昨天有个球友找我说他拿到了英文的全文，好像是让我帮忙翻译一下，我当时看全文太长了，没立刻回复，后来再看就找不着了![[滴汗]](http://assets.imedao.com/ugc/images/face/emoji_13_coldsweat.png?v=1 "[滴汗]"){kind=small}
。看起来似乎有不少人想要全文都理解一下，我就自己想办法把语音转为文字再大致做了下翻译，因精力和能力有限，有些地方翻译不合适，还请理解和指正![[大笑]](http://assets.imedao.com/ugc/images/face/emoji_02_laughing.png?v=1 "[大笑]"){kind=small}
Good morning. It's my great pleasure to present at this year's JP Morgan Health Conference. Ascentage pharma made a great progress in last year. So first of all, Ascentage pharma is a patient-centric innovation with global breakthrough therapies. Our vision is to become global leading integrated bio-pharmaceutical company to address global unmet medical needs. We build our value with a patient first, science-based and data-driven. I think that this has been our core value since the beginning of the Ascentage about 15 years ago.
早上好。很高兴能出席今年的 JP 摩根健康大会。亚盛医药在去年取得了长足的进步。所以首先，亚盛医药是以患者为中心的创新、具有全球突破性疗法。我们的愿景是成为全球领先的一体化生物医药公司，以解决全球未满足的医疗需求。我们以患者优先、基于科学和数据驱动的方式建立我们的价值。我认为这也我们从大约15年前亚盛建立时的核心价值。
One thing I think we use this slide to highlight the blood cancer market is actually very huge. There are always a lot of questions about Ascentage pipeline market size is small. I think this tells you even though by in terms of patient number, the hematology malignancy cancer patient may be only 6% of all cancer cases a year, but in terms of products and annual sale or market size is more than 30%, over 90 billion dollars in the next couple years. If you look specifically, the indication is our pipeline focused on like a CML, CLL and of course Multiple myeloma. This is an multi-billion dollar annual sales, more than 10 billion a year, especially like a multiple myeloma. I think this just highlights the market size of Ascentage of product pipeline and not small, actually pretty big. As you know before the PD-1 launched in the cancer oncology market, the first one every year, number one sales is a small molecule drug for the leukemia or myeloma. The first small molecule over 10 billion dollar annual sale is actually single indication in small molecule drug.
有一点，我觉得我们用这张幻灯片来突出血液瘤市场其实是非常巨大的。总有很多人质疑亚盛管线市场规模小，我来告诉 大家，尽管就患者数量而言，血液系统恶性肿瘤患者每年可能仅占所有癌症病例的6%，但就产品和年销售额或市场规模而言，超过30%，在未来几年超过900亿美元。具体来说，适应症是我们的产品线，重点关注CML、CLL和MM。这是一个数十亿美元的年销售额，每年超过100亿，尤其像多发性骨髓瘤。我觉得这只是突出了亚盛产品管线的市场规模其实挺大的。正如大家所知，在 PD-1 在肿瘤市场上市之前，第一个年销售额排名第一的是治疗白血病或骨髓瘤的小分子药物，年销售额超过100亿美元的第一个小分子实际上是小分子药物中的单一适应症。
I think this is a one-slide summarize everything we do and the progress we made last year. As you can see two things, I want you focus on. First let's look at our pipeline progress even though this is a one-slide, busy, but let's focus on two things. First if we look at the really commercialize the product, the first one Olverembatinib, HQP1351, we actually made two important progress last year. Of course, the first one the beginning of the year about this time was the really good price covered by the NRDL. I think that's really something we are really proud of. Second we got a full approval for the resistant CML not just limited to the mutation. Those are important progress we received last year but more importantly if you look at our second most important pipeline product, Lisaftoclax. Now we have three here as entered registration trial. The first one is a global phase III trial clear by FDA for the previously BTK treated the CLL or SLL and also in China for the resistance after BTKi. the CLL/SLL we are going to file NDA this year. So, you can see very close to in the registration study trial and also we got clearance by the CDE for the first line the treatment naive CLL in combination with Acala. I think that those three you can see is already in the registration trial for the global study and the one ready for filing the NDA this year in China. But if you look closely, actually, I think we'll tell you a little more data but another thing I think is new to this meeting is actually we also got a clearance by CDE for the AML global registration study. I think I can tell more in the following slides. Another very important key differentiation of Ascentage advantage is that if you look at all these pipelines, first we all have global rights, second we conducted trials in not only China but the US and the global. I think that this is a really unique in terms of our pipeline we made a lot of progress in last year.
这张幻灯片，总结了我们所做的一切和我们去年取得的进展。 大家只需要看到两样东西。首先让我们看看我们的产品线进展，尽管这张幻灯片很拥挤，但让我们关注两件事。首先如果我们看看真正商业化的产品，第一个Olverembatinib，HQP1351，我们去年实际上取得了两个重要的进展。当然，年初以非常好的价格续约了医保，我认为这是我们非常自豪的事情。其次，我们获得了耐药 CML 的完全批准，而不仅仅限于突变人群。这些都是我们去年取得的重要进展，但更重要的是，如果大家看一下我们第二重要的管线产品Lisaftoclax。现在我们有三个进入注册试验。第一种是 FDA 批准的全球 III 期试验，用于治疗既往 BTK 治疗的 CLL 或SLL，也在中国开展用于治疗 BTKi 后的耐药性的注册临床。我们将于今年提交 NDA 的CLL/SLL。因此，大家可以在注册临床试验旁边，我们获得了 CDE 联合阿卡替尼用于一线治疗初治 CLL 的许可。我认为 大家能看到这三个已经在全球研究的注册试验，并且已经准备好今年在中国提交NDA。但是，如果大家再仔细看，实际上，我想我们会告诉大家更多的数据，但在这次会前刚刚得到的新消息，实际上我们也获得了 CDE 对 AML 全球注册研究的许可。我想我可以在下面的幻灯片中进一步阐述。亚盛的优势也是另一个非常重要的差异化，如大家看到的所有这些管线，首先我们都有全球权利，其次我们不仅在中国进行试验，而且在美国和全球进行试验。我认为，就我们去年取得了很大进展的管线而言，这是一个真正独一无二的。
The highlight here is really the three registration trials clear by regulatory agency. The first one as I mentioned Lisaftoclax APG-2575 for the global phase III registration trial with the BTK previous treated. I think you all understand appreciate under the project optimum it's not that easy to get the FDA clearance for the global registration studies. I think that we're very proud after all the data and the discussion with the FDA, we finally got this approved. We also have a CDE approved in China but also global study for the first line in combination with Acala for the CLL and SLL. I think that this is also important milestone. Thirdly but also important for the Olverembatinib as already marketed in China for treating the full approval for treating the CML. Actually, in the real world, we actually have more patients benefit found this drug for the Philadelphia chromosome-positive ALL and I'm very glad that CDE cleared this for the first line treatment. I think those three-registration trials plus I just announced the AML registration study with Lisaftoclax highlights the important achievement for the last year and also very important clinical catalyst for this year. Another thing I think we're really proud is that Olverembatinib we received full approval by CDE for patients who failed or intolerant first and second line TKI in the CML as this will brought more patient base and we are the first only third generation available inhibitor in China and of course as I mentioned we have a good price to enter the NRDL. we expanding to more patients base and the patients has a long DOT(duration of treatment), so the prices are important. We also made a tremendous clinical progress the last year, as I mentioned we're going to submit the NDA to CDE this year and we of course had a lot of data and release news release during the ASCO and the ASH and those with a lot of potentially first-in-class.
这里的亮点是监管机构明确的三项注册试验。我提到的第一个是Lisaftoclax APG-2575用于 BTK 既往治疗的全球 III 期注册试验。我认为 大家都理解，在项目最终获得 FDA 批准进行全球注册研究并不那么容易。我认为在所有数据和与 FDA 的讨论后，我们非常自豪，我们最终获得了批准。我们还在中国获得了 CDE 批准在全球研究中与 阿卡替尼 联合用于 CLL /SLL 一线治疗的批准。我认为这也是重要的里程碑。第三，对已在中国上市的 Olverembatinib，在 治疗 CML 上获得了完全批准。实际上，在现实世界中，我们发现该药物治疗费城染色体阳性 ALL 的患者获益更多，我很高兴 CDE 将其作为一线治疗药物。我认为那三个注册试验加上我刚刚宣布的 Lisaftoclax 的 AML 注册研究突出了我们去年的重要成就，也是今年非常重要的临床催化剂。我认为我们真正自豪的另一件事是，Olverembatinib获得了 CDE 的完全批准，可用于一线和二线 TKI 治疗失败或不耐受的 CML 患者，因为这将让更多的患者从中获益，我们是中国首个唯一的第三代抑制剂，当然正如我提到的，我们以非常好的价格续约医保。我们扩大了患者人群，患者DOT（治疗持续时间）较长，因此价格很重要。我们在去年也取得了巨大的临床进展，正如我提到的，我们将在今年向 CDE 提交NDA，当然，我们在 ASCO 和 ASH 期间以及具有大量潜在首创产品的研究中拥有大量数据并发布新闻。
Little more details on the Olverembatinib and this is our really globally best-in-class product. I think if you look at the market and you sell just as an CML alone two of the second generation inhibitors generated four billion dollars annual sales for the last three years. I think the overall market is a six billion dollars but more importantly there's more practice and also the data to show to make the best drug to patients early. Okay, as you see just now the data moving the drug to the first line and show great safety and efficacy our the sub-of-class is potentially global best-in-class BCL2 inhibitor, we are the second one after venetoclax enter the clinical trial enter the registration trial, I think with the NDA filing and the other global registration study we anticipate to be the second enter the market globally of course the CLL and the other hematological indications, AML and MDS, we also generate huge market for this new transforming agent. I think that we present the data last year that the single agent or combination have a great response in the RR-CLL patients and also we enter the global phase 3 registration study. I think those global registration study truly meet the unmet medical need with a competitive advantage with a clear data. I think that's a very important for those three global registration studies, especially in the Philadelphia chromosome-positive ALL that's the first line and also for the CLL we got an NDA filing this year. we got a first line treatment combination with Akala and also globally combination, and on top we call it briefly add-on strategy for the patient who previously treated with the BTK inhibitor. I think that this will really fast enrollment benefit patients with the best the combination to targeted agent chemo-free. I think that this clinically validated product is well designed the trials and clear by the regulatory agency will maximize our probability of success. a little bit more detail on the full approval for the CML in China. as I said this is the first and only market a third generation TKI inhibitor in China, so with the full approval we'll be able to address more broader patient based in China.
关于 Olverembatinib 的更多详细信息，这是我们真正的全球同类最佳产品。我认为，如果 大家看看市场， 单单CML这个适应症，两个第二代TKI抑制剂就在过去三年产生了40亿美元的年销售额。我认为整体市场是60亿美元，但更重要的是，更多的临床实践和数据显示，需要尽早把最好的药物给到患者。好的，正如大家刚才看到的将药物推向一线并显示出良好的安全性和疗效的数据，我们潜在的全球同类最佳 BCL2 抑制剂，是继 venetoclax 进入临床试验后进入注册试验的第二个BCL2，我认为随着 NDA 申报和其他全球注册研究，我们预计将是第二项进入全球市场的BCL2，当然包括 CLL 和其他血液学适应症 AML 和MDS，我们将为这个创新产品开拓巨大的市场。我认为，我们展示了去年的数据，即单药或联合治疗在 RR-CLL 患者中有很好的疗效，我们也进入了全球3期注册研究。我认为那些全球注册研究以清晰的数据，以竞争优势真正满足了未满足的医疗需求。我认为这三项全球注册研究非常重要，尤其是在费城染色体阳性 ALL 一线治疗，还有我们今年将要NDA的CLL适应症。我们还拿到了与阿卡替尼的一线联合治疗注册研究以及全球联合治疗注册研究，最重要的是，我们将其称为既往接受过 BTK 抑制剂治疗患者的ADD-ON策略。我认为，这将真正快速入组，使患者从最佳联合靶向药物无化疗治疗中获益。我认为针对这一经过临床验证的产品精心设计的试验，并且监管机构明确表示，这将使我们的成功概率最大化。关于 CML 在中国完全获批的更多详细信息，正如我所说，这是中国第一个也是唯一一个第三代 TKI 抑制剂的上市，因此在完全批准的情况下，我们将能够解决更广泛的中国患者问题。
in China actually CML is more than the CLL with the annual 20 to 30 thousand new patients overall because all the target drug benefit patients can survive long and I think that the patient based in China is over 200,000 but more importantly I think that the globally if you look at the global space, the two of the second generation inhibitor DASA and the NILO already generate annual four billion dollar sale. I think the two late-stage asset we'll also generate at least all one billion. I think that the recent estimate is the late stage CML market size is over two billion dollars. Okay, so I think more importantly we're really proud that the Olverembatinib also listed as an emerging treatment options by the NCCN guideline this is just new actually last week I think we had a more recognition of Olverembatinib in the global CML community. I think with the FDA potentially approval for the registration study, I think that this is maybe, say a little more, we had a great discussion with the FDA about a global registration studies. I think that we have agreed most of the global registration study design, but of course we're waiting for the final clearance which we don't think that there's any problem because we have a very strong data in US studies.
在中国，CML实际上比 CLL 更多，总体上每年有2万至3万新患者，因为所有的目标药物获益患者都可以长期生存，我认为中国的患者超过20万，但更重要的是，我认为全球如果大家看全球市场空间，两个第二代TKI抑制剂 DASA 和 NILO 已经产生了每年40亿美元的销售额。我认为，我们这两个后期资产，每个都将产生至少10亿市场。我认为最近的估计是后期 CML 市场规模超过20亿美元。没错，所以我认为更重要的是，我们对Olverembatinib 被 NCCN 指南列为潜在新治疗选择感到自豪，这只是上周刚刚获知的消息，我认为全球 CML 界对 Olverembatinib 有了更多的认可。随着 FDA 可能批准注册研究，我认为这可能是，更多地说，我们与 FDA 就全球注册研究进行了一次全面的讨论。我认为我们已经就全球注册研究设计大部分达成一致，但当然我们正在等待最终批准，我们认为没有任何问题，因为我们在美国研究中有非常有力的数据。
this just a couple highlights of the data here, firstly as we presented at the ASH meeting in China. we did this randomized registration study for the full approval as you can see with the patient who has previously treated with three TKI's, basically the last line there's no any other option but because of the requirement for the RCT design, we do have to have control but the best available treatment in this case clinically is actually a patient no any other options, but because of the design, they do have to enter this group but you can see event free survival EFS is a huge difference over ten times and of course no patient do have to switch because that's looking for the best for the patient.
这只是这里数据的几个亮点，首先是我们在中国 ASH 会议上公开的，我们进行了这项随机注册研究，以获得完全批准，正如大家所看到的，在既往接受过3种 TKI 治疗的患者中，基本上最后患者没有任何其他治疗选择，但由于 RCT 设计的要求，我们必须有对照组，即在临床上这种情况下的最佳可用治疗，实际上是患者没有任何其他选择，但由于设计，他们确实必须进入该对照组，但大家可以看到，无病生存-EFS有巨大的差异，差不多是对照组的10倍，当然患者不能切换治疗，因为这是寻找患者的最佳治疗的方案。
but I think more importantly our data now since the first approval two years ago for the mutation patient and more importantly since our first of phase I trial about seven years ago, our very first patient joined our trial about seven years ago still benefit our drug and about 80 percent of patients enter our phase I trial. those are the last time patient no any other option. 80 percent of them still our drug benefit. this is a tremendous data in terms of number patients time and safety, so as you can see in this left side of the chart, the benefit, the efficacy actually increased over time but more importantly this is really uncommon oncology drug the safety profile also increased over time, because a part of the reason is the CML patients the cancer in the bone marrow when you clear the cancer cells some depends the actual patient. the disease related AE like a thrombocytopenia, neutropenia actually reduce over time. I think that the duration of the treatment is a huge benefit for the patients but also in terms of our commercial sales.
但我认为更重要的是，我们的数据是自两年前首次批准突变患者以来的数据，更重要的是，自我们大约7年前首次 I 期试验以来的数据，大约7年前，我们的首例患者加入我们的试验，约80%的患者仍然从我们一期试验的药物中获益。这些后线患者没有任何其他好选择，其中80%仍然是我们的药物获益。就患者人数、时间和安全性而言，这是一个优异的数据，如图所示，获益和疗效实际上随时间增加，但更重要的是，其安全性特征也随时间改善，这确实是一种不常见的肿瘤药物效果，部分原因是 CML 患者清除癌细胞时跟患者骨髓内的癌细胞有关。疾病相关AE，如血小板减少症、中性粒细胞减少症实际上随时间推移而减少。我认为，持续的缓解对患者来说是巨大的益处，对我们的商业销售方面也是如此。
a few more study especially this is a global phase two study lead by Doctor. xxx at MD Anderson this is a US study as you can see we have a benefit for the patients in US who fail ponatinib or ascinimib, actually we have the patients who felt both actually benefit from our drug. I think this is really strong evidence our drug is truly the best in class globally. in addition to the CML, Olverembatinib combined with venetoclax and some the chemotherapy also achieve a great response, this is the CMR, is the cancer cells less than 1 in 10,000 achieve over 60 percent. Okay, the more importantly, they achieve this response in very short period of time and if you look at the survival curve we have an even really flat almost 100% during the over a year time period I think again we demonstrate clinically Olverembatinib in the ALL indications, I think that's the base also for our clearance by CDE for the first line treatment. okay so I can see those patients who achieve for the CR very rapidly, especially very deep response, complete the molecular response are very high with those patients. I think our goal is actually moving to chemo-free. Okay, so not just with the Olverembatinib for ALL, but more importantly with like in this case a Blinatumomab generate the patient the chemo-free but a more durable response I think the eventual goal for the ALL is the chemo-free and also transplant free okay, I think a ALL patient can survive without the side effect without transplant that will be huge benefit for the patients globally. we also move this indication to the AML, I think due to the time, I just give a very quick result, because our drug Olverembatinib is a multi-mechenism inhibitor also importantly inhibit FLT3 and in combination there's also data in the clinic with venetoclax or in future with our 2575 can treat the AML patients. you can see the CR rate is very high, so overall we consider our Olverembatinib is a globally best-in-class third generation TKI inhibitor in terms of efficacy safety and more importantly with the patient who fell either Ponatinib, ascinimib both still see really deep and a broad response.
还有几项研究，尤其是这是由 MD Anderson的Doctor Jabbour领导的一项全球 II 期研究。这是一项美国研究，因为大家可以看到我们对 ponatinib 或 ascinimib 治疗失败的美国患者有益处，实际上我们让患者都感觉到从我们的药物中获益。我认为这确实是强有力的证据，我们的药物确实是全球同类中最好的药物。除 CML 外，Olverembatinib联合 venetoclax 和一些化疗也获得了很大的缓解，就是CMR，是癌细胞低于万分之一的患者达到60%以上。没错，更重要的是，他们在很短的时间内实现了这种缓解，如果大家观察生存曲线，我们在一年多的时间内甚至达到了几乎100%的平稳水平，我想我们再次证明了 Olverembatinib 在 ALL 适应症中的临床应用，我认为这也是我们获得 CDE 批准用于一线治疗的基础。没错，我可以看到那些达到 CR 的患者非常迅速，尤其是非常深度的缓解，完全分子学缓解的患者比例非常高。我认为我们的目标实际上是无化疗。没错，不仅仅是 Olverembatinib 治疗ALL，更重要的是，在这种情况下，Blinatumomab为患者带来了无化疗但更持久的缓解，我认为 ALL 的最终目标是无化疗和无移植，我认为，ALL患者可以在不接受移植的情况下存活且不会出现副作用，这将为全球患者带来巨大获益。我们还将该适应症拓展至AML，我认为，由于时间的原因，我只是做一个非常简单的介绍，因为我们的药物 Olverembatinib 是一种多机制抑制剂，也显著地抑制FLT3，并且在临床中也有关于 venetoclax 或未来使用我们的2575治疗 AML 患者的数据。大家可以看到 CR 率非常高，因此，总体而言，我们认为我们的 Olverembatinib 在疗效安全性方面是全球最佳的第三代 TKI 抑制剂，更重要的是，对于Ponatinib、ascinimib治疗失败的患者，仍然可以看到真正的深度和广泛的缓解。
in addition to the Olverembatinib, I think our really important asset is Lisaftoclax, we anticipate this drug to be launched in China next year and with the FDA clearance for the global phase 3 registration trial for the CLL as we have published this in the design. this is really I think our clinical team very smart design in the face of the CLL landscape and the competition, we call this simply the 1.5 line treatment because we take a patients who are not the received best response for the single agent BTK but then add on to our drug. we already know all the clinical data, this is the best combination for the CLL patients and also we have the first line combo with Acala in China. as I announced the AML also clear by the CDE, I think all the indications and the potential in multiple myeloma will make this drug another candidate for global over billion dollar market as you all know actually our drug 2575 enter a clinic trial five years ago. from the day one we designed this differently than venetoclax. Okay, of course with the data to support, first you can see this is a daily dose ramp up, five days without the leading dose of a BTK and the five days after reaching 400 milligram combination with Acala. with the clinical data, okay, so you give the patient really convenient in the schedule without the hospitalization in most cases. more importantly, you give a patient best drug combination early, okay, so patient will benefit rather than waist the months or weeks and more importantly this is the phase I summary I think we just present this is at the ASH. very importantly in the RR-CLL heavily pre-treated. the patient this is phase I data. if we look at our CR population is very similar to venetoclax. if you look at our the PFS and also MRD as a very close similar to the venetoclax and OS haven't been reached okay and more important I think that's our key differentiation our design is a patient friendly.
除 Olverembatinib 外，我认为我们真正重要的资产是Lisaftoclax，我们预计该药物将于明年在中国上市，并在 FDA 批准的 CLL 全球3期注册试验中上市，因为我们已公开了这个试验设计。这真的是，我觉得我们的临床团队，在面对 CLL竞争格局做出的非常聪明的设计，我们将其简单称为1.5线治疗，因为我们选择的患者是接受 BTK 单药治疗未能获得最佳缓解的患者，但随后加用我们的药物。我们已经知道的所有临床数据，这是 CLL 患者治疗的最佳组合，同时我们在中国也开展了与 阿卡替尼 的一线联合治疗研究。正如我宣布的，CDE也批准了AML，我认为在所有适应症和多发性骨髓瘤中的潜力将使该药物成为全球超过10亿美元市场的另一个候选药物，正如大家所知，实际上我们的药物2575在5年前进入临床试验。从第一天开始，我们的设计与 venetoclax 不同。好的，当然有数据支持，首先大家可以看到这是一个每日剂量上升，开始治疗前不需要引入BTK治疗和五天后达到400毫克与阿卡联合。大家看这些临床数据，因此，在大多数情况下，大家可以在不住院的情况下按照时间表为患者提供真正方便的治疗。更重要的是， 大家可以及早给患者最好的药物组合，没错，因此，而不是让患者浪费数月或数周，更重要的是，这是I期总结，我认为我们只是在 ASH 上展示这一点。非常重要的是，在既往接受过大量治疗的 RR-CLL 患者中。如果我们观察 CR 人群与 venetoclax 非常相似。如果大家看我们的 PFS 和 MRD 与 venetoclax 和 OS 非常相似，目前都尚未达到，更重要的是，我认为这是我们的重要差异化，我们的设计是患者友好的。
our data support by our clinical efficacy safety and the PK that you can see in the single agent we can achieve in the ORR in the RR patient population 67 percent, but of course, the combination even do better so almost 100 percent. Okay, this is our patient population remember single agent, we all know BTK or BCR2 alone can’t achieve 100 percent ORR, so that's very important but more important a differentiation is in the safety profile. this is a global study phase II combination with Acala, you look at the grade 3 or 4 AE, especially neutropenia is much less than the venetoclax. Okay, with over 800 patients treated, okay, for this drug in last five years with this design we haven't really even reached the MTD, we don't have a DDI issue with any of BTKi with tested, we don't even have any no DLT, didn't reach MTD at the highest dose we tested is a 1200 mg, so I think that this is the data supported with a five-year study over 800 patients and close to 400 patients in the CLL monotherapy combination demonstrate our convenience safety profile and also no DDI with any the BTK and other drugs. I think with the time I just probably I feel more promised data here, we just released the first data actually from the US study in the RR multiple myeloma and AL amyloidosis patients and once you can see our neutropenia in this, you know heavily pretreated, poor condition multiple myeloma patient, is about only 10% fibro-neutropenia, is only 3.3% and we receive a very good response in terms of VGPR or PR and ORR is about 67%. but more importantly, the first time data released last month at the ASH over 100 patient in the AML, MDS. Okay, we achieved tremendous efficacy in the combination with AZA in the RR-AML patient or treatment naive for older/unfit AML patients. you can see ORR is 70% and more importantly, the safety profile is also very favourable, I think with the summary here, of course we didn't do head2head comparison, we consider this is a potential the best in class the BCL2 inhibitor globally with the validation of 800 plus patients and closer to 400 in the CLL over five years study. okay this is not just the based on one or two study or based on the what's to be plan, I think that with this clear daily dose ramp-up design and the patient benefit in the single agent or combination and really importantly we have a clearance if we combine, two CLL, one AML, this is three global registration study and we are filing our CLL patient NDA in China, so we are clearly the leader in the BCL2 space and also clear the differentiation with the venetoclax.
我们的数据支持我们药物的疗效，安全性和PK，大家可以在单药治疗中看到，我们可以在 RR 患者人群中达到67%的ORR，但当然，联合治疗甚至更好，几乎达到100%。好的，这是我们的患者人群，记住是单药治疗，我们都知道 BTK 或 BCR2 单药治疗无法达到100% ORR，所以这非常重要，但更重要的是在安全性特征上的差异化。这是一项与 阿卡替尼 联合用药的全球 II 期研究， 大家看3级或4级AE，尤其是中性粒细胞减少症远低于venetoclax。没错，在过去5年中有超过800例患者接受了该药物的治疗，我们甚至还没有真正达到MTD，我们测试过的所有BTKi 都没有 DDI 问题，我们甚至没有任何DLT，在我们测试的最高剂量 1200 mg 下也没有达到MTD，因此，我认为这是一个超过800例患者和接近400例 CLL 单药治疗组合患者的5年研究支持的数据，证明了我们的便利和安全性特征，并且与任何 BTK 和其他药物均无DDI。我想随着时间的推移，我可能会在这里看到更多承诺的数据，我们刚刚发布了 RR 多发性骨髓瘤和 AL 淀粉样变性患者的美国研究的首个试验数据，一旦大家看到我们的中性粒细胞减少症，大家就知道接受过大量预治疗、病情较差的多发性骨髓瘤患者，中性粒细胞减少症仅约为10%，发热性的仅为3.3%，我们在 VGPR 或 PR 方面获得了非常好的缓解，ORR约为67%。但更重要的是，上个月 ASH 首次发布了超过100例AML、MDS患者的数据。没错，我们在 RR-AML 患者或老年/不适合 AML 患者初治患者中联合 AZA 取得了很好的疗效。大家可以看到 ORR 为70%，更重要的是，安全性特征也非常不错，我认为通过此处的总结，当然我们没有进行头对头比较，我们认为这是全球 BCL2 抑制剂类药物中潜在的最佳药物，在5年 研究中验证了800例以上患者和接近400例CLL患者。没错，这不仅仅是基于一项或两项研究或基于计划的研究，我认为，通过这种明确的每日剂量递增设计以及单药治疗或联合治疗观察到的患者获益，我们获得了批准，非常重要的是，如果我们获得了联合治疗2个 CLL 和1个AML，这是3项全球注册研究，我们正在中国提交 CLL 患者的NDA，因此，我们显然是 BCL2 领域的领导者，也明确了与 venetoclax 的差异化。
we also have other first-in-class pipeline in the development and highlight here is the APG 115 our MDM2 P53 inhibitor, this one will more in the combination with our Lisaftoclax. I think I have a really great potential, we already demonstrated clinical data in the paediatric settings, I think this combination is also great in terms of two target agents chemo-free and also our own data with the two small molecular drug in the paediatric or other heme indications. our third generation also made a great progress last year, you can see is a single agent for the those who failed the current second generation ALK inhibitor, we see good response, we aim to discuss with CDE for the potential registration study. I think our DURO BCL2 inhibitor also making progress but of course this one still need more data in terms of moving into the registration study, but I think our combination was Osimertinib already demonstrated a good efficacy and had an oral presentation last year at ASMO and of course the 1387 is a potentially first-in-class drug and IAP inhibitor demonstrate potential in oncology and also in the anaemia.
我们在开发中也有其他一流的管线，这里强调的是 APG 115， 我们的 MDM2 P53 抑制剂，这将更多地与我们的 Lisaftoclax 结合。我认为具有非常大的潜力，我们已经展现了儿科领域中的临床数据，我认为这种组合在两种靶向药物无化疗方面也很好，也是我们自己在儿科或其他血红素适应症中使用两种小分子药物的数据。我们的第三代EGFR TKI去年也取得了很大的进步，大家可以看到，目前第二代 ALK 抑制剂治疗失败的患者使用的是单药治疗，我们观察到良好的疗效，我们的目的是与 CDE 讨论潜在的注册研究。我认为我们的 DURO BCL2 抑制剂也取得了进展，但当然，该抑制剂在进入注册研究方面仍需要更多数据，但我认为我们与奥希替尼的组合已经表现出良好的疗效，并在去年在 ASMO 上有口头报告，当然1387是一种潜在的首创药物，IAP抑制剂在肿瘤学和贫血中表现出潜力。
I think that the key catalyst for the coming year is a really focused on the clinic, right. so we anticipate FDA clearance for Olverembatinib registration studies, Lisaftoclax NDA filing and more importantly, this list here three actually four global registration study including the AML data I just announced and of course we will expand NDRL coverage for the full approval. I think moving forward we really anticipate a percentage will be global leading biotech company by the year of three years from now. we'll have a global sale, we can be truly Pharma company where we generate revenue and a profit from our own products. I think this one that our summary. I think is very clear we have a cluster of the 500 globally granted patterns, over thousand pending and a very strong clinical data with the FDA clearance global registration study. I think even just one last slide summarize where we are, I think if you look at the all six major hematological malignancies, we move for single agent first single agent CML, already marketed, go into the global registration study, single agent CLL finished a registration study, filing the NDA and then combination with SOC to the AML, ALL and then after that is the MDS MM. so I tell my team and especially my investors very simple, we move a single agent first to the CLL, CML and then combination for ALL, AML and then to MDS, MM. you can easily calculate this is a huge potential in the global leading position, I think, of moving forward, a lot of people ask me always what's the guidance, I think the guidance come from confidence and the data. okay I think one thing I have to say with today our 15 years in the world R&D, four years on Hong Kong stock market. I can say this is really clearly Ascentage currently is hugely undervalued and also have huge potential to be the global leader in the hematological space. thank you!
我认为，未来一年的关键催化剂是真正专注于临床，没错。因此，我们预计 FDA 将批准 Olverembatinib 注册研究、Lisaftoclax NDA申报，更重要的是，这里列出的三个，实际上是四个全球注册研究，包括我刚刚宣布的 AML 注册研究，当然我们将扩大 NDRL 的覆盖范围，以获得完全批准。我认为，我们确实预计，到三年后，公司将可能成为全球领先的生物科技公司。我们的产品将在全球范围进行销售，我们可以成为真正的制药公司，从我们自己的产品中获得收入和利润。我认为这是我们的总结。我认为非常清楚的是，我们拥有差不多500个全球性专利，超过1000个正在申请中，以及基于非常强大的临床数据FDA 批准全球注册研究。我想，即使是最后一张幻灯片总结了我们在哪里，我想如大家看所有六大血液恶性肿瘤，我们就为单药首个单药CML，已经上市，进入全球注册研究，单药 CLL 完成了注册研究，提交NDA，然后与 SOC 联合治疗AML、ALL，然后是MDS和MM。因此，我告诉我的团队，尤其是我的投资者，非常简单，目前的开发策略，单药先搞定CML/CLL，联合用药搞定AML/ALL，最后搞定MDS/MM。 大家可以轻易的看出我们在全球领先位置的这种巨大潜力。很多人总是问我要指引，我觉得自信和数据就是最好的指引，我们也已经在全世界范围内耕耘研发了15年，在港交所上市4年来，我认为，也是显而易见的，亚盛有非常大的潜力成为血液瘤领域全球巨头，目前被极大的低估。谢谢大家！