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Strongbridge Biopharma plc Announces Presentation of New Data Comparing the In Vitro Effects of Levoketoconazole, the Active Ingredient in RECORLEV™, and Ketoconazole on Human Cortisol Production

November 20, 2018

In Vitro Data Show Preliminary Evidence That Levoketoconazole Inhibits ACTH Secretion and May Have Anti-Tumor Effect on Pituitary Adenoma Cells

First Study in Primary Human Adrenal Cells Suggests Levoketoconazole, the Pure 2S,4R Enantiomer of Ketoconazole, May Be a More Potent Inhibitor of Cortisol Secretion Compared to Ketoconazole

Results Presented Alongside Encore SONICS Data at the 17th Annual European Network for the Study of Adrenal Tumors (ENS@T) Meeting

DUBLIN, Ireland and TREVOSE, Pa., Nov. 20, 2018 (GLOBE NEWSWIRE) -- Strongbridge Biopharma plc, (Nasdaq: SBBP), a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs, announced today that new in vitro data from a study of levoketoconazole, the active ingredient in RECORLEV™, an investigational cortisol synthesis inhibitor being evaluated in Phase 3 studies for endogenous Cushing’s syndrome, will be presented at the 17th Annual European Network for the Study of Adrenal Tumors (ENS@T) Meeting taking place in Florence, Italy from November 22 - 23, 2018.

Led by Drs. Sara G. Creemers, Leo Hofland, and Richard A. Feelders from Erasmus University Medical Center in Rotterdam, the Netherlands, the study aimed to compare the direct effects of levoketoconazole on basal and ACTH-stimulated adrenocortical steroid production to those of racemic ketoconazole. Researchers evaluated steroid production by human adrenal cell lines and in primary adrenocortical cultures after treatment with both compounds. The effects of both levoketoconazole and racemic ketoconazole on pituitary tumor cells were also assessed.

“These results provide important mechanistic insights that confirm prior studies demonstrating that levoketoconazole may inhibit steroidogenic enzymes more potently compared to racemic ketoconazole,” said Richard A. Feelders, M.D., Ph.D., lead investigator and endocrinologist at Erasmus University Medical Center. “Additionally, these data provide preliminary evidence that suggest levoketoconazole may be a more potent suppressor of pituitary corticotroph growth and ACTH secretion, which may have important clinical implications given the majority of Cushing’s syndrome patients requiring chronic medication have a pituitary adenoma that secretes excess ACTH. Combined with the recently reported Phase 3 SONICS data showing a favorable efficacy, safety, and tolerability profile, these data suggest the potential for levoketoconazole to offer novel therapeutic advantages not currently addressed by existing treatment options.”

In one analysis, the effects of two concentrations (0.05 and 5 µM) of levoketoconazole and ketoconazole on the steroid profile were studied in ACTH secretion-associated adrenal hyperplasia, which resulted in an accumulation of progesterone (>167% versus >96%; P < 0.01) and a decrease in cortisol (<37% versus <11%; P < 0.05) after exposure to levoketoconazole. A greater accumulation of 11-DOC (the immediate precursor of cortisol) was observed with racemic ketoconazole (P < 0.01 versus levoketoconazole). Under ACTH stimulation, steroid inhibition dose-response results indicate greater potency of levoketoconazole compared to racemic ketoconazole.

A separate analysis showed that when corticotroph pituitary tumor cells were treated with levoketoconazole and racemic ketoconazole, only levoketoconazole demonstrated inhibition of ACTH secretion after just three days of treatment (P = 0.0436 vs. racemic ketoconazole), whereas both levoketoconazole and racemic ketoconazole inhibited ACTH secretion after seven days of treatment. Furthermore, two primary ACTH-secreting corticotroph pituitary adenoma cultures were examined for cell amount and ACTH secretion after seven days of treatment with levoketoconazole and racemic ketoconazole. Levoketoconazole significantly inhibited cell proliferation in one culture (P < 0.001 versus control), and a significant difference between levoketoconazole and racemic ketoconazole was observed in both cultures, suggesting a stronger effect by levoketoconazole.

Presentation Details:

-- Oral Presentation #OC24– Levoketoconazole, the Single 2S,4R Enantiomer of Ketoconazole, is a Potential Novel Steroid Synthesis Inhibitor for Medical Treatment of Cushing’s Syndrome; Richard A. Feelders; NAPACA Oral Communications OC23-28, Nov. 23, 2018, 11:40 – 13:00 CET -- Poster #PP57:Safety and Efficacy of Levoketoconazole in Cushing Syndrome: Initial Results From the Phase 3 SONICS Study; Rosario Pivonello; Poster Guided Session/Networking, Nov. 22, 2018, 11:15 – 12:45 CET

About Endogenous Cushing’s SyndromeEndogenous Cushing’s syndrome (CS) is a rare but serious and potentially lethal endocrine disease caused by chronic elevated cortisol exposure. Most people with CS have a variety of signs and symptoms – many of which, when they occur by themselves, are common and do not necessarily point to an underlying disease; this makes recognition of CS difficult. Common presenting symptoms include weight gain or obesity, fatigue, muscle weakness, headaches, mood or sleep disturbances, facial rounding or redness, excess body hair growth in women or baldness in men, thinned skin with stretch marks, easy bruising and other skin changes including acne, mood or sleep disturbances and irregular periods or loss of libido. Patients are often found by their doctors to have new-onset or worsening of high blood pressure, abnormal levels of blood lipids, such as cholesterol, polycystic ovaries and abnormal blood glucose or diabetes. People with uncontrolled disease are seriously ill and have a 2- to 4-fold higher mortality rate than age- and gender-matched controls, mainly due to metabolic and cardiovascular complications. Treatment options for CS include surgery, radiation therapy, and medical treatment. CS most commonly affects adults ages 20-50 and is more prevalent in females, accounting for about 70 percent of all cases.

About Strongbridge BiopharmaStrongbridge Biopharma is a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs. Strongbridge’s rare endocrine franchise includes RECORLEV™ (levoketoconazole), a cortisol synthesis inhibitor currently being studied in Phase 3 clinical studies for the treatment of endogenous Cushing’s syndrome, and veldoreotide extended release, a pre-clinical next-generation somatostatin analog being investigated for the treatment of acromegaly and potential additional applications in other conditions amenable to somatostatin receptor activation. Both RECORLEV and veldoreotide have received orphan drug designation from the FDA and the European Medicines Agency. The Company’s rare neuromuscular franchise includes KEVEYIS® (dichlorphenamide), the first and only FDA-approved treatment for hyperkalemic, hypokalemic, and related variants of primary periodic paralysis. KEVEYIS has orphan drug exclusivity in the United States.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the federal securities laws. The words “anticipate,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “project,” “target,” “will,” “would,” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements of historical facts, contained in this press release, are forward-looking statements, including statements related to the potential advantages of RECORLEV, the release of additional planned analyses of the SONICS study, Strongbridge’s strategy, plans, status and results of SONICS and other clinical trials, outcomes of product development efforts and objectives of management for future operations. Forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those expressed in such statement, including risks and uncertainties associated with clinical development and the regulatory approval process, the reproducibility of any reported results showing the benefits of RECORLEV, the adoption of RECORLEV by physicians, if approved, as treatment for any disease and the emergence of unexpected adverse events following regulatory approval and use of the product by patients. Additional risks and uncertainties relating to Strongbridge and its business can be found under the heading “Risk Factors” in Strongbridge’s Annual Report on Form 10-K for the year ended December 31, 2017 and subsequent filings with the SEC. These forward-looking statements are based on current expectations, estimates, forecasts and projections and are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors. The forward-looking statements contained in this press release are made as of the date of this press release, and Strongbridge Biopharma does not assume any obligation to update any forward-looking statements except as required by applicable law.

Contacts:

Corporate and Media Relations Elixir Health Public Relations Lindsay Rocco +1 862-596-1304 lrocco@elixirhealthpr.com

Investor Relations U.S.: The Trout Group Marcy Nanus +1 646-378-2927 mnanus@troutgroup.com

Europe: First House Geir Arne Drangeid +47 913 10 458 strongbridgebio@firsthouse.no

USA 900 Northbrook Drive Suite 200 Trevose, PA 19053 Tel. +1 610-254-9200 Fax. +1 215-355-7389

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