Alnylam Pharmaceuticals, Inc.

Adam Castoreno

Mark K Schlegel

James D McIninch

Charalambos Kaittanis

Frederic Tremblay

Martin A Maier

Stuart Milstein

Vasant R Jadhav

Kevin Fitzgerald

Jayaprakash K Nair

Mark Keating

Kirk Brown

Kristina Yucius

Elane Fishilevich

Muthiah Manoharan

Kallanthottathil G Rajeev

Muthusamy Jayaraman

Klaus Charisse

Rubina G Parmar

Alexander V Kel'in

Christopher S Theile

Sarah Solomon

Leila Noetzli

Mangala Meenakshi Soundarapandian

Anna Borodovsky

Ivan Zlatev

Jingxuan Liu

Pushkal Garg

Jeffrey Zuber

Lucas D BonDurant

Jason Gilbert

Patrick Haslett

Lucas Bondurant

Jae Kim

Karyn Schmidt

Dhaval Oza

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Patatin-Like Phospholipase Domain Containing 3 (PNPLA3) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a PNPLA3 gene and to methods of preventing and treating an PNPLA3-associated disorder, e.g., Nonalcoholic Fatty Liver Disease (NAFLD).

Patatin-like phospholipase domain containing 3 (PNPLA3) iRNA compositions and methods of use thereof

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the CIDEB gene, as well as methods of inhibiting expression of CIDEB, and methods of treating subjects that would benefit from reduction in expression of CIDEB, such as subjects having a CIDEB-associated disease, disorder, or condition, using such dsRNA compositions.

Cell death-inducing DFFA-like effector B (CIDEB) iRNA compositions and methods of use thereof

The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the ketohexokinase (KHK) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a KHK gene and to methods of treating or preventing a KHK-associated disorder in a subject.

Ketohexokinase (KHK) iRNA compositions and methods of use thereof

The invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs at one or more internal positions on at least one strand, optionally via a linker or carrier.

Extrahepatic delivery

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the complement component C3 gene (C3). The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupis nephritis (LN), bullous pemphigoid, Pemphigus, e.g., Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF), and C3 glomerulopathy.

Complement component C3 iRNA compositions and methods of use thereof

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the complement component C3 gene (C3). The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupis nephritis (LN), bullous pemphigoid,, e.g.,(PV) and(PF), and C3 glomerulopathy.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Factor XII (F12) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an F12 gene and to methods of preventing and treating an F12-associated disorder, e.g., heredity angioedema (HAE), prekallikrein deficiency, malignant essential hypertension, hypertension, end stage renal disease, Fletcher Factor Deficiency, thromboembolic disease, inflammatory disease, or Alzheimer's Disease.

Factor XII (F12) iRNA compositions and methods of use thereof

The present invention relates, in general to agents that modulate the pharmacological activity of siRNAs. In addition, the invention relates generally to methods and systems for use in assessing the efficacy and safety of a pharmaceutical composition for use in the treatment or prophylaxis of a disease.

Tunable Reversir™ compounds

One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, optionally via a linker or carrier. Another aspect of the invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a Huntingtin (HTT) gene, as well as methods of inhibiting expression of an HTT gene and methods of treating subjects having an HTT-associated disease or disorder, e.g., Huntington's disease, using such dsRNAi agents and compositions.

Huntingtin (HTT) iRNA agent compositions and methods of use thereof

The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the complement factor B (CFB) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a CFB gene and to methods of treating or preventing a CFB-associated disease in a subject.

Complement factor B (CFB) iRNA compositions and methods of use thereof

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the transthyretin (TTR) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an TTR gene and to methods of preventing and treating an TTR-associated disorder, e.g., senile systemic amyloidosis (SSA), systemic familial amyloidosis, familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy (FAC), leptomeningeal/Central Nervous System (CNS) amyloidosis, and hyperthyroxinemia.

Transthyretin (TTR) iRNA compositions and methods of use thereof

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a SOD1 gene, as well as methods of inhibiting expression of a SOD1 gene and methods of treating subjects having a SOD1-associated neurodegenerative disease or disorder, e.g., Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS), using such dsRNAi agents and compositions.

Superoxide dismutase 1 (SOD1) iRNA compositions and methods of use thereof for treating or preventing superoxide dismutase 1-(SOD1-) associated neurodegenerative diseases

The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the xanthine dehydrogenase (XDH) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an XDH gene and to methods of treating or preventing an XDH-associated disease in a subject.

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Framingham, MA, United States of America

Adam Castoreno