Alnylam Pharmaceuticals Reports Second Quarter 2022 Financial Results and Highlights Recent Period Activity Achieved Second Quarter 2022 Global Net Product Revenues of $214 Million for ONPATTRO , GIVLAARI , and OXLUMO (3

Achieved Second Quarter 2022 Global Net Product Revenues of $214 Million for ONPATTRO , GIVLAARI , and OXLUMO (33% Growth vs. Same Period Last

Received FDA Approval of AMVUTTRA (vutrisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults -

Expects to Report Topline Results from APOLLO-B Phase 3 Trial of Patisiran in Patients with ATTR Amyloidosis with Cardiomyopathy Within the Next Three Weeks -

- Reiterated 2022 Financial Guidance, Including Combined Net Product Revenues of $870-$930 Million -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--July 28, 2022--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today reported its consolidated financial results for the second quarter ended June 30, 2022 and reviewed

recent business highlights.

"We're pleased with our second quarter results which delivered strong growth in both patient demand and product revenues. A notable achievement in the quarter was the recent approval of AMVUTTRA, which becomes our fifth RNAi therapeutic

approved in under four years, and marks our continued progress in building a multi-product TTR franchise. We're excited to have initiated the U.S. launch and look forward to potential additional global approvals and subsequent rollout," said

Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. "We are also eager for a number of important milestones over the rest of the year, including topline results from the APOLLO-B Phase 3 study of patisiran in ATTR amyloidosis with

cardiomyopathy patients, which we've announced today are expected within the next three weeks. Additionally, we plan to continue to advance our robust pipeline, with clinical data expected across several prevalent disease programs in NASH,

HBV, gout, and early-onset Alzheimer's disease with ALN-APP, our first investigational RNAi therapeutic targeting a CNS disorder. We believe the first half of 2022 has been one of steady progress and commercial execution, and we look forward

to the many important milestones through the end of the year, moving us further along our path toward achieving our Alnylam P5x25 goals."

Second Quarter 2022 and Recent Significant Corporate Highlights

Commercial Performance

TTR Franchise: ONPATTRO (patisiran) & AMVUTTRA (vutrisiran)

Achieved global net product revenues for ONPATTRO for the second quarter of 2022 of $153 million, representing a 12% increase compared to Q1 2022.

Attained over 2,400 hATTR amyloidosis patients with polyneuropathy worldwide on commercial ONPATTRO treatment as of June 30, 2022, up from over 2,200 commercial patients as of March 31, 2022, representing 9% quarterly growth.

Received 133 Start Forms in the U.S. for AMVUTTRA from launch through July 22, 2022 with 34% representing patients new to Alnylam and 66% representing patients switching from ONPATTRO.

GIVLAARI (givosiran)

Achieved global net product revenues for the second quarter of 2022 of $45 million, representing a 28% increase compared to Q1 2022.

Attained over 420 patients worldwide on commercial GIVLAARI treatment as of June 30, 2022, up from over 400 commercial patients as of March 31, 2022, representing 5% quarterly growth.

Achieved global net product revenues for the second quarter of 2022 of $15 million, representing a 2% increase compared to Q1 2022.

Attained over 200 patients worldwide on commercial OXLUMO treatment as of June 30, 2022, up from over 160 commercial patients as of March 31, 2022, representing 25% quarterly growth.

Launch in the U.S. and other markets is ongoing, with focus on patient onboarding, removing access hurdles and enhancing medical education.

Vutrisiran (the non-proprietary name for AMVUTTRA), a subcutaneously administered RNAi therapeutic in development for the treatment of ATTR amyloidosis and Stargardt Disease

Received FDA approval of AMVUTTRA for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval of vutrisiran for the treatment of hereditary transthyretin-mediated amyloidosis

(hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy.

Reported new 18-month results from exploratory cardiac endpoints from the HELIOS-A Phase 3 study in hATTR amyloidosis patients with polyneuropathy.

Lumasiran (the non-proprietary name for OXLUMO), for the treatment of primary hyperoxaluria type 1 (PH1), and in development for the treatment of recurrent kidney stone disease

Presented new results from the ILLUMINATE-A Phase 3 study in patients with PH1.

Presented new results from the 12-month analysis of the ILLUMINATE-B Phase 3 open-label pediatric study in patients less than six years of age with PH1.

Presented new results from the ILLUMINATE-C Phase 3 study in patients with advanced PH1.

Cemdisiran, in development for the treatment of complement-mediated diseases, in collaboration with Regeneron.

Reported positive topline results from the Phase 2 study in patients with immunoglobulin A nephropathy (IgAN).

Alnylam is working with Regeneron to finalize plans for the Phase 3 clinical development of cemdisiran in IgAN, with the potential to initiate a program by late 2022.

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

Sanofi presented positive data from the Phase 3 ATLAS-PPX study evaluating the efficacy and safety of once-monthly fitusiran (80 mg) in adults and adolescents with severe hemophilia A or B who were previously treated with prior factor or

bypassing agent (BPA) prophylaxis.

The study met the primary endpoint and demonstrated fitusiran prophylaxis significantly reduced bleeding episodes compared to prior factor or BPA prophylaxis.

Early- and mid-stage investigational RNAi therapeutic pipeline programs and RNAi platform

Published preclinical results in Nature Biotechnology based on novel conjugate technology facilitating delivery of siRNA to the CNS and other extrahepatic tissues.

Vir Biotechnology presented new results from its ongoing Phase 2 clinical trial of ALN-HBV02 (VIR-2218), as well as preclinical data evaluating ALN-HBV02 in combination with VIR-3434, in patients with chronic hepatitis B virus

Initiated a Phase 1 study of ALN-XDH in patients with gout.

Published research findings in Nature Communications identifying mutations in the INHBE gene associated with protection against abdominal obesity and metabolic syndrome.

Alnylam announces today that it expects to report topline results from the pivotal APOLLO-B Phase 3 study of patisiran in ATTR amyloidosis patients with cardiomyopathy within the next three weeks.

In addition, the Company announces today that it plans to present results from the Phase 2 study of cemdisiran in patients with IgAN at the 18th European Meeting on Complement in Human Disease (EMCHD) being held August

26-29, 2022 in Bern, Switzerland.

In addition, in mid- and late-2022, Alnylam intends to:

Launch vutrisiran in the EU, assuming a favorable adoption of the CHMP opinion by the European Commission, for the treatment of hATTR amyloidosis patients with polyneuropathy.

Report topline results from Part B of the Phase 1 study of ALN-HSD in patients with NASH.

Report results on a biannual dose regimen for vutrisiran.

Initiate a Phase 3 study of vutrisiran in patients with Stargardt Disease.

File an Investigational New Drug (IND) application and initiate a Phase 1 study for ALN-TTRsc04 in healthy volunteers.

Complete enrollment in the Phase 2 study of lumasiran in patients with recurrent renal stones.

Complete enrollment in the KARDIA-2 Phase 2 study of zilebesiran (at or around year-end).

Vir Biotechnology plans to report additional results from its Phase 2 study of ALN-HBV02 in combination with VIR-3434 in patients with chronic HBV infection in the second half of 2022.

Report preliminary results from the Phase 1 study of ALN-APP in patients with early-onset Alzheimer's disease.

Report preliminary results from the Phase 1 study of ALN-XDH in patients with gout.

* CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in the second quarter 2021. CER is a Non-GAAP measure.

Net product revenues increased 33% at actual currency during the second quarter of 2022, as compared to the prior year, and 40% at CER. The increase is primarily due to increased patients on ONPATTRO and GIVLAARI.

Net Revenues from Collaborations

Net revenues from collaborations decreased 85% during the second quarter of 2022, as compared to the prior year, primarily due to a decrease in revenue from our collaboration with Regeneron resulting from the timing of reimbursable

Research & Development (R&D) Expenses

GAAP and Non-GAAP R&D expenses increased during the second quarter of 2022, as compared to the prior year, primarily due to increased early development and study activities, increased employee headcount and other expenses to support

our development activities.

Selling, General & Administrative (SG&A) Expenses

GAAP and Non-GAAP SG&A expenses increased during the second quarter of 2022, as compared to the prior year, primarily due to increased employee headcount and other expenses to support our commercial portfolio.

Other Financial Highlights

GAAP other expense, net, increased during the second quarter of 2022, as compared to the prior year, primarily due to an approximate $32 million increase in the fair value of our development derivative liability and an increase in

interest expenses of approximately $9 million related to additional draws on our term loan facility.

Cash, cash equivalents and marketable securities were $2.11 billion as of June 30, 2022, compared to $2.44 billion as of December 31, 2021, with the decrease primarily due to our operating loss in the second quarter of 2022.

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

2022 Financial Guidance1

Full year 2022 financial guidance is reiterated and consists of the following:

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 and revenue growth excluding the impact

of changes in foreign exchange rates. 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 and realized and unrealized (gains) losses

on marketable equity securities. 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 realized and unrealized (gains) losses 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

Percentage changes in revenue growth at CER are presented excluding the impact of changes in foreign currency exchange rates for investors to understand the underlying business performance. The current period's foreign currency revenue

values are converted into U.S. dollars using the average exchange rates from the prior period.

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 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 second quarter 2022 results as well as expectations for the future via conference call on Thursday, July 28, 2022 at 8:30 am ET. To access the call, please register online at

https://register.vevent.com/register/BId099ca291c69486ea91a87453136e78a. Participants are requested to register at a minimum 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived

on the same web page for six months.

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