Ligand Initiates Phase 2 Trial with LGD-6972 in Type 2 Diabetes

SAN DIEGO-- Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) announces the initiation of a Phase 2 clinical trial with the Company’s glucagon receptor antagonist LGD-6972 for the treatment of type 2 diabetes mellitus (T2DM). This randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of LGD-6972, as an adjunct to diet and exercise, in subjects with T2DM whose blood glucose levels are inadequately controlled with metformin.

The multiple site study is expected to enroll 148 subjects with T2DM who will be treated with one of 3 doses of LGD-6972 (5 mg, 10 mg, or 15 mg) or placebo once daily for 12 weeks. The primary endpoint of the study is the change from baseline in hemoglobin A1c. Secondary endpoints include the change from baseline in fasting plasma glucose, insulin, glucagon and GLP-1, as well as changes in lipids, blood pressure and body weight. Up to 30 clinical sites located across the U.S. will be participating in the study, which Ligand estimates will be completed in late 2017.

“We are pleased to be initiating the Phase 2 trial for LGD-6972 and to continue to build upon the dataset we’ve assembled for this important asset. Glucagon antagonism has continued to emerge as a leading non-insulin mechanism for type 2 diabetes,” said John Higgins, Chief Executive Officer. “We look forward to obtaining data next year, and to potential future partnering of this asset, consistent with our shots-on-goal business model.”

Glucagon receptor antagonists are a leading non-insulin mechanism in development for the treatment of T2DM. Based on the Phase 1 trial results that were published online in Diabetes, Obesity and Metabolism in August¹, Ligand believes LGD-6972 could have best-in-class properties given its potency in lowering plasma glucose in patients with T2DM and its preliminary safety profile.

About Ligand’s Glucagon Receptor Antagonist Program

Glucagon is a hormone produced by the pancreas that stimulates the liver to produce glucose (sugar). Overproduction of glucose by the liver is an important cause of high glucose levels in patients with T2DM and is believed to be due in part to inappropriately elevated levels of glucagon. Glucagon receptor antagonists are designed to lower glucose levels by reducing the production of glucose by the liver. Glucagon receptor antagonists are novel molecules that have demonstrated a reduction of glucose and hemoglobin A1c (HbA1c) in mid-stage clinical trials.

Preclinical studies have shown that LGD-6972 is highly potent and selective and inhibits glucagon-induced hyperglycemia in both rats and monkeys, and that it also significantly lowers glucose in a mouse model of T2DM. Additionally, LGD-6972 significantly lowered fasting and non-fasting glucose levels in a mouse model of type 1 diabetes and also reduced HbA1c, ketone bodies and free fatty acids. LGD-6972 also has been shown to have additive effects when used in combination with insulin therapy and may also be useful in an insulin-sparing regimen.

About Diabetes

Diabetes is a growing global epidemic that currently affects more than 415 million people worldwide². In North America, approximately 44 million people have diabetes². If current trends continue, by 2050 fully 33% of the U.S. population will be affected³. People with T2DM either are resistant to the effects of insulin or do not produce enough insulin to maintain a normal glucose level. Sustained high glucose levels can cause diabetic complications such as heart disease, stroke, kidney failure, neuropathy, lower-limb amputations and blindness. Although T2DM is more common in adults, it increasingly affects children as childhood obesity increases. An estimated 90% to 95% of Americans with diabetes have T2DM⁴.

The market for diabetes drugs is expected to nearly double to $68 billion by 2022⁵ as treatment paradigms shift toward combination therapies and novel non-insulin drugs. The top 10 non-insulin diabetes drugs had total sales of $12 billion in 2014, and sales are expected to increase to $20 billion by 2020⁶.

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 the timing, size, number of clinical sites, and protocol for the Phase 2 trial with LGD-6972, the potential for LGD-6972 to treat patients with type 2 diabetes, the potential for LGD-6972 to be a best-in-class treatment option for T2DM, the anticipated safety and pharmacological profile in future clinical trials, the number of patients affected by diabetes, the number of patients who may be affected by diabetes in the future, the annual total sales of non-insulin diabetes drugs and the expected future sales of such drugs. Actual events or results may differ from our expectations. For example, Ligand may be unable to enroll a sufficient number of patients in the Phase 2 clinical trial for LGD-6972, or otherwise be unable to complete the Phase 2 trial for a number of reasons beyond Ligand’s control, including reported adverse side effects from the trial or additional data regarding LGD-6972; there can be no assurance that the Phase 2 trial will meet its primary or secondary endpoints; even if the Phase 2 trial is successful, there can be no assurance of success in future clinical trials; the safety and tolerability data from a new clinical trial in LGD-6972 may conflict with the results of the Phase 1 clinical trials; the number of patients diagnoses with diabetes may be more or fewer than Ligand believes; and the total sales of non-insulin diabetes drugs is dependent on market acceptance of such drugs. 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.

References

1. Eric G. Vajda, et al. Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type 2 diabetes mellitus, Diabetes Obes Metab 2016, 9999, n/a. DOI:10.1111/dom.12752
2. Diabetes: Facts and Figures. International Diabetes Federation website. http://www.idf.org/about-diabetes/facts-figures.
3. James P Boyle, et al. Projection of the year 2050 burden of diabetes in the U.S. adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. American Diabetes Association, Population Health Metrics. 2010 Oct 22;8:29
4. 2014 National Diabetes statistics report. Centers for Disease Control and Prevention website. http://www.cdc.gov/diabetes/data/statistics/2014StatisticsReport.html.
5. Type 2 Diabetes-Global Drug Forecast & Market Analysis to 2022. GlobalData
6. Thomson Reuters Cortellis, 2020 sales based on analyst consensus projections, 2015

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Ligand Pharmaceuticals Incorporated
Todd Pettingill, 858-550-7500
investors@ligand.com
or
LHA
Bruce Voss, 310-691-7100
bvoss@lhai.com

Source: Ligand Pharmaceuticals Incorporated

Released September 13, 2016