Naldemedine Tosylate

1月2日，中国生物制药有限公司（01177.HK）宣布，中国生物制药附属公司正大天晴药业集团股份有限公司（正大天晴）与平安盐野义有限公司（平安盐野义）签订独家市场推广协议。据此，正大天晴获授予阿片类药物引起的便秘（以下简称“OIC”）治疗药物纳地美定(Naldemedine)在中国大陆地区的独家市场推广权，初步为期十一年。 纳地美定（Naldemedine）是由平安盐野义的母公司盐野义制药株式会社开发的外周μ-阿片受体拮抗剂，它可以在外周组织（特别是肠道神经系统）中，通过拮抗阿片类药物对肠道神经系统的生理影响，调节肠道的蠕动和分泌活动，从根本上治疗OIC。目前，该药物已在美国、欧盟、日本、中国台湾及中国香港地区获批上市。此外，于2022年作为临床急需药品引入海南省人民医院乐城院区。 阿片类药物在临床上被广泛用作镇痛药，世界卫生组织推荐将其作为缓解癌症疼痛的治疗药物[1]。但临床实践发现，长期使用会导致各种不良反应，其中50%-80%使用阿片类药物的患者会出现OIC的不良反应。由于OIC会影响患者生活质量与治疗依从性，进而影响临床治疗效果，因此，怎样有效治疗OIC并平衡镇痛与不良反应的发生已成为临床亟须解决的问题之一[2]。目前在中国，OIC患者还没有针对性的治疗手段，主要是通过生活方式改变（如增加膳食纤维），阿片类药物转换、泻药/大便软化剂等一些有限的治疗策略来改善[3]。 纳地美定（Naldemedine）将为中国OIC患者带来全新的治疗方案。目前，在国内开展的一项III期临床试验（Naldemedine治疗癌痛患者合并OIC的多中心、包含安慰剂对照治疗期与开放治疗期两阶段的研究）达到了主要疗效终点。通过本次合作，中国生物制药旗下正大天晴成为Naldemedine在中国的独家市场推广伙伴，将可尽早惠及国内患者，助力癌症疼痛人群。 中国生物制药董事会主席谢其润表示，此次正大天晴与平安盐野义的合作是一个良好开端。纳地美定在中国市场有着广阔前景，将填补国内 OIC 治疗领域的空白，为患者带来新的希望。“我们对这款药物的疗效与市场潜力充满信心，未来双方将以此次合作为契机，积极探索在更多医药领域的合作可能，共同为推动中国医药事业发展、提升患者健康福祉而努力。” 关于Naldemedine 纳地美定（Naldemedine）是一种具有口服活性的外周阿片受体拮抗剂，对μ、δ和κ阿片受体具有强效拮抗作用。该药物包含一个与阿片受体拮抗剂环丙甲羟二羟吗啡酮相关的结构，该结构与侧链相连接，与环丙甲羟二羟吗啡酮相比，该分子具有更高的极性和更低的脂溶性。从而提示纳地美定（Naldemedine）在临床剂量水平产生具有临床重要浓度的条件下不容易通过血脑屏障。多项非临床和临床研究也表明，口服给药后，纳地美定（Naldemedine）可通过拮抗阿片类药物在外周肠受体的作用而有效治疗OIC，而且不会削弱阿片类药物作用于CNS（中枢神经系统）受体所介导的镇痛效果。 关于平安盐野义 平安盐野义创立于2020年，以母公司日本盐野义制药株式会社研发的新药为首，致力于在中国提供新的医疗服务以及优质的仿制药物等丰富医疗保健解决方案，并以持续不断为人们提供健康和高品质的生活为使命开展业务。 参考文献： [1]WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents[R]. Geneva：World Health Organization，2018. [2]倪嘉淳, 蔡增进, 江琼, 等.  药物治疗阿片类药物所致便秘的研究进展 [J] . 中国全科医学, 2022, 25(12) : 1499-1505. DOI: 10.12114/j.issn.1007-9572.2021.02.092. [3]中华医学会, 等. 慢性便秘基层诊疗指南（2019年） [J] . 中华全科医师杂志, 2020, 19(12) : 1100-1107 声明： 1.本新闻稿旨在促进医药信息的沟通和交流，仅供医疗卫生专业人士参阅，非广告用途。 2.本公司不对任何药品和/或适应症作推荐。 3.本新闻稿中涉及的信息仅供参考，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。若您想了解具体疾病诊疗信息，请遵从医生或其他医疗卫生专业人士的意见或指导。 ● 普莱医药抗菌肽产品培来加南申报上市，正大天晴已获中国独家合作权 ● 中国生物制药与国药控股签署战略合作协议 ● 优势互补共创“产学研”新格局 正大天晴与香港中文大学医学院签署合作框架协议 ● 重磅合作！中国生物制药联合博奥信与Aclaris Therapeutics达成全球合作协议

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)