Second Quarter 2013 and Recent Significant Corporate HighlightsKey “Alnylam 5x15” Program Highlights
- Reported Positive Phase II Data for ALN-TTR02, an RNAi Therapeutic Targeting Transthyretin (TTR) for the Treatment of TTR-Mediated Amyloidosis (ATTR). Interim results from a Phase II study showed that multiple doses of ALN-TTR02, an intravenously delivered RNAi therapeutic, led to robust and statistically significant (p<0.001) knockdown of serum TTR protein levels of up to 93%. Knockdown of TTR, the disease-causing protein in ATTR, was found to be rapid, dose dependent, and durable, with similar activity observed toward both wild-type and mutant protein. In addition, ALN-TTR02 was found to be generally safe and well tolerated in this study. The Phase II study has nearly completed enrollment with about 30 patients, and Alnylam intends to present the final data from this study at the IXth International Symposium on Familial Amyloidotic Polyneuropathy (ISFAP) to be held in Rio de Janeiro, Brazil, November 10 – 13, 2013. In addition, the company remains on track to initiate in mid-2013 an open-label extension (OLE) study of ALN-TTR02 for patients treated in the Phase II study. The OLE study will include a number of clinical endpoint measures including Neuropathy Impairment Score, or “NIS,” and initial data are expected to be presented in 2014. Furthermore, the company intends to start a Phase III pivotal trial for ALN-TTR02 in FAP patients by the end of 2013.
- Announced Top-Line Phase I Results for ALN-TTRsc, a Subcutaneously Administered RNAi Therapeutic Targeting TTR for the Treatment of ATTR. ALN-TTRsc achieved robust and statistically significant (p<0.01) knockdown of serum TTR protein levels of greater than 80% in healthy volunteer subjects, in line with results previously reported in non-human primates. In addition, ALN-TTRsc was found to be generally safe and well tolerated. These top-line human study results are the first to be reported for Alnylam’s proprietary GalNAc-siRNA conjugate delivery platform, enabling subcutaneous dosing of RNAi therapeutics with a wide therapeutic index. Full results from the Phase I study will be presented at the Annual Scientific Meeting of the Heart Failure Society of America (HFSA), being held September 22 – 25, 2013 in Orlando, Fla.
- Advanced ALN-AT3, a Subcutaneously Administered RNAi Therapeutic Targeting Antithrombin (AT) for the Treatment of Hemophilia and Rare Bleeding Disorders (RBD), Toward Investigational New Drug (IND) Filing. Alnylam presented new pre-clinical data with ALN-AT3 at the XXIV Congress of the International Society on Thrombosis and Haemostasis (ISTH) that was held June 29 – July 4, 2013 in Amsterdam. The new pre-clinical results demonstrated that ALN-AT3 can normalize thrombin generation and improve hemostasis in hemophilia mice and fully correct thrombin generation in a non-human primate (NHP) hemophilia “inhibitor” model. In addition, the company presented results of tolerability studies that support a broad therapeutic index for ALN-AT3 in the hemophilia setting. Alnylam is completing a number of IND-enabling pre-clinical and CMC studies, and now expects a one quarter shift in the program timeline, resulting in the filing of an IND in the fourth quarter of 2013 and initiation of a Phase I clinical trial in early 2014.
- Advanced ALN-AS1, a Subcutaneously Administered RNAi Therapeutic Targeting Aminolevulinic Acid Synthase-1 (ALAS-1), for the Treatment of Porphyria. New pre-clinical data in rodent models of acute intermittent porphyria (AIP) were presented at the International Congress of Porphyrins and Porphyrias, which was held May 16 – 18, 2013 in Lucerne, Switzerland. Results demonstrated that RNAi therapeutics targeting ALAS-1 can completely block the abnormal production of toxic intermediates of the heme biosynthesis pathway that cause the symptoms and disease pathology of AIP. The new research results support the advancement of RNAi therapeutics as a promising strategy for the prevention and/or treatment of acute attacks in patients with AIP. The company is on track to designate a GalNAc-siRNA development candidate, ALN-AS1, in late 2013 and plans to file an IND in 2014.
- Designated ALN-CC5, a Subcutaneously Administered RNAi Therapeutic Targeting Complement Component C5 for the Treatment of Complement-Mediated Diseases, as a New “Alnylam 5x15” program. Alnylam presented pre-clinical data with ALN-CC5 at the 6 th International Conference on Complement Therapeutics that was held June 18 – 23, 2013 in Kos, Greece. The new research demonstrated potent, dose-dependent, and durable RNAi-mediated knockdown of serum C5 and inhibition of complement-mediated hemolytic activity of approximately 90%. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), neuromyelitis optica, amongst others. C5, which is predominantly expressed in liver cells, is a genetically and clinically validated target; loss-of-function human mutations are associated with an attenuated immune response against certain infections, and intravenous anti-C5 monoclonal antibody therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. A subcutaneously administered RNAi therapeutic that silences C5 represents a novel approach to the treatment of complement-mediated diseases. The company is performing additional optimization of the current GalNAc-siRNA conjugate lead molecule and expects to nominate its ALN-CC5 development candidate in late 2013.
- Advanced Additional “Alnylam 5x15” Programs. Alnylam continued to advance additional programs as part of its “Alnylam 5x15” product strategy, including ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of beta-thalassemia and iron-overload disorders; and ALN-AAT, an RNAi therapeutic targeting alpha-1-antitrypsin (AAT) for the treatment of liver disease associated with AAT deficiency. At its recent R&D Day, the company provided an update from its ALN-PCS program, which is partnered with The Medicines Company, showing pre-clinical results with a GalNAc-siRNA conjugate targeting PCSK9 (ALN-PCSsc) that enables subcutaneous dose administration. Specifically, in non-human primate studies performed in the absence of concomitant statin therapy, ALN-PCSsc showed greater than 80% knockdown of plasma PCSK9 with greater than 50% reductions in LDL-c.
- Expanded Management Team. Alnylam appointed John Frenz, Ph.D., to the position of Vice President of Manufacturing. Before joining Alnylam, Dr. Frenz was the Vice President of Operations at GlobeImmune, Inc., where he oversaw clinical supply of seven products across two Phase II and multiple Phase I trials. Prior to GlobeImmune, John was at Genentech, Inc., where he was Plant Manager of Biochemical Manufacturing in South San Francisco. In that role he oversaw the production of all of Genentech’s clinical products and about half of its commercial production.
|Alnylam Pharmaceuticals, Inc.|
|Unaudited Condensed Consolidated Statements of Comprehensive Loss|
|(In thousands, except per share amounts)|
|Three Months Ended||Six Months Ended|
|June 30,||June 30,|
|Net revenues from research collaborators||$8,687||$20,884||$27,329||$41,471|
|Research and development (1)||24,215||21,723||46,394||42,797|
|General and administrative (1)||5,784||11,228||12,051||21,634|
|Total operating expenses||29,999||32,951||58,445||64,431|
|Loss from operations||(21,312||)||(12,067||)||(31,116||)||(22,960||)|
|Other income (expense):|
|Equity in loss of joint venture (Regulus Therapeutics Inc.)||-||(1,139||)||-||(2,028||)|
|Other (expense) income||(11||)||(21||)||(6||)||170|
|Total other income (expense)||259||(889||)||488||(1,364||)|
|Loss before income taxes||(21,053||)||(12,956||)||(30,628||)||(24,324||)|
|Benefit from income taxes||2,884||-||3,446||-|
|Net loss per common share - basic and diluted||($0.29||)||($0.25||)||($0.45||)||($0.50||)|
|Weighted average common shares used to compute basic and diluted net loss per common share||61,661||51,280||60,424||48,877|
|Unrealized gain (loss) on marketable securities, net of tax||7,309||(25||)||12,468||103|
|(1) Non-cash stock-based compensation expenses included in operating expenses are as follows:|
|Research and development||$2,200||$1,998||$4,287||$4,086|
|General and administrative||1,177||1,098||2,165||2,166|
|Alnylam Pharmaceuticals, Inc.|
|Unaudited Condensed Consolidated Balance Sheets|
|(In thousands, except share amounts)|
|June 30,||December 31,|
|Cash, cash equivalents and total marketable securities||$379,512||$226,228|
|Billed and unbilled collaboration receivables||460||104|
|Prepaid expenses and other current assets||4,205||2,641|
|Property and equipment, net||18,045||19,799|
|Investment in equity securities of Regulus Therapeutics Inc.||60,336||38,748|
|Accounts payable and accrued expenses||18,254||15,978|
|Total deferred revenue||131,196||132,291|
|Total deferred rent||4,933||5,198|
|Total stockholders’ equity (62.5 million and 52.5 million common shares issued and outstanding at June 30, 2013 and December 31, 2012, respectively)||308,175||134,053|
|Total liabilities and stockholders' equity||$462,558||$287,520|