Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2011 Financial Results
“2011 was a year of remarkable clinical achievement for Alnylam and for
RNAi therapeutics. Notably, we reported on positive clinical data in
three distinct programs over the past 12 months, including human proof
of RNAi mechanism in our ALN-VSP liver cancer program, human proof of
concept in our ALN-TTR program for transthyretin-mediated amyloidosis,
and clinical efficacy in our ALN-PCS severe hypercholesterolemia
“With clear evidence that RNAi can work in patients, our strategy in
2012 is to focus our near term ‘Alnylam 5x15’ efforts on what we believe
to be our highest value opportunities, driving key programs toward
pivotal trials,” said
The net loss according to accounting principles generally accepted in
the U.S. (GAAP) for the fourth quarter of 2011 was
Research and Development Expenses
Research and development (R&D) expenses were
General and Administrative Expenses
General and administrative (G&A) expenses were
Equity in loss of joint venture was
Interest income was
Other income was
2012 Financial Guidance
Alnylam expects that its cash, cash equivalents and total marketable
securities balance will be greater than
“Alnylam continues to maintain a solid balance sheet, ending the year
Fourth Quarter 2011 and Recent Significant Corporate Highlights
Key “Alnylam 5x15” Program Highlights
Advanced Clinical Developmentof ALN-TTR Program for Transthyretin(TTR)-Mediated Amyloidosis (ATTR). Alnylam continued to advance its ALN-TTR program, which targets the TTR gene for the treatment of ATTR.
- Alnylam reported positive preliminary clinical results from its ALN-TTR01 Phase I clinical study, showing that ALN-TTR01 was generally safe and well tolerated and resulted in a statistically significant lowering of TTR serum levels in ATTR patients. ALN-TTR01 is comprised of an siRNA formulated in a first generation lipid nanoparticle (LNP). The company has completed enrollment in its ALN-TTR01 Phase I clinical study and expects to report final data in the first half of 2012.
Alnylam is also advancing ALN-TTR02, which uses the same siRNA as
ALN-TTR01, but is formulated in a more potent, proprietary second
generation LNP which was used in its ALN-PCS program demonstrating
preliminary clinical efficacy. The company announced today that it
has received acceptance by the
U.K.Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase I trial with ALN-TTR02. The new clinical trial is designed as a randomized, single-blind, single-ascending dose study, enrolling up to 32 healthy volunteer subjects. The objectives of the study are to evaluate safety and tolerability, as well as clinical activity as measured by serum TTR levels following a single dose of ALN-TTR02, with subjects being enrolled into five sequential dose cohorts ranging from 0.01 to 0.50 mg/kg. Alnylam plans to begin enrollment in this clinical trial in the first half of 2012 and expects to report data in the third quarter of 2012. In addition, the company also plans to start a Phase II multi-dose clinical study of ALN-TTR02 in ATTR patients in the second half of 2012 and, assuming positive results, expects to start a pivotal trial for ALN-TTR02 in 2013.
- Alnylam also announced plans to advance ALN-TTRsc, which utilizes a GalNAc-conjugate delivery approach and subcutaneous dose administration. Pre-clinical studies have shown that once weekly dosing with ALN-TTRsc enables robust and sustained silencing of TTR over a multi-week period. Alnylam plans to file an investigational new drug (IND) or IND equivalent for ALN-TTRsc in the second half of 2012, with data expected in the first half of 2013. ALN-TTRsc provides an opportunity for product differentiation in the ATTR indication.
Advanced Developmentof ALN-APC Program for Hemophilia. Alnylam presented pre-clinical data from its ALN-APC program at the 53rd American Society of Hematology (ASH) Meeting. Results showed dose-dependent silencing of the protein C mRNA with an ED50 of approximately 0.02 mg/kg. Further, when administered as a single dose of 0.3 mg/kg, the LNP-formulated siRNA achieved greater than 75% silencing of protein C mRNA with effects lasting for weeks. The company plans to advance its ALN-APC program toward the clinic with a goal of initiating a Phase I clinical trial in the first half of 2013 with data expected in the second half of 2013.
- Reported Positive Preliminary Clinical Results in ALN-PCS Severe Hypercholesterolemia Program. Alnylam achieved positive preliminary results from its ongoing clinical trial of ALN-PCS, a systemically delivered RNAi therapeutic targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) for the treatment of severe hypercholesterolemia. These results showed safety and tolerability as well as potent, robust, and statistically significant knockdown of PCSK9 plasma levels and reductions in low-density lipoprotein cholesterol (LDL-C) levels, a clinically validated endpoint. Results also documented for the first time major advances in delivery of RNAi therapeutics using second generation LNPs in human studies. The Phase I clinical study is ongoing with planned dose escalation and Alnylam expects to report additional data in the first half of 2012. Alnylam plans to partner its ALN-PCS program prior to initiating a Phase II clinical study.
- Selected ALN-TMP for Hemoglobinopathies as Fifth “Alnylam 5x15” Program. Alnylam designated ALN-TMP as its fifth “Alnylam 5x15” program. ALN-TMP comprises a systemically delivered RNAi therapeutic targeting transmembrane protease, serine 6 (Tmprss6) for the treatment of hemoglobinopathies, including beta-thalassemia and sickle cell anemia. Hemoglobinopathies are defined by genetic defects in the globin chains of hemoglobin and are associated with chronic anemia, extra-medullary hematopoiesis, and iron overload. Tmprss6, a genetically validated target expressed on hepatocytes, normally functions by cleaving hemojuvelin, resulting in reduced hepcidin levels and increased iron mobilization. As presented at the recent ASH meeting, pre-clinical animal model studies with ALN-TMP have demonstrated corrective effects on iron overload in addition to broader disease modifying effects including improvements in hemoglobin levels and spleen histopathology. Alnylam plans to partner this program prior to initiating a Phase I clinical study.
- Presented Data at ASH for ALN-HPN Refractory Anemia Program. ALN-HPN is a systemically delivered RNAi therapeutic targeting the hepcidin pathway via transferrin receptor subtype 2 (TFR2) for the treatment of refractory anemia. At the recent ASH meeting, new pre-clinical data on ALN-HPN were presented documenting TFR2 as the ideal target for hepcidin pathway antagonism and demonstrating efficacy in anemia models. The company plans to partner its ALN-HPN program prior to initiating a Phase I clinical study.
Key Partner-Based Program Highlights
Completed Enrollment in Phase IIb Clinical Study of ALN-RSV01.
Alnylam completed patient enrollment in its Phase IIb clinical study
with ALN-RSV01, an RNAi therapeutic for the treatment of respiratory
syncytial virus (RSV) infection. The Phase IIb trial was designed as a
multi-center, randomized, double-blind, placebo-controlled study in
RSV-infected lung transplant patients. The company expects to report
results in mid-2012. The ALN-RSV program is partnered with
Kyowa Hakko Kirin Co., Ltd.in Asiaand Cubist Pharmaceuticals, Inc.worldwide except Asia.
- Completed Phase I Clinical Study of ALN-VSP. Alnylam completed treatment of patients in the Phase I clinical study protocol with ALN-VSP, a systemically delivered RNAi therapeutic targeting both vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP) for the treatment of liver cancers. Data from the Phase I clinical study showed that ALN-VSP was generally well tolerated, demonstrated evidence for anti-tumor activity, and was found to mediate RNAi activity in both hepatic and extra-hepatic tumors. Currently three patients with disease control continue to receive ALN-VSP under an extension protocol; these include an endometrial patient that has been on drug for over 20 months, and two additional patients, one with advanced renal cell cancer and the other with pancreatic neuroendocrine tumor, with continued stable disease after over one full year of treatment. The company intends to partner ALN-VSP prior to initiating a Phase II clinical study.
- Published Pre-clinical Results with ALN-HTT. Pre-clinical data related to the company’s ALN-HTT program, an RNAi therapeutic drug-device combination for the treatment of Huntington’s disease, were recently published in the journal Experimental Neurology. The company expects to file an IND and advance ALN-HTT into clinical trials in the second half of 2012.
Business and Organizational Highlights
Formed Collaboration with
GlaxoSmithKlineon RNAi Technology for Vaccine Production. Alnylam formed a collaboration on its newly disclosed VaxiRNATM technology with GlaxoSmithKline(GSK) focused on certain GSK vaccine products, including influenza. Alnylam’s VaxiRNA platform applies siRNAs for the silencing of target genes that limit or prevent efficient growth of viruses in vaccine manufacturing systems, including those in cell culture and in chicken eggs. GSK, a leading vaccine manufacturer, is the first company to form a collaboration accessing this new platform.
Implemented Corporate Restructuring to Align with Focused Efforts. In
January 2012, Alnylam announced a strategic corporate restructuring, including an approximate 33% reduction in its workforce. The workforce reduction was implemented in order to align the company’s resources to a more focused execution on ALN-TTR and ALN-APC programs with accelerated clinical development plans. Alnylam expects the reduction in personnel costs, along with other external costs, to result in a savings of approximately $20 millionin 2012 operating expenses. Alnylam estimates that it will incur one-time restructuring costs of approximately $4 millionin connection with the restructuring, including employee severance, benefits, and related costs, which it expects to incur in the first quarter of 2012.
Conference Call Information
Management will provide an update on the company, discuss fourth quarter
and 2011 results, and discuss expectations for the future via conference
A live audio webcast of the call will also be available on the News & Investors page of the company’s website, www.alnylam.com. An archived webcast will be available on the Alnylam website approximately two hours after the event.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About “Alnylam 5x15™”
The “Alnylam 5x15” strategy, launched in
Alnylam is a biopharmaceutical company developing novel therapeutics
based on RNA interference, or RNAi. The company is leading the
translation of RNAi as a new class of innovative medicines with a core
focus on RNAi therapeutics for the treatment of genetically defined
diseases, including ALN-TTR for the treatment of transthyretin-mediated
amyloidosis (ATTR), ALN-PCS for the treatment of severe
hypercholesterolemia, ALN-HPN for the treatment of refractory anemia,
ALN-APC for the treatment of hemophilia, and ALN-TMP for the treatment
of hemoglobinopathies. As part of its “Alnylam 5x15TM”
strategy, the company expects to have five RNAi therapeutic products for
genetically defined diseases in clinical development, including programs
in advanced stages, on its own or with a partner by the end of 2015.
Alnylam has additional partner-based programs in clinical or development
stages, including ALN-RSV01 for the treatment of respiratory syncytial
virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and
ALN-HTT for the treatment of Huntington’s disease. The company’s
leadership position on RNAi therapeutics and intellectual property have
enabled it to form major alliances with leading companies including
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam’s future
expectations, plans and prospects, including without limitation,
Alnylam’s expectations regarding its “Alnylam 5x15” product strategy,
Alnylam’s views with respect to the potential for RNAi therapeutics,
including ALN-TTR02 and ALN-TTRsc, ALN-APC, ALN-PCS, ALN-HPN, ALN-TMP,
ALN-VSP, ALN-RSV01 and ALN-HTT, its expectations with respect to the
timing and success of its clinical and pre-clinical trials, the expected
timing of regulatory filings, including its plan to file IND or IND
equivalent applications and initiate clinical trials for ALN-TTR02,
ALN-TTRsc, ALN-APC and ALN-HTT, its expectations regarding reporting
data from its ongoing and planned clinical studies, including its
studies for ALN-TTR01, ALN-TTR02, ALN-TTRsc, ALN-APC, ALN-PCS and
ALN-RSV, its plans to seek collaborations for its ALN-PCS, ALN-HPN,
ALN-TMP and ALN-VSP programs, its expected cash position as of
Alnylam Pharmaceuticals, Inc.
Unaudited Condensed Consolidated Statements of Operations
(In thousands, except per share amounts)
Three Months Ended
|Net revenues from research collaborators||$20,455||$21,192||$82,757||$100,041|
|Research and development (1)||23,369||26,080||99,295||106,384|
|General and administrative (1)||10,672||7,522||38,280||37,727|
|Total operating expenses||34,041||33,602||137,575||144,111|
|Loss from operations||(13,586)||(12,410)||(54,818)||(44,070)|
|Other income (expense):|
|Equity in loss of joint venture (Regulus Therapeutics Inc.)||(954)||(916)||(3,505)||(7,639)|
|Other (expense) income||1||6,351||(531)||6,403|
|Total other income (expense)||(717)||5,907||(2,831)||1,069|
|Loss before income taxes||(14,303)||(6,503)||(57,649)||(43,001)|
|Provision for income taxes||—||(427)||
|Net loss per common share - basic and diluted||$(0.33)||$(0.16)||$(1.36)||$(1.04)|
Weighted average common shares used to compute basic
(1) Non-cash stock-based compensation expenses
|Research and development||$2,637||$2,489||$10,921||$11,689|
|General and administrative||1,445||1,723||5,755||7,429|
|Alnylam Pharmaceuticals, Inc.|
|Unaudited Condensed Consolidated Balance Sheets|
|(In thousands, except share amounts)|
|December 31,||December 31,|
|Cash, cash equivalents and total marketable securities||$260,809||$349,904|
|Income taxes receivable||—||10,669|
|Prepaid expenses and other current assets||4,158||6,889|
|Property and equipment, net||14,643||18,289|
|Investment in joint venture (Regulus Therapeutics Inc.)||564||3,616|
|Intangible assets, net||275||448|
|Accounts payable and accrued expenses||$18,140||$20,428|
|Total deferred revenue||140,853||211,108|
|Total deferred rent||4,211||3,353|
|Other long-term liabilities||716||143|
Total stockholders’ equity (42.7 million and 42.3 million
|Total liabilities and stockholders' equity||$281,917||$393,265|
This selected financial information should be read in conjunction with
the consolidated financial statements and notes thereto included in
Alnylam’s Annual Report on Form 10-K which includes the audited
financial statements for the year ended
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice President, Investor Relations and
Michael Mason, 617-551-8327
Vice President, Finance and Treasurer