BCX-17725

—Q2 2024 ORLADEYO net revenue grows 34 percent y-o-y to $108.3 million— —Full-year 2024 ORLADEYO revenue guidance increased to $420-$435 million (previously $390-$400 million)— —Company generates GAAP operating profit of $8.8 million in second quarter ($21.9 million non-GAAP operating profit)— —Pipeline continues to advance— RESEARCH TRIANGLE PARK, N.C., Aug. 05, 2024 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) today reported financial results for the second quarter ended June 30, 2024, and provided a corporate update. “The first half of 2024 has been outstanding for BioCryst due to the success we are having in the marketplace with ORLADEYO. As a result, we are increasing our full year guidance for ORLADEYO, advancing multiple programs toward the clinic in the next 18 months and moving the company closer to profitability,” said Jon Stonehouse, president and chief executive officer of BioCryst. ORLADEYO® (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks ORLADEYO net revenue in the second quarter of 2024 was $108.3 million (+34 percent year-over-year (y-o-y)).Operational improvements drove revenue above expectations for the second quarter. This included a three percent increase in the overall rate of paid patients relative to the end of 2023, which now stands at 74.4 percent.New patient starts continued at the same high rate seen in the prior two quarters, matching the new patient demand seen in the first three quarters of the launch in 2021, and patient retention remained strong. We continue to see more than 60 percent of patients on paid therapy staying on for at least a year.A recent market research study showed that 52 percent of allergist/immunologists are extremely likely to prescribe ORLADEYO to more patients, up from 29 percent in early 2023.With additional recent approvals and reimbursement authorizations in Europe and Latin America, ORLADEYO is now commercially available to patients in more than 20 countries. Ex-U.S. ORLADEYO revenue in the second quarter increased 51 percent y-o-y and accounted for 11 percent of global ORLADEYO net revenues. “Our second quarter revenue growth and increased full year guidance for ORLADEYO reflect strong underlying demand and favorable patient outcomes, combined with our continuing focus on improving patient services and market access operations. The real-world experience of patients who respond to ORLADEYO is consistent with the 91 percent reduction in attacks from baseline that we saw in long-term clinical trials. The potential for patients to have that high level of HAE attack control in a once-daily pill is a major differentiator in the marketplace that makes ORLADEYO’s trajectory toward $1 billion in peak sales increasingly clear,” said Charlie Gayer, chief commercial officer of BioCryst. Rare Disease Pipeline The goal with our pipeline is to build on our success with ORLADEYO by bringing additional selected, highly differentiated rare disease products to patients. The company remains on track to submit a regulatory filing in 2025 to expand the ORLADEYO label to enable children as young as two years of age to receive an oral granule formulation of ORLADEYO. ORLADEYO would be the first oral prophylactic therapy for children with HAE.The company has completed its clinical evaluation of its oral Factor D inhibitor, BCX10013. The drug was safe and well tolerated at all doses studied, however the level of clinical activity observed was less than other therapies on the market and potential partners have declined to make the additional investment required to evaluate higher doses. BioCryst plans to discontinue development, consistent with its previously announced plans.The company expects to advance BCX17725, its KLK-5 inhibitor for the treatment of Netherton syndrome, into the clinic by the end of 2024. Netherton syndrome is a serious, rare, lifelong genetic disorder affecting the skin, hair and immune system. People with Netherton syndrome often have red, scaly, inflamed skin, fragile hair, and are more likely to develop skin infections, allergies, asthma and eczema. Netherton syndrome can be life threatening, especially during infancy when patients are vulnerable to dehydration and recurrent infections. Currently, there is no approved treatment for Netherton syndrome. In 2025, the company plans to advance avoralstat, a plasma kallikrein inhibitor, into a clinical trial of patients with diabetic macular edema (DME). DME is an important cause of vision loss in diabetes and is due to leakage from the blood vessels in the retina. While current treatments focus on VEGF inhibition, DME can develop from other mechanisms, such as the kallikrein-bradykinin pathway. This is supported by observations that many DME patients have an incomplete response to intravitreal anti-VEGF therapies that are administered every four to eight weeks. Avoralstat targets the kallikrein-bradykinin system on the retinal vascular endothelial cells and may result in less vascular leakage and less edema. Avoralstat, delivered to the suprachoroidal space as a depot formulation, is designed to provide high dose levels to the retinal vessels with long-lasting exposure, which could result in less frequent injections and a reduced burden on patients and the healthcare system. Second Quarter 2024 Financial Results For the three months ended June 30, 2024, total revenues were $109.3 million, compared to $82.5 million in the second quarter of 2023 (+32.5 percent year-over-year (y-o-y)). The increase was primarily due to $108.3 million in ORLADEYO net revenue in the second quarter of 2024, compared to $81.0 million in ORLADEYO net revenue in the second quarter of 2023 (+33.7 percent y-o-y). R&D expenses for the second quarter of 2024 decreased to $37.6 million from $51.2 million in the second quarter of 2023 (-26.6 percent y-o-y), primarily due to decreased spending on BCX10013 and the discontinuation of the BCX9930 program. These reductions were partially offset by increased investment in BCX17725, avoralstat and other discovery programs, and our ongoing ORLADEYO pediatric trial. Selling, general and administrative expenses for the second quarter of 2024 increased to $61.2 million, compared to $51.0 million in the second quarter of 2023 (+20.0 percent y-o-y), primarily due to an increase in commercial expenses to support growing revenue, newly launched regions and expanded international operations. In addition, there was an increase in general and administrative expenses, primarily related to an increase in resourcing to support our accounting and IT functions. Total operating expenses were $100.6 million for the second quarter of 2024, compared to $103.2 million in the second quarter of 2023 (-2.5 percent y-o-y). Non-cash stock compensation was $13.2 million for the second quarter of 2024. Total operating expenses, not including non-cash stock compensation for the second quarter of 2024 were $87.4 million, compared to $90.4 million in the second quarter of 2023 (-3.3 percent y-o-y). The company generated a GAAP operating profit of $8.8 million in the second quarter of 2024. This compares to a GAAP operating loss of $20.7 million in the second quarter of 2023. Adjusted for non-cash stock compensation, the non-GAAP operating profit was $21.9 million in the second quarter of 2024, compared to a non-GAAP operating loss of $7.9 million in the second quarter of 2023. Interest expense was $24.7 million in the second quarter of 2024, compared to $28.9 million in the second quarter of 2023 (-14.5 percent y-o-y). The decrease was primarily due to a decrease in the amortization of interest associated with our royalty financing obligations. Net loss for the second quarter of 2024 was $12.7 million, or $0.06 per share, compared to a net loss of $75.3 million, or $0.40 per share, for the second quarter of 2023. In the second quarter of 2023, there was a $29.0 million one-time debt extinguishment fee related to the close-out of the Athyrium debt facility. Excluding this one-time event, non-GAAP net loss for the second quarter of 2023 was $0.24 per share. Cash, cash equivalents, restricted cash and investments totaled $338.1 million at June 30, 2024, compared to $415.7 million at June 30, 2023. Operating cash use for the second quarter of 2024 was $0.2 million. Non-GAAP Pro forma Financial Measures The information furnished in this release includes non-GAAP pro forma financial measures that differ from measures calculated in accordance with generally accepted accounting principles in the United States of America (GAAP), including financial measures labeled as “non-GAAP” or “adjusted.” We believe providing these non-GAAP measures, which show our pro forma results with these items adjusted, is valuable and useful since they allow the company and investors to better understand the company’s financial performance in the absence of these one-time events and allow investors to more accurately understand our second quarter 2023 and second quarter 2024 results and more easily compare them to future results. These non-GAAP pro forma measures also correspond with the way we expected Wall Street analysts to compare our results. Our non-GAAP pro forma measures should be considered only as supplements to, and not as substitutes for or in isolation from, our other measures of financial information prepared in accordance with GAAP, such as GAAP revenue, operating income, net income, operating profit and earnings per share. Our references to our second quarter 2023 and first six months 2023 “non-GAAP pro forma” financial measures of adjusted net loss and adjusted earnings per share constitute non-GAAP financial measures. They refer to our GAAP results, adjusted to show the results without the one-time loss on the extinguishment of the Athyrium term loans. Our reference to our second quarter 2024 and first six months 2024 “non-GAAP pro forma” financial measure of non-GAAP operating profit constitutes a non-GAAP financial measure. It refers to our GAAP results, adjusted to show the results without including non-cash stock compensation expense. Financial Outlook for 2024 Based on the operational improvements and strong patient and physician demand for ORLADEYO seen in the first half of 2024, the company is raising its outlook for full year 2024 global net ORLADEYO revenue to be between $420 million and $435 million (previously $390 million to $400 million). The company maintains its prior operating expense outlook, and expects full year 2024 operating expenses to be between $365 million and $375 million, flat to full year 2023 operating expenses. This operating expense outlook does not reflect non-cash stock compensation expense, or one-time expenses related to the previously announced workforce reduction implemented in the first quarter of 2024. Based on the company’s disciplined approach to capital allocation, and the increased revenue guidance for ORLADEYO, the company is confident that it will achieve a full-year operating profit in 2024 (not including non-cash stock compensation), be approaching quarterly positive earnings per share (EPS) and positive cash flow in the second half of 2025 (not including non-cash stock compensation) and be profitable on an EPS basis, with positive cash flow, for full year 2026. The company expects it can achieve these financial milestones without raising additional funds and does not intend to draw the additional $150 million of debt available to it from Pharmakon. Conference Call and WebcastBioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 1-844-481-2942 for domestic callers and 1-412-317-1866 for international callers. A live webcast and replay of the call will be available online in the investors section of the company website at www.biocryst.com. About BioCryst Pharmaceuticals BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with complement-mediated and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause BioCryst’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: BioCryst’s ability to successfully implement or maintain its commercialization plans for ORLADEYO; risks related to the planned discontinuation of the development of BCX10013; BioCryst’s ability to successfully progress its pipeline development plans as described herein; risks related to the reduction in size of BioCryst’s R&D organization; the results of BioCryst’s partnerships with third parties may not meet BioCryst’s current expectations; risks related to government actions, including that decisions and other actions, including as they relate to pricing, may not be taken when expected or at all, or that the outcomes of such decisions and other actions may not be in line with BioCryst’s current expectations; the commercial viability of ORLADEYO, including its ability to achieve sustained market acceptance; ongoing and future preclinical and clinical development of product candidates may take longer than expected and may not have positive results; the FDA or other applicable regulatory agency may require additional studies beyond the studies planned for products and product candidates, may not provide regulatory clearances which may result in delay of planned clinical trials, may impose certain restrictions, warnings, or other requirements on products and product candidates, may impose a clinical hold with respect to product candidates, or may withhold, delay or withdraw market approval for products and product candidates; product candidates, if approved, may not achieve market acceptance; BioCryst’s ability to successfully commercialize its products and product candidates; BioCryst’s ability to successfully manage its growth and compete effectively; risks related to the international expansion of BioCryst’s business; timing for achieving profitability and positive cash flow may not meet management’s expectations; statements and projections regarding financial guidance and goals and the attainment of such goals may differ from actual results based on market factors and BioCryst’s ability to execute its operational and budget plans; and actual financial results may not be consistent with expectations, including that revenue, operating expenses and cash usage may not be within management’s expected ranges. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which identify important factors that could cause actual results to differ materially from those contained in BioCryst’s projections and forward-looking statements. BCRXW Contact:John Bluth+1 919 859 7910jbluth@biocryst.com BIOCRYST PHARMACEUTICALS, INC.CONSOLIDATED FINANCIAL SUMMARY(In thousands, except per share) Statements of Operations (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Revenues: ORLADEYO $108,288 $81,009 $197,155 $149,423 Other 1,044 1,482 4,938 1,846 Total revenues 109,332 82,491 202,093 151,269 Expenses: Cost of product sales 1,699 894 2,964 1,825 Research and development 37,623 51,247 84,116 99,635 Selling, general and administrative 61,214 50,997 120,578 98,864 Royalty 35 56 162 63 Total operating expenses 100,571 103,194 207,820 200,387 Income (loss) from operations 8,761 (20,703) (5,727) (49,118) Interest income 3,554 3,750 7,585 7,128 Interest expense (24,733) (28,915) (49,239) (56,311)Foreign currency (losses) gains, net (84) 301 (135) 72 Loss on extinguishment of debt — (29,019) — (29,019)Loss before income taxes $(12,502) $(74,586) $(47,516) $(127,248)Income tax expense 172 740 537 1,411 Net loss $(12,674) $(75,326) $(48,053) $(128,659) Basic and diluted net loss per common share $(0.06) $(0.40) $(0.23) $(0.68) Weighted average shares outstanding 206,425 189,118 206,244 188,815 Balance Sheet Data (in thousands) June 30, 2024 December 31, 2023 (unaudited) (Note 1)Cash, cash equivalents and investments $336,344 $388,987 Restricted cash 1,795 1,804 Receivables 68,759 56,950 Total assets 472,419 516,960 Secured term loan 313,822 303,231 Royalty financing obligation 523,633 531,599 Accumulated deficit (1,729,212) (1,681,159)Stockholders’ deficit (475,606) (455,528)Shares of common stock outstanding 206,629 205,771 Note 1: Derived from audited financial statements. Reconciliation of Adjusted Net Loss and Adjusted Diluted Earnings Per Share (in thousands) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 GAAP net loss $(12,674) $(75,326) $(48,053) $(128,659)Less: One-time R&D restructuring expense — — (1,264) — Less: One-time loss on extinguishment of Athyrium term loans — (29,019) — (29,019)Adjusted net loss $(12,674) $(46,307) $(46,789) $(99,640) GAAP basic and diluted net loss per common share $(0.06) $(0.40) $(0.23) $(0.68) Adjusted basic and diluted net loss per common share $(0.06) $(0.24) $(0.23) $(0.53) Reconciliation of Adjusted Income (Loss) from Operations (in thousands) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 GAAP income (loss) from operations $8,761 $(20,703) $(5,727) $(49,118)Less: Stock-based compensation expense (13,173) (12,841) (26,825) (26,848)Adjusted income (loss) from operations $21,934 $(7,862) $21,098 $(22,270)

▲8月15-16日 苏州 NDC2024生物医药创新者峰会  扫码报名  注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。 新药开发难于上青天！ “基于结构的药物设计、创立早期与日本公司合作免疫抑制剂、首先上市了抗病毒药物、现在专注于罕见疾病”这样的描述可能很容易让人想到制药界的现象级黑马福泰制药。本篇内容我们主要挖掘了一家乍一看与福泰制药有许多相似之处的公司，这家公司同样诞生于1980年代，经历了几次转型，现在是一家管线精简，领域较为专注的制药公司。 BioCryst Pharmaceuticals是一家全球性的生物技术公司，致力于改善补体介导疾病和其他罕见疾病患者的生活。BioCryst利用其在结构引导药物设计方面的专业知识，开发first-in-class或best-in-class的口服小分子和蛋白质疗法，以靶向难以治疗的疾病。BioCryst已经将ORLADEYO®（berotralstat）商业化，这是首款口服的、每日一次的血浆激肽释放酶抑制剂，用于治疗遗传性血管性水肿（HAE）。 截图自药融云数据库 01 从流感到补体疾病 BioCryst是一家拥有悠久历史的生物技术公司，在药物发现、开发和商业化方面拥有30多年的经验。其发展历程充满了起起落落、学习与洞察、失败与成功。 1986年，BioCryst成立于美国阿拉巴马州伯明翰市，由当地商人William Spencer三世、阿拉巴马大学伯明翰分校生物化学晶体学教授兼大分子晶体学中心主任Charles Bugg博士和John Montgomery博士共同创立。1988年，Yarlagadda S. Babu博士加入BioCryst成为其第一位员工，目前他依然担任公司的首席发现官（CDO）。1994年，BioCryst公司在纳斯达克上市（NASDAQ:BCRX），同一年，联合创始人Charles Bugg博士被任命为BioCryst的董事长兼首席执行官，直到2007年退休。 1997年，BioCryst与日本鸟居制药（Torii Pharmaceutical）建立合作，共同开发一种用于治疗类风湿性关节炎、T细胞癌和特应性皮炎的PNP抑制剂BCX-34。然而鸟居制药在1998年被日本烟草收购，该协议随之解除，BioCryst重获权益。药融云数据www.pharnexcloud.com显示，BCX-34（Peldesine）的研究已终止。 截图自药融云数据库 1998年，BioCryst和强生公司达成了一项全球合作，专注于开发流感药物。据了解，该项目研究团队由Babu博士领导，研发代号为BCX-1812。然而口服BCX-1812无法充分进入血液，难以达到治疗效果，3年后（2001），强生公司终止合作。BioCryst也在2002年暂停了研究工作。但随后爆发的甲型（H5N1）禽流感病毒改变了BCX-1812的命运。2005年，BioCryst获得美国FDA批准，重启BCX-1812的人体研究，这一次BCX-1812被改为静脉注射制剂，疗效得到了大幅提升。2006年，BioCryst在北卡罗来纳州的三角地区建立了第一家工厂，该工厂专注于支持临床开发和监管工作。据了解，美国卫生及公众服务部与BioCryst签订了价值2.348亿美元合同，以促进BCX-1812的开发。BCX-1812便是日后重要的抗流感病毒药物帕拉米韦，一种病毒神经氨酸酶抑制剂。2009年，美国FDA在H1N1流感大流行期间首次颁发了帕拉米韦的紧急使用授权。 在美国以外，BioCryst与韩国绿十字公司（2006）和日本盐野义制药（2007）分别建立了合作，共同开发帕拉米韦注射液。2010年1月，盐野义制药在日本获得了帕拉米韦的批准，用于治疗单纯季节性流感的成人、儿童和婴儿，以及那些有流感相关并发症的高危患者，标志着BioCryst发现的药物首次获得监管批准，该药物以RAPIACTA®为商品名在日本上市销售。当年8月，绿十字公司在韩国获得了帕拉米韦的批准，用于治疗A型和B型流感病毒，包括H1N1大流行和禽流感，商品名为PERAMIFLU。2014年，BioCryst的RAPIVAB®（帕拉米韦注射液）首次获得FDA完全批准，3年后，儿科适应症获批。 2013年开始，BioCryst调整管线战略，专注于其遗传性血管性水肿（HAE）和抗病毒项目，HAE核心项目分子BCX7353于当年9月被发现，也就是后来的ORLADEYO®（berotralstat）。2019年，BioCryst与日本鸟居制药再度“牵手”，签订了在日本商业化berotralstat的许可协议。随后BioCryst又与多家公司建立了合作伙伴关系，以推动该药在美国以外的地区商业化，包括Neopharm Group，NewBridge Pharmaceuticals，Pint Pharma，Swixx BioPharma和Er-Kim Pharmaceuticals。ORLADEYO®（berotralstat）于2020年12月获得FDA批准，当月便启动销售，此后已在全球多个市场推出。 2021年，BioCryst启动了其口服因子D抑制剂BCX9930在补体介导疾病中的关键试验。2022年，BioCryst改进了其产品线战略，专注于补体介导的疾病，宣布推出下一代口服因子D抑制剂BCX10013。 目前，BioCryst的总部已迁至美国北卡罗来纳州达勒姆，欧洲总部位于爱尔兰都柏林，卓越探索中心扎根于公司的创始之地——阿拉巴马州伯明翰，并在世界各地设有许多其他区域办事处。首席执行官Jon Stonehouse于2007年从默克公司加入BioCryst，首席医学官William P. Sheridan博士于2008年从安进公司加入BioCryst。 02 研发管线围绕补体系统和罕见病 BioCryst目前的研发管线主要围绕补体介导的疾病和其他罕见病，适应症领域横跨过敏/免疫学、皮肤科、肾病学、神经病学、血液学以及眼科。 ORLADEYO®（berotralstat）是BioCryst发现和开发的一种血浆激肽释放酶抑制剂，每日一次口服，用于预防成人和12岁及以上儿童患者遗传性血管性水肿（HAE）的发作。该药是第一个也是唯一一个针对遗传性血管性水肿的靶向口服预防性疗法，还是首款预防HAE发作的口服非甾体药物，于2020年12月获得FDA批准上市，目前已在全球多个市场推出。 遗传性血管性水肿（HAE）是一种可能危及生命的罕见疾病，患病率在1/33000到1/67000之间。该病由一种称为C1酯酶抑制剂（C1-INH）的蛋白质的遗传缺陷引起。C1-INH在防止缓激肽形成系统过度活跃和介导HAE肿胀方面起着重要作用。HAE症状包括不同部位反复水肿，包括手、脚、面部、生殖器和气道。气道肿胀特别危险，可导致窒息死亡。此外，患者常出现由肠壁肿胀引起的严重腹痛、恶心和呕吐。如不及时治疗，HAE患者通常每个月都会有多次发作，每次发作的肿胀可持续2到4天。 2023年1月，ORLADEYO®（berotralstat）用于治疗2-12岁儿童遗传性血管性水肿（HAE）的关键研究APeX-P正式启动，并在2024年5月6日完成患者入组。BioCryst预计该试验的数据将支持在2025年在美国递交一份sNDA申请，使ORLADEYO®标签扩展至2岁以上儿童HAE患者，届时该药将成为首个儿童HAE的口服预防性药物。BioCryst针对儿童患者专门开发了ORLADEYO®的小儿颗粒剂型。 同时，BioCryst正在研究其他针对补体系统的经典途径、凝集素途径、终末途径和替代途径的口服药物和蛋白质疗法。 BCX10013是BioCryst在研的每日一次的口服补体因子D抑制剂，可靶向补体系统的替代途径。因子D是补体替代途径中必不可少的酶，因此因子D是解决补体介导疾病的一个潜力靶点。 2023年8月，BioCryst宣布启动BCX10013针对阵发性夜间血红蛋白尿（PNH）患者的剂量范围试验。2023年11月3日，BioCryst在研发日活动上展示了160 mg队列健康志愿者试验的数据，该数据强调了在该剂量水平下达到的替代途径抑制的强度和持续时间，支持每日一次给药的临床剂量。 2024年1月，BioCryst宣布BCX10013正在进行的概念验证临床试验若取得best-in-class数据，公司计划向合作伙伴授权BCX10013的后期开发和商业化权益，据披露，目前该试验仍在进行中，公司预计将在今年晚些时候对外合作或停止该项目。 2023年11月3日研发日活动上，BioCryst宣布正在开发一种口服补体C5抑制剂，与目前批准的注射和输注型抗C5疗法相比（如依库珠单抗和Ravulizumab），这可能是首款口服靶向疗法。该公司表示，该药有望使全身性重症肌无力（gMG）患者转变治疗模式，并在疾病早期就开始治疗。gMG是一种慢性自身免疫性神经肌肉疾病，临床表现为全身骨骼肌收缩无力，在运动后恶化。 同日官宣的还有一款双功能补体抑制剂抗C2单克隆抗体，它也可以抑制补体系统的替代途径。该研究性候选药物有可能成为补体系统的经典、凝集素和替代途径的first-in-class联合抑制剂，以治疗复杂的补体介导肾脏疾病，如免疫球蛋白A肾病（IgAN）和狼疮性肾炎，这些疾病受多种补体途径的影响。 另外，该公司还宣布正在开发一种经典途径和凝集素途径补体抑制剂，用于治疗自身免疫性溶血性贫血，包括冷凝集素病（CAD）和温抗体型自身免疫性溶血性贫血（wAIHA）。目前治疗CAD和wAIHA等疾病的药物也是注射和输注剂型，BioCryst开发了一种口服补体C2抑制剂有望转变患者治疗模式。从作用机制上看，抑制C2可以通过阻断经典途径和凝集素途径来减少自身免疫性溶血性贫血的红细胞破坏（溶血）。 BioCryst开发的BCX17725是一种选择性融合蛋白KLK5抑制剂，旨在为内瑟顿综合征患者提供潜在best-in-class的疾病修饰治疗。内瑟顿综合征（Netherton syndrome, NS）是一种罕见的，终身的遗传性疾病，常出现在新生儿或婴儿期。该病是由KLK5的天然抑制剂（SPINK5）基因功能丧失突变引起，KLK5是一种负责调节皮肤脱落的丝氨酸蛋白酶。患者皮肤表现为红色、鳞状和发炎，易发生反复的免疫反应。内瑟顿综合征可能危及生命，特别是在婴儿期，患者容易脱水和反复感染。目前尚无药物获批治疗该病。该公司预计在2024年底将BCX17725推向临床，目标在2026年提供针对内瑟顿综合征的概念验证结果。 Avoralstat是BioCryst开发的一种血浆激肽释放酶抑制剂，先前其口服制剂被研究用于治疗遗传性血管性水肿（HAE）并开展了3期试验，根据药融云数据www.pharnexcloud.com提供线索，该药针对HAE开展的3期研究并未取得积极结果。 截图自药融云数据库 不过此前的研究显示，Avoralstat具有高效力和低溶解度，该公司认为这两个特征对于治疗糖尿病黄斑水肿（DME）的同时降低患者眼部给药频率十分重要。 2023年11月3日，BioCryst宣布与Clearside Biomedical签订了许可协议，使用Clearside的SCS Microinjector®注射技术，通过脉络膜上腔间隙将Avoralstat递送到眼底，治疗糖尿病黄斑水肿（DME）患者。DME是糖尿病患者视力丧失的最常见原因，尽管有每月注射的抗血管内皮生长因子（VEGF）疗法，但至少有三分之一的患者持续患有DME。 根据许可协议，Clearside Biomedical获得500万美元的预付许可费，并有资格获得高达3000万美元的临床和监管里程碑付款，以及三次批准后的里程碑付款，基于销售的里程碑付款总计4750万美元。BioCryst计划在2025年推进该药针对DME患者的临床试验。公司预计Avoralstat有望成为DME领先的2线治疗方法。 BioCryst计划在未来5年内提供6个分子的概念验证数据，下图为BioCryst研发管线预期里程碑： 03 财务状况 2023全年，BioCryst公司总收入为3.314亿美元（约合24亿人民币），其中ORLADEYO®（berotralstat）净收入达3.26亿美元，同比增长30%；全年R&D费用为2.166亿美元，同比减少14%，主要是由于BCX9930和BCX9250研发终止；全年的SG&A费用增至2.139亿美元，同比增长34%，主要是由于增加投资扩大和加强美国商业团队，以及扩大国际业务。全年利息支出为1.082亿美元，而2022年全年为9910万美元；其他费用主要包括偿还定期贷款的债务清偿损失2900万美元，以及100万美元的净外汇损失。2023年全年净亏损为2.265亿美元，或每股1.18美元，而2022年全年净亏损为2.471亿美元，或每股1.33美元。 2023全年BioCryst研发开支分布： 2024年第一季度，BioCryst公司总收入为9280万美元，同比增长34.9%，其中ORLADEYO®（berotralstat）净收入为8890万美元，同比增长30%；第一季度R&D费用为4650万美元，同比减少3.9%，主要是由于公司计划将BCX10013项目对外授权或者终止后期开发导致的支出减少，以及终止BCX9930项目；SG&A费用增至5940万美元，同比增长24%。第一季度利息支出为2450万美元，同比减少10.6%。2024年第一季度净亏损为3540万美元，或每股0.17美元，而2023年第一季度的净亏损为5330万美元，或每股0.28美元。 2024年Q1BioCryst研发开支分布： 截至2024年3月31日，现金、现金等价物、限制性现金和投资总额为3.384亿美元，去年同期为4.031亿美元，公司预计到2024年底，现金总额将超过3亿美元。 由于第一季度ORLADEYO®（berotralstat）在美国的销售表现优于预期，BioCryst预测该产品2024全年全球净收入在3.9亿美元至4亿美元之间，预计公司2024年全年运营费用将在3.65亿美元至3.75亿美元之间，与2023年全年运营费用持平。基于此，BioCryst有信心在2024年实现全年营业利润（不包括非现金股票薪酬），2025年下半年季度每股收益（EPS）接近为正，现金流为正（不包括非现金股票薪酬），并在2026年全年实现每股收益盈利，现金流为正。 BioCryst预期2029年ORLADEYO®（berotralstat）在美国的业绩将达到8亿美元，该药的全球销售峰值有望达到10亿美元。 截至2024年5月底，BioCryst总市值为13.6亿美元。发稿前为12.75亿美元（约合92亿），每股6.18美元。 来源：companiesmarketcap 此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐 参考： NMPA/CDE； 药融云数据www.pharnexcloud.com； FDA/EMA/PMDA； 相关公司公开披露（正文图片均来自企业官方，除非另有说明）； https://www.biocryst.com/； https://www.biocryst.com/science/pipeline/； https://companiesmarketcap.com/biocryst-pharma/marketcap/； https://mp.weixin.qq.com/s/ZGBjzdI2j6h6h9XC5VQBQQ；等等。 [ 重磅苏州生物医药峰会推荐 ] 8月15日论坛3：XDC领域的差异化创新和国际化策略 09:00-09:20ADC的CMC相关发补问题解析及案例 09:20-09:40PDC药物开发进展 09:40-10:00如何利用Linker改革攻克传统ADC毒性/耐药等难题 10:00-10:20MIDD视角下的ADC药物开发 10:20-10:40TROP-2 ADC药物开发进展 10:40-11:00深层分子影像分析赋能新药开发 11:00-11:20ADC+IO联合疗法的研发进展 11:20-12:00圆桌：如何从早期设计降低XDC的临床失败？ 12:00-13:30午餐 13:30-13:50New Drug Modality在未被满足临床上的探索--放射性偶联药物 13:50-14:1068Ga-NY104核素药物开发 14:10-14:30 靶向Nectin4核素偶联药物的开发 14:30-14:50 RDC靶点内卷，如何做源头创新？ 14:50-15:10HER2靶点核素药物研发 15:10-15:30核素药物全球化专利布局挑战与策略 15:30-15:50急性髓系白血病（AML）领域的布局和实践 15:50-16:10 RDC药物的CMC开发策略及监管要求 16:10-16:30 全球ADC出海的机会还剩多少? 初步确认嘉宾 排名不分先后，按照姓名首字母A-Z 蔡家强，宜联生物，CSO 方鹏，诺宇医药，董事长 刘翠华，百奥泰生物高级副总裁 刘   艳，米度生物，首席医学官 吕   明，尚健生物，董事长 秦   刚，启德医药，CEO  苏   霞，康龙化成，临床药理&定量药理高级总监 单   波，博锐创合 ，CEO 邵   军，同宜医药，COO 唐华东，植德律所，合伙人 王忠民，康方生物，副总裁 夏明德，英诺湖，CEO 习宁，范恩柯尔，创始人&CEO 须涛，智核生物，CEO 通瑞药业（嘉宾行程确定中） 扫码报名参会 【关于药融圈】 药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。