B7H3-directed GADLEN product

DS-8201引爆ADC后，整个赛道热度不断升温，海内外药企都在跑步入局。目前，全球已有15款ADC药物获批上市，还有400多款ADC药物处于不同研发阶段。这几年，随着获批数量不断增加，新玩家的不断加入，整个ADC赛道，尤其HER2靶点已经极致内卷。就在所有人不顾一切向前冲的时候，一个被忽略的事实却是，ADC热度虽高、DS-8201疗效也确实炸裂，但在此前相当长一段时间，整个ADC赛道的药物销售额并不高。2022年，ADC药物的销售总额不过77.02亿美元。要知道，同期老药王修美乐的销售额达到212亿美元。也就是说，火热的ADC赛道的商业化成绩单，还不及一款超级重磅炸弹药物的一半。当然，对于ADC赛道来说，这样的成绩单注定只是暂时的。如今，ADC的市场规模正在快速增长，今年上半年已经突破50亿美元。按照这样的趋势，2023年ADC市场规模有望突破100亿美元。毋庸置疑的是，随着适应症的拓展、商业化提速，ADC的市场规模必将在未来迈上更高的台阶。01实体瘤ADC乘风破浪从2000年第一款ADC药物获批上市算起，耗时23年，ADC赛道才终于突破了百亿美元大关。23年前，“魔法子弹”穿越百年证明了自己能够成药。彼时辉瑞带着首款ADC药物上市。但碍于安全性和疗效，这款药物没能引起波澜。ADC赛道也在十几年时间中默默无闻。直到DS-8201引爆整个ADC赛道，才开始有越来越多的药企注意到这一领域。随着整个赛道的热度复苏，越来越多的玩家参与其中，ADC药物的销量也在不断爬坡，市场规模也以肉眼可见的速度扩张。2023年上半年，所有ADC药物的销售额已经突破50亿美元，按照这样的趋势来看，ADC行业在2023年将成功突破百亿美元销售额门槛。而在这个过程中，为ADC赛道做出最大贡献的，非实体瘤ADC药物莫属。目前为止，在全球获批上市的15款ADC药物中有7款靶向血液学适应症，8款靶向实体瘤适应症。而这8款ADC药物，在上半年销售额合计达到34.19亿美元，为ADC领域贡献一大半的收入。其中，靶向HER2的DS-8201和T-DM1贡献最大。DS-8201，自2019年获批上市后销售额不断增长，到今年上半年销售总额达11.69亿美元。并且，DS-8201仍在不断进击，以拿下更多的适应症。DS-8201年销售额破百亿美元，或许也只是时间问题。不过，有人欢喜有人忧愁，同为HER2 ADC药物的T-DM1，在DS-8201的挤压下已经辉煌不再。虽然今年上半年其销售额仍然有11.95亿美元，略胜DS-8201一筹，但在下半年情况或许就将发生变化。毕竟，上半年T-DM1的销售增长近乎停止，不难推测，2023年DS-8201将力压T-DM1成为ADC领域的新王。除了这两款产品，全球首个获批上市的TROP2 ADC药物trodelvy，上半年销售额达到4.82亿美元；全球首个获批治疗局部晚期或转移性尿路上皮癌的ADC药物，Padcev上半年销售额达到5.13亿美元。按照这一趋势，这两款药物都有望在2023年突破10亿美元大关。值得一提的是，由ImmunoGen研发的Elahere，上市仅半年时间，2023年上半年销售额也达到了1.07亿美元。通过这些药物的表现，我们也不难看出，在实体瘤领域ADC的优势所在。02血液瘤ADC稍逊一筹尽管ADC发迹于血液瘤，2000年，FDA批准的第一款ADC药物Mylotarg，就是用于治疗急性髓系白血病。此后上市的多款ADC药物，大多也是用于治疗血液瘤。但在血液瘤领域，ADC的表现则稍逊一筹，仅有Adcetris和Polivy两款ADC药物表现较为可圈可点。其中，Adcetris是一款靶向CD30的ADC药物，早在2011年这款药物就获批上市，用于治疗霍奇金淋巴瘤（HL）和系统性间变性大细胞淋巴瘤（sALCL），可谓是ADC领域的元老。Adcetris也是1977年以来，HL领域批准的首个创新药。此后，随着适应症的不断拓展，其销售额缓步提升。2022年，Adcetris销售额合计达14.69亿美元，在全球ADC药物销售额排行榜中位列第二。今年上半年，Adcetris销售额排名滑落至第三名，但仍达到8.21亿美元。血液瘤领域另一款潜力产品是靶向CD79的ADC药物Polivy。自2019年上市以来，Polivy销售额从2020年的1.81亿美元，增长至2022年的5.91亿美元。今年上半年，其销售额达到4.05亿美元，同比增长114%，按照这一趋势，Polivy有很大可能在今年突破10亿美元的门槛。03未竞的战争当然，全球药企对于ADC的向往，并不会因为ADC在血液瘤领域的表现而受到影响。事实上，当下ADC的火爆程度依旧，仍有不少药企在加码ADC领域。好的一点是，如今布局ADC的药企正在逐渐回归理智，已经很少有玩家，头铁继续冲向HER2、TROP2等内卷的靶点。更多的药企开始在ADC领域选择差异化打法，比如在靶点上进行差异化探索，在适应症上瞄准未满足的临床需求。所以我们也能发现，最近一段时间以来，国内药企围绕着ADC申报的临床，更多集中于一些小众靶点。比如，豪森药业、迈威生物、百济神州布局了B7H3 ADC，复宏汉霖布局了STEAP1 ADC，昂阔医药布局了CDH6 ADC，恒瑞医药、百济神州布局了CEA ADC。与HER2、TROP2等热门靶点相比，这些药企们选择的靶点竞争格局要好得多。通过这样的布局，这些玩家或许也能在ADC领域开拓出一片新的天地。不过，这些FIC药物的研发难度，自然也会比HER2这样的成熟靶点高许多。作为勇敢者的回报，这些药企一旦成功也会获得可观的回报。ADC赛道的未来，也将会在这些勇敢者的探索下，走向更广阔的天地，百亿美元只是ADC赛道商业化的开端，ADC领域的竞赛不会结束。相反，这场竞赛只会随着各方实力的增强而愈演愈烈。ADC世界永远是强者的天堂。来源 | 氨基观察（药智网获取授权转载）撰稿 | 方涛之责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信） 阅读原文，是受欢迎的文章哦

– Presented complete data from Phase 1A clinical trial of SL-172154 as monotherapy in platinum-resistant ovarian cancer (PROC) at the American Society of Clinical Oncology (ASCO) 2023 annual meeting, including data supporting 3 mg/kg as the appropriate dose for each PROC combination cohort – – Completed enrollment in the dose-escalation portion of the Phase 1A/B clinical trial of SL-172154 in relapsed/refractory acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS); and expect to complete enrollment in both frontline expansion cohorts in HR-MDS and TP53 mutant AML in the fourth quarter of 2023 – – Enrollment progressing in the Phase 1B clinical trial of SL-172154 in combination with liposomal doxorubicin in PROC, completion of enrollment and initial data expected in the fourth quarter of 2023 – – Enrollment progressing in the Phase 1B clinical trial of SL-172154 in combination with mirvetuximab soravtansine in PROC; initial data expected in the fourth quarter of 2023 – AUSTIN, TX and DURHAM, NC, Aug. 10, 2023 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, today reported financial results for the quarter ended June 30, 2023, and provided recent business highlights. “We are pleased with our continued progress in enrollment in our ongoing trials in the second quarter of 2023, and in particular to now have four different expansion cohorts well underway in our AML/HR-MDS and PROC trials,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “We believe that data from our dose-escalation study in PROC presented at ASCO demonstrated that SL-172154 may be a differentiated CD47 inhibitor due to the integrated CD40 agonist function, and we look forward to sharing initial combination data across multiple tumors and lines of therapy by the end of the year.” 2023 Anticipated Milestones ARC Platform SL-172154 (SIRPα-Fc-CD40L) Complete enrollment and initial data from the ongoing Phase 1B clinical trial of SL-172154 in combination with liposomal doxorubicin in PROC expected in the fourth quarter of 2023. Initial data from the ongoing Phase 1B clinical trial of SL-172154 in combination with mirvetuximab soravtansine in PROC expected in the fourth quarter of 2023. Complete dose-escalation data, as monotherapy and in combination with azacitidine, for Phase 1A clinical trial of SL-172154 in primarily relapsed/refractory AML and HR-MDS expected in the fourth quarter of 2023. Completion of enrollment in the frontline TP53 mutant AML dose-expansion cohort and frontline HR-MDS dose-expansion cohort from our ongoing Phase 1A/B clinical trial of SL-172154 and initial data expected in the fourth quarter of 2023. Second Quarter 2023 Recent Business Highlights and Other Recent Developments ARC Clinical-Stage Pipeline SL-172154 (SIRPα-Fc-CD40L) Presented Complete Dose-Escalation Data from Phase 1A Monotherapy Clinical Trial of SL-172154 in PROC at the 2023 ASCO Annual Meeting: This open-label, multi-center, dose-escalation clinical trial evaluated the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered intravenously in patients with PROC. SL-172154 had near-full CD47 and CD40 target engagement and CD40-dependent pharmacodynamic effects observed at the 3 mg/kg dose. SL-172154 had a favorable safety and tolerability pro doses. The best response per RECIST 1.1 was stable disease in six (22%) patients. Completed Enrollment in Dose-escalation Portion of Phase 1A/B Clinical Trial of SL-172154 in AML and HR-MDS: This trial is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 as both monotherapy and in combination with azacitidine. In the dose-escalation portion of this trial, enrollment is complete. We are now enrolling patients in the dose expansion cohorts, evaluating SL-172154 in combination with azacitidine in both frontline HR-MDS patients and in frontline TP53 mutant AML. We expect to complete enrollment for the two expansion cohorts in the fourth quarter of 2023. We expect to share complete data from the dose-escalation portion of the trial and initial data from the frontline expansion cohorts in the fourth quarter of 2023. Enrollment Progressing in Phase 1B Clinical Trial of SL-172154 in Combination with Liposomal Doxorubicin in PROC: Enrollment is continuing in this trial, which is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, using the selected dose of 3 mg/kg, in combination with liposomal doxorubicin in patients with PROC. We completed enrollment in the safety run in portion of this trial in the second quarter of 2023 and expect to complete enrollment in the expansion cohort and present initial data from the trial in the fourth quarter of 2023. Enrollment Progressing in Phase 1B Clinical Trial of SL-172154 in Combination with Mirvetuximab Soravtansine in PROC. This trial is evaluating the safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of SL-172154 administered in combination with mirvetuximab soravtansine in patients with PROC. Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which provides for both direct tumor cell killing as well as enhanced macrophage phagocytosis through binding with Fc gamma receptors and has received accelerated approval for PROC patients whose tumors are shown to be FRα positive, defined as ≥75%, as determined by the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. Preclinical studies have shown that both of these killing mechanisms are complementary to the mechanism of SL-172154 by enhancing the activity of macrophages to phagocytose FRα- expressing ovarian cancer cells, and that SL-172154 may broaden the activity of mirvetuximab, particularly in patients with tumors that express lower levels of FRα. We intend to enroll patients with broader FRα expression, including those with “high” (greater than ≥75%), “medium” (≥50% to <75%), and “low” (≥25% to <50%) expression of FRα, as determined by the VENTANA FOLR1 (FOLR1-2.1). We expect to present initial data from the trial in the fourth quarter of 2023. Gamma Delta T Cell Engager (GADLEN) Platform GADLEN Preclinical Compounds In an initial non-human primate toxicology study, presented at the 2023 Annual Meeting of the American Association for Cancer Research, we observed dose-dependent B cell depletion following administration of a CD20-directed GADLEN. Subsequently, in the second quarter of 2023, we performed an additional toxicology study in non-human primates that was designed to expand upon the initial non-human primate study. In this second study, the depth and durability of B cell depletion were inferior to that reported in published studies with other B cell depleting agents. We are working to determine the underlying scientific cause for these differences in B cell response, and whether these are due to species differences between humans and cynomolgus macaques, or due to aspects inherent to gamma delta T cell biology. We do not currently plan to Investigational New Drug application for any GADLEN compounds until these data are better understood. Second-Quarter 2023 Financial Results Cash and Cash Equivalents and Investments: As of June 30, 2023, cash and cash equivalents and investments were $117.2 million, as compared to $214.2 million as of June 30, 2022. Research and Development (R&D) Expenses: R&D expenses were $18.2 million for the quarter ended June 30, 2023, as compared to $23.0 million for the quarter ended June 30, 2022. This decrease was primarily driven by a decrease in expense associated with the manufacture of clinical trial materials to support our ongoing clinical trials. General and Administrative (G&A) Expenses: G&A expenses were $4.7 million for the quarter ended June 30, 2023, as compared to $4.7 million for the quarter ended June 30, 2022. Net Loss: Net loss was $21.3 million for the quarter ended June 30, 2023, or $0.50 per basic and diluted share, as compared to a net loss of $27.4 million for the quarter ended June 30, 2022, or $0.65 per basic and diluted share. 2023 Financial Guidance Shattuck believes its cash and cash equivalents and investments will be sufficient to fund its operations through year-end 2024, beyond results from its Phase 1 clinical trials of SL-172154. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from business development transactions, and/or additional costs associated with clinical development activities that may be undertaken. About SL-172154 SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC® fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with PROC (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439). About Shattuck Labs, Inc. Shattuck Labs, Inc. (NASDAQ: STTK) is a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease. Compounds derived from Shattuck’s proprietary Agonist Redirected Checkpoint, (“ARC®”), platform are designed to simultaneously inhibit checkpoint molecules and activate costimulatory molecules with a single therapeutic. The company’s lead SL-172154 (SIRPα-Fc-CD40L) program, which is designed to block the CD47 immune checkpoint and simultaneously agonize the CD40 pathway, is being evaluated in multiple Phase 1 trials. Shattuck has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit: Forward-Looking Statements Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, our expectations regarding plans for our preclinical studies, clinical trials and research and development programs, plans for clinical trial design, the anticipated timing of the results from our preclinical studies and clinical trials, anticipated timing of enrollment in our clinical trials, anticipated timing for preclinical development updates, potential safety and clinical benefit of our product candidates, and expectations regarding the time period over which our capital resources will be sufficient to fund our anticipated operations. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While we believe these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in our filings with the U.S. Securities and Exchange Commission (the “SEC”)), many of which are beyond our control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of our preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of our clinical trials; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; liquidity and capital resources; and other risks and uncertainties identified in our Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent disclosure documents filed with the SEC. We claim the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We expressly disclaim any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. The Company intends to use the investor relations portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD. Investor & Media Contact: Conor Richardson Vice President of Investor Relations Shattuck Labs, Inc. InvestorRelations@shattucklabs.com SHATTUCK LABS, INC. CONDENSED BALANCE SHEETS (In thousands) June 30, 2023 December 31, (unaudited) 2022 Assets Current assets: Cash and cash equivalents $ 71,893 $ 47,379 Investments 45,279 113,901 Prepaid expenses and other current assets 19,278 23,304 Total current assets 136,450 184,584 Property and equipment, net 16,015 17,671 Other assets 2,805 3,069 Total assets $ 155,270 $ 205,324 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 2,011 $ 7,170 Accrued expenses and other current liabilities 10,983 17,795 Total current liabilities 12,994 24,965 Non-current operating lease liabilities 3,818 4,202 Total liabilities 16,812 29,167 Stockholders’ equity: Common stock 5 5 Additional paid-in capital 399,609 396,041 Accumulated other comprehensive loss (74 ) (877 ) Accumulated deficit (261,082 ) (219,012 ) Total stockholders’ equity 138,458 176,157 Total liabilities and stockholders’ equity $ 155,270 $ 205,324 SHATTUCK LABS, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Unaudited) (In thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Collaboration revenue $ 200 $ 50 $ 257 $ 50 Operating expenses: Research and development 18,205 22,963 34,872 42,150 General and administrative 4,742 4,745 9,793 9,724 Expense from operations 22,947 27,708 44,665 51,874 Loss from operations (22,747 ) (27,658 ) (44,408 ) (51,824 ) Other income (expense) 1,401 287 2,338 (75 ) Net loss $ (21,346 ) $ (27,371 ) $ (42,070 ) $ (51,899 ) Unrealized gain (loss) on investments 265 (581 ) 803 (548 ) Comprehensive loss $ (21,081 ) $ (27,952 ) $ (41,267 ) $ (52,447 ) Net loss per share – basic and diluted $ (0.50 ) $ (0.65 ) $ (0.99 ) $ (1.22 ) Weighted-average shares outstanding – basic and diluted 42,467,664 42,380,454 42,453,513 42,369,102