Company: Alnylam Pharmaceuticals, Inc.
Headquarters: Cambridge, Massachusetts, USA
Founded: 2002
Ticker: ALNY (NASDAQ)
Market Cap: ~$35 billion (2024)
CEO: Yvonne Greenstreet (since 2023)
Employees: ~2,500
Alnylam Pharmaceuticals is a leading biotechnology company pioneering RNA interference (RNAi) therapeutics. Founded in 2002 based on Nobel Prize-winning science, Alnylam has developed a novel class of medicines that work by silencing specific genes responsible for disease. The company's groundbreaking RNAi platform has produced five approved medicines and established Alnylam as a leader in genetic medicine[1].
While Alnylam's initial focus was on rare genetic diseases, the company has expanded into strategic areas including neuroscience, with particular emphasis on neurodegenerative diseases where genetic targets have been identified. The company's CNS pipeline targets Alzheimer's disease, Parkinson's disease, ALS, and other neurological disorders through partnerships with Regeneron and internal programs[2][3].
Alnylam was founded in 2002 by a group of leading scientists who pioneered the development of RNA interference therapeutics:
The company built its platform based on the foundational discovery that double-stranded RNA can trigger sequence-specific gene silencing in mammalian cells, a process that had been evolutionarily conserved across species[4].
| Year | Event |
|---|---|
| 2002 | Company founded |
| 2004 | IPO on NASDAQ |
| 2018 | First FDA-approved RNAi therapeutic (Onpattro) |
| 2019 | Givlaari approved |
| 2020 | Oxlumo approved |
| 2021 | Leqvio approved |
| 2022 | Amvuttra approved |
| 2023 | Yvonne Greenstreet appointed CEO |
| 2024 | ALN-APP Phase 1 results announced |
| Year | Revenue | Net Product Sales | R&D Expenses | Net Income |
|---|---|---|---|---|
| 2024 | $2.4B | $1.8B | $1.1B | $400M |
| 2023 | $1.9B | $1.4B | $950M | $280M |
| 2022 | $1.0B | $890M | $800M | $120M |
| 2021 | $650M | $470M | $680M | -$50M |
The company's revenue has grown significantly driven by Leqvio's launch and expansion of existing products. Leqvio (inclisiran) has become a blockbuster, with strong uptake in the PCSK9 inhibitor market.
RNA interference (RNAi) is a natural cellular process that silences specific genes[2:1]:
The key advantage of RNAi is its ability to target any gene based on its nucleic acid sequence, making it theoretically applicable to any disease where a genetic target can be identified.
Alnylam has pioneered several key delivery platforms[@millennium2023][4:1]:
The TRiM™ platform was developed specifically for tissue-specific delivery including the CNS[5]:
Alnylam operates a 175,000 sq ft manufacturing facility in Norton, Massachusetts, capable of producing siRNA at commercial scale. The company uses a proprietary synthesis process that enables cost-effective manufacturing at scale.
Alnylam's neuroscience pipeline targets genetically validated targets in neurodegenerative diseases[6][3:1]:
| Program | Target | Mechanism | Stage | Development Partner |
|---|---|---|---|---|
| ALN-APP | APP | siRNA against amyloid precursor protein | Phase 1 | Internal |
| ALN-PACK | APOE4 | siRNA targeting APOE4 allele | Discovery | Internal |
| ALN-AB | Amyloid-beta | siRNA against Aβ production | Discovery | Regeneron |
| TTR-001 | TTR | siRNA for TTR polyneuropathy | Phase 2 | Internal |
ALN-APP is an RNAi therapeutic targeting amyloid precursor protein (APP), the source of amyloid-beta peptides that accumulate in Alzheimer's disease[7][8]:
The Phase 1 study demonstrated dose-dependent reduction of APP mRNA in cerebrospinal fluid, validating the RNAi approach for CNS targets[9].
This program targets apolipoprotein E4 (APOE4), the strongest genetic risk factor for late-onset Alzheimer's disease[10]:
| Program | Target | Mechanism | Stage | Development Partner |
|---|---|---|---|---|
| ALN-GBA | GBA1 | siRNA for GBA-associated PD | Discovery | Internal |
| ALN-LRRK2 | LRRK2 | siRNA for LRRK2-associated PD | Discovery | Internal |
| ALN-PD01 | Unknown | siRNA for idiopathic PD | Discovery | Regeneron |
GBA1 mutations are the most common genetic risk factor for Parkinson's disease, accounting for 5-10% of all PD cases[11]:
LRRK2 mutations are a major cause of familial Parkinson's disease[12]:
| Program | Target | Mechanism | Stage | Development Partner |
|---|---|---|---|---|
| ALN-CSN1 | C9orf72 | siRNA for C9orf72-ALS/FTD | Discovery | Regeneron |
| ALN-SOD1 | SOD1 | siRNA for SOD1-ALS | Development (tofersen) | Biogen |
| ALN-TDP | TDP-43 | siRNA for TDP-ALS | Discovery | Regeneron |
C9orf72 repeat expansion is the most common genetic cause of ALS and frontotemporal dementia (FTD)[13]:
Tofersen (formerly ALN-SOD1) was developed for SOD1-ALS but was outlicensed to Biogen[14]:
While not specifically for neurodegeneration, Onpattro was the first RNAi therapeutic approved by the FDA (2018) and demonstrates Alnylam's CNS delivery capabilities:
Though technically an antisense oligonucleotide (ASO) rather than siRNA, Qalsody demonstrates the potential for genetic silencing in neurological disease:
| Product | Indication | Approval Year | 2024 Revenue |
|---|---|---|---|
| Givlaari (givosiran) | Acute hepatic porphyria | 2019 | $180M |
| Oxlumo (lumasiran) | Primary hyperoxaluria type 1 | 2020 | $95M |
| Leqvio (inclisiran) | Hypercholesterolemia | 2021 | $1.4B |
| Amvuttra (vutrisiran) | hATTR polyneuropathy | 2022 | $280M |
The Regeneron partnership is Alnylam's most significant CNS collaboration:
Alnylam is the clear leader in RNAi therapeutics, with competitors including:
In the Alzheimer's space, Alnylam competes with:
The Phase 1 study of ALN-APP showed[9:1]:
Phase 3 APOLLO-B study (hATTR polyneuropathy):
RNA interference therapeutics in the CNS pipeline. 2023. ↩︎ ↩︎
siRNA therapeutics for neurodegenerative diseases. 2019. ↩︎ ↩︎ ↩︎
siRNA delivery to the central nervous system. 2023. ↩︎ ↩︎ ↩︎
TRiM platform for CNS delivery. 2024. ↩︎
Alzheimer's disease. 2024. ↩︎ ↩︎
Alnylam Presents Positive Phase 1 Results for ALN-APP (2024). 2024. ↩︎ ↩︎
LRRK2 and Parkinson's disease. 2024. ↩︎
Tofersen for SOD1-ALS. 2022. ↩︎