Precemtabart tocentecan

Raises Full Year 2026 Revenue and Cash Outlook Driven by Continued Business Momentum Conference Call to Begin Today at 4:30 p.m. ET EMERYVILLE, Calif.--(BUSINESS WIRE)-- OmniAb, Inc. (NASDAQ: OABI), a provider of cutting-edge discovery research technology to enable the discovery of next-generation therapeutics, today reported financial results for the three and six months ended June 30, 2026, provided operating and partner program progress, and updated 2026 financial guidance. “We are pleased to report a strong quarter and to increase our revenue and cash outlook for 2026 based on continued momentum in our business. Recent updates from partner programs have been very encouraging with important advancements in clinical development,” stated Matt Foehr, Chief Executive Officer of OmniAb. “We continue to efficiently leverage and expand the reach of our core and highly differentiated discovery technologies, as we also focus on our promising xPloration® platform. We recently expanded our executive leadership with the addition of Chief Operating Officer Amechi Nwachuku, who has quickly integrated into our team to drive and strengthen this area. We believe we’re well positioned to accelerate growth, and we look forward to providing business updates and technology highlights and plans at our October Investor and Analyst Day.” Second Quarter 2026 Financial Results Revenue for the second quarter of 2026 was $13.4 million, compared with $3.9 million in the prior-year period, with the increase driven primarily by milestone revenue. Service revenue increased primarily due to the commencement of new ion channel programs, and xPloration revenue increased on higher instrument sales and related consumables. Cost of xPloration revenue was $0.6 million for the second quarter of 2026, compared with $0.3 million for the same period in 2025. The increase was due to increased instrument and consumable sales. Research and development expense was $9.6 million for the second quarter of 2026, compared with $10.9 million for the same period in 2025, with the decrease due to lower personnel expense related to share-based compensation and salary expense and lower facility-related costs. General and administrative expense was $6.7 million for the second quarter of 2026, compared with $7.7 million for the same period in 2025, with the decrease primarily due to lower personnel expense related to share-based compensation and salary expense and lower professional fees. Amortization of intangibles decreased to $3.1 million for the second quarter of 2026, compared with $3.2 million for the same period in 2025. Other operating expense (income) increased to $0.2 million for the second quarter of 2026 from ($1.9) million for the same period in 2025, primarily as a result of a net $2.0 million one-time gain from the sale of a small-molecule program in the second quarter of 2025. Total costs and operating expenses were $20.1 million for the second quarter of 2026, flat with $20.1 million for the same period in 2025. Cash costs and operating expenses were $13.3 million for the second quarter of 2026, compared with $11.9 million for the same period in 2025 (see note regarding "Use of Non-GAAP Financial Measure" below for further discussion of this non-GAAP measure). Net loss for the second quarter of 2026 was $5.9 million, or $0.05 per share, compared with a net loss of $15.9 million, or $0.15 per share, for the same period in 2025. Year-to-Date Financial Results Revenue for the first half of 2026 was $27.8 million, compared with $8.1 million for the same period in 2025, with the increase primarily related to milestone revenue. Service revenue increased primarily due to the commencement of new ion channel programs, and xPloration revenue increased on higher instrument sales and related consumables. Cost of xPloration revenue was $0.6 million for the first half of 2026, compared with $0.3 million for the same period in 2025. The increase was due to increased instrument and consumable sales. Research and development expense was $19.2 million for the first half of 2026, compared with $23.5 million for the same period in 2025, with the decrease due to lower personnel expense related to share-based compensation and salary expense, lower external expenses associated with legacy small-molecule ion channel programs and lower facility-related costs. General and administrative expense was $13.3 million for the first half of 2026, compared with $15.6 million for the same period in 2025, with the decrease primarily due to lower personnel expense related to share-based compensation and salary expense and lower professional fees. Amortization of intangibles increased to $9.1 million for the first half of 2026, compared with $6.5 million for the same period in 2025, primarily due to a $2.9 million non-cash impairment related to the discontinuation of certain legacy small-molecule ion channel programs recorded in the first quarter of 2026. Other operating expense (income) for the first half of 2026 was $0.1 million compared to ($2.7) million for the same period in 2025. The prior-year period included a net $2.0 million one-time gain from the sale of a small-molecule program in the second quarter of 2025. Total costs and operating expenses were $42.3 million for the first half of 2026, compared with $43.1 million for the same period in 2025. Cash costs and operating expenses were $25.5 million for the first half of 2026, compared with $26.6 million for the same period in 2025 (see note regarding "Use of Non-GAAP Financial Measure" below for further discussion of this non-GAAP measure). Net loss for the first half of 2026 was $13.6 million, or $0.11 per share, compared with a net loss of $34.1 million, or $0.32 per share, for the same period in 2025. As of June 30, 2026, OmniAb had cash, cash equivalents and short-term investments of $52.0 million. 2026 Financial Guidance OmniAb revises 2026 financial guidance and now expects revenue to be in the range of $32 million to $36 million, versus $28 million to $33 million previously, and costs and operating expenses to be in the range of $84 million to $88 million, versus $83 million to $88 million previously. Cash costs and operating expenses are expected to be in the range of $51 million to $55 million, versus $50 million to $55 million previously (see note regarding "Use of Non-GAAP Financial Measure" below for further discussion of this non-GAAP measure). The Company now expects to end the year with cash and cash equivalents in the range of $37 million to $41 million, versus $33 million to $38 million previously. The full-year 2026 effective tax rate is expected to be approximately 0%. Second Quarter 2026 and Recent Business Highlights During the second quarter of 2026, OmniAb entered into new license agreements with EnRosa Therapeutics and argenx. As of June 30, 2026, the Company had 110 active partners and 425 active programs, including 34 OmniAb-derived programs in clinical development or being commercialized. Business and partner highlights from the second quarter of 2026 and recent weeks included the following: JNJ-5322 Ramantamig (JNJ-79635322), a tri-specific antibody targeting (BCMA x GPRC5D x CD3), has advanced to Phase 3 from Phase 1 clinical trials. The Phase 3 study is randomized study comparing JNJ-79635322 and an anti-BCMAxCD3 bispecific antibody in participants with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy including a PI, an IMiD, and an anti CD38 antibody. Precemtabart tocentecan (M9140) Merck KGaA, announced the first patient has been dosed in the Phase 3 PROCEADE®-CRC-03 trial evaluating precemtabart tocentecan, a potential first‑in‑class investigational anti‑CEACAM5 antibody‑drug conjugate (ADC), for the treatment of metastatic colorectal cancer based on Phase 1 data. The Phase 3 study will assess the efficacy and safety of precemtabart tocentecan, alone or with bevacizumab, in patients with metastatic colorectal cancer who are intolerant- or refractory-to, or progressed after, systemic therapies. Phase 1 data from the PROCEADE-CRC-01 study showed predictable and manageable safety in more than 100 patients with heavily pretreated metastatic colorectal cancer. At the recommended dose for Phase 3 development (2.8 mg/kg Q3W; n=29), confirmed objective response rate was 20.7% (95% CI: 8.0, 39.7), median PFS was 6.9 months (95% CI: 4.4, 9.5), and median OS was not reached after a median follow-up of 13.1 months (95% CI: 8.7, NE). TEV- '408 Teva Pharmaceuticals announced plans for its TEV-’408, an investigational anti-interleukin-15 monoclonal antibody, to advance into a Phase 2b study in vitiligo in the fourth quarter of 2026 following encouraging results from an ongoing Phase 1b, open-label study in adults with active or stable non-segmental vitiligo (NSV). Topline results in Phase 1b trial evaluating TEV-'408 for vitiligo showed improvements in skin pigmentation in patients with active or stable NSV. TEV-’408 was well-tolerated with no safety signals observed. At baseline, 66% of enrolled participants had vitiligo affecting more than 10% of body surface area, representing a population with limited treatment options. At week 24, in evaluable participants, nearly 75% of patients reported improvement in facial vitiligo, with half reporting “much” or “very much” improved, 42% achieved F-VASI50 and 21% achieved F-VASI75, 55% of patients reported improvement in total body vitiligo, and 7% achieved T-VASI50. Teva Pharmaceuticals and Royalty Pharma entered into a funding agreement of up to $500 million to accelerate the clinical development of TEV-'408 for vitiligo. Topline results of the Phase 2a trial evaluating TEV-'408 for celiac disease continue to be expected in the second half of 2026. IMVT-1402 Immunovant announced preliminary week 16 IMVT-1402 results in the difficult-to-treat rheumatoid arthritis trial that showed clinically meaningful response rates of 72.7% ACR20, 54.5% ACR50 and 35.8% ACR70. Immunovant’s development plans for IMVT-1402 remain on track across all six announced indications. They expect to provide further updates on the potentially registrational IMVT-1402 difficult-to-treat rheumatoid arthritis program and report topline data from the proof-of-concept trial of IMVT-1402 in cutaneous lupus erythematosus in the second half of calendar year 2026. In calendar year 2027, topline data are anticipated for the potentially registrational trials evaluating IMVT-1402 in Graves’ disease and myasthenia gravis. Topline data are expected to follow in calendar year 2028 for the potentially registrational trials of IMVT-1402 in chronic inflammatory demyelinating polyneuropathy and Sjögren’s disease. BI 3802876 Boehringer Ingelheim has commenced its Phase 2a double-blind, placebo-controlled study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 3802876 in participants with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The study is to evaluate BI 3802876 tolerance and dose response in MASH patients. Sugemalimab Arrotex Pharmaceuticals entered into an exclusive commercialization agreement with CStone Pharmaceuticals for Sugemalimab, a fully human anti–PD-L1 monoclonal antibody, covering all approved and future indications in Australia and New Zealand. The agreement includes potential commercialization across stage III and IV non-small cell lung cancer, gastric cancer, esophageal squamous cell carcinoma, and extranodal NK/T-cell lymphoma, subject to regulatory approval by Australia's Therapeutic Goods Administration. VXA-222 VERAXA Biotech announced the advancement of bispecific ADC (bsADC) program VXA-222, following successful achievement of a key technical milestone in its alliance with OmniAb. The program is moving into its next collaboration phase with OmniAb's discovery work successfully concluded. VXA-222 utilizes an “AND-gate” logic to address two different target antigens present on solid tumors with one molecule. Additional Updates The company appointed Amechi Nwachuku to the newly-created position of Executive Vice President and Chief Operating Officer, primarily responsible for managing the strategy, operations and commercial maximization of xPloration. OmniAb will host an Investor and Analyst Day on October 6, 2026 at its corporate headquarters in Emeryville, CA. The agenda for the day will include presentations by management, panel discussions, and a lab tour for those attending in-person. For additional information and participation details, please visit. Conference Call and Webcast OmniAb management will host a conference call with accompanying slides today beginning at 4:30 p.m. ET (1:30 p.m. PT) to discuss this announcement and answer questions. To participate via telephone, please dial (833) 461-5787 using the conference ID 545137839. Slides, as well as the live and replay webcast, are available here. About OmniAb® OmniAb licenses cutting-edge discovery research technology to pharmaceutical and biotech companies and academic institutions to enable the discovery of next-generation therapeutics. Our technology platform creates and screens diverse antibody repertoires and is designed to quickly identify optimal antibodies and other target-binding proteins for our partners’ drug development efforts. At the heart of the OmniAb platform is what we call Biological Intelligence™, which powers the immune systems of our proprietary, engineered transgenic animals to create optimized antibody candidates for human therapeutics. We believe the OmniAb animals comprise the most diverse host systems available in the industry. These technologies paired with xPloration, our AI-powered high-throughput single B-cell screening platform, are used to identify fully-human antibodies with exceptional performance and developability characteristics. We provide our partners both integrated end-to-end capabilities and highly customizable offerings, which address critical industry challenges and provide optimized discovery solutions. Our business model aligns scientific and economic interests of our partners through structured agreements that generally include upfront/access fees, service revenue, milestones and royalties on commercial sales. For more information, please visit www.omniab.com. Forward-Looking Statements OmniAb cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. Words such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” and similar expressions, are intended to identify forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: statements regarding the value of our portfolio and growth prospects of our business; the ability to add new partners and programs; the ability to efficiently leverage and expand the reach of our technologies; continuation of our innovation efforts and the expected value and performance of our technologies and the opportunities they may create, potential contributions to our business by our xPloration partner access program; scientific presentations and clinical and regulatory events of our partners and the timing thereof and their perspectives on and expectations for their product candidates; and our 2026 financial guidance. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our future operating results and success is dependent on acceptance of our technology platform and technologies by new and existing partners, as well as on the eventual development, approval and commercialization of products developed by our partners for which we have no control over the development plan, regulatory strategy or commercialization efforts; biopharmaceutical development is inherently uncertain; risks arising from changes in technology; the competitive environment in the life sciences and biotechnology platform market; risks associated with quality and timing in manufacturing our xPloration instruments and related consumables and our reliance on a limited number of third-party manufacturers and suppliers; our failure to maintain, protect and defend our intellectual property rights; difficulties with performance of third parties we will rely on for our business; government healthcare reform, legislative measures and regulatory developments in the United States and foreign countries; unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price; the potential impact of tariffs, trade policies, geopolitical instability and conflicts, inflation and interest rate changes; we may not achieve our financial guidance; our operating expenses may be higher than we anticipate, including if we decide to engage in activities not currently in our plan or if we face unexpected, or higher than anticipated, expenses; we may use our capital resources sooner than we expect; and other risks described in our prior press releases and filings with the SEC, including under the heading “Risk Factors” in our annual report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Partner Information The information in this press release regarding partnered products and programs comes from information publicly released by our partners. Note Regarding Use of Non-GAAP Financial Measure This press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and also actual and projected cash costs and operating expenses, which is a non-GAAP financial measure, adjusted to exclude share-based compensation, depreciation and amortization of intangibles. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. However, OmniAb believes the presentation of actual and projected non-GAAP cash costs and operating expenses, when viewed in conjunction with GAAP figures, provides investors with a more meaningful understanding of our operating performance. Cash costs and operating expense is not intended to be considered in isolation or as a substitute for costs and operating expenses. A reconciliation between actual and projected GAAP costs and operating expenses and non-GAAP costs and operating expenses is provided later in this press release. OMNIAB, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands, except share and per share data) June 30, 2026 December 31, 2025 (Unaudited) ASSETS Current assets: Cash and cash equivalents $ 24,336 $ 25,524 Short-term investments 27,659 28,501 Accounts receivable, net 10,328 7,390 Prepaid expenses and other current assets 3,690 3,926 Total current assets 66,013 65,341 Intangible assets, net 116,068 125,149 Goodwill 83,979 83,979 Property and equipment, net 8,475 9,428 Operating lease right-of-use assets 14,461 15,545 Restricted cash 560 560 Other long-term assets 701 912 Total assets $ 290,257 $ 300,914 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 2,088 $ 1,879 Accrued expenses and other current liabilities 4,499 6,291 Current contingent liabilities 940 1,044 Current deferred revenue 2,258 3,161 Current operating lease liabilities 3,973 3,879 Total current liabilities 13,758 16,254 Long-term contingent liabilities 25 315 Deferred income taxes, net 882 785 Long-term operating lease liabilities 14,940 16,455 Long-term deferred revenue 309 — Other long-term liabilities 69 78 Total liabilities 29,983 33,887 Stockholders' equity: Preferred stock, $0.0001 par value; 100,000,000 shares authorized at June 30, 2026 and December 31, 2025; no shares issued and outstanding at June 30, 2026 and December 31, 2025 — — Common stock, $0.0001 par value; 1,000,000,000 shares authorized at June 30, 2026 and December 31, 2025; 145,390,398 and 144,308,383 shares issued and outstanding at June 30, 2026 and December 31, 2025, respectively 15 14 Additional paid-in capital 440,024 433,180 Accumulated other comprehensive income (loss) (20 ) 12 Accumulated deficit (179,745 ) (166,179 ) Total stockholders’ equity 260,274 267,027 Total liabilities and stockholders’ equity $ 290,257 $ 300,914 OMNIAB, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) (in thousands, except per share data) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Revenue: License and milestone revenue $ 9,515 $ 1,242 $ 21,540 $ 3,263 Service revenue 2,473 1,936 4,580 3,839 xPloration revenue 1,161 608 1,215 650 Royalty revenue 266 111 507 299 Total revenue 13,415 3,897 27,842 8,051 Costs and operating expenses: Cost of xPloration revenue 610 262 625 265 Research and development 9,586 10,864 19,226 23,466 General and administrative 6,653 7,684 13,272 15,599 Amortization of intangibles 3,053 3,228 9,081 6,456 Other operating expense (income), net 150 (1,922 ) 104 (2,672 ) Total costs and operating expenses 20,052 20,116 42,308 43,114 Loss from operations (6,637 ) (16,219 ) (14,466 ) (35,063 ) Other income (expense), net: Interest income 434 436 921 973 Other income (expense), net (9 ) 27 68 28 Total other income, net 425 463 989 1,001 Loss before income taxes (6,212 ) (15,756 ) (13,477 ) (34,062 ) Income tax benefit (expense) 353 (119 ) (89 ) (13 ) Net loss $ (5,859 ) $ (15,875 ) $ (13,566 ) $ (34,075 ) Net loss per share, basic and diluted $ (0.05 ) $ (0.15 ) $ (0.11 ) $ (0.32 ) Weighted-average shares outstanding, basic and diluted 128,795 106,148 128,521 105,886 OMNIAB, INC. RECONCILIATION OF GAAP COSTS AND OPERATING EXPENSES TO NON-GAAP CASH COSTS AND OPERATING EXPENSES Three Months Ended June 30, Six Months Ended June 30, (in thousands) 2026 2025 2026 2025 Costs and operating expenses (GAAP) $ 20,052 $ 20,116 $ 42,308 $ 43,114 Less: Depreciation of property and equipment 577 864 1,183 1,830 Less: Amortization of intangible assets 3,053 3,228 9,081 6,456 Less: Share-based compensation 3,159 4,111 6,499 8,255 Cash costs and operating expenses (Non-GAAP) $ 13,263 $ 11,913 $ 25,545 $ 26,573 (in millions) 2026 Forecast Costs and operating expenses (GAAP) $84 to $88 Less: Depreciation and amortization 18 Less: Share-based compensation 15 Cash costs and operating expenses (Non-GAAP) $51 to $55 OmniAb, Inc. investors@OmniAb.com X@OmniAbTech Alliance Advisors IR Vivian Cervantes vcervantes@allianceadvisors.com (973) 873-7724

氨基观察-创新药组原创出品 作者 | 沙晓威 被视为继CLDN18.2后消化道肿瘤最大希望的CDH17，迎来了首份临床成绩单。 2026 ESMO-GI大会上，首款CDH17 ADC药物AMT-676治疗结直肠癌患者的I期临床数据公布，在可评估的晚期结直肠癌125名患者中，AMT-676所有剂量（1.6-10.0mg/kg）治疗组的ORR为18%，高剂量组（≥7.2mg/kg）为21%。 相较于标准化疗，AMT-676的疗效提升显著。但与其他ADC进行非头对头比较，如cMet、EpCAM ADC，AMT-676的治疗效果并不突出甚至不及前者。 更令人的担忧的是AMT-676的毒性。临床中有1例患者出现结肠炎，尽管发生在8mg/kg高剂量组中，但这一风险与CDH17在正常消化道组织中承担的屏障功能相关，也为整个CDH17 ADC赛道敲响了潜在毒性的警钟。 当然，这只是CDH17 ADC的临床数据首秀，虽然为火热的赛道浇下一盆冷水，但并不能彻底否定靶点的价值，也不能代表所有CDH17药物的研发前景。目前围绕该靶点的研发管线多达几十款，覆盖ADC、CAR-T、TCE等不同技术路线，其中十余款已经进入临床阶段。 随着更多的管线公布临床数据，惊喜可能会不断出现。 / 01 / 靶点火热，首秀平淡 过去两年，CDH17是全球创新药领域最受关注的新兴靶点之一。 CDH17是一种细胞间黏附分子，主要在胃肠道上皮细胞中发挥细胞间黏附作用。而在胃癌、结直肠癌和胰腺癌中，CDH17表达上调明显。 尤其是在结直肠癌患者中，CDH17的表达率更是接近100%。当前的结直肠癌领域，现有治疗方案虽然不断被HER2、RAS等靶向药丰富，但对低表达或晚线患者来说，治疗选择依然有限，传统化疗的疗效也存在明显天花板。因此，CDH17被认为是结直肠癌治疗的又一突破口。 该靶点更大的成药潜力，来自正常组织与肿瘤组织的表达位置差异。正常情况下，CDH17位于细胞紧密连接处，不会暴露于细胞表面。而在肿瘤细胞中，由于细胞极性丧失，CDH17发生重新分布暴露于细胞表面。这样的状态尤其适配ADC药物的设计思路。 短短两年，全球已有30余款CDH17 ADC管线布局，超10款进入临床，GSK、罗氏等跨国药企也相继通过BD入局。CDH17由此成为继CLDN18.2之后最拥挤的ADC赛道。 在这一背景下，CDH17 ADC的第一份人体临床数据也备受关注。 AMT-676是普众生物自主研发的CDH17 ADC，也是全球首个进入临床Ⅱ期阶段的CDH17 ADC。此次公布的临床数据是全球多中心、规模较大的I期临床，共有125名患者参与，具有相当的参考价值。 遗憾的是，这份首秀成绩单并不出彩。 在125例可评估的晚期结直肠癌患者中，AMT-676所有剂量组ORR为18%，高剂量组为21%。当前临床上标准治疗（化疗组）的ORR仅为3%，FTD-TPI联合贝伐珠单抗的ORR也仅为6%。单看这一数据，AMT-676已经展现出明确的抗肿瘤活性。 但如果放到整个结直肠癌ADC赛道进行横向比较，AMT-676的疗效并不突出。CEACAM5、cMET、EpCAM均是当前结直肠癌ADC赛道的热门靶点，各自代表性药物均已公布Ⅰ期临床数据，疗效与AMT-676相比也不逊色。 比如，Cytomx的EpCAM ADC管线Versetatug masetecan在56名可评估疗效的晚期结直肠癌患者中，接受每三周一次8.6 mg/kg剂量组治疗后的确认ORR为20%，10mg/kg剂量组为32%。两组的中位无进展生存期分别为6.8和7.1个月。 艾伯维的MET ADC Temab-A在122名可评估患者中，整体ORR为15.6%，其中3mg/kg剂量组为24.4%，中位PFS为4.6个月。默沙东的CEACAM5 ADC药物M9140在60例患者，2.8mg/kg/组的ORR为31%，2.4mg/kg组的ORR为12.9%。 当然，上述数据来自不同临床试验，患者来源、剂量设计等均存在差异，不能进行头对头比较，但至少可以说明，AMT-676的疗效并未跑出差异化优势。 / 02 / 双重安全性风险 相比不够亮眼的疗效，CDH17 ADC暴露的安全性问题更值得行业关注。 AMT-676临床数据显示，3级以上TRAEs发生率为72%，在8 mg/kg和12 mg/kg剂量队列中各发生1例剂量限制性毒性（DLT），分别为3级结肠炎和发热性中性粒细胞减少症。 其中，3级结肠炎事件发生在8 mg/kg剂量组，提示该药存在疗效依赖剂量爬坡、治疗窗口偏窄的风险。 尽管公司并没有披露结肠炎病例的详细信息，但这类不良反应在cMet、EpCAM ADC治疗中未出现过。而根据现有的文献资料提示，这可能与CDH17自身的生物学特征存在联系。 市场看好CDH17，很大程度上是因为它在肿瘤组织中的高表达，以及与正常组织之间表达位置的差异。但不可忽略的是，CDH17在正常组织中依然广泛表达，其功能就是介导肠道上皮细胞间的黏附，维护肠道屏障。 研究表明，缺乏CDH17的动物模型肠道通透性显著增加，使得肠道内的细菌和毒素更容易侵入黏膜下层，从而导致机体对化学诱导性结肠炎敏感。因此，当ADC通过CDH17识别肿瘤细胞时，非特异性结合到正常组织细胞上，就可能会触发炎症反应。 此外，当前的研究对CDH17的整体机制尚未完全阐明，其是否与肿瘤细胞表面的其他分子相互作用，进而产生毒性也尚未可知。 另一重安全性风险则指向AMT-676药物本身。研究中发现其中一名结直肠癌患者在单次给予1000 mg剂量（相当于10 mg/kg）后，发生与治疗相关的5级事件（中性粒细胞减少性脓毒症）。 中性粒细胞减少是ADC药物常出现的血液学毒性反应，高级别脓毒症则常出现在高载荷量ADC药物中。上述提到的CEACAM5 ADC药物M9140同样在治疗结直肠癌患者时出现了1例5级中性粒细胞减少性脓毒症。M9140的载荷为exatecan，DAR=8，属于高载荷量ADC药物。 而AMT-676的DAR=4，载荷量相对较低。这提示AMT-676或许存在脱靶效应，使得药物被健康造血干细胞非特异性摄取。 整体来看，无论是安全性还是疗效，AMT-676与市场的期望都存在一定差距。 / 03 / 下一个能否破局？ 当然，一项临床数据不足以给整个赛道下结论。 CDH17高表达占比近100%的结肠癌领域，仍存在巨大的未满足临床需求与市场空间，值得持续探索。根据新药情报库统计，目前共有50余项CDH17相关的药物，其中仅CDH17 ADC就有超10款已经进入临床阶段，中国药企是研发主力军。 各管线正在依托自身的ADC技术平台，探索差异化优势。 比如映恩生物与GSK合作开发的DB-1324采用DAR 8的载荷量，提高药物的杀伤性；迈威生物的7MW4911则选用DAR 4的载荷量，配合专用DNA拓扑异构酶I抑制剂MF-6，旨在通过血浆稳定性、可控的药物释放及旁观者效应来提高疗效。 诺诚健华的ICP-B208也是基于自身专有的ADC技术平台开发，采用独特的亲水性连接子及高活性载荷，临床前研究显示该药在CDH17低表达人群中同样具有优异的抗肿瘤活性。 除此之外，还有双靶点策略。比如针对CDH17与CLDN18.2就是通过同时锁定两个消化道肿瘤靶点促进受体介导的内吞，同时实现更广谱的抗肿瘤效果。2026年7月10日，橙帆医药的CDH17/CLDN18.2双抗ADC药物VBC108临床试验申请获得受理，即将成为全球首个进入临床阶段的CDH17/CLDN18.2双抗ADC。 而CDH17的潜力，也不仅限于ADC。目前，TCE、CAR-T等不同技术路线同样在探索这一靶点。 CDH17×CD3双特异性抗体通过招募T细胞直接杀伤CDH17阳性肿瘤细胞，理论上可以绕开ADC对于毒素载荷和内吞效率的部分限制。ARB202就是一款CDH17×CD3 TCE，早期临床显示，该分子能特异性杀伤靶肿瘤细胞，同时不损伤正常、CDH17阴性的组织，安全性良好。 CAR-T则进一步利用细胞治疗的优势实现更强的持续性杀伤。临床前研究表明，CHM 2101只浸润肿瘤细胞，对正常细胞没有损伤。 当然，这些药物当前均处于早期临床阶段，安全性、有效性仍有待进一步验证。 / 04 / 总结 从CDH17靶点被挖掘出肿瘤治疗价值至今两年多的时间，这条赛道上已经涌现了众多玩家，从ADC到TCE、CAR-T，几乎所有主流技术路径都在该靶点上寻求突破。 围绕这一靶点的交易同样火热，罗氏与翰森制药、Arrivent与乐普生物之间的ADC交易均超过10亿美元。市场都在期待下一个CLDN18.2的诞生，赛道热度也丝毫不低于当年的TIGIT。 不可否认，CD H17的首份临床数据，并不出彩。但这只是开始， CDH17靶点在消化道肿瘤的故事还远没有讲完。