Alnylam Pharmaceuticals Reports Third Quarter 2017 Financial Results and Highlights Recent Period Activity - Reported Positive APOLLO Phase 3 Results for Patisiran, with Plans for First New Drug Application (NDA) Filing

Pharmaceuticals Reports Third Quarter 2017 Financial Results and

Highlights Recent Period Activity

Reported Positive APOLLO Phase 3 Results for Patisiran, with Plans for

First New Drug Application (NDA) Filing by Year-End -

Advanced Four RNAi Therapeutics in Late-Stage Development, Including

Initiation of ENVISION Phase 3 Study for Givosiran in Acute Hepatic

Maintained Strong Balance Sheet with $1.15 Billion in Cash and Plans to

End 2017 with Greater than $1 Billion in Cash -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--November 7, 2017--Alnylam

Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics

company, today reported its consolidated financial results for the third

quarter 2017, and highlighted recent progress in advancing its pipeline.

"In our view, 2017 has proven to be a remarkable year for RNAi

therapeutics, for Alnylam, and, most importantly, for the patients that

we serve. With patisiran, our recent APOLLO Phase 3 study results

demonstrate what we believe to be the transformative potential for RNAi

therapeutics as a new class of innovative medicines. With these data, we

expect to submit our first regulatory filings in the coming months, and

are planning for the possibility of having regulatory approval for

patisiran in mid-2018," said John Maraganore, Ph.D., Chief Executive

Officer of Alnylam. "We have also made significant progress across our

other programs, including the initiation of our ENVISION Phase 3 program

for givosiran in acute hepatic porphyrias and, with our partners at The

Medicines Company, the ORION Phase 3 program in hypercholesterolemia.

Additionally, we aim to resume dosing in all fitusiran studies,

including the ATLAS Phase 3 program, as soon as possible. These

milestones position Alnylam with multiple late-stage clinical assets,

while we concurrently transition into a fully integrated commercial

company with the goal of delivering innovative medicines to patients

Third Quarter 2017 and Recent Significant Corporate Highlights

Advanced patisiran, an investigational RNAi therapeutic in development

for the treatment of patients with hereditary ATTR (hATTR)

amyloidosis, with positive results from the APOLLO Phase 3 study

Patisiran met its primary endpoint (p = 9.26 x 10-24)

with a 34.0 point mean difference relative to placebo and a

negative 6.0 point mean change (improvement) relative to baseline

in the modified neuropathy impairment score (mNIS+7) at 18 months,

as well as all secondary endpoints (p less than 0.001), including

a 21.1 point mean difference relative to placebo and a negative

6.7 point mean change (improvement) relative to baseline in the

NORFOLK Quality of Life-Diabetic Neuropathy score (NORFOLK QOL-DN)

(p = 1.10 x 10-10), at 18 months.

Patisiran also demonstrated a favorable safety and tolerability

profile relative to placebo. The most commonly reported adverse

events (AEs) for patisiran were generally mild to moderate and

included peripheral edema (29.7 percent) and infusion-related

reactions (IRRs) (18.9 percent), and the frequency of deaths and

serious adverse events (SAEs) was similar in the patisiran and

placebo groups. No deaths were considered drug-related.

Specifically, the Company believes that these data support a

potentially "best-in-class" product profile, with significant

benefit relative to placebo, negative mean and median values

(improvement) for mNIS+7 and QOL measures relative to baseline,

and encouraging safety and tolerability.

In addition, patisiran achieved significant effects in the study's

cardiac subpopulation, including on disease biomarker,

echocardiographic, and functional parameters.

The Company believes the totality of the APOLLO data are

consistent with a clinically meaningful impact for patisiran on

hATTR amyloidosis, and plans to submit an NDA for patisiran by the

end of 2017 and a Marketing Authorisation Application (MAA)

Advanced ALN-TTRsc02, a subcutaneously administered investigational

RNAi therapeutic in development for the treatment of ATTR amyloidosis.

Presented updated Phase 1 data showing up to 95% transthyretin

(TTR) knockdown with a single 50 mg dose, with durability

supportive of a once quarterly and, possibly, bi-annual

subcutaneous dose regimen.

Reaffirmed guidance to initiate a Phase 3 program for ALN-TTRsc02

Advanced givosiran, an investigational RNAi therapeutic in development

for the treatment of acute hepatic porphyrias (AHPs), with initiation

of the ENVISION Phase 3 study.

The Company reached alignment with the U.S. Food and Drug

Administration (FDA) on the design of ENVISION, including an

interim analysis based on reduction of urinary aminolevulinic acid

(ALA), a biomarker that the FDA considers to be reasonably likely

to predict clinical benefit.

The Company has also reached alignment on the ENVISION Phase 3

study design with the European Medicines Agency (EMA).

The Company is guiding that it expects interim analysis results in

mid-2018 and, pending FDA review of the program at the time of

interim analysis and assuming positive results, it expects to

submit an NDA at or around year-end 2018.

Advanced fitusiran, an investigational RNAi therapeutic in

development for the treatment of hemophilia A and B with or

without inhibitors, with new positive data from the Phase 2

open-label extension (OLE) study presented at the International

Society on Thrombosis and Haemostasis 2017 Congress.

Results from the Phase 1 study were published in The New

England Journal of Medicine in a paper titled, "Targeting of

Antithrombin in Hemophilia A or B with RNAi Therapy."

Announced the initiation of the ATLAS Phase 3 program, a global,

multicenter clinical program designed to evaluate the safety and

efficacy of fitusiran in patients with hemophilia A and B with or

The Company temporarily suspended dosing in all ongoing studies of

fitusiran following the observation of a fatal thrombotic SAE that

occurred in a patient with hemophilia A without inhibitors who was

receiving fitusiran in the Phase 2 OLE study. Alnylam and

fitusiran study investigators have aligned on a risk management

plan for further advancement of fitusiran and are now conferring

with global regulators with the goal of resuming dosing as soon as