Prostate specific membrane antigen tumour activated T-cell engager therapy (Janux Therapeutics/Merck & Co)

Continued clinical execution across TRACTr programs JANX007 and JANX008 JANX007 enrolling in Phase 1b Taxane-naïve patient population in metastatic castration-resistant prostate cancer (mCRPC) JANX008 enrolling expansion cohorts in defined tumor settings Initiated Phase 1 study of JANX011 in healthy volunteers Entered collaboration and exclusive worldwide license agreement with Bristol Myers Squibb to develop a novel tumor-activated therapeutic for solid tumors Appointment of William Go, M.D., Ph.D., as Chief Medical Officer Strong year-end cash position supporting continued pipeline execution JANX007 enrolling in Phase 1b Taxane-naïve patient population in metastatic castration-resistant prostate cancer (mCRPC) JANX008 enrolling expansion cohorts in defined tumor settings SAN DIEGO--(BUSINESS WIRE)-- Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage biopharmaceutical company developing a broad pipeline of novel immunotherapies, today reported financial results for the fourth quarter and full year ended December 31, 2025, and provided a business update. “The past year marked a period of significant execution and progress for Janux as we continued to translate the promise of our tumor-activated platform into meaningful clinical and strategic advances. Recent JANX007 clinical results demonstrate clinical activity and a consistent and predictable safety profile in mCRPC and support continued advancement in taxane-naïve patients as well as other expansion cohorts,” said David Campbell, Ph.D., President and CEO of Janux. “In early 2026, we announced a collaboration with Bristol Myers Squibb that provides near-term capital and further validates the potential of our platform. We also continue to strengthen our team to support the next phase of clinical and pipeline growth. With additional product candidates entering the clinic in 2026, we believe Janux is well positioned to execute on our clinical strategy and continue to build long-term value for patients and shareholders.” BUSINESS HIGHLIGHTS AND RECENT DEVELOPMENTS: Clinical & Pipeline Progress Janux presented updated interim Phase 1 data for JANX007 (PSMA-TRACTr) in December 2025. As of the October 15, 2025 data cutoff, 109 patients had been treated across Phase 1 cohorts:Durable clinical activity was observed across both once-weekly (QW) and every-two-week (Q2W) cohorts, with median radiographic progression-free survival (rPFS) ranging from 7.9 to 8.9 months. The rPFS in the Q2W cohort compared favorably to the QW expansion group. Data demonstrated high prostate-specific antigen (PSA) response rates including deep PSA declines. Anti-tumor activity was observed, with confirmed and unconfirmed partial responses in 30% (8/27) of RECIST-evaluable patients. Ongoing dose optimization of JANX007 monotherapy is focused on taxane-naïve mCRPC.The Phase 1 study also includes expansion cohorts evaluating JANX007 in combination with darolutamide, an androgen receptor pathway inhibitor, to further characterize safety and clinical activity in taxane-naïve mCRPC. Additional expansion cohorts are evaluating JANX007 monotherapy in patients with PARP inhibitor-refractory mCRPC, supporting assessment of activity in a high-unmet-need population. JANX008 (EGFR-TRACTr) continues to enroll in its Phase 1 clinical trial in a defined group of solid tumors, with expansion cohorts underway to further characterize safety and clinical activity. JANX011 (CD19-ARM) is actively enrolling its Phase 1 clinical trial in healthy volunteers. Durable clinical activity was observed across both once-weekly (QW) and every-two-week (Q2W) cohorts, with median radiographic progression-free survival (rPFS) ranging from 7.9 to 8.9 months. The rPFS in the Q2W cohort compared favorably to the QW expansion group. Data demonstrated high prostate-specific antigen (PSA) response rates including deep PSA declines. Anti-tumor activity was observed, with confirmed and unconfirmed partial responses in 30% (8/27) of RECIST-evaluable patients. The Phase 1 study also includes expansion cohorts evaluating JANX007 in combination with darolutamide, an androgen receptor pathway inhibitor, to further characterize safety and clinical activity in taxane-naïve mCRPC. Additional expansion cohorts are evaluating JANX007 monotherapy in patients with PARP inhibitor-refractory mCRPC, supporting assessment of activity in a high-unmet-need population. Strategic Collaboration In January 2026, Janux announced a collaboration and exclusive worldwide license agreement with Bristol Myers Squibb to develop a novel tumor-activated therapeutic targeting a validated solid tumor antigen.Under the terms of the agreement, Janux is eligible to receive $50 million in upfront and near-term milestone payments, with the potential for additional development, regulatory and commercial milestones totaling approximately $800 million, as well as tiered royalties on global product sales, if successful. Janux will lead preclinical development through IND submission, with Bristol Myers Squibb assuming responsibility for subsequent clinical development and global commercialization. Under the terms of the agreement, Janux is eligible to receive $50 million in upfront and near-term milestone payments, with the potential for additional development, regulatory and commercial milestones totaling approximately $800 million, as well as tiered royalties on global product sales, if successful. Janux will lead preclinical development through IND submission, with Bristol Myers Squibb assuming responsibility for subsequent clinical development and global commercialization. Corporate & Leadership Janux recently announced the appointment of William Go, M.D., Ph.D. as Chief Medical Officer, strengthening the Company’s clinical leadership as additional programs enter the clinic in 2026 and progress toward later-stage development. Upcoming Milestones The Company expects to provide additional clinical data for JANX007 in 2026 or present these data at a future medical meeting. The Company expects to provide an additional clinical update for JANX008 in 2026. The Company expects to announce an initial clinical update from the Phase 1 study of JANX011 in healthy volunteers by year-end 2026. FOURTH QUARTER AND FULL YEAR 2025 FINANCIAL RESULTS: Cash and cash equivalents and short-term investments: As of December 31, 2025, Janux reported cash and cash equivalents and short-term investments of $966.6 million, compared to $1.03 billion on December 31, 2024. Research and development expenses: Research and development expenses were $31.5 million for the quarter and $125.9 million for the year ended December 31, 2025, compared to $20.8 million and $68.4 million for the same quarter and year in 2024. General and administrative expenses: General and administrative expenses were $10.9 million for the quarter and $41.8 million for the year ended December 31, 2025, compared to $8.2 million and $41.0 million for the same quarter and year in 2024. Net loss: Net loss was $31.9 million for the quarter and $113.6 million for the year ended December 31, 2025, compared to $20.2 million and $69.0 million for the same quarter and year in 2024. About Janux Therapeutics Janux is a clinical-stage biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr), Tumor Activated Immunomodulator (TRACIr), and Adaptive Immune Response Modulator (ARM) platforms. Janux’s first clinical candidate, JANX007, is a TRACTr that targets prostate-specific membrane antigen (PSMA) and is being investigated in a Phase 1 clinical trial in adult patients with mCRPC. Janux’s second clinical candidate, JANX008, is a TRACTr that targets epidermal growth factor receptor (EGFR) and is being studied in a Phase 1 clinical trial for the treatment of multiple solid tumors. Janux is also advancing its first ARM platform clinical candidate, JANX011, a CD19-ARM for the potential treatment of autoimmune diseases in a Phase 1 study in healthy adult volunteers. Janux continues to generate a number of additional TRACTr, TRACIr, and ARM programs for potential future development. For more information, please visit www.januxrx.com and follow us on LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, Janux’s ability to bring new treatments to cancer patients in need, expectations regarding the timing, scope and results of Janux’s development activities, including its ongoing and planned preclinical studies and clinical trials, and the potential benefits of Janux’s product candidates and platform technologies, expectations regarding the use of Janux’s platform technologies to generate novel product candidates and the strength of Janux’s balance sheet and the adequacy of cash on hand. Factors that may cause actual results to differ materially include the risk that interim results of a clinical trial are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data and as more patient data becomes available, including the risk that unconfirmed responses may not ultimately result in confirmed responses to treatment after follow-up evaluations, the risk that compounds that appear promising in early research do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Janux may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings and applications, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties Janux faces, please refer to Janux’s periodic and other filings with the Securities and Exchange Commission, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Janux assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. 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. Janux Therapeutics, Inc. Condensed Balance Sheets (in thousands) December 31, 2025 December 31, 2024 Assets Current assets: Cash and cash equivalents $ 52,334 $ 430,605 Short-term investments 914,233 594,568 Prepaid expenses and other current assets 9,320 8,493 Total current assets 975,887 1,033,666 Restricted cash 816 816 Property and equipment, net 3,852 4,864 Operating lease right-of-use assets 18,402 19,286 Other long-term assets 2,608 2,884 Total assets $ 1,001,565 $ 1,061,516 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 4,971 $ 4,026 Accrued expenses 17,633 11,684 Current portion of operating lease liabilities 2,393 1,749 Total current liabilities 24,997 17,459 Operating lease liabilities, net of current portion 19,746 21,276 Total liabilities 44,743 38,735 Total stockholders’ equity 956,822 1,022,781 Total liabilities and stockholders’ equity $ 1,001,565 $ 1,061,516 Janux Therapeutics, Inc. Condensed Statements of Operations and Comprehensive Loss (in thousands, except share and per share data) Three Months Ended December 31, Year Ended December 31, 2025 2024 2025 2024 Collaboration revenue $ — $ — $ 10,000 $ 10,588 Operating expenses: Research and development 31,548 20,806 125,896 68,388 General and administrative 10,853 8,216 41,771 41,047 Total operating expenses 42,401 29,022 167,667 109,435 Loss from operations (42,401 ) (29,022 ) (157,667 ) (98,847 ) Total other income — 8,806 — 29,853 Net loss $ (42,401 ) $ (20,216 ) $ (157,667 ) $ (68,994 ) Other comprehensive gain (loss): Unrealized gain (loss) on available-for-sale securities, net 10,455 (5,668 ) 44,042 1,498 Comprehensive loss $ (31,946 ) $ (25,884 ) $ (113,625 ) $ (67,496 ) Net loss per common share, basic and diluted $ (0.51 ) $ (0.36 ) $ (1.83 ) $ (1.28 ) Weighted-average shares of common stock outstanding, basic and diluted 62,145,668 56,832,374 61,966,999 53,751,480 Investors: Chad Rubin Endurance Advisors crubin@enduranceadvisors.com 646.319.3261 Media: Jessica Yingling, Ph.D. Little Dog Communications Inc. jessica@litldog.com 858.344.8091

本文为节选内容，更多报告请关注公众号：微之火一、TCE 已在 SCLC、mCRPC 中读出成熟的临床数据，并显示出前线治疗的充分潜力（一）SCLC：DLL3 TCE成为后线基石疗法，与PD-(L)1/ADC联用有望进一步扩展适用空间DLL3 是神经内分泌肿瘤治疗的潜力靶点，肿瘤组织内表达特异性强。小细胞肺癌（（SCLC）是肺癌中侵袭性极强的异源性神经内分泌肿瘤，根据 Rudin CM（（2021）的研究显示，SCLC 约占所有肺癌病例的 13%-17%，SCLC 患者预后较差，广泛期非小细胞肺癌（ES-SCLC）确诊后的中位生存期仅为 6-12 月。根据《中华肿瘤杂志》的统计数据显示，中国新发 ES-SCLC 患者约每年 11 万人；根据 Mount Sinai 统计数据显示，美国 SCLC 年新发患者约 3-3.5 万人。DLL3 是一种 Notch信号通路的抑制性配体，它通过阻止 Notch 受体在细胞表面的呈现来抑制 Notch信号，从而促进肿瘤生长、增殖和转移，并抑制肿瘤微环境中的免疫反应。在神经内分泌肿瘤细胞表面异常高表达（尤其在小细胞肺癌中超 80%），而在正常组织中表达极低。DLL3 TCE 填补 SCLC 后线治疗的空白。当前 SCLC 治疗一线治疗以免疫治疗联合铂类化疗为主，而标准二线疗法主要仍为化疗，例如拓扑替康、芦比替尼、紫杉醇等等，缺乏有效的靶向疗法，如今靶向 DLL3 的双特异性 T 细胞接合器、ADC、双/三抗等药物研发有望填补 SCLC 在靶向治疗上的空缺，为 SCLC 治疗开辟了全新路径。针对 DLL3 靶点的疗法主要包括多抗、ADC 与细胞治疗。DLL3 靶向疗法中多抗为代表的药物包括安进的 CD3/DLL3 双抗塔拉妥单抗，该疗法针对 2 线与 3 线的SCLC 患者临床试验的疗效突出，已获批上市，并在 2025WCLC 中在 1 线化疗免疫联合治疗后联用 PD-L1 抑制剂维持治疗的 DeLLphi-塔拉妥单抗外，泽璟制药 ZG006 目前已推进至 III 期临床阶段，BI/中国生物制药的 obrixtamig、恒瑞医药的 SHR-7787、第一三共/默沙东合作的 Gocatamig 已进入 II 期临床阶段。ADC 疗法方面，再鼎医药的 zocilurtatug pelitecan、恒瑞医药/IDEAYA 的 SHR-7787 目前研发进度领先。（二）mCRPC：PSMA、STEAP1、KLK2 等靶点均验证抗肿瘤潜力，TCE 有望成为 mCRCP 的基石疗法PSMA：mCRPC 经典靶点，临床适用场景有望推进至 Pluvicto 前线PSMA 表达特异性强，已成为 mCRPC 诊疗的关键靶点。PSMA（（前列腺特异性膜抗原）是一种由 750 个氨基酸组成的 II 型跨膜糖蛋白，包含胞内区、跨膜区和胞外区三个结构域。在良性前列腺细胞中，PSMA 主要分布于细胞质和腺体顶端面；恶性转化后，其定位转移至前列腺导管腔面，胞外区暴露并形成配体结合位点。前列腺腺癌中 PSMA 表达水平较良性组织升高 100–1000 倍，且随肿瘤去分化及转移性 CRPC 的进展进一步增加，因此 PSMA 成为诊疗一体化的理想靶点。PSMA 胞外区含多个结合位点，可与放射性配体结合用于影像或放射性配体治疗（RLT）；同时，PSMA 抑制剂通过叶酸结合位点或锌结合位点，抑制其酶功能并干预肿瘤生长，从而展现出在前列腺癌诊断与治疗中的重要价值。PSMA 在前列腺之外，主要表达的器官为唾液腺，因此，唾液腺成为了 PSMA 靶向疗法主要的剂量限制器官，以 JANX007 Ia 期数据为例，33%的患者（1%为 3 级及以上）出现口干的 TRAE，这一靶点相关不良反应可能会成为相关疗法开发上值得注意的问题。Pluvicto 突破 mCRPC 后线治疗，当前已在 2 线治疗中展现获益。在晚期 mCRPC领域，传统治疗选择有限，一线主要依靠化疗（如多西他赛）或内分泌治疗（ARPI，如阿比特龙、恩杂鲁胺），而后线方案相对稀少，包括免疫检查点抑制剂（如帕博利珠单抗）或 PARP 抑制剂（如奥拉帕利），患者在 1 线及 2 线治疗失败后往往缺乏有效选择。近年来，PSMA 靶向放射性配体治疗代表药物 Pluvicto 的出现，为 mCRPC 治疗开辟了新路径。Pluvicto 通过衰变产生的β射线精准照射 PSMA阳性肿瘤细胞，引发 DNA 损伤并实现肿瘤杀伤，实现了“精准+放疗+系统治疗”的三位一体模式。Pluvicto 已在 III 期试验中验证出在 2 线 mCRPC 治疗中明确的生存获益，PSMAfore 试验在 1 线 ARPI 进展且未接受过紫杉醇治疗的 mCRPC患者中，相比更换 ARPI 的亚组，mPFS 为 11.6 个月（HR=0.49），mOS 约 23.7个月，ORR 50%，PSA 反应率 51%。除 RLT 外，PSMA 靶向药物还包括 ADC、TCE、双抗、CAR-T 等，大部分适应症为后线 mCRPC 治疗。STEAP1：Xaluritamig 已推进至 III 期临床，CD28 三抗 TCE 布局丰富STEAP1 靶点在前列腺癌、膀胱癌等癌症中具有促进癌细胞增殖转移的作用。STEAP1（（Six Transmembrane Epithelial Antigen of the Prostate）表达在许多组织表面的细胞与细胞的连接处，尤其是在前列腺分泌上皮细胞的表达水平较高。STEAP1 主要功能是调控细胞氧化还原平衡，并调节促炎性细胞因子相关通路，在前列腺癌、膀胱癌等癌症中，STEAP1 显著高表达，能促进癌细胞的增殖和转移。在 mCRPC 中，STEAP1 基因启动子的低甲基化和性激素（如 DHT）的调控失衡共同导致了 STEAP1 蛋白的过度表达，高表达的 STEAP1 进而通过促进细胞增殖、抑制细胞凋亡、以及介导肿瘤细胞与基质细胞的通讯等方式，驱动mCRPC 的进展。KLK2：Pasritamig 推进至 III 期，岸迈生物 EM1031 实现对外授权KLK2 表达受雄激素调控，在前列腺癌进展中具有关键作用。KLK2（Human kallikrein 2）是一种具有胰蛋白酶样活性的丝氨酸蛋白酶，主要在前列腺中表达，其在精浆中的浓度约为 PSA 的 1%。KLK2 作为激肽释放酶家族成员，在前列腺中与 PSA 协同发挥作用，能特异性切割 proPSA 的 N 端肽链，激活其功能，是PSA 生物活性的关键调节因子。其基因表达受雄激素调控，启动子区域的雄激素反应元件（ARE）使其表达水平与雄激素受体（AR）活性密切相关，体现出典型的激素依赖性表达模式。KLK2 还能促进血管生成和肿瘤微环境重塑，增强肿瘤侵袭性，尤其在前列腺癌进展中发挥重要作用。二、TCE 在卵巢癌、消化系统肿瘤、肝细胞癌中已初步展现应用潜力，泛癌肿靶点有望实现突破（一）卵巢癌：两款 MUC16 TCE 读出初步临床数据MUC16 是卵巢癌的特异性抗原，在肿瘤进展中扮演重要作用。MUC16 是一种跨膜型粘蛋白，是膜结合型粘蛋白家族中的已知最大分子。它的结构主要包括高度糖基化的 N 端结构域、大量串联重复序列、跨膜区以及一个较短的胞质尾部。MUC16 在超过 80%的卵巢癌组织中高表达，而在正常卵巢组织中表达水平极低或不可检测。MUC16 的跨膜结构及不同结构域能够协同介导多条信号通路，从而在肿瘤发生发展中发挥多方面功能，MUC16 可通过激活 PI3K/AKT 信号通路等方式促进癌细胞黏附、生长和转移，从而推动肿瘤进展。（二）消化系统肿瘤：CLDN18.2 TCE 管线进入 III 期临床，MUC17 靶点处于早期探索阶段CLDN18.2：国内企业 TCE 研发进度领先，有望满足后线胰腺癌、胃癌未满足的临床需求CLDN18.2 在胃癌等肿瘤中参与肿瘤的侵袭与增殖。CLDN18.2 是 Claudin 家族的成员之一，主要通过调控上皮细胞膜的选择性通透性维持组织屏障功能。在胃癌发生发展过程中，CLDN18.2 的表达和定位发生显著异常：约 20-30%的病例存在表达下调或缺失，并促进癌细胞的侵袭和增殖。正常情况下定位于紧密连接的CLDN18.2，在细胞极性丧失后暴露于细胞膜表面，成为可及的免疫和药物靶点；此外，CLDN18-ARHGAP 融合基因（如 CLDN18–ARHGAP26）在弥漫型和年轻患者胃癌中较常见，可推动恶性转化。这些异常不仅参与胃癌的发生发展，也凸显了 CLDN18.2 作为消化道肿瘤特异性治疗靶点的价值。（三）肝细胞癌：Sanofi GPC3/TCR 纳米抗体初步读出数据GPC3 靶向疗法有望弥补肝癌 2 线治疗的空白。当前肝细胞癌（（HCC）治疗已进入“手术+系统治疗+局部治疗”多模式时代，肝癌 1 线治疗主要为靶向+免疫联合方案，而此前获批的 2 线药物（（如瑞戈非尼、卡博替尼和雷莫芦单抗等单药治疗），在 1 线已采用靶向加免疫治疗的前提下，无论单药使用还是联合免疫检查点抑制剂，有效率均较低，难以满足临床需求。GPC3（（脂酰肌醇醇蛋白糖糖 3）是一种细胞膜锚定糖蛋白，在 HCC 中特异性高表达，GPC3 参与 HCC 的进展，通过Wnt、Hippo/YAP 等信号通路发挥促癌作用，该靶点是 HCC 诊断的临床生物标志物，也是肿瘤靶向疗法的有效靶标。当前针对 GPC3 靶点，已有多种药物形式进入临床研究阶段，包括 TCE、ADC、肿瘤疫苗、CAR-T、靶向肽等，是当前肝细胞癌靶向疗法的重点领域。返回搜狐，查看更多