Ironwood Pharmaceuticals Enters into U.S. Licensing Agreement with AstraZeneca for Lesinurad

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Ironwood
Pharmaceuticals, Inc. (NASDAQ:IRWD) announced today that it has
entered into a licensing agreement with AstraZeneca
plc for the exclusive U.S. rights to lesinurad. Lesinurad 200mg
tablets were approved as ZURAMPIC^® by the U.S. Food and Drug
Administration (FDA) in
December 2015 for use in combination with a xanthine oxidase
inhibitor (XOI) for the treatment of hyperuricemia associated with
uncontrolled gout.
Gout is a serious, progressive and debilitating form of inflammatory
arthritis. As many as two million patients in the U.S. on
urate-lowering therapy remain inadequately controlled, as XOI
treatment alone is not sufficient to achieve their treatment goals.
ZURAMPIC is not recommended for the treatment of asymptomatic
hyperuricemia and should not be used as monotherapy.
Under the terms of the agreement, Ironwood will make an up-front payment
to AstraZeneca of $100 million to acquire exclusive U.S. rights to all
products containing lesinurad, including the fixed-dose combination of
lesinurad and allopurinol. AstraZeneca plans to submit the
fixed-dose combination program for FDA regulatory review in the second
half of 2016. Ironwood will pay AstraZeneca tiered single-digit
royalties on product sales as well as sales-related and other milestones
of up to $165 million. AstraZeneca will manufacture and supply ZURAMPIC,
provide certain product support services to Ironwood and complete the
FDA post-approval commitment on Ironwood’s behalf.
“This transaction enables Ironwood to leverage our strong commercial
capabilities to advance a durable franchise of innovative medicines
addressing a significant unmet need in which patients are highly
motivated and seeking relief – this is precisely the kind of opportunity
the Ironwood team is successfully executing on in IBS-C and CIC,” said
Tom McCourt, Chief Commercial Officer of Ironwood. “With focused
investment into the gout franchise over time, we believe we can maximize
cash flows and accelerate our progress as a top-performing commercial
biotechnology company: following this transaction, we expect to execute
on at least five new launches in the U.S. by 2020, beginning with
ZURAMPIC in the second half of 2016 and continuing with, if approved, 72
mcg linaclotide in 2017 and a lesinurad-allopurinol fixed-dose
combination in 2018.”
Luke Miels, Executive Vice President, Global Product and Portfolio
Strategy, AstraZeneca, said, “We’re pleased to be entering into this
agreement with Ironwood, a company with whom we already have a number of
successful commercial partnerships. Our new agreement with Ironwood will
ensure the successful launch of ZURAMPIC in the U.S., while allowing us
to concentrate our resources on the innovative medicines in our main
therapy areas.”
The development of AstraZeneca’s gout portfolio is led by Ardea
Biosciences, a wholly-owned subsidiary. The transaction does not include
the transfer of any AstraZeneca or Ardea employees or facilities.
AstraZeneca also retains ownership of the rest of the Ardea portfolio,
including RDEA3170, a Phase IIb-ready, potent, selective uric acid
reabsorption inhibitor. Under the terms of the agreement, Ironwood will
have certain rights to potentially access RDEA3170 in gout indications
in the U.S. The licensing agreement is expected to close in the second
quarter of 2016, subject to antitrust approval in the U.S.
Ironwood Financial Considerations
Ironwood expects to pay the $100 million up-front fee from cash on hand
and does not anticipate requiring any financing to complete the
transaction. Ironwood is updating its 2016 cash flow guidance: the
company now expects to use less than $70 million in cash for operations
in 2016, up from less than $60 million as previously guided, to
incorporate ZURAMPIC integration and launch investments. Ironwood
expects to provide updated guidance regarding total operating expenses
for 2016 during its second quarter 2016 investor update. Initially,
Ironwood expects less than $75 million in annual incremental commercial
expenses associated with the gout franchise, with focused investment
over time to maximize cash flow. The transaction is not expected to
affect 2016 LINZESS marketing and sales expenses.
Ironwood expects the transaction to be cash flow accretive in 2019 and
beyond and to add significant revenue, with annual U.S. sales estimated
to exceed $300 million at peak and commercial margins expected to exceed
60% by 2022. ZURAMPIC and the lesinurad-allopurinol fixed-dose
combination product have patent protection into at least 2028.
Additionally, Ironwood expects to become cash flow positive during 2018
and believes that the growing contribution from its commercial business
and cash on hand are sufficient to fully fund its core business
inclusive of the gout franchise without the need to raise additional
capital.
Webcast Information: Conference Call Today at 8:00 a.m. ET
Ironwood will host a conference call and webcast at 8:00 a.m. Eastern
Time on Tuesday, April 26, 2016. Individuals interested in participating
in the call should dial (877) 643-7155 (U.S. and Canada) or (914)
495-8552 (international) using conference ID number 98937375. To access
the webcast, please visit the Investors section of Ironwood’s website at www.ironwoodpharma.com
at least 15 minutes prior to the start of the call to ensure adequate
time for any software downloads that may be required.
The call will be available for replay via telephone starting April 26,
2016, at approximately 11:00 a.m. Eastern Time, running through 11:00
a.m. Eastern Time on May 3, 2016. To listen to the replay, dial (855)
859-2056 (U.S. and Canada) or (404) 537-3406 (international) using
conference ID number 98937375. The archived webcast will be available on
Ironwood’s website for 14 days beginning approximately one hour after
the call has completed.
About ZURAMPIC® (lesinurad) 200mg tablets
ZURAMPIC® (lesinurad) is the first Selective Uric Acid Reabsorption
Inhibitor (SURI); it works selectively to complement xanthine oxidase
inhibitors (XOIs) in the treatment of 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 urate transporter (URAT1) and organic anion
transporter 4 (OAT4), involved in uric acid reabsorption in the kidney.
In humans, it does not inhibit OAT1 and OAT3, which are drug
transporters in the kidney associated with drug-drug interactions. 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.
Important Safety Information

Contraindications:

• 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, and
  evaluate for signs and symptoms of acute uric acid nephropathy.
  ZURAMPIC should not be initiated in patients with an eCLcr less than
  45 mL/min
• Cardiovascular events: Major adverse cardiovascular events were
  observed with ZURAMPIC; a causal relationship has not been established

Adverse Reactions:

• 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: https://www.azpicentral.com/zurampic/zurampic.pdf.
About Hyperuricemia and Gout
Gout is a serious, progressive and debilitating form of inflammatory
arthritis that affects more than 8 million people in the U.S., with
approximately 4 million of those patients on treatment, creating a
market estimated at $1 billion. Approximately 2 million gout patients
suffer from uncontrolled gout, in which traditional first-line xanthine
oxidase inhibitor (XOI) treatment alone is not sufficient to achieve
target serum uric acid (sUA) levels. Among patients treated in clinical
trials, less than 50% of patients on the XOI allopurinol 300mg reached
sUA target levels <6.0mg/dL.
The underlying cause of gout is hyperuricemia (elevated sUA), which
leads to the deposition of crystals primarily in the joints and also in
other tissues. This can result in recurrent attacks of inflammatory
arthritis and, if left uncontrolled, could lead to chronic, progressive
arthritis and tophus (visible deposits of urate crystals) formation. The
goal of sUA lowering treatment is to reduce sUA levels to the target
level of <6.0mg/dL as recommended by both the American College of
Rheumatology (ACR) and the European League Against Rheumatism (EULAR).
For patients who cannot reach this target on an XOI alone, the current
ACR and EULAR guidelines recommend adding an agent that increases uric
acid excretion.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (NASDAQ: IRWD) is a commercial biotechnology
company focused on creating medicines that make a difference for
patients, building value for our fellow shareholders, and empowering our
passionate team. We are advancing an innovative pipeline of medicines in
multiple areas of significant unmet need, including irritable bowel
syndrome with constipation (IBS-C)/chronic idiopathic constipation
(CIC), vascular and fibrotic diseases, and refractory gastroesophageal
reflux disease, among others. We discovered, developed and are
commercializing linaclotide, the U.S. branded prescription market leader
in the IBS-C/CIC category, and we are applying our proven R&D and
commercial capabilities to advance multiple internally-developed and
externally-accessed product opportunities. Ironwood was founded in 1998
and is headquartered in Cambridge, Mass. For more information, please
visit www.ironwoodpharma.com
or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in three
main therapy areas – respiratory, inflammation, autoimmune disease
(RIA), cardiovascular and metabolic disease (CVMD) and oncology – as
well as in infection and neuroscience. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of patients
worldwide. For more information please visit: www.astrazeneca.com
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including, but not limited to, statements about the benefits
anticipated from the addition of the gout franchise to Ironwood’s
portfolio; the timing of the closing of the lesinurad transaction; development,
launch and commercialization plans for lesinurad and our product
candidates; market size, growth and opportunity, including peak sales,
and potential demand for lesinurad, as well as its potential impact on
applicable markets; the potential indications for, and benefits of,
lesinurad; the anticipated timing of regulatory developments for the
fixed-dose combination of lesinurad and allopurinol; the design, timing
and results of clinical and preclinical studies; the timing of filings
with regulatory authorities; expected periods of patent exclusivity; and
our company’s financial performance and results, and guidance and
expectations related thereto, including our projected cash needs and
expectations regarding the need for future financings, expectations
regarding the accretive nature of the transaction and the timing of such
accretion, revenue from the transaction, commercial margin, cash flows,
operating expenses, commercial expenses, the effect of the transaction
on 2016 LINZESS marketing and sales expense, and the timing of providing
updated guidance on total operating expenses following closing. Each
forward‐looking statement is subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied in such statement. Applicable risks and uncertainties include,
but are not limited to, the risk that the transaction does not close or
is delayed; the risk that we are unable to successfully integrate
lesinurad into our existing business or are unable to realize the
anticipated benefits of the lesinurad transaction; those related to our
growth strategy; decisions made by U.S. regulatory authorities, the U.S.
Patent and Trademark Office and their foreign counterparts; intellectual
property rights of competitors or potential competitors; efficacy,
safety and tolerability of lesinuard, linaclotide and our product
candidates; competition in disease states; the commercial potential of
lesinurad, linaclotide, our product candidates and the other products
that we promote; and the risk that we are unable to manage our operating
expenses and capital expenditures due to foreseeable or unforeseeable
events or occurrences. Applicable risks also include those that are
listed under the heading “Risk Factors” and elsewhere in Ironwood’s
Annual Report on Form 10-K for the year ended December 31, 2015 and in
our subsequent SEC filings. These forward-looking statements (except as
otherwise noted) speak only as of the date of this press release, and
Ironwood undertakes no obligation to update these forward-looking
statements.
LINZESS is a trademark owned by Ironwood Pharmaceuticals, Inc. Any other
trademarks referred to in this press release are the property of their
respective owners. All rights reserved.