 for a potential annual dosing regimen. Together, these efforts highlight our commitment to

ATTR amyloidosis for years to come, said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. With sights set on our Alnylam P5x25 five-year

vision announced earlier this year, we believe we are well positioned and on our way to achieving these ambitious goals. With this strategy we intend to deliver transformative medicines for rare and prevalent diseases to patients around the world,

advancing a robust and high-yielding clinical pipeline of first and/or best-in-class product candidates stemming from our organic product engine, while delivering

exceptional financial performance.

Second Quarter 2021 and Recent Significant Corporate Highlights

Commercial Performance

Patisiran (the non-proprietary name for ONPATTRO), in development for the treatment of the cardiomyopathy of

both hereditary and wild-type ATTR amyloidosis

Vutrisiran, a subcutaneously administered investigational RNAi therapeutic in development for the

treatment of ATTR amyloidosis

Lumasiran (the non-proprietary name for OXLUMO), for the treatment of primary hyperoxaluria type 1 (PH1)

non-proprietary name for Leqvio) for the treatment of hypercholesterolemia or mixed dyslipidemia, in collaboration with Novartis

Fitusiran, in development for the treatment of hemophilia A or B with and without inhibitors, in

collaboration with Sanofi

Early- and mid-stage RNAi therapeutic pipeline programs

Additional Business Updates

In mid- and late 2021, Alnylam intends to:

Financial Results for the Quarter Ended June 30, 2021

Based on the strong commercial performance of our products in the first half of the year, with growth in combined net product revenues nearly double the

same period in 2020, we are increasing our revenue guidance for 2021, and now expect to achieve between $640 million and $665 million in combined net product revenues across our three wholly owned commercial brands for the full year 2021.

We re also pleased to now recognize royalty revenue from Novartis sales of Leqvio, and believe that commercial success of this important medicine could be a meaningful contributor to our growth in the future, said Jeff Poulton,

Chief Financial Officer of Alnylam. We remain focused on delivering strong topline growth while continuing to demonstrate disciplined investment in our operations, and believe this will transition us toward a self-sustainable financial

profile, aligned with our Alnylam P5x25 strategy.

Financial highlights

(in thousands, except per share amounts)

Net Product Revenues

Net Revenues from Collaborations

Year-to-Date 2021 Expenses

Research & Development (R&D) Expenses

Selling, General & Administrative (SG&A) Expenses

Other Financial Highlights

Other (Expense) Income

Cash and Investments

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

2021 Updated Financial Guidance

Full year 2021 financial guidance consists of the following:

*Excludes $160-$180 million of stock-based from estimated GAAP R&D and

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and non-recurring gains outside the ordinary course of the Company s business. 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 items included in GAAP

presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are stock-based compensation expenses, unrealized losses (gains) on marketable

equity securities, costs associated with our strategic financing collaboration, and gain on contractual settlement. 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 has excluded the impact of the

unrealized losses (gains) on marketable equity securities because the Company does not believe these adjustments accurately reflect the performance of the Company s ongoing operations for the period in which such gains or losses are reported,

as their sole purpose is to adjust amounts on the balance sheet. The Company has excluded the impact of the costs associated with our strategic financing collaboration and gain on settlement because the Company believes these items are non-recurring transactions outside the ordinary course of the Company s business.

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 and are better able to compare the

Company s performance between periods. 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 of selected 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 second quarter 2021 results as well as expectations for the future via conference call on Tuesday,

August 3, 2021 at 8:30 am ET.

To access the call, please dial 877-312-7507 (domestic) or +1-631-813-4828 (international) five minutes prior to the start time and refer to conference ID 8870516. A replay of the call will be available beginning at 11:30 am ET

on the day of the call. To access the replay, please dial 855-859-2056 (domestic) or +1-404-537-3406 (international) and refer to conference ID 8870516.

A live audio webcast of the call will

be available on the Investors section of the Company s website at www.alnylam.com/events. An archived webcast will be available on the Alnylam website approximately two hours after the event.

About ONPATTRO (patisiran)

ONPATTRO is an RNAi therapeutic that was approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults.

ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an

intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. ONPATTRO blocks the production of TTR in the liver,

reducing its accumulation in the body s tissues in order to halt or slow down the progression of the polyneuropathy associated with the disease. For more information about ONPATTRO, visit ONPATTRO.com.

ONPATTRO Important Safety Information

Infusion-Related Reactions

Infusion-related reactions

(IRRs) have been observed in patients treated with ONPATTRO (patisiran). In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated

patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of

IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR

occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or

life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation

ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients