Ligand Establishes Program to Develop Captisol-Enabled, Next-Generation Contrast Agents for Diagnostic Imaging

January 18, 2018

Focus will be on hospital-based products that could benefit from reduced renal
toxicity
Leverages Captisol® and new intellectual property from Verrow Pharmaceuticals
acquisition

SAN DIEGO–(BUSINESS WIRE)– Ligand Pharmaceuticals Incorporated (NASDAQ:
LGND) announces initiation of a program to develop contrast agents with reduced renal
toxicity. Contrast agents are injectable solutions used during diagnostic imaging
procedures. Through this new, internally-funded program, Ligand intends to advance
products toward proof-of-concept, followed by selling or out-licensing them for further
development and commercialization. The program will leverage Ligand’s patented
Captisol® technology, as well as data and intellectual property obtained through its
acquisition of Verrow Pharmaceuticals.

“We view this new initiative as a valuable expansion of Ligand’s pipeline of internally
developed programs that utilize our proprietary technologies and IP,” said John Higgins,
Chief Executive Officer of Ligand. “Contrast agents are an important component of the
diagnostic imaging market; however, they can be toxic and are known to cause kidney
damage in some patients. Captisol is a patented, specialized cyclodextrin that plays a role
in protecting kidneys from the damaging effects of these agents. This is a potentially highly
lucrative product opportunity that Ligand is able to pursue given our ownership of Captisol
and our relationships with inventors and scientists in the cyclodextrin field. We are excited
to have this program in development and to have secured the associated program rights
through our recent acquisition of Verrow Pharmaceuticals.”

Verrow Pharmaceuticals is a privately-held Lenexa, Kansas-based medical invention
company that Ligand acquired in January 2018 for $2 million in cash plus earnouts.

  • Program Highlights:
    Contrast agents are used to enhance diagnostic imaging. Despite their benefits and
    widespread use, contrast agents put an estimated one-fourth of users at risk for
    renal damage.1
  • Captisol-enabled (CE) iohexol has been shown to prevent nephrotoxicity by more
    than 50% in animal models.2
  • Large U.S. market of approximately 20 million imaging procedures per year with
    iodinated contrast agents, representing an estimated $1.5 billion in annual sales.3
  • Initial internal program focused on a CE formulation of iohexol given the large global
    market, lack of alternatives and focused development path for use in the
    cardiovascular setting.
  • CE-iohexol program to focus on partnering-enabling studies, with an estimated $6
    million of program spend by Ligand over approximately three years.
  • Acquisition of Verrow Pharmaceuticals opens opportunities for broader
    “nephroprotection use” of Captisol in other hospital-based diagnostics and
    treatments.

About Captisol-enabled iohexol

Iohexol (marketed as OMNIPAQUE™ by GE Healthcare) is the most widely-used
injectable diagnostic contrast agent for imaging procedures with global sales exceeding
$500 million and no generic competition in the U.S. Iohexol has a reported incidence of
contrast medium-induced nephropathy of 26%1, and therefore a significant opportunity
exists for a safer alternative formulation. CE-iohexol is expected to potentially establish a
new safety standard that enables a future partner to gain meaningful market share. Ligand
plans to perform preclinical and clinical partnering-enabling studies for the program.
About Verrow Pharmaceuticals
Verrow Pharmaceuticals is a medical invention company founded to discover and patent
uses of modified cyclodextrins to reduce acute kidney injury during medical interventions
including iodine, or gadolinium-based contrast agents, anticancer agents and
aminoglycosides. Ligand acquired the assets and related liabilities of Verrow in January of
2018.

About Captisol®
Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed
to optimize the solubility and stability of drugs. Captisol was invented and initially
developed by scientists in the laboratories of Dr. Valentino Stella, University Distinguished
Professor at the University of Kansas’ Higuchi Biosciences Center for specific use in drug
development and formulation. This unique technology has enabled several FDA-approved
products, including Amgen’s Kyprolis®, Baxter International’s Nexterone®, Spectrum’s
EVOMELA® and Melinta Therapeutics’ Baxdela™. There are many Captisol-enabled
products currently in various stages of development.

About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company focused on developing or acquiring technologies
that help pharmaceutical companies discover and develop medicines. Our business model
creates value for stockholders by providing a diversified portfolio of biotech and
pharmaceutical product revenue streams that are supported by an efficient and low
corporate cost structure. Our goal is to offer investors an opportunity to participate in the
promise of the biotech industry in a profitable, diversified and lower-risk business than a
typical biotech company. Our business model is based on doing what we do best: drug
discovery, early-stage drug development, product reformulation and partnering. We
partner with other pharmaceutical companies to leverage what they do best (late-stage
development, regulatory management and commercialization) to ultimately generate our
revenue. Ligand’s Captisol® platform technology is a patent-protected, chemically modified
cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
OmniAb® is a patent-protected transgenic animal platform used in the discovery of fully
human mono-and bispecific therapeutic antibodies. Ligand has established multiple
alliances, licenses and other business relationships with the world’s leading
pharmaceutical companies including Novartis, Amgen, Merck, Pfizer, Celgene, Gilead,
Janssen, Baxter International and Eli Lilly.

Follow Ligand on Twitter @Ligand_LGND.

Forward-Looking Statements
This news release contains forward-looking statements by Ligand that involve risks and
uncertainties and reflect Ligand’s judgment as of the date of this release. These include
statements regarding: Ligand’s plans to initiate the contrast agent program using CEiohexol;
the market size of contrast agent procedures and the addressable market for
Ligand’s new program; the potential to establish a proof-of-concept that CE-iohexol will
reduce renal toxicity and establish a new safety standard and for Ligand to partner the
program; Ligand’s estimated spend on the new program; and Ligand’s belief that the
Verrow acquisition solidified Ligand’s intellectual property position and will open up new
market opportunities for Captisol. Actual events or results may differ from our
expectations. For example, there can be no assurances that the contrast agent program
will be successful in identifying or developing products; Ligand may incur costs associated
with the acquisition of Verrow Pharmaceuticals, including unforeseen liabilities, which may
exceed the cost of the acquisition; Ligand may choose to abandon the program for any
reason or no reason; the anticipated benefits of CE-iohexol, including the possible
improvements in kidney safety, may not materialize; and Ligand may be unable to secure
licensing partners or buyers for products developed from the contrast agent program. The
failure to meet expectations with respect to any of the foregoing matters may reduce
Ligand’s stock price. Additional information concerning these and other important risk
factors affecting Ligand can be found in Ligand’s prior press releases available at
www.ligand.com as well as in Ligand’s public periodic filings with the Securities and
Exchange Commission, available at www.sec.gov. Ligand disclaims any intent or
obligation to update these forward-looking statements beyond the date of this press
release, except as required by law. This caution is made under the safe harbor provisions
of the Private Securities Litigation Reform Act of 1995.

Ligand Pharmaceuticals Incorporated
Todd Pettingill
(858) 550-7893
investors@ligand.com
@Ligand_LGND
or
LHA Investor Relations
Bruce Voss
(310) 691-7100
bvoss@lhai.com
Source: Ligand Pharmaceuticals Incorporated