BYSI 万春医药 2019年第3季度财报电话会议文字稿中英文

Operator

各位好，欢迎参加BeyondSpring 2019年第三季度电话会议。我是Rob，今天会议的操作员。请注意本次通话正在录音。现在，请主持人KCSA战略传播高级副总裁David Schemelia发言。

David Schemelia

谢谢主持人，也感谢各位参加今天的电话会议。我想提醒听众，今天通话中的发言可能包含前瞻性陈述，涉及BeyondSpring的临床和临床前研发活动及结果、监管和商业计划、行业趋势、市场潜力、合作计划以及财务预测等方面。虽然管理层认为其假设、预期和预测在当前可用信息下是合理的，但请勿过度依赖这些前瞻性陈述。公司实际结果可能因多种原因与本次通话中讨论的内容存在重大差异，包括公司20-F文件及其他向SEC提交文件中前瞻性陈述和风险因素部分描述的原因，这些文件可在BeyondSpring网站投资者关系部分查阅。今天参加会议的有BeyondSpring董事长兼首席执行官黄岚博士、研发执行副总裁兼首席医疗官Ramon Mohanlal博士、首席运营官Richard Daly以及首席财务官Edward Liu。现在我很高兴请黄博士发言。黄博士？

Lan Huang

感谢大家参加今天的电话会议。谢谢David。对于那些刚刚开始关注我们公司故事的投资者，BeyondSpring是一家全球性生物制药公司，专注于开发针对未满足医疗需求的变革性免疫肿瘤癌症疗法。上个季度非常令人兴奋，我们实现了几个重要里程碑。首先，我们的核心资产、首创药物Plinabulin正按计划在未来6至18个月内在中国和美国提交针对非小细胞肺癌和化疗引起的中性粒细胞减少症（CIN）适应症的新药上市申请。其中，针对CIN的中国申请预计在2020年第一季度率先提交。其次，随着Plinabulin被验证为有效的抗原呈递细胞（APC）诱导剂，近期在Cell期刊上发表的研究表明，Plinabulin具有未来与PD1或PDL1抗体以及化疗或放疗联合形成三联疗法治疗多种癌症适应症的潜力。最后但同样重要的是，Plinabulin最近在美国获得了脑肿瘤专利，其强大的专利组合包括在36个司法管辖区获得的75项授权专利，保护期至2036年，包括物质组成专利。因此，我们有很长的专利保护期来实现Plinabulin的临床和商业潜力。自上次更新以来，我们继续推进临床研究。10月份，我们报告了首例患者入组了公司的106研究，这是一项全球性III期临床试验，评估Plinabulin联合G-CSF预防CIN，旨在显示其在CIN和骨痛控制方面优于单独使用G-CSF。如您所知，G-CSF是过去30年来CIN的标准治疗，全球年销售额超过70亿美元。此外，我很高兴地报告，经过5年与巴塞尔大学和马萨诸塞总医院顶尖科学家的合作努力，我们揭示了Plinabulin在癌症治疗和CIN控制中的独特机制。Plinabulin作为诱导树突状细胞成熟和T细胞活化的强效剂的新型抗癌机制于9月发表在权威同行评审期刊Cell publications、Chem和cell reports上。最近，Plinabulin通过逆转化疗引起的骨髓抑制来控制CIN的机制，及其通过不同机制减少多种化疗引起的CIN的效果本月发表在cancer chemotherapy and pharmacology上。这篇论文进一步验证了我们在人体研究中观察到的Plinabulin持久的抗癌益处以及在多种化疗中的CIN控制作用，并与G-CSF产生协同效应。在融资方面，10月下旬，我们完成了一次公开发行，显著扩大了机构股东基础，并加强了资产负债表，同时我们推进临床管线向美国和中国的NDA提交迈进。因此，正如您所见，BeyondSpring过去几个月非常忙碌。总而言之，我们将Plinabulin视为一个药物管线。迄今为止，Plinabulin已治疗超过580名患者，耐受性良好。Plinabulin的基本适应症是非小细胞肺癌和CIN，多项临床研究证实了Plinabulin的益处，其中一些具有高度统计学意义。二线和三线非小细胞肺癌以及CIN适应症都是严重未满足的医疗需求领域。首先，在EGFR野生型的二线和三线非小细胞肺癌患者中（占西方患者的85%），可用的获批疗法非常有限，当前治疗选择的中位总生存期仅为8至10个月，但代价是严重的不良事件，如严重中性粒细胞减少和生活质量下降。即使是PD1抑制剂单药治疗，缓解率也仅为20%左右，与标准治疗多西他赛相比，中位生存获益仅为2.8个月。其次，在CIN方面，当前的标准治疗是G-CSF单药治疗，其中长效版本Neulasta是市场领导者。然而，使用Neulasta后，约90%接受高风险化疗的患者仍会出现3级或4级中性粒细胞减少。3级或4级中性粒细胞减少需要降低化疗剂量、延迟下一个周期、降低治疗方案强度或完全停止治疗。因此，我们称之为"四个D"，所有这些都会显著降低患者的生存结果。因此，我们非常有信心Plinabulin有潜力改变当前的治疗格局，并大幅改善患者的总体结果和生活质量。我们的监管策略是在2020年第一季度在中国提交CIN的NDA，在2020年下半年提交非小细胞肺癌的NDA。我们还计划在2020年下半年在美国提交CIN的NDA，在2021年上半年提交非小细胞肺癌的NDA。这种在中国和美国的分阶段NDA提交策略允许两国监管机构在我们提交CIN适应症的NDA时充分审查Plinabulin的临床前安全性和CMC部分。当提交非小细胞肺癌适应症时，由于相同的临床前和CMC部分已经过审查，我们预计审查和批准过程将大大加快。FibroGen已采用这种方法，其创新的首创资产成功在中国率先获得监管批准，时间表领先于美国批准。今年11月，我们与美国FDA成功举行了NDA前会议，并就Plinabulin两个适应症的NDA提交所需的安全性数据要求达成一致。我们相信Plinabulin在Plinabulin、PD1或PDL1抗体以及放疗或化疗联合治疗多种癌症类型的三联疗法中具有变革潜力。这种三联疗法优化了免疫疗法的效用，因为放疗或化疗产生肿瘤抗原，Plinabulin的DC成熟实际上优化了这些肿瘤抗原向细胞毒性T细胞的呈递，而检查点抑制剂使活化的T细胞能够杀死癌细胞。换句话说，Plinabulin踩油门，PD1松刹车。因此，这种三联疗法可能是一种强大的鸡尾酒疗法，类似于强大的HIV鸡尾酒疗法，后者将HIV从致命疾病转变为患者具有正常预期寿命的慢性疾病。此外，我们仍按计划推进三个临床前免疫药物BPI-002、BPI-003和BPI-004，以及一个利用泛素介导降解途径的研究平台，这是诺贝尔奖获奖技术，可以靶向70%的[听不清]靶点，我们有一支获奖级别的团队正在从事这项工作。现在，我将电话转交给Ramon Mohanlal博士，他将更详细地讨论我们最近的临床发展。

Lan Huang

Thank you for joining today’s call. Thank you, David. For those of you who are just now starting to follow our story, BeyondSpring is a global biopharmaceutical company focused on the development of transforming immunooncology cancer therapies for unmet medical needs. The last quarter had been very exciting with a few significant milestones achieved. First, our lead asset, first-in-class agent, Plinabulin is on-track to file an NDA for non-small cell lung cancer and the prevention of chemotherapy induced neutropenia or CIN indications in China and in the U.S. in the next 6 to 18 months. Leading with the filing in China for CIN around Quarter 1, 2020. Second, with Plinabulin validated as a potent inducer for Antigen Presenting Cells or APC inducer was recent publications in Cell Journals, Plinabulin has the potential to future indications with triple combo combining with PD1 or PDL1 antibodies and chemo or radiation for multiple cancer indications. Last, but not the least, Plinabulin’s recent U.S. patent granted in brain tumors as to its robust patent portfolio of 75 granted patents in 36 jurisdictions with protection to 2036, including composition for matter patent. Thus, we have a very long patent runway to realize Plinabulin’s clinical and commercial potential. Since our last update, we continue to progress in our clinical studies. In October, we reported that the first patient was enrolled in the company’s Study 106, a global Phase 3 clinical trial with Plinabulin in combination with G-CSF to prevent CIN, designed to show superiority in CIN and bone pain control compared to G-CSF alone. As you know, G-CSF is the standard-of-care for CIN for the last 30 years with annual sales over $7 billion globally. In addition, I’m very pleased to report that after 5 years of effort collaborating with leading scientists at University of Basel and Massachusetts General, we have uncovered Plinabulin’s unique mechanism in cancer treatments and in CIN control. Plinabulin’s anti-cancer in new mechanism as a potent agent to induce dendritic cell maturation and T-cell activations were published in the prestigious peer-reviewed Cell publications, Chem and cell reports in September. Recently, Plinabulin’s mechanisms in CIN control by reversing chemo-induced bone marrow suppression, and its effects in reducing CIN of multiple chemo was different mechanism was published in cancer chemotherapy and pharmacology this month. This paper further validates what we have observed in human studies in Plinabulin’s durable anti-cancer benefit and in CIN control with multiple chemo and synergizes with G-CSF. On the financing side, in late October, we completed a public offering significantly expanding our institutional shareholder base and strengthening our balance sheet as we advance our clinical pipeline towards NDA submissions in the U.S. and China. So, as you see it has been a very busy few months for BeyondSpring. All in all, we view Plinabulin as a pipeline in a drug. To date, Plinabulin has treated more than 580 patients with good tolerability. The fundamental indications of Plinabulin are in non-small cell lung cancer and in CIN with multiple clinical studies confirming Plinabulin’s benefit some with high statistical significance. Both of the second and third-line non-small-cell lung cancer and the CIN indications are severely unmet medical needs indications. First, in patients with second and third line non-small cell lung cancer who are EGFR wild type, which accounts to 85% of Western patient, there are very few approved therapies available, and current treatment options have a modest medium OS or overall survival rate of 8 to 10 months, but as expense of severe adverse events such as severe neutropenia and quality of life. Even response rate with PD1 inhibitor mono-therapy is around 20% with a median survival benefit of only 2.8 months, compared to Docetaxel, the standard-of-care in this patient population. Secondly, in CIN, the current standard-of-care is G-CSF monotherapy with a long-lasting version Neulasta being the market leader. However, after using Neulasta, about 90% of patients with high-risk chemotherapies still develop grade 3 or 4 neutropenia. Grade 3 or 4 neutropenia requires the chemotherapy dose to be reduced, the next cycle be delayed, the regime to be downgraded or be discontinued altogether. So, we call this the four d’s, all of which result in significantly reduced survival outcomes for patients. Thus, we're very confident Plinabulin has the potential to disrupt the current treatment landscape and greatly improve overall patient outcomes and quality-of-life. Our regulatory strategy is submitting NDAs in China for CIN in the first quarter of 2020 and for non-small cell lung cancer in the second half of 2020. We also plan to submit NDAs in the U.S. for CIN in the second half of 2020 and for non-small cell lung cancer in the first half of 2021. This staggered NDA filing strategies for both China and the U.S. allows agencies in both countries to sufficiently review the Plinabulin’s pre-clinical safety and CMC sections while we submit for the NDA for the CIN indication. And when it comes to the submission for the non-small cell lung cancer indications since the same pre-clinical and the CMC sections of Plinabulin submissions have being reviewed, we expect the review and approval process will be much accelerated. Such an approach has been adopted by FibroGen with its innovative first-in-class asset, which successfully obtained regulatory approval in China first with a speedy timeline ahead of the U.S. approval. In November of this year, we had a successful pre-NDA meeting with the U.S. FDA and reached alignment that our current safety data needs requirements for the NDA filings for both indications of Plinabulin. We believe Plinabulin’s transforming potential in triple combo of combining Plinabulin, PD1 or PDL1 antibodies and radiation or chemotherapy for the treatment of multiple cancer types. This triple combination approach optimizes utility of immunotherapy as radiation or chemotherapy generates tumor antigen Plinabulin’s DC maturation in fact optimizes presentation of this tumor antigen to cytotoxic T-cells and checkpoint inhibitors enabled activated T-cells to kill cancer cells. In other words, Plinabulin steps on the gas, PD1 releases the break. So, this triple combination approach could be a powerful cocktail that resembles the powerful HIV cocktail therapy, which transformed HIV from a [death] disease to a chronic disease with patients having normal life expectancy. In addition, we remain on track to advance three pre-clinical immune agents, BPI-002, BPI-003, and BPI-004 and a research platform using ubiquitin-mediated degradation pathways to Nobel Prize winning technology, which can target 70% of [indiscernible] target, as we have award-leading team working on this. Now, I'm turning the call over to Dr. Ramon Mohanlal who will discuss our recent clinical development in more detail.

Ramon Mohanlal

谢谢，Lan。首先，我想更新一下我们主要资产Plinabulin的注册临床试验进展。第一，非小细胞肺癌研究103是一项554名患者的3期注册研究，评估Plinabulin联合多西他赛与单用多西他赛在二线和三线非小细胞肺癌中的抗癌效果，主要终点为中位总生存期。截至目前，我们已在美国、澳大利亚和中国招募了约480名患者。该研究有两个预先设定的中期分析。第一个在达到三分之一患者死亡时进行；第二个在达到三分之二患者死亡时进行。今年早些时候，我们达到了第一个中期分析点，数据和安全监测委员会（DSMB）建议试验继续按方案规定的患者数量进行。该试验在439名患者死亡时的最终结果预计将于2020年下半年公布。第二，研究105和106评估Plinabulin在预防化疗引起的中性粒细胞减少症（CIN）方面的效果。我们已与美国和中国FDA达成一致，105和106研究将支持广泛的CIN适应症标签，涵盖所有癌症、所有化疗方案，并与G-CSF联合使用。研究105是一项2/3期注册试验，在美国、中国、俄罗斯和乌克兰的晚期乳腺癌、激素难治性前列腺癌和晚期非小细胞肺癌患者中，评估Plinabulin在标准多西他赛方案后的效果。该试验2期部分的先前数据已证明，在化疗当天单次给药周期的Plinabulin与Neulasta同样有效，且具有显著减少骨痛、改善生活质量、相比Neulasta提供更优的免疫谱，并具有减轻血小板减少症潜力的优势。Plinabulin基于非G-CSF的独特作用机制使其在预防CIN方面可能与Neulasta形成互补。去年12月，我们宣布在研究105的预先设定中期分析中，其3期部分达到了主要终点，即40毫克固定剂量的Plinabulin与6毫克Neulasta在第一周期的DSN方面具有非劣效性。研究106评估Plinabulin联合Neulasta与单用Neulasta在预防接受TAC化疗（乳腺癌患者中多西他赛、多柔比星和环磷酰胺的三联组合）患者CIN和骨痛方面的效果。该试验2期部分的先前顶线数据表明：首先，在治疗CIN方面有显著疗效改善；其次，经历3级或4级CIN的患者百分比显著降低；第三，经历骨痛的患者减少90%以上；最后，在标准治疗基础上添加Plinabulin可减少潜在的免疫抑制表型。研究106的3期部分将在双盲研究中比较40毫克固定剂量的Plinabulin联合6毫克Neulasta与单用6毫克Neulasta。该研究旨在显示第一周期DSN方面的优效性作为主要终点。我们已于10月在该研究中招募了首名患者。迄今为止的数据表明，Plinabulin为预防接受化疗患者的CIN和骨痛提供了一种新方法。减少中性粒细胞减少和骨痛将使更多患者能够接受全剂量化疗并完成化疗治疗，这意味着在G-CSF基础上添加Plinabulin有潜力显著改善当前的CIN标准治疗，从而带来更好的抗癌效果和患者生活质量。Plinabulin的积极临床结果已被世界领先会议接受进行展示。9月下旬和10月初，我们在ESMO上展示了两张海报。第一张海报聚焦研究103的新颖试验设计及其与失败的Javelin Lung 200试验相比的成功之处。研究人员推测，Javelin的开放标签设计（首先）和单盲的研究103试验设计是Javelin失败的原因，因为患者在首次给药前就退出了研究。第二张海报评估了研究106中Neulasta联合Plinabulin对绝对中性粒细胞和血小板计数的影响，并测量了血小板减少症的发生频率。我们的数据显示，该联合方案在CIN控制、血小板计数和骨痛方面似乎具有优于Neulasta的产品特性。此外，我们最近在ASH上展示了两篇关于研究105的电子出版物，重点介绍了Plinabulin保护造血干细胞的能力，这些干细胞可分化为中性粒细胞和所有白细胞类型。作用机制的临床前论文与此信息一致。最后，BeyondSpring在ASH上展示了关于研究106的海报，该海报为在Neulasta基础上添加Plinabulin提供了理论依据，因为它们在预防化疗方面具有互补的作用机制，可实现协同效应。接下来，我将把电话交给Rich，他将讨论我们的商业和合作战略。

Ramon Mohanlal

Thank you, Lan. First, I would like to provide an update to our registrational trials for our lead asset Plinabulin. First, non-small cell lung cancer Study 103, is a 554 patient Phase 3 registrational study, evaluating the anti-cancer effects of Plinabulin in combination with Docetaxel, compared to Docetaxel alone in second and third-line non-small-cell lung cancer, with its primary endpoint of median overall survival. To date, we have enrolled approximately 480 patients in the U.S., Australia, and China. The study has two pre-specified interim analysis. The first, when one-third of the patient’s [death] is reached; and the second when two-thirds of the patient [death] are reached. Earlier this year, we reached the first interim analysis and the Data and Safety Monitoring Board or DSMB recommended the trial to continue with no change to the protocol specified number of patients. Final results of the trial at a [death rate] of 439 patients are expected to be available in the second half of 2020. Second, studies 105 and 106 evaluates Plinabulin’s effect in the prevention of chemotherapy induced neutropenia. We have aligned with U.S. and China FDA that 105 and 106 studies would support a broad CIN label for all cancers, all chemo’s, and to be combined with G-CSF. Study 105 is a Phase 2, 3 registrational trial of Plinabulin, after the standard regimen of docetaxel in advanced breast cancer, hormone refractory prostate cancer, and advanced non-small cell lung cancer patients in the U.S., China, Russia, and the Ukraine. Previous data from the Phase 2 portion of this trial already demonstrated that Plinabulin given as a single dose cycle on the same day of chemotherapy, would be as effective as Neulasta with the benefit of causing much less bone pain, improved quality of life, offering a superior immune profile compared with Neulasta, and having the potential to mitigate thrombocytopenia. Plinabulin’s non-G-CSF based unique mechanism of actions potentially makes it complimentary to Neulasta in presenting CIN. In December last year, we announced in the pre-specified interim analysis, the Phase III portion of Study 105, met its primary endpoint of non-inferiority with Plinabulin at a 40-milligram fixed dose versus Neulasta at 6-milligram for DSN in the first cycle. Study 106 evaluates the combination of Plinabulin with Neulasta, versus Neulasta alone to prevent CIN and bone pain in patients receiving TAC chemotherapy, which is a triple combination of taxotere, doxorubicin and cyclophosphamide in breast cancer patients. Previous top line data from the Phase II portion of this trial suggests; firstly, a significant improvement in efficacy in treating CIN; secondly, a significant decrease in the percentage of patients experiencing Grade 3 or 4 CIN; thirdly, more than 90% reduction in patients experiencing bone pain; and lastly, a reduced potential immune suppressive phenotype, when adding Plinabulin to the standard of care. The Phase III portion of Study 106 will compare Plinabulin at the 40-milligram fixed dose, combined with 6-milligram Neulasta versus 6-milligram of Neulasta alone in a double-blind study. The intent of the study is to show superiority in DSN in the first cycle, as a primary endpoint. We have already enrolled the first patient in this study in October. The data generated to-date suggest that Plinabulin offers a novel approach to preventing CIN and bone pain in patients receiving chemotherapy. Minimizing neutropenia and bone pain would allow more patients to receive a full dose of chemotherapy and complete their chemotherapy treatment implying that the addition of Plinabulin to G-CSF has the potential to significantly improve the current CIN standard of care, resulting in better anti-cancer outcomes and patient's quality of life. Positive clinical results of Plinabulin have been accepted for presentation at world-leading conferences. In late September and early October, we presented two posters at ESMO. The first poster focus on the Novel Trial Design for Study 103 and its success compared with the failed Javelin Lung 200 trial. Researchers surmise that the open label design of Javelin, first, the single blinded Study 103 trial attributed it to Javelin failure, as patients dropped out of the study prior to receiving the first dose. The second poster evaluated in Study 106, the effects of Neulasta combined with Plinabulin on absolute neutrophil and platelet counts and measured the frequency of thrombocytopenia. Our data show that the combination appears to have a superior product profile, often Neulasta in CIN control, platelet counts, and bone pain. Additionally, we recently presented two e-publications on Study 105 at ASH, highlighting Plinabulin's ability to protect hematopoietic stem cells, which differentiates into neutrophils and all the white blood cell types. The mechanism of action pre-clinical [paper] is consistent with this message. Lastly, BeyondSpring presented the poster at ASH on Study 106, which provides rationale for the addition of Plinabulin to Neulasta, due to their complementary mechanism of action for the Prevention against chemotherapy, to achieve synergy. With that, I'll now turn the call over to Rich, who will discuss our commercial and partnership strategy.

Richard Daly

谢谢，Ramon。正如您所听到的，我们的临床数据继续支持我们的信念，即Plinabulin能够改善标准治疗，并对癌症患者的生活产生积极影响。这包括那些需要预防化疗诱导的中性粒细胞减少症的患者，以及那些在非小细胞肺癌治疗中寻求创新新选择的患者。为此，我们正在努力推进我们的组织，在这两个方向上实现商业化。在我们等待2020年额外临床数据发布的同时，即将到来的一年对公司以及我们希望能够服务的患者和医疗提供者来说，都蕴含着巨大的希望。首先，我们将讨论CIN。最近发表在《柳叶刀》上的数据预测，从现在到2040年，化疗周期将从980万增加到1500万，增长53%。我们认同CIN领域这一增长导向的机遇观。如前所述，尽管使用了G-CSF，CIN仍然持续存在，并导致临床医生改变或减少患者在整个治疗方案中的剂量，这可能对抗癌结果产生毁灭性影响。事实上，CIN是化疗方案变更的最常见原因。我们的临床项目和最近完成的专有市场研究告诉我们，Plinabulin与G-CSF联合使用，有潜力在改善标准治疗和提升患者生活质量方面发挥重要作用。即使是化疗剂量的微小变化或化疗输注的短暂延迟，也可能对总生存期产生不利影响。化疗剂量仅减少15%就可能导致总生存期减少50%。这一事实并未被肿瘤学家忽视。事实上，在盲法市场研究中了解到Plinabulin联合G-CSF组合疗法的益处后，我们采访的65%的医生和KOL对使用Plinabulin治疗患者的前景感到兴奋。显然，医生们对CIN的新治疗选择持开放态度，并理解市场上存在高度未满足的医疗需求。我们的市场研究和临床研究继续为Plinabulin作为能够改善癌症治疗标准治疗的疗法提供依据。通过开发Plinabulin与G-CSF疗法协同并增强其效果，目标是让[HCP's]能够避免之前提到的四个D，并提供稳定的化疗剂量、持续的化疗周期和最强大的化疗方案。此外，我们的专有市场研究继续表明，肿瘤学家对Plinabulin的产品特性持积极态度，医生们能迅速理解Plinabulin和G-CSF互补作用机制的逻辑。这指的是Plinabulin起效速度与G-CSF延迟起效的对比、更优的绝对中性粒细胞计数以及骨痛的减轻。Plinabulin联合G-CSF的组合在使肿瘤学家及其患者能够坚定不移地坚持个体化治疗计划并避免四个D方面显示出巨大的前景。此外，我们的目标超越了预防中性粒细胞减少和骨痛。我们将Plinabulin的临床益处视为医疗提供者可能实现更好化疗结果的一种方式，使肿瘤学家能够为患者选择最合适、最积极的疗法，并确信中性粒细胞减少症可以显著减少，患者可以继续接受其靶向化疗。我们正在进行的临床和市场数据生成继续给我们信心，即Plinabulin联合G-CSF的组合疗法可以提供改进的标准治疗。此外，我们认为，诸如化疗增长和组合疗法成功等市场动态凸显了CIN的增长机遇。简而言之，组合疗法被证明能为临床医生、患者和支付方带来诸多益处，包括显著减少中性粒细胞减少症（目标是避免4个D）、推动使用最强化疗剂量的稳定持续周期、改善骨痛状况以确保增强的治疗体验、以及可能更高的持久性，和提示抗癌活性的临床数据。我们的临床数据验证了明显差异化的产品特性，而我们的市场研究表明，市场对改善CIN标准治疗的新疗法存在明确且迫切的需求。现在转向非小细胞肺癌。非小细胞肺癌是当今所有医学领域中最令人兴奋的治疗领域之一，并且持续快速发展。随着IO疗法在一线治疗中获得批准，护理方面的进步为二线和三线治疗创造了新选择的需求，IO疗法的进展为BeyondSpring、Plinabulin和患者带来了巨大机遇。迄今为止，Plinabulin在我们非小细胞肺癌项目中的临床数据证明了其作为二线和三线治疗有效药物的前景。考虑到晚期患者[剂量]有效选择有限，我们对Plinabulin为非小细胞肺癌患者提供具有临床意义的数据和结果的前景感到兴奋。在我们考虑Plinabulin的生命周期管理时，我们着眼于其与IO化合物联合的早期工作。我们希望我们能够证明其益处超越目前单独使用IO所见的疗效。这可能代表着一个额外的重大增长机遇，以帮助正在努力应对这种毁灭性疾病的患者和医疗提供者。现在，转向业务发展。我们相信Plinabulin作为CIN和非小细胞肺癌的抗癌疗法具有巨大潜力。如前所述，我们最近对超过100名HCP以及支付方进行的市场研究使我们相信，我们迄今为止生成的数据展示了差异化的产品特性。此外，这些肿瘤学家和支付方的接受度表明市场存在未满足的需求。我们在业务发展努力中看到了这些反响的共鸣，潜在合作伙伴表现出浓厚兴趣。随着我们为即将到来的数据拐点做准备，我们已做好充分准备，通过我们的市场进入策略，在美国和海外最大化Plinabulin的价值。最近的一项ZS研究显示，由于美国损益表的潜在优势，10家在美国推出其首个肿瘤产品的公司中有7家选择独立上市。尽管70%的公司在欧洲为CIN和非小细胞肺癌寻求合作，但美国占全球价值的75%以上，我们准备通过业务发展和商业化努力来优化这一价值。我们期待在未来向您更新我们的进展。最后，我们的临床特性非常出色，填补了市场上明确的未满足需求。我们有潜力设定新的护理标准。我们的市场研究表明，HCP们认识到Plinabulin是一种具有显著临床潜力的差异化产品。HCP们也对在CIN的预防和治疗中使用Plinabulin以保持患者接受最合适、最积极的化疗方案的机会感到兴奋。随着我们准备在中国和美国为CIN和非小细胞肺癌提交Plinabulin的NDA申请，我们的美国和全球商业化计划与我们的开发和监管时间表保持一致。我们正在采取措施确保BeyondSpring能够将Plinabulin推向市场，从而为患者、医疗提供者和股东优化利益。在此，我现在将电话转交给Edward，他将提供财务更新。Edward？

Richard Daly

Thanks, Ramon. As you heard, our clinical data continues to support our belief that Plinabulin can improve the standard-of-care and positively affect the lives of cancer patients. Those who require the prevention of chemo-induced neutropenia and those seeking innovative new options in the treatment of non-small cell lung cancer. To that end, we are working diligently to advance our organization toward commercialization on both fronts. As we await additional clinical readouts in 2020, the upcoming year holds immense promise for the company and potentially for the patients and providers we hope to serve. First, will address CIN. Recently published data and Lancet forecast continued growth of chemotherapy from 9.8 to 15 million cycles between now and 2040, a 53% increase. We share this growth-oriented view of the opportunity in CIN. As mentioned earlier, CIN continues to persist despite the use of G-CSF and cause clinicians to change or reduce dose of patients through the regimens, which can have devastating effects on anti-cancer outcome. In fact, CIN is the most frequent cause of change for chemotherapy regimens. Our clinical program and recently completed proprietary market research tells us that Plinabulin used together with G-CSF has the potential to play a major role in both improving the standard of care and benefiting the patient's quality of life. Even small changes in chemotherapy doses or brief delays in chemotherapy infusion can have detrimental effects on overall survival. Just a 15% reduction in chemotherapy doses can result in a 50% reduction in overall survival. This fact is not lost on oncologists. In fact, upon learning about the benefits of Plinabulin, plus G-CSF combination therapy in blinded market research, 65% of doctors and KOLs we interviewed were excited of the prospect of treating patients with Plinabulin. It's clear doctors are receptive to new treatment options for CIN and understand there is a high unmet medical need in the market. Our market research and clinical research continues to build the case for Plinabulin, as a therapy that can improve the standard of care in cancer therapy. By developing Plinabulin to work with and to enhance G-CSF therapy, the goal is to allow [HCP's] to avoid the four D’s mentioned earlier, and provide stable chemotherapy doses, sustained chemotherapy cycles, and the strongest chemotherapy regimens. Moreover, our proprietary market research continues to indicate that oncologists are favorable towards the Plinabulin product profile and physicians quickly grasp the logic of the complementary mechanisms of action of both Plinabulin and G-CSF. This means the speed of Plinabulin’s onset versus the delayed onset of G-CSF, the superior absolute neutrophil count and the reduction of bone pain. The Plinabulin plus G-CSF combination shows tremendous promise in enabling oncologist and their patients to adhere unabated to the individualized treatment plan and avoid the four Ds. Additionally, our goals go beyond preventing neutropenia and bone pain. We see Plinabulin's clinical benefits, as a way for providers to potentially generate better chemotherapeutic outcomes, empower oncologists to choose the most appropriate, most aggressive therapy for patients, and have confidence that neutropenia can be significantly reduced and patients can remain on their targeted chemotherapy. Our ongoing data generation both clinical and market research continues to give us confidence that combination therapy that is Plinabulin plus G-CSF can offer an improved standard of care. Additionally, we believe that market dynamics such as the growth of chemotherapy and the success of the combination approach highlights CIN the growth opportunity. In short, the combination approach is proving to provide a number of benefits for clinicians, patients and payers, including significantly reduced neutropenia, with the goal of avoiding the 4 Ds, and driving a stable, sustained cycle with the strongest doses of chemo, and improved bone pain profile to ensure enhanced therapeutic experience, and the potential for greater persistency, and clinical data that suggests anti-cancer activity. Our clinical data validates a clearly differentiated product profile and our market research indicates a clear and compelling market need for new therapies to improve the standard of care in CIN. Now transitioning to non-small cell lung cancer. Non-small cell lung cancer is one of the most exciting therapeutic areas in all of medicine today and continues to evolve rapidly. Advances in the care with the approval of IO therapies for first line creates a need for new options in second and third-line therapy, the advancement of IO therapy presents a great opportunity for BeyondSpring, Plinabulin, and patients. Plinabulin’s clinical data to-date in our non-small cell therapy lung cancer program demonstrates the promise as an effective agent in second and third-line therapy. Given a [dose of] effective options for patients at this advanced stage, we are excited about the prospects of delivering clinically meaningful data and results for patients with Plinabulin for non-small cell lung cancer. As we consider lifecycle management for Plinabulin, we look to our early work in combination with IO compounds. It is our hope that we may demonstrate benefits over and above that which is currently seen with IO alone. This may represent an additional significant growth opportunity to help patients and providers struggling to address this devastating disease. Now, moving onto business development. We believe Plinabulin has tremendous potential as a CIN and non-small cell lung cancer – anti-cancer therapy. As mentioned earlier, our most recent market research with over 100 HCPs, as well as payers, gives us confidence that the data we have generated to-date demonstrate a differentiated product profile. Additionally, receptivity of these oncologists and payers, the profile is indicative of an unmet market need. We see these responses echoed in our business development efforts with great interest coming from potential partners, as we prepare for upcoming data inflection points, we are well positioned to maximize the value Plinabulin both here in the U.S. and abroad, through our go-to-market strategies. A recent ZS study showed that 7 out of 10 companies launching their first oncology product in U.S. went to market on their own, due to the potential strength of the U.S. P&L. While 70% partnered in Europe for both CIN and non-small cell lung cancer, the U.S. represents more than 75% of the global value, and we are prepared to optimize this value through our business development and commercialization efforts. We look forward to updating you on our progress as we go forward. In closing, our clinical profile is excellent and fills a clear unmet need in the market. We have the potential to set a new standard of care. Our market research indicates HCP's recognize that Plinabulin is a differentiated product with significant clinical potential. HCP's are also excited about the opportunity to use Plinabulin in the prevention and treatment of CIN, to keep patients on the most appropriate, most aggressive came up every regimen. As we prepare to file NDAs for Plinabulin in China and the U.S. for CIN and non-small cell lung cancer, our U.S. and global commercialization plans are aligned with our development and regulatory timelines. We are taking steps to ensure BeyondSpring can bring Plinabulin to market, so that we optimize the benefits for patients, providers, and shareholders. With that, I'll now turn the call over to Edward, who'll provide a financial update. Edward?

Edward Liu

谢谢，Rich。现在我将简要讨论我们第三季度及2019年的财务业绩。有关这些业绩的更多详细信息，请参阅我们今天早上发布的新闻稿以及我们的6-K文件，这两份文件均可在我们网站的投资者关系栏目中查阅。接下来，我将重点介绍一些关键数据。2019年第三季度的研发费用为720万美元，而去年同期为1410万美元。减少的690万美元主要归因于：与临床试验相关的CRO费用及其他服务费减少390万美元，临床前试验费用减少50万美元，以及非现金股份薪酬减少50万美元。2019年第三季度的行政及管理费用为250万美元，而2018年同期为150万美元。增加的100万美元主要是由于本季度发生的70万美元市场调研费用。2019年第三季度，BeyondSpring的净亏损为940万美元，而去年同期为1490万美元。截至第三季度末，我们的现金余额为2470万美元。第三季度之后，我们于10月24日成功完成了2580万美元的后续股权发行。此次交易由德诚资本领投，并吸引了来自美国优质机构投资者的强劲需求。这笔交易连同7月份的融资，持续显著改善了我们的股票流动性。凭借强劲的资产负债表，我们相信当前的现金资源足以支持我们的临床试验，并在美国和中国提交Plinabulin用于治疗化疗引起的中性粒细胞减少症和非小细胞肺癌的新药申请，同时推进我们的免疫肿瘤学产品管线以及泛素化蛋白降解研究平台。接下来，我将把电话交还给Lan进行总结。Lan？

Lan Huang

谢谢，Edward。正如您所知，我们对我们的临床开发工作和数据流感到非常自豪，这进一步验证了Plinabulin改善癌症治疗的有利药物特性。Plinabulin是唯一一种结合抗癌和CRM预防潜力的在研新型药物。展望未来，我们预计2020年将有许多重要的数据和监管里程碑，这将使我们从临床阶段公司转变为商业阶段公司。与我们的股东、投资者和合作伙伴一起，我们正在努力继续创造价值，为全球医疗需求严重未满足的患者提供创新药物。我期待在未来几个月向您更新我们在实现这一目标方面的进展。我们整合了美国和中国的资源，以在全球两大医药市场实现时间和成本效率。我们相信这种独特且可扩展的商业模式将为我们的股东带来最大回报。对于那些与我们同行至今的各位，我们感谢您的信任和支持；对于那些新加入我们使命的各位，2020年将是激动人心的一年，因为我们预计Plinabulin在美国和中国的NDA申请即将提交。我们期待继续与您同行。感谢您的关注，现在我将会议交还给主持人。

Operator

谢谢。[主持人说明] 我们的第一个问题来自H.C. Wainwright的Joe Pantginis。请开始提问。

Joe Pantginis

大家好，早上好，感谢接受提问。Lan，鉴于你们在中国市场拥有如此独特的渠道，基于你们在那里的关系，以及像'千人计划'、'千人计划创新奖'等荣誉。我只是好奇，你们与中国食品药品监督管理局（CFDA）和中国政府就定价和报销以及生产等方面的讨论进展如何。作为这个问题的一部分，除了数据之外，你们还需要完成哪些工作才能提交NDA？

Lan Huang

非常感谢您，Joe，也感谢您对我们公司以及Plinabulin的持续支持和信任。是的，感谢您提出这个很好的问题。正如您所见，我不仅获得了政府的'千人计划'奖项，而且Plinabulin也获得了中国政府的[听不清]支持，这基本上是国家政府最重要的创新资助。这确实为我们提供了监管速度优势，包括加速审评以及未来可能被纳入国家医保。一个快速审评的例子是，针对我们的CIN适应症，我们在提交资料包后一个月内就获得了CFDA的III期临床试验申请批准，这确实是一个历史记录，因为大多数此类批准需要一到两年时间。所以，正如您所见，我们确实与CFDA就我们资料包的提交准备情况进行了持续讨论，从我们的目标来看，我们正按计划在2020年第一季度提交申请。目前在生产方面，我们确实使用中国的CMO为中国国内NDA申报进行生产。关于临床试验数据的[实际]当前细节，正如我一直所说，105项III期中期数据加上106项II期数据支持申报。这些都已经准备就绪。至于安全性数据库，也已经准备就绪，因为我们已经用Plinabulin治疗了580名患者，而安全性数据库只需要300例。此外，试验质量已经过检查。所以，实际上所有数据都已准备好提交。但您还提到了关于定价以及可能进入医保系统的问题。我们或许可以以FibroGen作为一个重要例子，对吧？FibroGen确实拥有这种创新的first-in-class贫血药物，并且首先获得了中国FDA的批准，最近在今年年初，然后在美国批准之前，在所有数据提交后两个月内就获得了快速批准。其次，它最近刚刚进入了国家医保，定价非常好，因为它是该类别中唯一的药物。所以您可以看到，Plinabulin可能也会遵循类似FibroGen的步骤，这为我们树立了非常好的榜样。而且您知道，实际上FibroGen的首席医疗官Peony Yu博士，她是我们科学顾问委员会的成员。

Lan Huang

Thank you so much, Joe, and thank you for your continued support and belief in our company, and also in Plinabulin. So, yes, thanks for this great question. So, as you see, that not only I do have the – 1000 Talent Award from the government, but also, we – Plinabulin also has [indiscernible] from the Chinese government, and that basically is the most important innovation grant from the State government. And that does give us the regulatory speed and in the expedited review and also later to be potentially included in the national insurance. One example for the speedy review is, for our CIN indication, we received the CTA for Phase III initiation from CFDA within one month, after package submission, which is really a historical record because most of those approval takes one year to two years. So, as you see that, we do have continued discussion with the CFDA regarding the submission readiness of our package, and as you see from the – our target, we are on track to submit quarter one of 2020, and currently for the manufacturing, we do use CMOs in China to manufacture for the China domestic, NDA filing. And so that's check and a clinical trial data [actually] current details, as always, I said is, 105 Phase 3 interim plus the 106 Phase II data is supporting submission. And so those are set. And for the safety database, that's set because we have already had 580 patients treated was Plinabulin's. The safety database is only 300. And also, the quality for the trials has been checked. So, those actually have all the data ready to be submitted. And, but then you had a question regarding the pricing, and then potentially getting to the insurance system. So, we probably can use FibroGen as a significant example, right? So, FibroGen does have this innovative first-in-class anemia drug, and – got China FDA approval first, recently in the beginning of the year, and then you ahead of the U.S. approval and that was a speedy approval after all data is two months, afterwards, it was approved. And then secondly, it just recently got into the national insurance, it was a very good pricing, because it is the only drug in the category. So, you can see that Plinabulin potentially could also follow similar steps like FibroGen, which has set very, very good example for us. And as you know, actually Dr. Peony Yu, who is the Chief Medical Officer of FibroGen, she is our SAB Board.

Joe Pantginis

太好了。非常感谢您的解答，非常有帮助。祝大家节日快乐。

Lan Huang

谢谢。

Operator

谢谢。[接线员指示] 下一个问题来自William Blair的Andy Hsieh。请提问。

Andy Hsieh

好的，感谢回答我的问题，并对所有进展表示祝贺。关于第三阶段103试验，即Dublin-3试验，我有一个问题。看起来时间安排有所推迟，是否是由于事件发生率低于预期？我很好奇你们在那方面观察到了什么情况？

Lan Huang

是的，可能我可以先开始，然后Ramon可以补充其他细节。正如Ramon讨论中提到的，我们已经入组了超过480名患者，总计划是554名患者。所以，入组是按计划进行的，但这当然是一个事件驱动的研究，对吧？所以我们必须等待达到那个事件。如果事件没有达到，那么时间线就会被推迟。这就是原因，与研究执行或其他任何事情无关，一切都按计划进行。

Ramon Mohanlal

是的。我是Ramon。谢谢，Lan。我没有什么要补充的。这是一个事件驱动的试验。所以我们必须让数据自然发展，事件会随着时间推移而收集，这决定了时间线。

Andy Hsieh

明白了，好的。那么真的无法看出是哪个治疗组导致了延迟吗？

Lan Huang

我们不知道，这对我们是盲态的，对吧。在中期分析之前我们不能进行任何分析——但某种程度上说——如果我们的[听不清]进展缓慢，慢一点反而更好，但我们无法看到这些数据，正如你所见，但这是个很好的问题。

Andy Hsieh

好的。那么关于你讨论的专利，这很棒。对于——我想是其中一个多晶型专利，有效期到2036年。这个专利是否有资格延期？我记得有一个条款允许延期，考虑到监管审查和研发时间。所以基本上问题是，2036年是最坏情况，还是已经包含了延期？

Lan Huang

是的。感谢这个很好的问题，因为专利有效期对于实现Plinabulin的潜力非常重要。这个2036年是那个一水合物专利的确切到期日，虽然它是一个多晶型专利，但我们获得了[物质组成]专利，只有这种API可以用于药品生产。所以这是一个非常强的专利。实际上你提到的，是的，我们选择的专利有潜在的五年延期可能，根据美国FDA的规定，我们有资格获得最多五年的延期，因为我们的专利律师已经对此进行了所有计算，包括临床试验延迟和审查时间。所以这可能让我们延长到2041年。这甚至给了Plinabulin更长的市场独占期。

Andy Hsieh

哦，太好了。

Lan Huang

然后对于中国，实际上也是一样。中国政府也在建立专利链接制度，也可能延长几年，因为欧盟、日本和美国都有这种专利延期制度。中国正在实施这一制度。在中国，这个一水合物专利也已经获得授权。

Andy Hsieh

我明白了。好的，是的，这是个好消息。感谢解释。这就是我的所有问题。再次祝贺。

Lan Huang

非常感谢您的支持。

Operator

谢谢。现在我们的问答环节已经结束。我将把话筒交还给管理层进行最后的总结发言。

Lan Huang

非常感谢您宝贵的时间和持续的支持。祝您度过愉快的一天，节日快乐。

Operator

谢谢。今天的电话会议到此结束。您现在可以断开线路。感谢您的参与。