Alnylam - Silent No More

(RTTNews) - Alnylam Pharmaceuticals Inc. (ALNY), which has had a steady climb over the last two years, crossed the $50 mark for the first time on Friday, thanks to positive developments in its RNAi clinical programs. RNAi, or RNA interference, technology aims at treating diseases in a fundamentally new way by silencing disease-causing genes.

Dubbed as "Alnylam 5x15", the company's core product strategy is to have five RNAi therapeutic programs in clinical development, including programs in advanced stages, on its own or with one or more collaborators, by the end of 2015.

Alnylam's five core programs are:

* ALN-TTR comprised of ALN-TTR02 and ALN-TTRsc, for the treatment of transthyretin-mediated amyloidosis, or ATTR.

Transthyretin-mediated amyloidosis, also known as ATTR, is caused by mutations in TTR gene, leading to accumulation of abnormal amyloid proteins and damage to body organs and tissue. This is an inherited, progressively debilitating and fatal disease.

ATTR, which is a significant orphan disease, has two predominant forms namely, familial amyloidotic polyneuropathy (FAP) and familial amyloidotic cardiomyopathy (FAC).

FAP patients are said to have a life expectancy of five to 15 years from symptom onset while the mean survival for FAC patients is approximately 2.5 years. There are no approved therapies for FAC. Liver transplant is the current standard of care for FAP and Pfizer's Vyndaqel is an approved therapy in the E.U.

The company reported positive interim results from a phase II study of ALN-TTR02 for the treatment of TTR-mediated amyloidosis last month. According to the results, ALN-TTR02 demonstrated robust knockdown of up to 93% of circulating wild-type and mutant TTR in a multi-dose study.

The final phase II data from the ALN-TTR02 study are scheduled for presentation at the IXth International Symposium on Familial Amyloidotic Polyneuropathy (ISFAP) to be held in Rio de Janeiro, Brazil, November 10-13, 2013.

A pivotal phase III trial for ALN-TTR02 in familial amyloidotic polyneuropathy patients is expected to be initiated by the end of 2013.

ALN-TTRsc for the treatment of transthyretin-mediated amyloidosis is under phase I testing. Promising results from an ongoing phase I ALN-TTRsc trial were reported last week.

According to the company, ALN-TTRsc achieved robust and statistically significant knockdown of serum TTR protein levels of greater than 80% in healthy volunteer subjects in the phase I trial.

Additional results from the phase I trial of ALN-TTRsc will be presented at the Annual Scientific Meeting of the Heart Failure Society of America, being held September 22-25, 2013 in Orlando, Florida.

A phase II study of ALN-TTRsc in familial amyloidotic cardiomyopathy patients is expected to be initiated by the end of this year. If all goes well as planned, the company will commence a pivotal phase III trial for ALN-TTRsc in 2014.

Genzyme has an exclusive license to develop ALN-TTR02 and ALN-TTRsc in Japan and the Asia-Pacific region, while Alnylam retains all development and commercialization rights worldwide outside of this territory.

* ALN-AT3 for the treatment of hemophilia and rare bleeding disorders. Positive results from a pre-clinical study of ALN-AT3 were presented last month. The company intends to file an investigational new drug application for ALN-AT3 in mid-2013 and initiate a phase I study in late 2013.

* ALN-AS1 for the treatment of acute intermittent porphyria.

The company presented positive pre-clinical proof-of-concept data for ALN-AS1 in May of 2013. An investigational new drug filing for ALN-AS1 is expected to happen in 2014.

* ALN-PCS for the treatment of hypercholesterolemia. The ALN-PCS program includes ALN-PCS02, which has completed a phase I trial, and ALN-PCSsc, currently in pre-clinical development.

Alnylam has a global alliance with The Medicines Co. (MDCO) for the development of the ALN-PCS program that was inked in February of 2013.

* ALN-TMP for the treatment of beta-thalassemia and iron-overload disorders.

In pre-clinical studies, ALN-TMP has demonstrated corrective effects on iron overload in addition to broader disease modifying effects including improvements in hemoglobin levels, spleen histopathology and globin gene expression. The company plans to enter into partnership for the ALN-TMP program prior to initiating a phase I clinical trial.

Alnylam's partner-based programs in clinical development include:

- ALN-RSV01 for the treatment of respiratory syncytial virus infection in lung transplant patients, which has completed phase II testing. ALN-RSV01 failed to achieve the primary end point of a phase IIb trial, the results of which were announced in May of 2012.

However, with ALN-RSV01 demonstrating significant treatment effect, the company met with the FDA and European regulatory authorities last year and obtained preliminary guidance on the design of a potential phase III clinical trial.

The company's partner for developing ALN-RSV01 in Asia is Kyowa Hakko Kirin. Alnylam also had a partnership with Cubist Pharmaceuticals Inc. (CBST) for developing ALN-RSV01 in the rest of the world. But that deal was terminated this year and Alnylam intends to seek another partner to advance the ALN-RSV01 program into phase III testing.

- ALN-VSP for the treatment of liver cancers, which has successfully completed phase I trials. The ALN-VSP program is partnered with Ascletis Pharmaceuticals Co., Ltd., a privately held U.S.-China joint venture pharmaceutical company, for further advancement in the Chinese market while Alnylam retains all rights to the compound in the rest of the world.

Financial Numbers...

Alnylam has incurred significant operating losses since inception, and as of March 31, 2013, had an accumulated deficit of $516.0 million. The company has no marketed products and revenue is generated through research collaborations. The company's fiscal year ends in December.

Net loss narrowed to $9.0 million or $0.15 per share on revenues of $18.6 million in Q1-2013. This compared with a net loss of $11.4 million or $0.25 per share and revenues of $20.6 million in the year-ago quarter.

The company ended Q1-2013 with zero debt and cash, cash equivalents and fixed income marketable securities of $400.8 million.

Stock Tale...

Founded in 2002, Alnylam went public on the NASDAQ in June 2004, offering its shares at $6 each.

ALNY was trading around $7 when it was profiled on our site in October 2011. Since then, the stock has been on a steady ascent, touching an all-time high of $51 on July 12, 2013.

The stock is up 174% year to date, a pretty impressive performance in a time frame of six and a half months.

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