Xuan Yue Ning (bireociclib) / Sihuan Pharmaceutical - LARVOL DELTA

Associations between dynamic hematological indicators and outcomes in HR-positive, HER2-negative metastatic breast cancer treated with bireociclib or placebo plus fulvestrant: Findings from the BRIGHT-2 trial. (PubMed, Breast) - "Peripheral blood-derived indicators are prognostic markers for HR-positive, HER2-negative metastatic breast cancer. Elevated PLR during treatment indicates poor response to CDK4/6 inhibitors."

Journal • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Bireociclib plus letrozole/anastrozole versus placebo plus letrozole/anastrozole for the treatment of HR+/HER2- advanced breast cancer: Interim analysis of BRIGHT-3 study (ESMO 2025) - P3 | "In bireociclib group, the most common TEAEs were diarrhea [93.5% (all grades); 8.4% (≥grade 3)], neutropenia [78.7%; 29.3%], and anemia [61.6%; 6.1%]. Conclusions Bireociclib plus letrozole/anastrozole significantly prolonged PFS for patients with HR+/HER2- ABC as first or second-line therapy with well-tolerated toxicity."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Matching-adjusted indirect comparison of bireociclib plus fulvestrant versus dalpiciclib Plus fulvestrant as second-line treatment of HR+/HER2- advanced breast cancer (ABC) (ESMO 2025) - P3 | "Conclusions This MAIC analysis suggests comparable efficacy between bireociclib and dalpiciclib when combined with fulvestrant in HR+/HER2- ABC patients who progressed on or after prior endocrine therapy. The two agents display distinct safety profiles, with dalpiciclib showing more severe hematological toxicities and bireociclib exhibiting more gastrointestinal adverse events."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety outcomes across young to older age groups of patients with HR+/HER2 - advanced breast cancer treated with bireociclib plus endocrine therapy: A pooled analysis of BRIGHT studies (ESMO 2025) - P1/2, P3 | "The pts received bireociclib plus anastrozole/letrozole/fulvestrant or anastrozole/letrozole/fulvestrant alone as allocated and prespecified in the protocol. Treatment discontinuation due to TEAE was reported in 1.9% pts aged <65y with BE, 0.5% pts aged <65y with ET alone, 5.5% pts aged ≥65y with BE, 2.4% pts aged ≥65y with ET alone. Conclusions Bireociclib plus ET is an effective, well-tolerated treatment for elderly pts with HR+/Her2- ABC as first or second-line endocrine therapy."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ANNOUNCEMENT OF PHASE III CLINICAL STUDY DATA OF BIREOCICLIB FOR FIRST-LINE TREATMENT OF HR+/HER2 - ADVANCED BREAST CANCER AT ESMO 2025 (HKEXnews) - "As of January 10, 2025, the median follow-up time was 20.7 months. The results of this interim analysis showed that, as for efficacy, the median Progression-Free Survival (mPFS) for the Bireociclib group assessed by both the investigators and the independent review committee had not been reached, compared to 18.43 months and 19.55 months for the control group, respectively....In the intention-to-treat population, the objective response rate (ORR) in the Bireociclib group reached 63.5%, significantly superior to 42.5% in the control group."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Safety and tolerability of bireociclib for the treatment of advanced solid tumors as monotherapy and in combination with endocrine therapy: a multicenter, open-label, phase 1 clinical trial. (PubMed, BMC Med) - P1/2 | "Bireociclib demonstrated favorable efficacy and an acceptable safety profile both as monotherapy (RP2D-S of 480 mg BID) and in combination therapy (RP2D-C of 360 mg BID) for treating HR+/HER2- ABC patients."

Journal • Monotherapy • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

NDA OF BIREOCICLIB TABLETS’ NEW INDICATION, IN COMBINATION WITH AROMATASE INHIBITOR FOR FIRST-LINE TREATMENT OF HR+/HER2- ADVANCED BREAST CANCER, ACCEPTED BY NMPA (HKEXnews) - "The board of directors (the 'Board') of Sihuan Pharmaceutical Holdings Group...is pleased to announce that the New Drug Application (the 'NDA') for a new additional indication of Bireociclib Tablets (Trade Name: Xuan Yue Ning) (the 'Product'), a Class 1 innovative drug independently developed by the Group’s non-wholly owned subsidiary Xuanzhu Biopharmaceutical Co., Ltd. (the 'Xuanzhu Biopharm'), has been accepted for review by the National Medical Products Administration (the 'NMPA') of China. The specific indication accepted is: combined with aromatase inhibitors as the initial endocrine therapy for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ('HR+/HER2-') advanced breast cancer, and the treatment for patients who progressed after adjuvant therapy with Tamoxifen or Toremifene. This is the third indication for the Product to apply for NDA."

China filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Matching-adjusted indirect comparison of bireociclib plus fulvestrant versus abemaciclib plus fulvestrant as second-line treatment of HR+/HER2− advanced breast cancer. (ASCO 2025) - P3 | "This MAIC analysis suggests comparable efficacy between Bireociclib and Abemaciclib when combined with fulvestrant in patients with HR+/HER2- advanced breast cancer who progressed following prior endocrine therapy. The safety profiles of Bireociclib and Abemaciclib were generally comparable. However, Bireociclib demonstrated a lower risk of grade ≥ 3 diarrhea."

Clinical • Metastases • Anemia • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Brain metastasis incidence with bireociclib in HR+/HER2- advanced breast cancer: Pooled analysis of BRIGHT-1 and BRIGHT-2 study. (ASCO 2025) - P1/2, P3 | "This pooled analysis demonstrates numerically lower incidence of BM in HR+/HER2- MBC pts treated with bireociclib containing regimens, suggesting bireociclib's potential to reduce BM occurrence and inhibit intracranial lesions in ABC."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Dynamic hematological indicators as predictors of CDK4/6 inhibitors efficacy in HR-positive, HER2-negative metastatic breast cancer. (ASCO 2025) - P3 | "Funded by Chinese Academy of Medical Sciences Clinical Trial Registration Number: NCT05077449 Background: Birociclib, a novel CDK4/6 inhibitor, has been evaluated in the BRIGHT-2 study, a phase 3 randomized controlled trial (RCT), to assess its efficacy and safety when combined with fulvestrant versus placebo plus fulvestrant in the treatment of HR+/HER2- advanced breast cancer that progressed during or after prior endocrine therapy (NCT05077449). Peripheral blood-derived indicators, including ALC, NLR, MLR, PLR, SII, and PNI, are predictive of CDK4/6 inhibitor efficacy in HR-positive, HER2-negative metastatic breast cancer. Elevated PLR during treatment indicates poor response to CDK4/6 inhibitors."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Development and validation of an LC-MS/MS method for simultaneous determination of XZP-3287(bireociclib) and its metabolites in human plasma, and its clinical pharmacokinetics application. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "In conclusion, a method for the simultaneous detection of the pharmacokinetic profiles of XZP-3287 and its metabolites in human plasma had been successfully developed. The results demonstrated the efficacy, sensitivity, and reliability of this method."

Journal • PK/PD data • Breast Cancer • Oncology • Solid Tumor • CDK4

THE CLASS 1 INNOVATIVE DRUG BIREOCICLIB TABLETS INDEPENDENTLY DEVELOPED BY XUANZHU BIOPHARMACEUTICAL, AS MONOTHERAPY AND IN COMBINATION WITH FULVESTRANT, GRANTED MARKETING AUTHORIZATION BY NMPA FOR TWO INDICATIONS IN HR+/HER2- ADVANCED BREAST CANCER (HKEXnews) - "The board of directors....of Sihuan Pharmaceutical Holdings Group Co., Ltd...is pleased to announce that the class 1 innovative drug Bireociclib Tablets...has had its New Drug Application (NDA) approved by the National Medical Products Administration (the 'NMPA') with two indications: (1) as monotherapy for adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) local advanced or metastatic breast cancer who have progressed after receiving two or more lines of endocrine therapy and one chemotherapy in the metastatic stage; and (2) in combination with Fulvestrant for the treatment of adult patients with HR+/HER2- advanced or metastatic breast cancer who have progressed after prior endocrine therapy."

China approval • Evidence highlight • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • ER • HER-2 • PGR

BRIGHT-2 final analysis: A phase III trial of bireociclib plus fulvestrant as second-line endocrine therapy for patients with advanced HR+/HER2-breast cancer (AACR 2025) - P3 | "Bireociclib plus fulvestrant exhibited superior efficacy and manageable tolerability as second-line endocrine therapy for HR+/HER2- ABC after prolonged follow-up, with benefits across different subgroups and clinically appropriate dose reductions not compromising efficacy."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A Study of XZP-3287 in Combination With Letrozole/Anastrozole in Patients With Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=397 | Active, not recruiting | Sponsor: Xuanzhu Biopharmaceutical Co., Ltd. | Not yet recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Sep 2030 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Bireociclib plus fulvestrant for HR+/HER2- advanced female breast cancer progressed on or after endocrine therapy: phase 3 BRIGHT-2 study interim analysis. (PubMed, Nat Commun) - P3 | "Grade ≥3 adverse events were more frequent in the BF group (64.7%) than in the F group (18.8%), with neutropenia, leukopenia, and anemia being the most common. These findings suggest that BF is a promising therapeutic option for patients with HR+/HER2- ABC following ET failure."

Clinical • Journal • P3 data • P3 data: top line • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

THE PHASE 3 INTERIM CLINICAL ANALYSIS RESULTS OF THE INNOVATIVE DRUG BIREOCICLIB PLUS FULVESTRANT TO TREAT HR+/HER2- ADVANCED BREAST CANCER PUBLISHED IN THE ACADEMIC JOURNAL NATURE COMMUNICATIONS (HKEXnews) - P3 | N=300 | BRIGHT-2 (NCT05077449) | Sponsor: Xuanzhu Biopharmaceutical Co., Ltd. | "The phase 3 study interim analysis results of Bireociclib plus Fulvestrant for the treatment of HR+/HER2- advanced breast cancer (ABC) (BRIGHT-2, NCT05077449) has officially published in the top-tier journal Nature Communications, a sub journal of Nature....The study recruited 305 HR+/HER2- ABC patients who had progressed on or after endocrine therapy from 64 centers in China....The median follow-up time is 8.7 months, the median PFS of the combined treatment group reached 12.94 months, far exceeding the 7.29 months of Fulvestrant monotherapy group. All subgroups of patients benefited from combination treatment in terms of PFS, especially those with primary endocrine therapy resistance, bone-only metastasis, and liver metastasis. The Objective Response Rate (ORR) of the combination group was 39.7%, which could reduce tumor size, relieve symptoms, and bring survival benefits."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

An open-label, single-arm, multicenter, phase II trial of bireociclib as monotherapy for heavily pretreated HR-positive, HER2-negative advanced breast cancer patients: BRIGHT-1 trial. (PubMed, Cancer Commun (Lond)) - P1/2 | "Bireociclib monotherapy at 480 mg BID exhibited promising and sustained clinical activity, with no unexpected and acceptable toxicity in patients with recurrent or metastatic HR+/HER2- breast cancer who had progressed on or after previous therapy."

Journal • Monotherapy • P2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A Phase I/II Study of XZP-3287 in Metastasis Solid Tumors (clinicaltrials.gov) - P1/2 | N=402 | Active, not recruiting | Sponsor: Sihuan Pharmaceutical Holdings Group Ltd. | Recruiting ➔ Active, not recruiting | N=300 ➔ 402 | Trial completion date: Dec 2022 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ANNOUNCEMENT OF INTERIM RESULTS FOR THE SIX MONTHS ENDED 30 JUNE 2024 (HKEXnews) - "In January 2024, Bireociclib passed the registration on-site inspection and GMP compliance inspection, and the review of the NMPA is progressing smoothly...In April 2024, the NDA of 'Dexitinib Tablets' (code: XZP-3621), a Class 1 innovative drug independently developed by Xuanzhu Biopharm, was accepted by the Center for Drug Evaluation (CDE), NMPA. It is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC)."

China filing • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Bireociclib plus fulvestrant for advanced HR + /HER2 - breast cancer progressing after endocrine therapy: Interim analysis of a phase 3 trial (BRIGHT-2). (ASCO 2024) - P3 | "Bireociclib plus fulvestrant showed superior efficacy for pretreated HR+/HER2- ABC, especially in patients with primary resistance to ET, liver metastases or bone-only metastases. The toxicity of Bireociclib plus fulvestrant were well tolerated and manageable with no new safety signal."

Metastases • P3 data • P3 data: top line • Anemia • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • CDK4 • HER-2

BRIGHT-2: A Study of XZP-3287 in Combination With Fulvestrant in Patients With Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: Xuanzhu Biopharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A multicenter, single-arm, open-label trial of birociclib, a CDK4/6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer (ESMO 2023) - P1/2 | "The main results are shown in the table. Table: 404P Responses according to RECIST v1.1 Conclusions In patients with refractory HR+/HER2- MBC who have previously received chemotherapy and endocrine therapy, continuous dosing of single-agent birociclib exhibited promising and sustaining clinical activity with manageable toxicities, thus it provides an alternative orally single-agent therapy."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Xuanzhu Biotechnology, a subsidiary of Sihuan Pharmaceutical (0460.HK), independently developed single-agent Birociclib Phase II trial selected for 2023 ESMO, providing new ideas for patients with advanced HR+/HER2- breast cancer (ACN Newswire) - P1/2 | N=300 | NCT04539496 | Sponsor: Sihuan Pharmaceutical Holdings Group Ltd. | "The results of the phase II multi-center clinical trial of Birociclib, an innovative CDK4/6 inhibitor independently developed by Xuanzhu Biotechnology, were presented in the form of a poster at the 2023 European Society of Medical Oncology (ESMO) conference....As of November 30, 2022, the Independent Review Committee (IRC) assessment confirmed that the ORR was 29.0%, 38 cases (29%) achieved partial response (PR), the median DoR was 14.8 months, the DCR was 73.7%, and the CBR was 42.0 %, the median PFS was 11 months, and the 24-month OS rate was 62.9%. The study results show that Birociclib is safe and well-tolerated."

P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Sihuan Pharmaceutical (0460.HK): The marketing application for a new drug independently developed by its subsidiary Xuanzhu Biotech to treat advanced breast cancer has been accepted by the State Food and Drug Administration [Google translation] (ACN Newswire) - "Sihuan Pharmaceutical Holdings Group Limited...is pleased to announce that Xuanzhu Biotechnology Co., Ltd. ('Xuanzhu Bio')...has independently developed a Class 1 new drug Birociclib (XZP-3287 CDK4/6 (Cycle-Dependent Kinase 4) and 6) inhibitor) ('Birociclib ')'s New Drug Application (NDA) was accepted by the China National Medical Products Administration. Specifically: Birociclib single agent is used for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (Her2)-positive patients with disease progression after receiving two or more endocrine therapies and one chemotherapy in the metastatic stage."

Non-US regulatory • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Xuanzhu Biotechnology, a subsidiary of Sihuan Pharmaceutical, independently developed a new Class 1 drug birociclib and applied for listing [Google translation] (ACN Newswire) - "Sihuan Pharmaceutical Holdings Group Limited...is pleased to announce that Xuanzhu Biotechnology Co., Ltd. ('Xuanzhu Bio'), a non-wholly owned subsidiary of the Group, independently developed the Class 1 innovative drug Birociclib (XZP-3287, CDK4/6 (cell cycle) The new drug application (NDA) for pyrosinib-dependent kinase 4 and 6 inhibitor) ('Birociclib') has recently been accepted by the China National Medical Products Administration ('NMPA')."

Non-US regulatory • Breast Cancer • Oncology • Solid Tumor