Decitabine/Cedazuridine

端午不卷，写点自己感兴趣的东西吧。 题记：也许从我们决定让一个分子漂洋过海开始，就误以为对岸只有一座灯塔。所有人朝着同一束光划桨，挤在同一片礁石前。可海面上其实泊着不止一条船，有些船身陈旧、灯也不亮，却比谁都清楚怎么把货稳稳卸上欧美日的码头。它们不缺船员，缺的是仓里那几格一直空着的位置。 过去几年，中国Biotech出海的故事几乎被美国MNC包圆了。默沙东礼来辉瑞，再不济也是欧洲的阿斯利康GSK罗氏，好像只有进了欧美巨头的管线表，一个中国资产才算拿到了全球化的准生证。 这两天Jerry一直在翻日本十大药企的财报，翻到一半突然意识到一件事：这条路从来都不止一个买家。日本药企长期被中国创新药圈当成配角——它们不爱讲故事，估值不性感，PR稿写得跟说明书一样。可真把账摊开，问题就来了：它们当中好几家的美国收入已经逼近甚至越过四成，手里握着欧美日三地现成的商业化牌照和销售队伍，自己的在研管线却一代比一代单薄。 一个手里有货、却接不上下一棒的成熟买家，和一个手里有货、却卖不动全球的中国Biotech——这中间，本该是有生意的。 Jerry今天想把这件事讲清楚，落点放在一家最典型的样本上：大塚控股。 先把账算清楚：十大日本药企里，半数的美国收入已经逼近或越过四成 定调之前，先上数据。下面这张表，是日本市值前十的药企在最新一个完整财年（FY2025）的营收、归母净利润，以及美国/北美收入占比。 注：各家地区收入披露口径并不统一——有的按客户所在地，有的按销售区域，有的把全球特许权也算进某一区域；下表美国/北美占比为参照性对比，非统一口径；凡公司未单独披露美国本土数据的，均标注为“估算”。 这张表至少可以修改大众的一些刻板记忆：把“日本药企＝守着本土市场”这个印象删掉。 武田、大塚、安斯泰来三家的美国/北美收入逼近或就是一半，协和麒麟、卫材也在三到四成的区间。中外制药表面上美国本土收入很低，但它本质是罗氏体系内的上市公司，海外销售几乎全是对罗氏的出口——它的全球放大器就是罗氏本身，把它算成“自带美国/全球出口”也说得过去。真正退守日本本土的，反而只有参天这类专科公司。 有意思的是，这批公司里美国收入占比最高的几家，估值反而不高。大塚TTM市盈率约15.8倍，安斯泰来约13倍，盐野义约12倍。一个收入近半来自美国、商业化网络铺满欧美日的成熟药企，市场给的价格还不如A股一个PEG刚转正的Biotech。这账，先放在这儿。 表里武田的归母净利我标了两个数。它FY2025因为美国Amitiza反垄断诉讼一次性计提了约4,025亿日元拨备，报告口径直接由盈转亏；剔除这笔官司账，它的Core净利约4,730亿日元，仍是十家里最高之一。看武田真实的盈利能力，要看后一个数——前一个数是法务部门的账，跟经营无关。 它们有钱、有队、有牌照，唯独自研接不上这一代创新 钱和队伍这一项，日本药企不缺。武田是Shire之后全球化最完整的日本药企；安斯泰来靠XTANDI（FY2025销售9,608亿日元）和PADCEV（2,212亿日元）把美国泌尿肿瘤市场打穿；第一三共靠Enhertu成了全日本最性感的创新资产。 短板在另一头：自研管线接不上趟。武田的VYVANSE专利悬崖还没走完，FY2025营收同比下滑；安斯泰来的XTANDI到期在即，公司自己指引FY2026 XTANDI要掉约500亿日元；大塚靠REXULTI、JYNARQUE、LONSURF这几个老品种撑着，2026年净利指引直接砍到2,650亿日元。这些公司共同的处境，是手里的现金牛在老去，而自研的下一代大单品没跟上。 连日本创新药里最能打的第一三共，DXd ADC的全球商业化也要拉上阿斯利康和默沙东——它和默沙东2023年那笔三款DXd ADC的合作，潜在总额最高220亿美元。日本最强的创新公司尚且如此，其余几家的“全球化”本质是专科型的放大能力，离辉瑞、默沙东那种全球超级机器还差着量级。 所以它们必须不断从外面买资产。日本药企不是突然对中国动心。说白了，它们全球化的第二曲线，天然需要外部弹药；而中国，刚好在这个时间点成了全球最密、最便宜、验证最快的管线供给池——Stifel的数据被Nature Reviews Drug Discovery 2025年引用：2024年大型药企引进的创新管线资产里，来自中国的比例已经到了31%。 呋喹替尼是最直接的证据。和黄把中国以外的全球权益给了武田，武田真把它推成了FRUZAQLA：2023年11月美国获批，2024年6月欧盟获批，2024年9月日本获批。一个中国临床开发出来的小分子，被一家日本药企接走、在欧美日连续落地——这件事本身，比首付款数字重要得多。 但日本药企各管一段，敲错了门，再便宜的管线也是白送 这一节是给中国Biotech的提醒，也是最容易被忽略的地方。 日本药企的BD几乎只围着自己已经建好的专科领域下注。给错了科室，资产再好、报价再低，对它也是负担，因为它没有那条赛道的销售队伍去承接。 大塚就是现成的例子。它主要要的是CNS和肾病/免疫；肿瘤这块，它在2025年已经通过旗下大鹏药品收了Araris——一个AraLinQ linker的ADC平台。也就是说，它的ADC工具箱刚补过货。这时候你拿一个普通的Topo-I ADC去敲大塚的门，大概率撞在它刚补完的平台上，重复建设，谈不动。 反过来看安斯泰来更清楚。它2025年从苏州的信诺维引进CLDN18.2 ADC（XNW27011），拿下大中华区以外全球权益，首付1.3亿美元、潜在里程碑最高13.4亿美元。它为什么要这个ADC？因为它手里已经有CLDN18.2单抗VYLOY，引进ADC是围着胃癌这条精准肿瘤管线做平台延展。它买的是补战略缺口的那一块，不会去凑拥挤赛道里的me-too。 把日本药企粗分一下，对中国Biotech的意义就出来了。 不同的门，开给不同的客人。中国Biotech第一步要做的，是认清自己手里的资产该去敲哪一类的门。 真正的合力，是中国的管线配上日本现成的商业化底盘 把前面三段收一下。中国Biotech可以借日本药企出海，但要想清楚一件事：日本龙头是专科型的全球化放大器，它能帮你把一个对路的专科资产推上欧美日，却没法替你包打所有赛道。 合力的公式很朴素：一个中国开发出来的资产，乘以一个日本药企现成的专科商业化底盘，等于一个全球可注册、可放量的产品。乘错了底盘，这道乘法的结果就是零。 要把这条逻辑讲透，最好的样本是大塚控股——一家商业化齐备、管线却接不上棒的典型。下半篇，专门拆它。 大塚早就不是日本本土药企，北美收入占了快一半 先给身份。大塚控股市值约5.74万亿日元，日本第三；FY2025营收2.4689万亿日元，归母净利3,632亿日元，TTM市盈率约15.8倍。 它的收入结构，是这篇文章里唯一一家美国/北美口径被公司精确披露的。 这张表的意思很直接：大塚北美收入占了快一半，日本本土只剩不到三成。它早就是一家全球化的专科药企，“日本本土公司”这个标签可以撕掉了。 估值上还有个坑得提醒：大塚TTM市盈率看着便宜，约15.8倍，但它2026年净利指引降到2,650亿日元，forward市盈率会被这个指引顶上去。它的估值锚更接近石药、中国生物制药调整后的水平，跟恒瑞、翰森那种创新药叙事溢价是两回事。 它不缺商业化——美国有OAPI，肿瘤有Taiho 大塚在美国是自建队伍，不是那种美国市场必须完全靠partner代销的药企。 第一套：Otsuka America Pharmaceutical（OAPI，1989年就有）和OPDC（2007年成立），在美国跑CNS精神科、肾病、肿瘤支持治疗。OAPI美国官网在售的产品包括ABILIFY系列、REXULTI、NUEDEXTA（CNS），JYNARQUE、SAMSCA、VOYXACT（肾病），以及IV BUSULFEX。 第二套：大鹏药品旗下的Taiho Oncology（全资子公司关系），总部在普林斯顿，专做口服抗肿瘤药，覆盖美、欧、加。 两套队伍合起来意味着，大塚适合接的，是那种专科医生集中、销售队伍不用铺到天上去的资产——CNS、肾病、罕见病、专科肿瘤、小分子靶向。指望它去打美国全科地推海啸的大单品，那不是它的活儿。 四条管线摆开，强在哪、空在哪，一目了然 把大塚的在研管线分四条线看。先看最强的CNS。 CNS是大塚的老本行，商业化能力极强。它的问题在于，2028年以后能长成大单品的新机制资产还不够多。 第二条线是肾病/免疫，核心是anti-APRIL的sibeprenlimab。 值得盯一眼的是HBM7020——大塚和和铂合作，把一个原本走肿瘤路线的BCMA×CD3 TCE迁到自身免疫。这是个信号：它愿意让TCE机制慢病化。 肿瘤主体在Taiho，不在大塚本体。 Taiho的基因是口服小分子、血液瘤、消化道肿瘤、精准靶向，ADC平台刚靠Araris补过。它不是大IO玩家。 第四条线是罕见病/眼科/感染——4D-150（湿性AMD基因治疗日本三期权益）、抗结核的delamanid等。这条线门槛太高，要很强的全球注册和质量体系，中国公司光靠中国数据很难切进去，这里不展开。 大塚真正缺的，是2027年以后能接上美国商业化的那批药 把上面四条线压成一张缺口表。这是全篇Jerry觉得最重要最重要的一张。 这张表一句话：大塚缺的不是早研故事，是能在2027到2030年接上它美国商业化体系的那批专科药。它的销售队伍养在那儿，等的是货。 给中国Biotech排个序：肾病自免最稳，CNS最难 按“匹配度×能不能成交”排，给中国Biotech五类机会，从最稳到最难。 第一，肾病/自免，最稳。大塚已经有JYNARQUE和sibeprenlimab，说明它在认真建肾病专科平台。中国手里如果有IgAN里和anti-APRIL互补的机制、FSGS/膜性肾病/狼疮肾炎、补体或CCR2通路、能跟sibeprenlimab联合或序贯、且有清晰蛋白尿/eGFR终点能做全球注册的后期资产，最对路。旁证：云顶新耀2026年6月刚从Dimerix引进DMX-200（FSGS方向，大中华＋韩国＋部分东南亚权益）。这不代表DMX-200一定卖大塚，而是肾病正在成为中国Biotech和亚洲药企重新定价的方向，有肾病底盘的大塚天然会盯这类资产。 第二，自免方向的TCE/双抗，新兴机会。大塚跟和铂合作HBM7020已经把话说明白了：它愿意把肿瘤的TCE机制迁到自免。中国做双抗的过去基本围着肿瘤转，真正有新BD空间的，可能是能慢病化、能皮下、低CRS的BCMA/CD19/CD20×CD3、CD38、BAFF/APRIL这类。大塚要的，是能被专科化、慢病化、安全性拿捏得住的自免TCE；又一个肿瘤TCE对它没用。 第三，差异化ADC，但必须绕开me-too。Taiho买了Araris补linker平台，意味着你再用“我也是TROP2/HER2 ADC”敲门是没用的。它更可能需要新靶点、脑转移有差异化数据、双payload或更好安全窗、能跟Taiho消化道肿瘤组合的ADC。安斯泰来收Evopoint那笔CLDN18.2 ADC，就是日本药企怎么看中国ADC的样板：补战略缺口的它要，凑赛道的它不要。 第四，精准小分子肿瘤药，适合Taiho。LONSURF、LYTGOBI、INQOVI、zipalertinib，没一个是大IO平台，全是精准、口服、后线、专科医生集中的路子。中国如果有EGFR/HER2罕见突变、KRAS差异化小分子、FGFR/DDR/合成致死、消化道小分子、血液瘤口服药、CNS转移友好型小分子，比泛肿瘤IO更对Taiho的胃口。 第五，CNS创新药，匹配度最高，门槛也最高。这条最微妙：大塚最懂CNS，意味着它对CNS资产也最挑。中国数据外推到美国本来就难，大塚不会为一个只有中国早期数据的精神科药物买单。要谈，最好有全球多中心数据、可复制的量表改善、机制差异化、安全性干净、已进美国临床，或者是长效制剂、RNA、神经退行这些它已经在看的方向。 但别把大塚当默沙东：三条风险线 一，大塚不是默沙东、阿斯利康。它是专科型的全球化放大器，离全球超级机器还差着量级，不适合所有肿瘤大单品。 二，CNS最强，等于对CNS最挑剔。别拿中国早期精神科数据去碰它，它在这块的经验比你深太多。 三，它会买，但更偏专科药、后期资产、战略嵌合度高的标的。普通me-too它不会给最高溢价，单笔首付和开发资源的天花板，也低于欧美Big Pharma。十亿美元级别的交易它做，超大额平台收购的频率比欧美低。 （说句题外话，Jerry以前总觉得日本药企保守得有点闷，后来才慢慢品出来，那种只在自己懂的科室下注的克制，恰恰是它们活得久的原因。） 中国Biotech的出海，正在从“卖给最有名的那个”，变成“卖给最缺这块、也最能把它推向全球的那个”。美国MNC是天花板，欧洲MNC是稳的，日本药企是被低估的专科全球化买家。大塚不是最大的买家，却可能是某些专科资产最合适的买家。它要的从来都不是一个中国故事，是一块能填进它2027年商业化体系的、全球可注册的拼图。 最后，出海这件事，到最后比的不是谁喊得响，谁接触的MNC多，谁被MNC看了更多的数据，最重要的是你手里那块货，正好补上了谁仓里空着的那一格。 风险提示：本文仅讨论行业/公司经营情况，投资需综合考虑公司经营、估值、管理层等多方面因素，建议读者审慎参考，本文不作为投资依据，不建议大家根据本文做出投资计划。 潮药bar知识星球：目前调研了和铂，复宏汉霖，康方，基石，映恩等，礼邦医药通过聆讯马上要打新了，基本面估值报告发星球了，需要的进入星球看，也可以和Jerry约礼邦医药的1V1路演。 除了这周的路演之外 1）我还会更新一个完整的包括近千条管线的血液瘤数据库，包括所有临床数据对比需要的信息。 2）我做了一个港股动态监测医药资金流向的小程序，内容非常全面！欢迎进入星球试用！另外写了个文献全文翻译的skill，可以帮你把每篇英文文献全部翻译并精美排版成中文文献！ 3）一个目前九大创新药企筹码分布持股明细的完整小程序，可以进星球领取！ 更多ASCO的及时解读请进星球！我们正在对每一项数据更新都写一篇深度数据对比报告！ 需要约1V1医药公司具体路演的请进星球，到时候和Jerry预约时间。这周已经被约满啦，得约下周了。所以大家要约的话请尽快来约，要不然得排到下个月啦。 感兴趣的朋友欢迎加入星球！

– Real-world study of revumenib shows 82% (9/11) ORR and 64% (7/11) CR/CRh rate among R/R NPM1m or KMT2Ar patients treated with revumenib monotherapy or combinations – – Ph 1 trial of revumenib with intensive chemotherapy in newly diagnosed NPM1m or KMT2Ar AML shows 97% (34/35) CRc and 86% (25/29) MRD negativity among CRc responders – – Post-hoc analysis of patients with R/R NPM1m, KMT2Ar, or NUP98r acute leukemia in the AUGMENT-101 trial who resumed revumenib post-HSCT shows an observed 1-year OS of 95% – – Phase 1 trial and expanded access experience shows 28% (7/25) ORR in R/R NUP98r acute leukemia, a subtype with a poor prognosis and high unmet need – – Ph 2 SAVE trial of revumenib with venetoclax and decitabine/cedazuridine in R/R NPM1m, KMT2Ar, or NUP98r AML shows 88% (37/42) ORR, 68% (25/37) MRD negativity among responders, and 45% (19/42) transplant rate – NEW YORK, June 11, 2026 (GLOBE NEWSWIRE) -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, today highlighted key Revuforj ® (revumenib) data presented at the European Hematology Association (EHA) 2026 Congress in Stockholm, Sweden. In total, 12 abstracts focused on revumenib, the Company’s first-in-class, FDA-approved menin inhibitor, were accepted for EHA 2026. The data presented span multiple acute leukemia subtypes and settings, including new real-world, post-transplant, and combination data from the relapsed/refractory (R/R) and frontline setting. “Collectively, the new data presented at EHA showcase the robust activity observed with revumenib across multiple acute leukemia subtypes and settings, highlighting the potential for revumenib to transform patient outcomes,” said Nick Botwood, MBBS, Head of Research & Development and Chief Medical Officer at Syndax. “In particular, we are encouraged to observe deep and durable remissions among patients with NPM1m, KMT2Ar, or NUP98r acute leukemia who received revumenib in combination with standard of care therapies in clinical trials or the real-world. The breadth of data presented at EHA highlights physicians’ enthusiasm for revumenib and bolsters our conviction that our ongoing pivotal frontline combination trials are positioned to deliver paradigm-changing results.” Overview of key revumenib data presented at EHA 2026: Abstract title: Revumenib in the real world: interim findings from the ROAR study in relapsed/refractory acute leukemia Abstract #: PF542 At the first interim analysis from ROAR, a multicenter real-world study of revumenib, 11 heavily pretreated patients with R/R NPM1 mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) acute leukemia (median of 2 prior lines of therapy) were response evaluable. Among this population, 64% (7/11) received revumenib monotherapy and 36% (4/11) received revumenib combination therapy. 82% (9/11) overall response rate 1 (ORR) and 64% (7/11) complete remission plus complete remission with partial hematological recovery (CR/CRh) rate among the response-evaluable population. 36% (4/11) of the response-evaluable population proceeded to a hematopoietic stem cell transplant (HSCT), of which 50% (2/4) had resumed revumenib post-HSCT at the data cut off. Revumenib was generally well-tolerated, with real-world safety findings consistent with the established safety pro revumenib. There were no events of differentiation syndrome (DS) or QTc prolongation above Grade 3 and no patient discontinued revumenib due to DS or QTc. Abstract title: Revumenib + intensive chemotherapy for newly diagnosed acute myeloid leukemia harboring genetic alterations in KMT2A, NPM1, or NUP98: updated phase 1 results from SNDX-5613-0708 Abstract #: PF489 97% (34/35) composite complete remission (CRc) and 77% (27/35) complete remission (CR) rate observed among newly diagnosed patients with NPM1m or KMT2Ar AML who received revumenib at dose level (DL) 1 or 2 in combination with intensive chemotherapy. DL1 was revumenib 110 or 220 mg q12hr with/without strong CYP3A4i. DL2 was the FDA-approved monotherapy dose of 160 or 270 mg q12hr with/without strong CYP3A4i. Response rates were similar across both dose levels. 86% (25/29) measurable residual disease (MRD) negativity among those with CRc and 87% (20/23) MRD negativity among those with CR, as determined by local testing. Durability data are still maturing. At the data cutoff, the median follow-up was 4.8 months and 2.9 months in DL1 and DL2, respectively. 60% (9/15) of patients in DL1 and 10% (2/20) in DL2 had proceeded to HSCT as of the data cutoff (this difference may be due to a higher proportion of patients with KMT2Ar and longer follow-up in DL1 than DL2); of the patients in DL1 who proceeded to HSCT, 67% (6/9) resumed revumenib post-HSCT. Safety pro broadly consistent across both revumenib dose levels and comparable with intensive chemotherapy alone. There were no treatment-emergent adverse events (TEAEs) of DS or QTc prolongation above Grade 3. No clinically meaningful pruritus was reported. Abstract Title: Revumenib therapy post hematopoietic stem cell transplant for patients with relapsed/refractory KMT2Ar, NPM1m, and NUP98r acute myeloid leukemia: post hoc analysis of outcomes from AUGMENT-101 Abstract #: PS1631 Post-hoc analysis included 19 heavily pretreated adults and children with R/R NPM1m, KMT2Ar, or NUP98r acute leukemia who resumed revumenib post-HSCT in the multicenter AUGMENT-101 trial. Median time from HSCT to resuming revumenib was 65 (range: 34-181) days. The median duration of revumenib therapy post-HSCT was 20 (range: 2-137) weeks at the data cutoff. Three patients remained on therapy, including two patients who had received more than two years of revumenib post-HSCT. Median overall survival (OS) and median relapse-free survival (RFS) were not reached, regardless of genetic subtype. The estimated 12-month OS and RFS rates were 95% and 79%, respectively. Safety pro consistent with the established safety pro revumenib. Treatment emergent adverse events leading to revumenib discontinuation were low at 5% of patients. No patients discontinued treatment due to cytopenias. These results build on data presented at EHA 2026 and ASCO 2026 from a pooled analysis of 24 adults and children who resumed revumenib post-transplant at a single-center. Abstract title: Clinical activity of revumenib in patients with relapsed/refractory NUP98-rearranged acute leukemias Abstract #: PS1607 28% (7/25) ORR observed among heavily pretreated adults and children with R/R NUP98r acute leukemia (median of 3 prior lines of therapy) who received revumenib in the Phase 1 portion of the AUGMENT-101 trial or via an expanded access program. The median duration of response was 6.7 months. 43% (3/7) of responders proceeded to HSCT and all resumed revumenib post-HSCT. Safety pro consistent with the established safety pro revumenib. No TEAEs led to treatment discontinuation. Abstract Title: Phase 1/2 study of the all-oral combination of revumenib (SNDX-5613) with decitabine/cedazuridine (ASTX727) and venetoclax (SAVE) in relapsed/refractory AML Abstract #: PF495 Results from the R/R cohort enrolled in the SAVE trial were recently published in the Journal of Clinical Oncology and simultaneously presented at EHA 2026. Key results include: 88% (37/42) ORR, 71% (30/42) CRc, and 60% CR/CRh (25/42) observed among heavily pretreated patients with R/R NPM1m, KMT2Ar, or NUP98r AML (median of two prior lines of therapy). 45% (19/42) of patients proceeded to HSCT, of which 63% (12/19) had resumed revumenib as post-HSCT maintenance at the data cutoff. The rates of MRD negativity by flow cytometry were 68% (25/37) among evaluable responders, 80% (24/30) among those with CRc, and 80% (20/25) among those with CR/CRh. With a median follow-up of 22 months, the median duration of response in patients with CR/CRh was 10.7 months among NPM1m patients, not reached among KMT2Ar patients, and 5.9 months among NUP98r patients. Revumenib was generally well-tolerated in combination with decitabine/cedazuridine and venetoclax. The most common TEAEs were consistent with the established safety pro revumenib and the combination partners. About Revuforj ® (revumenib) Revuforj (revumenib) is the first and only menin inhibitor that is FDA approved for the treatment of adult and pediatric patients one year and older with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible NPM1 mutation who have no satisfactory alternative treatment options or R/R acute leukemia with a KMT2A translocation as determined by an FDA-authorized test. Multiple trials of revumenib are ongoing or planned across the treatment landscape, including in combination with standard of care therapies in newly diagnosed patients with NPM1m or KMT2Ar AML. Revuforj (revumenib) IMPORTANT SAFETY INFORMATION WARNING: DIFFERENTIATION SYNDROME, QTc PROLONGATION, and TORSADES DE POINTES Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution. QTc prolongation and Torsades de Pointes have occurred in patients receiving Revuforj. Correct hypokalemia and hypomagnesemia prior to and during treatment. Do not initiate Revuforj in patients with QTcF > 450 msec. If QTc interval prolongation occurs, interrupt, reduce, or permanently discontinue Revuforj. WARNINGS AND PRECAUTIONS Differentiation Syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, rash, and/or hypotension. In clinical trials, DS occurred in 60 (25%) of 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia. Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype acute leukemia (MPAL), and 9% of patients with acute lymphoblastic leukemia (ALL); DS occurred in 18% of patients with NPM1m AML. DS was Grade 3 or 4 in 12% of patients and fatal in 2 patients. The median time to initial onset was 9 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%. Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours in adults or dexamethasone 0.25 mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids . QTc Interval Prolongation and Torsades de Pointes: Revuforj can cause QT (QTc) interval prolongation and Torsades de Pointes. Of the 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia in clinical trials, QTc interval prolongation was reported as an adverse reaction in 86 (36%) patients. QTc interval prolongation was Grade 3 in 15% and Grade 4 in 2%. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 10%, and the increase from baseline QTcF was greater than 60 msec in 24%. Revuforj dose reduction was required for 7% due to QTc interval prolongation. QTc prolongation occurred in 21% of the 34 patients less than 17 years old, 35% of the 146 patients 17 years to less than 65 years old, and 46% of the 61 patients 65 years or older. One patient had a fatal outcome of cardiac arrest, and one patient had non-sustained Torsades de Pointes. Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to and throughout treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation. Interrupt Revuforj if QTcF increases >480 msec and 500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns to ≤480 msec Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia Embryo-Fetal Toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj. ADVERSE REACTIONS Fatal adverse reactions occurred in 9 (4%) patients who received Revuforj, including 4 with sudden death, 2 with differentiation syndrome, 2 with hemorrhage, and 1 with cardiac arrest. Serious adverse reactions were reported in 184 (76%) patients. The most frequent serious adverse reactions (≥10%) were infection (29%), febrile neutropenia (20%), bacterial infection (15%), differentiation syndrome (13%), and hemorrhage (11%). The most common adverse reactions (≥20%) including laboratory abnormalities, were phosphate increased (51%), hemorrhage (48%), nausea (48%), infection without identified pathogen (46%), aspartate aminotransferase increased (44%), alanine aminotransferase increased (40%), creatinine increased (38%), musculoskeletal pain (37%), febrile neutropenia (37%), electrocardiogram QT prolonged (36%), potassium decreased (34%), parathyroid hormone intact increased (34%), alkaline phosphatase increased (33%), diarrhea (29%), bacterial infection (27%), triglycerides increased (27%), phosphate decreased (25%), differentiation syndrome (25%), fatigue (24%), edema (24%), viral infection (23%), decreased appetite (20%), and constipation (20%). DRUG INTERACTIONS Drug interactions can occur when Revuforj is concomitantly used with: Strong CYP3A4 inhibitors: reduce Revuforj dose Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec SPECIFIC POPULATIONS Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose. Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj. Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible. Pediatric: monitor bone growth and development in pediatric patients . Geriatric: no overall differences were observed in the effectiveness of Revuforj between patients who were 65 years and older, and younger patients. Compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older. To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or . Please see Full Prescribing Information , including BOXED WARNINGS. About Syndax Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company advancing innovative cancer therapies. Highlights of the Company's pipeline include Revuforj ®  (revumenib), an FDA-approved menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit  or follow the Company on  X  and  LinkedIn . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "believe," "could," "estimate," "expects," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" or the negative or plural of those terms, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, the acceptance of Syndax and its partners' products in the marketplace, sales, marketing, manufacturing and distribution requirements, and the potential use of its product candidates to treat various cancer indications and fibrotic diseases. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes to Revuforj's or Niktimvo’s commercial availability; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. References Overall response rate (ORR) includes CR, CRh, CRp, CRi, MLFS, and PR; Composite complete remission (CRc) includes CR, CRh, CRp, and CRi. CR = Complete remission CRh = Complete remission with partial hematologic recovery CRp = Complete remission with incomplete platelet recovery CRi = Complete remission with incomplete count recovery MLFS = Morphologic leukemia-free state PR = Partial response Syndax Contact Sharon Klahre Syndax Pharmaceuticals, Inc. sklahre@syndax.com Tel 781.684.9827 SNDX-G