Naldemedine Tosylate

OSAKA, Japan, May 30, 2025 - Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter "Shionogi") announced that the New Drug Application (NDA) for naldemedine tosilate (hereinafter “naldemedine”), a treatment for opioid-induced constipation (OIC), has been accepted in China. Naldemedine is a peripherally acting μ-opioid receptor antagonist (PAMORA) originally developed by our company. It has been launched in countries and regions such as Japan, the United States, Europe, and Taiwan, contributing to the improvement of symptoms in many patients suffering from opioid-induced constipation (OIC). In cancer pain management, opioid analgesics play a central role; however, their side effects can sometimes make continued treatment difficult. Among these, constipation is a common adverse effect observed in 40–80% of patients using opioid analgesics¹, ². It imposes a significant physical burden and greatly affects patients’ quality of life (QOL), making it a major challenge in pain management³, ⁴. In China, treatment options for OIC are limited, and current approaches mainly involve symptomatic treatments such as dose adjustments of opioids or the use of laxatives⁵. Therefore, there is a strong need for new therapeutic options to achieve better pain management. The approval of naldemedine in China is expected to contribute to improving the QOL of patients suffering from OIC. This new drug application is based on favorable results from a Phase III clinical trial⁶ conducted in China targeting patients with OIC. The application was submitted through our group company, Shionogi China Co., Ltd. (Head Office: Shanghai, China; Chairman and CEO: Tatsumori Yoshida.; hereafter "SCN"), Following approval, the sales of naldemedine in China will be handled by SCN which has entered into an exclusive license agreement with Chia Tai Tianqing Pharmaceutical Group Co., Ltd. ((Head Office: Jiangsu Province, China; CEO: Eric Tse.; hereinafter “CTTQ”) for the import and domestic distribution of the product⁷. CTTQ will be responsible for sales in mainland China, and our company will receive a certain amount of revenue based on sales volume. Shionogi has identified “contributing to a healthier and more prosperous life” as a key material issue and is committed to creating a society where everyone can live longer, more vibrant lives in their own way. We will continue to contribute to improving the QOL of patients suffering from various types of pain. About Naldemedine Naldemedine is a peripherally acting μ-opioid receptor antagonist that binds to μ-opioid receptors in the gastrointestinal tract and counteracts the peripheral effects of opioids, thereby improving OIC. Naldemedine has been approved in countries and regions including Japan, the United States, Europe, and Taiwan. It is marketed under the brand name Symproic® in Japan, the United States, and Taiwan, and as Rizmoic® in Europe. About Chia Tai Tianqing (CTTQ) CTTQ is a subsidiary of China Biopharma and serves as the core pharmaceutical company of the Chia Tai Group in China. It is engaged in the integrated research, development, manufacturing, and sales of pharmaceuticals, with over 14,000 employees. The company offers a wide range of products for infectious diseases, respiratory diseases, cancer, liver diseases, endocrine disorders, and more. Over 7,000 academic and sales staff are involved in providing medical information. Overview of the Phase III Clinical Trial in China This Phase III clinical trial was a multicenter, randomized, double-blind, placebo-controlled study conducted in China to evaluate the efficacy and safety of naldemedine in adult patients with opioid-induced constipation (OIC) who were receiving opioid analgesic therapy. The primary endpoint of the study was the proportion of patients who achieved three or more spontaneous bowel movements (SBMs) per week, along with an increase of at least one SBM per week from baseline. The naldemedine treatment group demonstrated a statistically significant improvement compared to the placebo group. Reference: 1. Droney, J. et al. : Support Care Cancer, 2008, 16 (5), 453 2. Kalso, E. et al. : Pain, 2004, 112 (3), 372 3. Abramowitz, L. et al. : J Med Econ., 2013, 16 (12), 1423 4. Bell TJ, et al. : Pain Med 10 (1), 35-42, 2009 5. Chinese Medical Association, et al. Guidelines for primary care of chronic Constipation (2019) [J]. Chinese General Practitioners Journal, 2020, 19(12): 1100–1107. 6. Chinese Clinical Trial Registry: Phase III clinical trial registration number: ChiCTR2400089290 7. Shionogi China Co., Ltd. Press release on January 2, 2025 Ping An-Shionogi Signs an Exclusive License Agreement with Chia Tai Tianqing Pharmaceutical, a Core Enterprise of Sino Biopharmaceutical, for Import and Domestic Distribution of Naldemedine, a Therapeutic Drug for Opioid-Induced Constipation Forward-Looking Statements This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise. For Further Information, Contact: SHIONOGI Website Inquiry Form: https://www.shionogi.com/global/en/contact.html

Total Company Net Revenue of $41 Million, an Increase of 7% versus Prior Year Net Income of $5.2 Million, EBITDA Margin of 22% and Operating Cash Generation of $11 Million Conference Call and Webcast Scheduled for 8:30 AM EST Today RALEIGH, N.C., May 06, 2021 (GLOBE NEWSWIRE) -- BioDelivery Sciences International (NASDAQ: BDSI), a growing specialty pharmaceutical company dedicated to patients living with serious and complex chronic conditions, today reported strong financial results for the first quarter ended March 31, 2021, including the following operational and performance highlights. Key Business Highlights Total Company net revenue for the first quarter increased by 7% versus the prior year period to $41.0 million. This growth was driven by BELBUCA® net sales of $36.4 million, which increased 9%, and Symproic® net sales of $4.4 million, which increased 5%. BELBUCA continued to deliver an all-time high quarterly market share, despite pandemic challenges and the impact of winter storm Uri. Total BELBUCA prescriptions were approximately 113,000 during the first quarter, representing year-over-year prescription volume growth of 9%. Total Symproic prescriptions were approximately 17,000 in the first quarter, consistent with prescriptions for the prior year period. Continued to achieve strong profitability, delivering $5.2 million of GAAP Net Income and an attractive 22% EBITDA margin in the first quarter of 2021. The Company repurchased 1.6 million shares in the quarter under its share buyback program, at an average price of $3.87 per share. “We again delivered solid top and bottom-line growth in a challenging quarter against the backdrop of the pandemic and weather-related disruptions, resulting in 22% EBITDA margin and $11 million operating cash flow generation,” stated Jeff Bailey, CEO of BDSI. “Our performance highlights the strength of our commercial team and the persistent market demand for our highly differentiated products. We expect continued success as the selling environment improves throughout the year, including increases of in-office patient visits and more face-to-face interactions with health care providers by our sales representatives.” First Quarter 2021 Financial Results Total Company Net Revenue for the first quarter of 2021 was $41.0 million, an increase of 7% compared to $38.3 million in the first quarter of 2020. Total product net revenue, including sales of BELBUCA and Symproic, grew 8% year over year. Severe winter weather conditions, especially in the South-Central region where the Company has strong market presence, affected patients’ access to their physicians and pharmacies. Additionally, the severe weather delayed shipments of the Company’s products to pharmacy distribution centers of the major wholesalers. BELBUCA Net Sales for the first quarter of 2021 were $36.4 million, an increase of 9% compared to $33.5 million in the first quarter of 2020. As we typically experience each year, BELBUCA gross to net deductions were lower in the first quarter, largely due to the Medicare coverage gap impact. Symproic Net Sales for the first quarter were $4.4 million, an increase of 5% compared to $4.2 million in the first quarter of 2020. Symproic net sales benefited from reduced gross to net deductions in the first quarter due to the typical decreases seen for Medicare coverage gap, as well as updates to our gross to net deductions related to channel estimates. Total Operating Expenses for the first quarter of 2021 were $27.8 million, compared to $26.7 million in the first quarter of 2020. The increase in spending as compared to fourth quarter of 2020 was driven by increased investments in sales and marketing and $3.0 million higher legal spend in the quarter, primarily due to costs associated with the Paragraph IV patent litigation. GAAP Net Income for the first quarter of 2021 was $5.2 million, or $0.05 per share, compared to GAAP net income of $5.0 million, or $0.05 per share, in the first quarter of 2020. EBITDA for the first quarter of 2021 was $9.2 million, or 22% of net sales, compared to $7.8 million or 20% of net sales, in the first quarter of 2020. Non-GAAP Net Income for the first quarter of 2021 was $8.5 million and reflects GAAP net income excluding stock-based compensation and non-cash amortization of intangible assets as compared to non-GAAP net income of $8.3 million in the first quarter of 2020, excluding the same items Cash Position: As of March 31, 2021, cash and cash equivalents were approximately $116.4 million, compared to $111.6 million as of December 31, 2020. The total cash flow generation over the quarter of $4.9 million includes continued strong operating cash generation of $11.1 million, partially offset by $6.1 million used to repurchase shares in the quarter. Financial Guidance The Company reiterates its 2021 financial guidance, with full year 2021 total Company net sales of $170 - $180 million, including full year 2021 BELBUCA net sales of $155 - $165 million. Total operating expenses are expected to be in the range of $115 - $120 million, as the Company continues to invest to support the growth of its brands, and EBITDA is expected to be in the range of $40 - $50 million in 2021. The Company expects to continue delivering positive operating cash flow throughout 2021. “Our confidence in the continued growth of our brands and the profitability of our business remains unchanged. This is demonstrated by our continuing investments behind our portfolio, together with the share repurchase program which is underway. We remain on track to drive long-term shareholder value, and are actively considering potential business development opportunities,” stated Jeff Bailey. Conference Call & Webcast Details BioDelivery Sciences will host a conference call and webcast today, May 6, 2021, at 8:30 a.m. ET to present first quarter 2021 results and to provide a business update. Dial-in details are as follows: ABOUT BIODELIVERY SCIENCES INTERNATIONAL, INC. BioDelivery Sciences International, Inc. (NASDAQ: BDSI) is a commercial-stage specialty pharmaceutical company dedicated to patients living with chronic conditions. BDSI has built a portfolio of products that includes utilizing its novel and proprietary BioErodible MucoAdhesive (BEMA®) technology to develop and commercialize, either on its own or in partnership with third parties, new applications of proven therapies aimed at addressing important unmet medical needs. BDSI's marketed products address serious and debilitating conditions, including chronic pain and opioid-induced constipation. CAUTIONARY NOTE ON FORWARD-LOOKING STATEMENTS This press release and any statements of employees, representatives, and partners of BioDelivery Sciences International, Inc. (“BDSI”) related thereto contain, or may contain, among other things, certain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve significant risks and uncertainties. Such statements may include, without limitation, statements with respect to BDSI’s plans, objectives, projections, expectations and intentions and other statements identified by words such as “projects,” “may,” “will,” “could,” “would,” “should,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential” or similar expressions. These statements are based upon the current beliefs and expectations of BDSI’s management and are subject to significant risks and uncertainties, including those detailed in BDSI’s filings with the Securities and Exchange Commission. Actual results (including, without limitation, the expectations for total company net sales, BELBUCA net sales, operating expenses, EBITDA and operating cash flows in 2021) may differ materially from those set forth or implied in the forward-looking statements. These forward-looking statements involve certain risks and uncertainties that are subject to change based on various factors (many of which are beyond BDSI’s control) including the risk that the current coronavirus pandemic impacts on our supply chain, commercial partners, patients and their physicians and the healthcare facilities in which they work, and our personnel are greater than we anticipate, as well as those set forth in our 2020 annual report on Form 10-K filed with the US Securities and Exchange Commission and subsequent filings. BDSI undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future presentations or otherwise, except as required by applicable law. Non-GAAP Financial Measures This press release includes information about certain financial measures that are not prepared in accordance with generally accepted accounting principles in the United States, or GAAP, including non-GAAP net income and EBITDA. These non-GAAP measures are not based on any standardized methodology prescribed by GAAP and are not necessarily comparable to similar measures presented by other companies. Non-GAAP net income adjusts for one-time and non-cash charges by excluding the following from GAAP net income: stock-based compensation expense and non-cash amortization of intangible assets. EBITDA excludes net interest, including both interest expenses and interest income, provision for (benefit from) income taxes, depreciation, and amortization. The Company's management and board of directors utilize these non-GAAP financial measures to evaluate the Company's performance. The Company provides these non-GAAP measures of the Company's performance to investors because management believes that these non-GAAP financial measures, when viewed with the Company's results under GAAP and the accompanying reconciliations, are useful in identifying underlying trends in ongoing operations. However, non-GAAP net income and EBITDA are not measures of financial performance under GAAP and, accordingly, should not be considered as alternatives to GAAP measures as indicators of operating performance. Further, non-GAAP net income and EBITDA should not be considered measures of our liquidity. A reconciliation of certain GAAP to non-GAAP financial measures has been provided in the tables included in this press release. © 2021 BioDelivery Sciences International, Inc. All rights reserved. Contact: Bob Yedid LifeSci Advisors 646-597-6989 Bob@LifeSciAdvisors.com BIODELIVERY SCIENCES INTERNATIONAL, INC. AND SUBSIDIARIES CONDENSED CONSOLIDATED BALANCE SHEETS (U.S. DOLLARS, IN THOUSANDS, EXCEPT SHARE AND PER SHARE AMOUNTS) (Unaudited) BIODELIVERY SCIENCES INTERNATIONAL, INC. AND SUBSIDIARIES CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (U.S. DOLLARS, IN THOUSANDS, EXCEPT SHARE AND PER SHARE AMOUNTS) (Unaudited) BIODELIVERY SCIENCES INTERNATIONAL, INC. AND SUBSIDIARIES CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (U.S. DOLLARS, IN THOUSANDS) (Unaudited) BIODELIVERY SCIENCES INTERNATIONAL, INC. AND SUBSIDIARIES RECONCILIATION OF NON-GAAP METRICS (U.S. DOLLARS, IN THOUSANDS) (Unaudited)