Conference Call to Discuss FDA Approval of OXLUMO™ (lumasiran)

November 24, 2020

© 2020 Alnylam Pharmaceuticals, Inc.

Agenda

Welcome

• Christine Lindenboom
  Senior Vice President, Investor Relations & Corporate Communications

Introduction

• John Maraganore, Ph.D. Chief Executive Officer

OXLUMO™ (lumasiran) Label & Data

• Akshay Vaishnaw, M.D., Ph.D. President of R&D

Commercialization Strategy

• Andy Orth
  Senior Vice President, Head of U.S. Business

Q&A Session

2

Alnylam Forward Looking Statements

This presentation contains forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. There are a number of important factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements. These important factors include: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic, such as the scope and duration of the outbreak, government actions and restrictive measures implemented in response, material delays in diagnoses of rare diseases, initiation or continuation of treatment for diseases addressed by our products, or in patient enrollment in clinical trials, potential supply chain disruptions, and other potential impacts to our business, the effectiveness or timeliness of steps taken by us to mitigate the impact of the pandemic, and our ability to execute business continuity plans to address disruptions caused by the COVID- 19 or any future pandemic; our ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of our product candidates, pre-clinical and clinical results for our product candidates; actions or advice of regulatory agencies; delays, interruptions or failures in the manufacture and supply of our product candidates and our marketed products, including OXLUMOTM (lumasiran); intellectual property matters including potential patent litigation relating to our platform, products or product candidates; our and our partner's ability to obtain regulatory approval for our product candidates, including inclisiran, and our ability to maintain regulatory approval and obtain pricing and reimbursement for products, including ONPATTRO® (patisiran), GIVLAARI® (givosiran) and OXLUMO; our ability to successfully launch, market and sell our approved products globally, including ONPATTRO, GIVLAARI and OXLUMO, and achieve net product revenues for ONPATTRO within our further revised expected range during 2020; our ability to successfully expand the indication for ONPATTRO in the future; competition from others using similar technology and developing products for similar uses; our ability to manage our growth and operating expenses within the reduced ranges of guidance provided by us through implementation of further discipline in operations to moderate spend and our ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; our ability to establish and maintain business alliances; our dependence on third parties, including Novartis, for the development, manufacture and commercialization of inclisiran, Regeneron, for development, manufacture and commercialization of certain products, including eye and CNS products such as ALN-APP and Vir for the development of ALN-COV and other potential RNAi therapeutics targeting SARS-CoV-2 and host factors for SARS-CoV-2; the outcome of litigation; and the risk of government investigations; as well as those risks and other factors more fully discussed in our most recent annual, quarterly and current reports filed with the SEC. If one or more of these factors materialize, or if any underlying assumptions prove incorrect, our actual results, performance or achievements may vary materially from any future results, performance or achievements expressed or implied by these forward-looking statements. All forward-looking statements speak only as of the date of this presentation and, except as required by law, we undertake no obligation to update such statements.

3

John Maraganore, Ph.D. Chief Executive Officer

Introduction

4

The third RNAi therapeutic is

NOW APPROVED IN THE U.S. & EU

5

Additional Launches Planned Over Next 18 Months

Akshay Vaishnaw, M.D., Ph.D.

President of R&D

OXLUMO™ (lumasiran) Label & Data

7

1 Includes patients that are presymptomatic, subclinical, or symptomatic

Met Primary and All Tested Secondary Endpoints with Encouraging Safety and Tolerability Profile

Efficacy Results and Safety Profile in Pediatric Patients Similar to Those Observed in ILLUMINATE-A

Data in graph are presented as mean ± SEM of observed values

10 1Viral infection, considered not related to the study drug by the Investigator

BL, baseline; M, month; SEM, standard error of the mean; ULN, upper limit of normal; AE, adverse event; SAE, serious adverse event

OXLUMO™ (lumasiran) Label for U.S.

11

Lumasiran Phase 3 Studies

Robust Registrational Program Evaluating Lumasiran Across all Ages and Full PH1 Disease Spectrum

Expanded Access Protocol (EAP) for PH1 patients initiated in U.S. and Europe

12

Andy Orth

Senior Vice President, Head of U.S. Business

Commercialization Strategy

13

OXLUMO Market Opportunity

Estimated U.S./EU Prevalence and Addressable Population

Patients in the U.S. / EU†

† US population=328MM, EU population (including UK) = 513MM

^ Includes patients that are presymptomatic, subclinical, or symptomatic

Sources: 1. Hopp K, et al. J Am Soc Nephrol. 2015 Feb 2; 2. Cochat et al. Nephrol Dial Transplant. 1995; 10: 3-7; 3. Kopp and Leumann. Nephrol Dial Transplant. 1995; 10: 2224-2227; 4. van Woerden, et al. Nephrol Dial Transplant. 2003; 18: 273-279; 5. Data on

14 file. Alnylam chart review studies (US and EU) estimated 17% transplant rate, rounded up to 20%; 6. Cochat P, et al. N Engl J Med. 2013 Nov 28;369(22):2163; 7. Harambat J. Clin J Am Soc Nephrol. 2012 Mar;7(3):458-65; 8. Kamoun A. Pediatr Nephrol. 1996 Aug;10(4):479-82.

OXLUMO Market Opportunity

First-in-Class Product in Ultra-Rare Orphan Disease

PREVALENCEDIAGNOSISDISEASE BURDEN COST BURDEN

LUMASIRAN | PRIMARY HYPEROXALURIA TYPE 1

>$500M potential market opportunity

15 1. Cochat et al. Nephrol Dial Transplant. 1995; 10: 3-7; 2. Kopp and Leumann. Nephrol Dial Transplant. 1995; 10: 2224-2227; 3. van Woerden, et al. Nephrol Dial Transplant. 2003; 18: 273-279; 4.Hopp R, et al. J Am Soc Nephrol. 2015;26:2559-2570; 5. Harambat J, et al. Kidney Int. 2010;77(5):443-449.

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Launching in a Pandemic

Execution Tailored to Meet Needs of Customers

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OXLUMO™ (lumasiran) FDA Approval

Q&A Session

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To those who say "impossible, impractical, unrealistic," we say:

CHALLENGE ACCEPTED

© 2020 Alnylam Pharmaceuticals, Inc.