- LINZESS® (linaclotide)
- Three LINZESS doses now available with the introduction of 72 mcg dose -
- Multiple 2017 pipeline catalysts expected, including IW-3718 Phase IIb data for uncontrolled GERD and DUZALLO™ approval -
"Ironwood made steady progress in the first quarter towards becoming a
top-performing commercial biotech company, with strong execution across
all facets of our business," said
First Quarter 2017 and Recent Highlights
Irritable Bowel Syndrome with Constipation (IBS-C) / Chronic Idiopathic Constipation (CIC)
U.S.net sales, as provided by Ironwood's U.S.collaboration partner Allergan plc, were $147.6 millionin the first quarter of 2017, an 8% increase compared to the first quarter of 2016. Ironwood and Allergan share equally in brand collaboration profits.
More than 700,000 total LINZESS prescriptions were filled in the
first quarter of 2017, a 17% increase compared to the first
quarter of 2016, per QuintilesIMS.
- Total LINZESS prescription volume in the first quarter of 2017 included over 26 million LINZESS capsules, a more than 20% increase in capsules compared to the same period in 2016, per QuintilesIMS.
Higher year-over-year growth in LINZESS prescription volume
compared to LINZESS net sales was primarily due to differences
in trade buying patterns, resulting in destocking of
$20 millionin inventory during the first quarter of 2017.
Since the launch of LINZESS in
December 2012, nearly 1.5 million unique patients have filled nearly 7.5 million prescriptions, per QuintilesIMS.
Net profit for the LINZESS
U.S.brand collaboration, including commercial and research and development (R&D) expenses, was $62.1 millionin the first quarter of 2017, a 6% increase compared to the first quarter of 2016.
- LINZESS commercial margin was 52% in the first quarter of 2017, compared to 55% in the first quarter of 2016.
A 72 mcg dose of LINZESS was introduced in
March 2017for the treatment of CIC in adult patients. The newly approved and now available dose is providing physicians with dosing flexibility, based on individual presentation or tolerability, in treating the large and heterogeneous population of adult CIC patients.
- More than 700,000 total LINZESS prescriptions were filled in the first quarter of 2017, a 17% increase compared to the first quarter of 2016, per QuintilesIMS.
- Linaclotide Delayed Release-1 (DR1). Ironwood and Allergan are evaluating DR1 in adult patients with IBS-C, with Phase III trials expected to begin in the second half of 2017.
Linaclotide Delayed Release-2 (DR2). Ironwood and Allergan are
evaluating DR2 in adult patients with non-constipation subtypes of
IBS, and plan to discuss next steps with the
FDAfor advancing DR2 into Phase IIb dose-ranging clinical trials.
ZURAMPIC® (lesinurad). In
October 2016, Ironwood began commercializing ZURAMPIC in the U.S.for the treatment of hyperuricemia in patients with uncontrolled gout who are already taking a xanthine oxidase inhibitor (XOI), such as allopurinol or Uloric® (febuxostat). ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia and should not be used as monotherapy.
U.S.net sales were $0.3 millionin the first quarter of 2017.
- Approximately 900 total ZURAMPIC prescriptions were filled in the first quarter of 2017, per QuintilesIMS.
DUZALLO (lesinurad-allopurinol fixed-dose combination). In
January 2017, Ironwood announced that the FDAaccepted for review a New Drug Application (NDA) for DUZALLO for the treatment of hyperuricemia in patients with uncontrolled gout. If approved, DUZALLO is expected to be commercially available in the second half of 2017 and would be the first fixed-dose, dual-mechanism treatment of hyperuricemia in patients with uncontrolled gout.
Uncontrolled Gastroesophageal Reflux Disease (GERD)
- IW-3718. IW-3718 is a wholly-owned asset being developed for the potential treatment of uncontrolled GERD. Data from a Phase IIb dose-ranging clinical trial of IW-3718 are expected in mid-2017, with results expected to include two key analyses:
1) degree of reduction in heartburn severity for IW-3718 in combination
with a proton pump inhibitor (PPI) versus PPI alone, and
2) definition of a clinically meaningful improvement based on patient-reported symptom relief, and referencing that improvement to IW-3718 treatment effects.
Vascular and Fibrotic Diseases
IW-1973. Ironwood expects to initiate Phase II trials of
IW-1973 during the second half of 2017 in three disease states:
resistant hypertension, heart failure with preserved ejection fraction
and diabetic nephropathy.
- Additionally, two Phase IIa studies are currently underway for IW-1973 in diabetic patients with hypertension. The first study is evaluating the effect of IW-1973 on endothelial function and explores its effects on biomarkers. The second study is a fourteen-day study evaluating the tolerability and blood pressure effects of IW-1973. Data from both studies are expected in the second half of 2017.
- IW-1701. Ironwood is enrolling patients with Type II achalasia in a Phase IIa randomized, double-blind, placebo-controlled single-dose study of IW-1701. This study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of IW-1701 in these patients. Data from this study are expected in the second half of 2017.
Global Collaborations and Partnerships
January 2017, Ironwood expanded its linaclotide European license agreement with Allergan to include all remaining unpartnered territories worldwide in exchange for a royalty as a percentage of net sales of the product. Ironwood and Allergan also entered into a commercial agreement to eliminate in full, in 2018 and all subsequent years, the adjustments to Ironwood's or Allergan's net profits from making fewer LINZESS calls on physicians in a given year than was previously required under the collaboration agreement for linaclotide in North America. Additionally, starting in late February 2017, Ironwood clinical sales specialists began providing third position details for DELZICOL® (mesalamine) for ulcerative colitis and CANASA® (mesalamine) for ulcerative proctitis to gastroenterology practitioners for two years.
Ironwood continues to co-promote Allergan's VIBERZI®
(eluxadoline) in the
U.S.for adults suffering from IBS with diarrhea.
March 2017, Ironwood's partner, Astellas Pharma Inc., announced that it launched LINZESS for adults with IBS-C in Japan. Additionally, in January 2017, Ironwood and Astellas announced that the Phase III clinical trial of linaclotide in Japanin adults with chronic constipation met its primary endpoint.
Ironwood continues to expect the
China Food and Drug Administrationto complete its review of the filing for approval to market linaclotide in Chinafor adult IBS-C patients in the first quarter of 2018. Ironwood is partnered with AstraZeneca ABfor development and commercialization of linaclotide in China.
Corporate and Financials
Total revenues were
$52.2 millionin the first quarter of 2017 compared to $66.0 millionin the first quarter of 2016. Included in total revenues was $49.5 millionassociated with Ironwood's share of the net profits from the sales of LINZESS in the U.S., as well as sales of linaclotide drug product, linaclotide royalties, co-promotion revenue and ZURAMPIC revenue. Total revenues in the first quarter of 2016 reflect a $15 millionmilestone achieved from Astellas related to the development of linaclotide for the treatment of adults with IBS-C in Japan.
- Total revenues were
Operating expenses were
$91.8 millionin the first quarter of 2017 as compared to $68.0 millionin the first quarter of 2016. Operating expenses in the first quarter of 2017 consisted of $0.5 millionin cost of goods sold, $33.7 millionin R&D expenses, $55.6 millionin selling, general and administrative (SG&A) expenses, $0.4 millionin acquired intangible asset amortization expenses, and a $1.6 millionloss on fair value remeasurement of contingent consideration.
- Contingent consideration and amortization of acquired intangible assets relate to Ironwood's licensing agreement with AstraZeneca for the exclusive U.S. rights to all products containing lesinurad.
- Operating expenses were
Interest Expense. Net interest expense was
$8.6 millionin the first quarter of 2017, primarily in connection with the $150 million8.375% Notes funded in January 2017and the approximately $336 millionconvertible debt financing funded in June 2015. Interest on the 8.375% Notes will be payable quarterly beginning June 15, 2017, and principal will be payable quarterly beginning March 15, 2019, subject to the terms of such notes.
Interest expense recorded in the first quarter of 2017
$5.1 millionin cash expense and $3.9 millionin non-cash expense.
- Interest expense recorded in the first quarter of 2017 includes
Loss on Extinguishment of Debt. A
$2.0 millionwrite-off related to the payoff of the Linaclotide PhaRMA 11% Notes was recognized in the first quarter of 2017.
Loss on Derivatives. Ironwood records a gain/loss on
derivatives related to the change in fair value of the convertible
note hedges and note hedge warrants issued in connection with the
convertible debt financing funded in
June 2015. A loss on derivatives of $2.2 millionwas recorded in the first quarter of 2017.
- Interest Expense. Net interest expense was
GAAP net loss was
$52.5 million, or $0.36per share, in the first quarter of 2017, compared to $13.3 million, or $0.09per share, in the first quarter of 2016.
Non-GAAP net loss was
$48.3 million, or $0.33per share, in the first quarter of 2017, compared to $11.7 million, or $0.08per share, in the first quarter of 2016. Non-GAAP net loss excludes the impact of mark-to-market adjustments on the derivatives related to Ironwood's convertible debt, as well as the amortization of acquired intangible assets and the fair value remeasurement of contingent consideration related to Ironwood's U.S.lesinurad license. See Non-GAAP Financial Measures below.
- GAAP net loss was
Ironwood ended the first quarter of 2017 with
$295 millionof cash, cash equivalents and available-for-sale securities. Ironwood used approximately $27.8 millionof cash for operations during the first quarter of 2017.
- Ironwood ended the first quarter of 2017 with
2017 Financial Guidance
Ironwood continues to expect:
R&D expenses to be in the range of
$145 millionto $160million.
SG&A expenses to be in the range of
$235 millionto $250million.
the combined Allergan and Ironwood total 2017 marketing and
sales expenses for LINZESS to be in the range of
$250 millionto $280 million.
net interest expense to be approximately
to use less than
$100 millionin cash for operations in 2017.
- R&D expenses to be in the range of
- Ironwood continues to expect:
Non-GAAP Financial Measures
The company presents non-GAAP net loss and non-GAAP net loss per share
to exclude the impact of net gains and losses on the derivatives related
to our convertible notes that are required to be marked-to-market, as
well as the amortization of acquired intangible assets and the fair
value remeasurement of contingent consideration associated with
Conference Call Information
Ironwood will host a conference call and webcast at
About LINZESS (linaclotide)
LINZESS® is the #1 prescribed brand for the treatment of adult patients
with irritable bowel syndrome with constipation (IBS-C) and chronic
idiopathic constipation (CIC), based on QuintilesIMS data. Since its
LINZESS is a once-daily capsule that helps relieve the abdominal pain and constipation associated with IBS-C, as well as the constipation, infrequent stools, hard stools, straining, and incomplete evacuation associated with CIC. The recommended dose is 290 mcg for IBS-C patients and 145 mcg for CIC patients, with a 72 mcg dose approved for use in CIC depending on individual patient presentation or tolerability. LINZESS should be taken at least 30 minutes before the first meal of the day.
LINZESS is contraindicated in pediatric patients less than 6 years of age. The safety and effectiveness of LINZESS in pediatric patients less than 18 years of age have not been established. In neonatal mice, linaclotide increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years if age and older to develop severe diarrhea and its potentially serious consequences. In adults with IBS-C or CIC treated with LINZESS, the most commonly reported adverse event was diarrhea.
LINZESS is not a laxative; it is the first medicine approved by the
About ZURAMPIC (lesinurad) 200mg tablets
ZURAMPIC (lesinurad) works in combination with xanthine oxidase inhibitors (XOIs) to treat hyperuricemia associated with uncontrolled gout. ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia and should not be used as monotherapy. XOIs reduce the production of uric acid; ZURAMPIC increases the excretion of uric acid. Together, the combination of ZURAMPIC and an XOI provides a dual mechanism of action that both decreases production and increases excretion of uric acid, thereby lowering serum uric acid (sUA) levels in patients who have not achieved target serum uric acid levels with XOI treatment alone. ZURAMPIC selectively inhibits the function of transporter proteins uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4), involved in uric acid reabsorption in the kidney. The safety and efficacy of ZURAMPIC was established in three Phase III clinical trials that evaluated a once-daily dose of ZURAMPIC in combination with the XOI allopurinol or febuxostat compared to XOI alone. The boxed warning for ZURAMPIC states that acute renal failure has occurred with ZURAMPIC and was more common when ZURAMPIC was given alone and reinforces that ZURAMPIC should be used in combination with an XOI.
LINZESS Important Safety Information
INDICATIONS AND USAGE
LINZESS (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS
LINZESS is contraindicated in patients less than 6 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. Use of LINZESS should be avoided in patients 6 years to less than 18 years of age. The safety and effectiveness of LINZESS have not been established in patients less than 18 years of age.
- LINZESS is contraindicated in patients less than 6 years of age due to the risk of serious dehydration.
- LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
- LINZESS is contraindicated in patients less than 6 years of age. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established. In neonatal mice, linaclotide increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences.
- Use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age.
- Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in < 1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.
Common Adverse Reactions (incidence ≥2% and greater than placebo)
- In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
- In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%). In a CIC trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs < 1%).
Please see full Prescribing Information including Boxed Warning: http://www.allergan.com/assets/pdf/linzess_pi
ZURAMPIC Important Safety Information and Limitations of Use
WARNING: RISK OF ACUTE RENAL FAILURE MORE COMMON WHEN USED WITHOUT A XANTHINE OXIDASE INHIBITOR (XOI)
- Severe renal impairment (eCLcr less than 30 mL/min), end-stage renal disease, kidney transplant recipients, or patients on dialysis
- Tumor lysis syndrome or Lesch-Nyhan syndrome
Warnings and Precautions:
- Renal events: Adverse reactions related to renal function have occurred after initiating ZURAMPIC. A higher incidence was observed at the 400-mg dose, with the highest incidence occurring with monotherapy use. Monitor renal function at initiation and during therapy with ZURAMPIC, particularly in patients with eCLcr below 60 mL/min or with serum creatinine elevations 1.5 to 2 times the pre-treatment value, and evaluate for signs and symptoms of acute uric acid nephropathy. Interrupt treatment with ZURAMPIC if serum creatinine is elevated to greater than 2 times the pre-treatment value or if there are symptoms that may indicate acute uric acid nephropathy. ZURAMPIC should not be restarted without another explanation for the serum creatinine abnormalities. ZURAMPIC should not be initiated in patients with an eCLcr less than 45 mL/min.
- Cardiovascular events: In clinical trials, major adverse cardiovascular events (defined as cardiovascular deaths, non-fatal myocardial infarctions, or non-fatal strokes) were observed with ZURAMPIC. A causal relationship has not been established.
- Most common adverse reactions with ZURAMPIC (in combination with an XOI and more frequently than on an XOI alone) were headache, influenza, blood creatinine increased, and gastroesophageal reflux disease
Indication and Limitations of Use for ZURAMPIC
ZURAMPIC is a URAT1 inhibitor indicated in combination with an XOI for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with an XOI alone.
- ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia
- ZURAMPIC should not be used as monotherapy
Please see full Prescribing Information, including Boxed Warning, at: http://www.azpicentral.com/zurampic/zurampic.pdf.
VIBERZI Important Safety Information
- Known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction; a history of pancreatitis; structural diseases of the pancreas.
- Alcoholism, alcohol abuse, alcohol addiction, or drink more than 3 alcoholic beverages per day.
- Severe hepatic impairment.
- A history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
Sphincter of Oddi Spasm:
- There is a potential for increased risk of sphincter of Oddi spasm, resulting in pancreatitis or hepatic enzyme elevation associated with acute abdominal pain (eg, biliary-type pain) with VIBERZI. These events were reported in less than 1% of patients receiving VIBERZI in clinical trials.
- Patients without a gallbladder are at increased risk. Consider alternative therapies before using VIBERZI in patients without a gallbladder and evaluate the benefits and risks of VIBERZI in these patients.
- Inform patients without a gallbladder that they may be at increased risk for symptoms of sphincter of Oddi spasm, such as elevated liver transaminases associated with abdominal pain or pancreatitis, especially during the first few weeks of treatment. Instruct patients to stop VIBERZI and seek medical attention if they experience symptoms of sphincter of Oddi spasm.
- There is a potential for increased risk of pancreatitis not associated with sphincter of Oddi spasm; such events were reported in less than 1% of patients receiving VIBERZI in clinical trials, and the majority were associated with excessive alcohol intake. All pancreatic events resolved upon discontinuation of VIBERZI.
- Instruct patients to avoid chronic or acute excessive alcohol use while taking VIBERZI. Monitor for new or worsening abdominal pain that may radiate to the back or shoulder, with or without nausea and vomiting, associated with elevations of pancreatic enzymes. Instruct patients to stop VIBERZI and seek medical attention if they experience symptoms suggestive of pancreatitis.
- The most commonly reported adverse reactions (incidence > 5% and greater than placebo) were constipation, nausea, and abdominal pain.
Please see full Prescribing Information for VIBERZI: http://www.allergan.com/assets/pdf/viberzi_pi
LINZESS® and CONSTELLA® are trademarks of
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about the development, launch,
introduction and commercial potential of linaclotide, lesinurad, our
product candidates and the other products that we promote and the
drivers, timing, impact and results thereof (including pipeline
catalysts); reduction of a significant risk from IW-3718, if Phase IIb
data is positive; market size, prevalence, growth and opportunity,
including peak sales and the potential demand for linaclotide, lesinurad
and our product candidates, as well as their potential impact on
applicable markets; the potential indications for, and benefits of,
linaclotide, lesinurad and our product candidates; the anticipated
timing of preclinical, clinical and regulatory developments and the
design, timing and results of clinical and preclinical studies; the
potential for, and timing of, regulatory submissions and approvals for
linaclotide, lesinurad and our product candidates, and the level of risk
associated with the path to approval; expected periods of patent
exclusivity; commercial strategy, including plans to secure payer access
and activate patients; the strength of the intellectual property
protection for linaclotide, lesinurad and our product candidates and our
intentions and efforts to protect such intellectual property; our
potential for sustainable, high-margin growth and shareholder returns;
and our financial performance and results, and guidance and expectations
related thereto (including the drivers and timing thereof), including
expectations related to Ironwood revenue CAGR and revenue growth,
Condensed Consolidated Balance Sheets
|Cash, cash equivalents and available-for-sale securities||$||295,339||$||305, 216|
|Accounts receivable, net||51,147||64,854|
|Prepaid expenses and other current assets||8,664||9,030|
|Restricted cash, current portion||1,190||-|
|Total current assets||357,853||380,181|
|Property and equipment, net||18,633||20,512|
|Convertible note hedges||150,509||132,521|
|Intangible assets, net||165,699||166,119|
|Liabilities and Stockholders' Equity|
|Accounts payable, accrued expenses and other current liabilities||$||57,502||$||62,941|
|Current portion of capital lease obligations||5,501||6,227|
|Current portion of deferred rent||588||7,719|
|Current portion of deferred revenue||741||-|
|Current portion of contingent consideration||14,561||14,244|
|Total current liabilities||78,893||91,131|
|Capital lease obligations||21||82|
|Note hedge warrants||133,424||113,237|
|Total stockholders' equity||29,637||66,716|
|Total liabilities and stockholders' equity||$||701,319||$||709,821|
Condensed Consolidated Statements of Operations
Three Months Ended
|Cost and expenses:|
|Cost of revenue, excluding amortization of acquired intangible asset||531||-|
|Research and development||33,702||31,842|
|Selling, general and administrative||55,604||36,168|
|Amortization of acquired intangible asset||420||-|
Loss on fair value remeasurement of contingent consideration
|Total cost and expenses||91,871||68,010|
|Loss from operations||(39,705||)||(1,968||)|
|Other (expense) income:|
|Interest expense, net||(8,588||)||(9,686||)|
|Loss on extinguishment of debt||(2,009||)||-|
|Loss on derivatives||(2,199||)||(1,643||)|
|Other expense, net||(12,796||)||(11,329||)|
|GAAP net loss||$||(52,501||)||$||(13,297||)|
|GAAP net loss per share—basic and diluted||$||(0.36||)||$||(0.09||)|
Three Months Ended
|Non-GAAP net loss||$||(48,268||)||$||(11,654||)|
|Non-GAAP net loss per share (basic and diluted)||$||(0.33||)||$||(0.08||)|
Weighted average number of common shares used in net loss
Reconciliation of GAAP Results to Non-GAAP Financial Measures
A reconciliation between net loss on a GAAP basis and on a non-GAAP basis is as follows:
Three Months Ended
|GAAP net loss||$||(52,501||)||$||(13,297||)|
|Mark-to-market adjustments on the derivatives related to convertible notes, net||2,199||1,643|
|Amortization of acquired intangible asset||420||—|
|Fair value remeasurement of contingent consideration||1,614||—|
|Non-GAAP net loss||$||(48,268||)||$||(11,654||)|
A reconciliation between diluted net loss per share on a GAAP basis and on a non-GAAP basis is as follows:
Three Months Ended
|GAAP net loss per share - basic and diluted||$||(0.36||)||$||(0.09||)|
|Adjustments to GAAP net loss per share (as detailed above)||0.03||0.01|
|Non-GAAP net loss per share - basic and diluted||$||(0.33||)||$||(0.08||)|
Three Months Ended
Commercial costs and expenses2
|Commercial profit on sales of LINZESS||$||76,686||$||74,988|
|Ironwood's share of net profit||$||38,343||$||37,494|
Ironwood's selling, general and administrative expenses4
|Ironwood's collaborative arrangement revenue||$||49,452||$||46,647|
1 Ironwood collaborates with Allergan on the development and
commercialization of linaclotide in
2Includes cost of goods sold incurred by Allergan as well as selling, general and administrative expenses incurred by Allergan and Ironwood that are attributable to the cost-sharing arrangement between the parties.
3Commercial margin is defined as commercial profit on sales of LINZESS as a percent of total LINZESS
4Includes Ironwood's selling, general and administrative expenses attributable to the cost-sharing arrangement with Allergan.
Director, Corporate Communications
Senior Director, Investor Relations
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