Endometrial Endometrioid Adenocarcinoma

该研究表明EXOSC5增加NTN4的表达，通过整合素β1/FAK/SRC途径激活c-MYC，为EC的诊断和治疗提供了潜在的途径。 子宫内膜癌(Endometrial carcinoma, EC)起源于子宫内膜的细胞层，是欧洲和北美女性生殖系统最常见的癌症。ECs分为两种临床病理类型:雌激素依赖型子宫内膜样腺癌(I型)和雌激素依赖型子宫浆液性癌和透明细胞癌(II型)。大多数EC病例(80%)属于I型。早期(I期或II期)EC患者预后普遍良好，但晚期(III期或IV期)或复发EC预后较差，5年总生存率约为15%。因此，发现新的致病基因，用于早期检测和作为治疗靶点是必要的。 图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38164180/ 近日，来自中国台湾阳明交通大学的研究者们在Int. J. Biol. Sci.杂志上发表了题为“EXOSC5 maintains cancer stem cell activity in endometrial cancer by regulating the NTN4/integrin β1 signalling axis”的文章，该研究表明EXOSC5增加NTN4的表达，通过整合素β1/FAK/SRC途径激活c-MYC，为EC的诊断和治疗提供了潜在的途径。 子宫内膜癌(EC)是一种常见类型的子宫癌，起源于子宫上皮。肿瘤干细胞(Cancer stem cells, CSCs)是一类具有高致瘤性的肿瘤细胞亚群，在肿瘤的恶性过程中起着至关重要的作用。靶向与csc相关的分子对于有效的癌症治疗至关重要。 本研究探讨了外泌体组分5 (EXOSC5)在EC中的作用。来自癌症基因组图谱的数据表明高EXOSC5 mRNA表达与EC不良预后相关。EXOSC5敲低会减少EC-CSC自我更新，并降低关键癌症干细胞蛋白(包括c-MYC和SOX2)的表达。有趣的是，这种基因敲除显著降低了EC肿瘤球的致瘤性和CSC频率。机制检查显示，在exosc5缺失的EC细胞中，netrin4 (NTN4)水平降低。此外，NTN4处理增强了EC细胞的CSC活性，当NTN4分泌时，它与整合素β1结合，随后触发FAK/SRC轴以提高c-MYC活性。EXOSC5与NTN4在93个EC组织中呈明显正相关。 EXOSC5在ECs中的预后潜力 图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38164180/ 综上所述，目前的研究明确强调了EXOSC5在EC复杂进展中的关键作用。EXOSC5表达升高与组织学分级升高和患者不良预后之间存在显著关联。有趣的是，本研究暗示在EXOSC5的下游被调节的NTN4可能是EC-CSC维持中不可或缺的调节因子。在机制上，研究者发现NTN4的分泌在与整合素β1结合后，激活FAK/SRC/β-catenin信号级联，从而放大MYC通路。这些发现支持了EXOSC5和NTN4作为EC预后诊断靶点的潜力。（生物谷 Bioon.com） 参考文献 Yu-Hao Huang et al. EXOSC5 maintains cancer stem cell activity in endometrial cancer by regulating the NTN4/integrin β1 signalling axis. Int J Biol Sci. 2024 Jan 1;20(1):265-279. doi: 10.7150/ijbs.86275.

Subgroup experienced efficacy and safety consistent with overall study population Advanced malignant PEComa tumors of gynecologic origin accounted for more than half of the evaluable patients enrolled in AMPECT Additional data presented highlight nab-sirolimus as potential approach for mTOR-driven gynecologic cancers LOS ANGELES, March 17, 2024 /PRNewswire/ -- Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage precision oncology company focused on developing and commercializing therapies for cancers with alterations in the mTOR pathway, today announced patients in the AMPECT trial whose malignant perivascular epithelioid cell tumor (PEComa) had gynecologic origins experienced efficacy and safety consistent with the overall study population. The AMPECT trial formed the basis for the FDA approval of the company's nab-sirolimus, FYARRO®, for advanced malignant PEComa regardless of mutational status. This new subgroup analysis will be presented during an oral plenary at the Society of Gynecologic Oncology (SGO) Annual Meeting in San Diego, CA on March 17, 2024. "In AMPECT, advanced malignant PEComa tumors originating from uterine, ovarian, pelvic or retroperitoneal sites had a response to nab-sirolimus consistent with that of the full study population, including overall response rate, onset and duration of tumor response," said Thomas J. Herzog, MD, Deputy Director, University of Cincinnati Cancer Center. "Malignant PEComa tumors of gynecologic or retroperitoneal origin accounted for more than half of the evaluable patients enrolled, offering important insights into this population and reinforcing the need for awareness and understanding of this rare but aggressive cancer among the gynecologic oncologist community." Oral plenary presentation details and study highlights include: Title: "Response to Treatment with nab-Sirolimus in Patients with Perivascular Epithelioid Cell Sarcoma (PEComa) of Gynecologic or Retroperitoneal Origin: Subgroup Analysis from AMPECT" Presenting Author: Thomas J. Herzog, MD Session Title: Focused Plenary V: Rare Care: Updates in Uncommon Cancers Location: Ballroom 20CD Date/Time: Sunday, March 17, 2024 – 1:45 PM to 2:45 PM Of the 31 patients enrolled in AMPECT, 16 had malignant PEComas originating from uterine, ovarian, pelvic or retroperitoneal sites Overall response rate to nab-sirolimus for the subgroup was 37.5% (6/16), consistent with the overall AMPECT population Subgroup responses were rapid and durable, with 1.4 months median time to response and 36.2 months median duration of response Safety profile of the subgroup was manageable and consistent with the overall AMPECT population Additional data presented at SGO further highlight nab-sirolimus as a potential approach for mTOR-driven gynecologic cancers. These presentations include a real-world study characterizing TSC1 and TSC2 inactivating alterations in patients with advanced gynecologic cancers; trial-in-progress updates for the ongoing, tumor agnostic, registration-intended PRECISION1 trial; and a Phase 2 study of nab-sirolimus in combination with letrozole for advanced or recurrent endometrioid-type endometrial cancer (EEC). "Overactivation of the mTOR pathway has been implicated in gynecological cancers," said Loretta Itri, MD, Chief Medical Officer at Aadi. "nab-Sirolimus is a nanoparticle albumin-bound (nab) mTOR inhibitor under investigation in TSC1- and TSC2-mutated tumors as well as other mTOR-driven tumors. We are diligently continuing to explore the potential of nab-sirolimus for this patient community in need of new therapies." Poster presentation details and highlights include: Title: "Analysis of inactivating TSC1 and TSC2 alterations in a real-world patient population with advanced gynecological cancers in the Foundation Medicine genomic database" Presenting Author: Lauren E. Dockery, MD, MS Session Title: Poster Session 1 Location: Exhibit Hall (Hall GH) Poster Number: 1176 Date/Time: Sunday, March 17, 2024 – 1:15 PM to 2:45 PM Registration-directed PRECISION1 study is enrolling patients with solid tumors harboring TSC1 and/or TSC2 inactivating alterations In a large real-world database of patients with advanced cancer, 1,342 (2.4%) of the 54,911 patients with gynecological cancers harbored at least one inactivating alteration in TSC1 or TSC2 TSC1 and/or TSC2 inactivating alterations were present in 3.6% of endometrial cancers, 2.0% of ovarian cancers and 1.5% of cervical cancers Title: "nab-Sirolimus Plus Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer: A Phase 2, Open-Label, Single-Arm, Prospective, Multi-Center Study" Presenting Author: Lauren E. Dockery, MD, MS Session Title: Poster Session 2 Location: Exhibit Hall (Hall GH) Poster Number: 2127 Date/Time: Monday, March 18, 2024 – 11:45 AM to 12:45 PM This ongoing phase 2, open-label, single-arm, multicenter study is evaluating nab-sirolimus in combination with letrozole for the treatment of patients with advanced or recurrent EEC Prior clinical studies with mTOR inhibitors and endocrine therapy have yielded promising results in EEC Title: "nab-Sirolimus for Malignant Solid Tumors Harboring Pathogenic Inactivating Alterations in TSC1 and TSC2 in a Phase 2, Multicenter, Open-Label Tumor-Agnostic Trial: PRECISION 1" Presenting Author: Debra L. Richardson, MD Session Title: Poster Session 2 Location: Exhibit Hall (Hall GH) Poster Number: 2126 Date/Time: Monday, March 18, 2024 – 11:45 AM to 12:45 PM TSC1 and/or TSC2 inactivating alterations have been observed in patients with gynecological cancers with a frequency of up to 5.0% in endometrial cancer, 2.2% in ovarian cancer and 1.5% in cervical cancer About Aadi Bioscience Aadi is a commercial-stage precision oncology company focused on the development and commercialization of therapies for cancers with alterations in the mTOR pathway, a key regulator of cell growth and cancer progression. To unlock the full potential of mTOR inhibition, Aadi uniquely combines nanoparticle albumin-bound (nab) technology with the potent mTOR inhibitor, sirolimus. Aadi received FDA approval and commercializes FYARRO® for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). Aadi is exploring nab-sirolimus in PRECISION1, a Phase 2 tumor-agnostic registration-intended trial in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. Aadi is also exploring nab-sirolimus in two single-indication Phase 2 trials for difficult-to-treat mTOR-driven cancers: neuroendocrine tumors (NETs), and advanced or recurrent endometrioid-type endometrial cancer (EEC) in combination with letrozole. More information on the Company's development pipeline is available on the Aadi website at and connect with us on Twitter and LinkedIn. Forward-Looking Statements This press release contains certain forward-looking statements regarding the business of Aadi Bioscience that are not a description of historical facts within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are based on the Company's current beliefs and expectations and may include, but are not limited to, statements relating to: expectations regarding the beneficial characteristics, safety, efficacy and therapeutic effects of FYARRO; expectations regarding the clinical responses and safety profile, regulatory approval and commercialization, and the sufficiency of the Company's existing capital resources and the expected timeframe to fund the Company's future operating expenses and capital expenditure requirements. Actual results could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, those associated with the uncertainties associated with the clinical development and regulatory approval of FYARRO in additional indications; the risk that interim or subgroup analysis results of clinical trials may not be reproduced and do not necessarily predict final results; the risk that 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 become available; the risk that unforeseen adverse reactions or side effects may occur in the course of commercializing, developing and testing FYARRO; and risks related to Aadi's estimates regarding future expenses, capital requirements and need for additional financing. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including under the caption "Item 1A. Risk Factors," and elsewhere in Aadi's reports and other documents that Aadi has filed, or will file, with the SEC from time to time and available at . All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Aadi undertakes no obligation to revise or update any forward-looking statement, or to make any other 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. This cautionary statement is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: [email protected] SOURCE Aadi Bioscience

FYARRO® sales of $6.3 million for Q4 2023 and $24.4 million for FY 2023 representing year-over-year growth of 21% and 60%, respectively Registration-directed PRECISION1 trial of nab-sirolimus in solid tumors with TSC1 or TSC2 inactivating alterations on track to complete enrollment by May; two-thirds interim analysis planned for Q3 2024 Phase 2 trials in Endometrial Cancer and Neuroendocrine Tumors (NETs) actively enrolling patients Conference call to be held today at 8:30 am EDT LOS ANGELES, March 13, 2024 /PRNewswire/ -- Aadi Bioscience, Inc (NASDAQ: AADI), a commercial-stage, precision oncology company focused on developing and commercializing therapies for cancers with alterations in the mTOR pathway, today announced financial results for the fourth quarter and full-year ended December 31, 2023, and highlighted recent corporate progress. "With strong execution against our commercial and development goals, 2023 was a year of progress and momentum for Aadi," said Dave Lennon, President and CEO of Aadi Bioscience. "As the preferred treatment for malignant PEComa, FYARRO saw significant growth and high penetration in academic and community settings. Clinically, we were encouraged by the interim results from the registration-directed PRECISION1 trial, and look forward to the two-thirds readout expected in Q3. We also initiated enrollment of two Phase 2 trials in what we believe are promising mTOR-driven cancer targets, endometrial cancer and neuroendocrine tumors, as we further characterize the potential of nab-sirolimus. With a commercial foundation, bold development vision and solid cash runway in to Q4 2025, we believe we are well-positioned to realize our ambition of becoming a multi-indication precision oncology company." Recent Operational Highlights FYARRO net product sales were $6.3 million in the fourth quarter, or 21% growth over the prior year period, and $24.4 million for full-year 2023, representing 60% growth year-over-year. PRECISION1 on track to complete enrollment by May 2024, with the two-thirds interim analysis expected in Q3 2024. Early data presented in December 2023 demonstrated sustained tumor reductions in heavily pre-treated population from investigator-assessed responses in first 40 patients across both arms. The safety pro consistent with the nab-sirolimus label and the mTOR inhibitor drug class. Enrollment of two single-indication Phase 2 trials underway to investigate the potential of nab-sirolimus for difficult-to-treat mTOR-driven cancers: neuroendocrine tumors (NETs), and advanced or recurrent endometrioid-type endometrial cancer (EEC) in combination with letrozole. NETs are rare, ~3,500 cases a year, with low response rates to existing recommended treatments. Preclinical models indicate improved target suppression relative to other mTORs in the NETS population. Endometrial cancer is the most common cancer of the female reproductive organs and one of the few cancers with increasing mortality. There are an estimated 10,000 cases of EEC diagnosed annually. Prior clinical studies with mTOR inhibitors and letrozole have yielded promising results in EEC. Fourth Quarter and Full-year 2023 Financial Results Cash, cash equivalents and short-term investments as of December 31, 2023, were $108.8 million as compared to $172.6 million as of December 31, 2022, which is expected to fund operations into Q4 2025 based on current plans. Total revenue for the quarter ended December 31, 2023, was $6.3 million, and $24.4 million for the full-year ended December 31, 2023, resulting from sales of FYARRO. Net loss for the three months ended December 31, 2023, was $16.3 million as compared to $13.9 million for the three months ended December 31, 2022. Net loss for the full-year ended December 31, 2023, was $65.8 million, as compared to $60.5 million for the same period in 2022. Conference Call Information The Aadi management team is hosting a conference call and webcast today at 8:30 am EDT (5:30 am PDT) to provide a corporate update and discuss results for the fourth quarter and full-year 2023. Participants may access a live webcast of the call on the "Investors & News" page of the Aadi Bioscience website at aadibio.com. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company's website for at least 30 days. About Aadi Bioscience Aadi is a commercial-stage precision oncology company focused on the development and commercialization of therapies for cancers with alterations in the mTOR pathway, a key regulator of cell growth and cancer progression. To unlock the full potential of mTOR inhibition, Aadi uniquely combines nanoparticle albumin-bound (nab) technology with the potent mTOR inhibitor, sirolimus. Aadi received FDA approval and commercializes FYARRO® for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). Aadi is exploring nab-sirolimus in PRECISION1, a Phase 2 tumor-agnostic registration-directed trial in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. Aadi is also exploring nab-sirolimus in two single-indication Phase 2 trials for difficult-to-treat mTOR-driven cancers: neuroendocrine tumors (NETs), and advanced or recurrent endometrioid-type endometrial cancer (EEC) in combination with letrozole. More information on the Company's development pipeline is available on the Aadi website at and connect with us on Twitter and LinkedIn. Forward-Looking Statements This press release contains certain forward-looking statements regarding the business of Aadi Bioscience that are not a description of historical facts within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are based on the Company's current beliefs and expectations and may include, but are not limited to, statements relating to: the Company's cash runway extending into the fourth quarter of 2025; the anticipated timing of commencement, enrollment, data releases and completion of the Company's clinical trials, including the expected full enrollment of the PRECISION 1 trial by May 2024 and the expected PRECISION 1 two-thirds interim analysis in 3Q 2024; the Company's anticipated growth and continued advancements, including in potential additional indications; expectations regarding the beneficial characteristics, safety, efficacy, therapeutic effects and the size of the potential targeted markets with respect to FYARRO, including in NETs and EEC; and the sufficiency of the Company's existing capital resources and the expected timeframe to fund the Company's future operating expenses and capital expenditure requirements. Actual results could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, uncertainties associated with the clinical development and regulatory approval of FYARRO in additional indications, including potential delays in the commencement, enrollment and completion of clinical trials for additional indications; failure to demonstrate the efficacy of FYARRO in clinical trials for additional indications; risks related to the release of interim, topline and preliminary data from clinical trials; the risk that unforeseen adverse reactions or side effects may occur in the course of commercializing, developing and testing FYARRO; risks associated with the failure to realize any value from FYARRO in light of inherent risks and difficulties involved in successfully bringing product candidates to market; risks relating to the Company's reliance on third party suppliers, some of which are sole suppliers; and risks related to the Company's estimates regarding future expenses, capital requirements and need for additional financing. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2022, including under the caption "Item 1A. Risk Factors," and in Aadi's subsequent Quarterly Reports on Form 10-Q, and elsewhere in Aadi's reports and other documents that Aadi has or will file, with the SEC from time to time and available at . All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Aadi undertakes no obligation to revise or update any forward-looking statement, or to make any other 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. This cautionary statement is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: IR@aadibio.com Company Codes: NASDAQ-NMS:AADI