Technical Analysis
Positive-Trend
Short Term Resistance: ~$78.00
Current Support: Exponential Moving Average (EMA)

Alnylam Pharmaceuticals, Inc. is a company I see value in. From a technical analysis, their positive uptrend is an attractive characteristic. Short-term, it is approaching a $78 resistance. If waiting for the “bounce” and “confirmation” on the exponential moving average of ~$72.15, ALNY may produce over an 8% profit.

The company is a biopharmaceutical company focused on the discovery, development and commercialization of RNA interference therapeutics for genetically defined diseases. They currently have an approved product, ONPATTRO (patisaran), and multiple pipeline products.

ONPATTRO (patisiran) lipid complex injection, for intravenous use
ONPATTRO contains a transthyretin-directed small interfering RNA and is indicated for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.²

APOLLO – Phase 3 clinical trial evaluating the efficacy and safety of patisiran in adults with hereditary ATTR (hATTR) amyloidosis with symptomatic polyneuropathy (previously known as familial amyloidotic polyneuropathy [FAP]) (NCT01960348).

Phase 3 clinical trial evaluating the efficacy and safety of patisiran in participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression after liver transplant is currently enrolling (NCT03862807).

Ribonucleic Acid-Based Therapeutics
Ribonucleic acid (RNA) is a simpler molecule than protein (4 nucleotide building blocks versus 20 amino acid building blocks) and is common to all living things. A ribonucleic acid (RNA)-targeted approach for disease treatment interacts with a specific RNA sequence so only a single gene product is targeted. The RNA-targeted agents are grouped by their mechanisms of action.¹

• Inhibitors of messenger RNA (mRNA) translation (antisense)
• Agents of RNA interference, including small interfering RNAs (siRNAs)
• Ribozymes, which are active RNA molecules that speed up chemical reactions
• Aptamers, which bind to proteins or other molecular ligands

Small Interfering RNA (siRNA) Technology
RNA interference is a “gene silencing” method, in which it binds selectively and with high affinity to RNA that encodes a target protein to prevent the target protein translation and expression. The siRNAs are short-double-stranded RNA molecules, usually containing 19 to 22 base pairs.⁴

Below is the mechanism of action of siRNAs.³

1. The enzyme Dicer RNase III splits the initial long double-stranded RNA into siRNAs.
2. The siRNAs are incorporated into the RNA-induced silencing complex (RISC), a ribonucleoprotein-endonuclease complex.
3. The siRNA unwinds and the antisense strand guides the complex to the target endogenous RNA sequence.
4. RISC then breaks down the target RNA transcript.

ONPATTRO (patisiran) Mechanism of Action
Patisiran is a double-stranded siRNA that causes degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.²

REFERENCES
1. Burnett JC, Rossi JJ. RNA-based therapeutics: current progress and future prospects. Chem Biol. 2012; 19(1):60-71.
2. ONPATTRO® (patisaran) lipid complex injection, for intravenous use [Prescribing Information, 2018]. Alnylam Pharmaceuticals, Inc., Cambridge, MA
3. Wang JH, Hendry BM, Sharpe CC. Silencing genes in the kidney: antisense or RNA interference? Nephrol Dial Transplant. 2008;23(7):2115-2118.
4. Watts JK, Corey DR. Gene silencing by siRNAs and antisense oligonucleotides in the laboratory and the clinic. J PAthol. 2012; 226(2):365-379.