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

Sihuan Pharmaceutical…is pleased to announce that the final analysis results of the Phase 3 BRIGHT-2 clinical study of Bireociclib…were officially published online recently, in the top-tier international medical journal JAMA Oncology (HKEXnews) - "In patients with progression after prior endocrine therapy, the median progression-free survival (mPFS) in the Bireociclib combination group was further extended from 12.9 months in the interim analysis to 14.7 months, significantly superior to the 7.3 months in the placebo combination group, successfully reducing the risk of disease progression or death by 46% (HR=0.54; 95% CI, 0.40–0.74; P<0.001)....In terms of depth of clinical response, the final analysis of the BRIGHT-2 study demonstrated a highly competitive objective response rate (ORR). Among subjects with measurable lesions, the ORR in the Bireociclib group reached 50.3%, significantly higher than the 16.7% in the control group."

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

Bireociclib Plus Fulvestrant in Advanced Breast Cancer After Endocrine Progression: The BRIGHT-2 Phase 3 Randomized Clinical Trial. (PubMed, JAMA Oncol) - P3 | "The final analysis of the BRIGHT-2 randomized clinical trial confirms improved PFS with the addition of bireociclib to fulvestrant, with manageable safety as a treatment option for patients with HR-positive, ERBB2-negative ABC with progression after prior endocrine therapy. ClinicalTrials.gov Identifier: NCT05077449."

Clinical • Journal • P3 data • 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 • ER • HER-2 • PIK3CA • TP53

Dynamic monitoring and identification of reliable biomarkers to predict efficacy of bireociclib and fulvestrant: An exploratory ctDNA analysis of the BRIGHT-2 study (AACR 2026) - P3 | "Dynamic clearance of ctDNA or specific gene mutations was correlated with improved efficacy and survival outcomes for CDK4/6 inhibitor.Conclusions Both baseline and dynamic monitoring of ctDNA demonstrated salient predictive value for treatment response and survival outcomes in hormone receptor-positive, HER2-negative breast cancer patients receiving bireociclib plus fulvestrant. These potential biomarkers warrant further validation through larger clinical trials and basic researches.Key words: CDK4/6 inhibitor, advanced breast cancer, biomarkers, bireociclib, prognosis."

Biomarker • Circulating tumor DNA • Clinical • 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 • CCND1 • ER • FGF19 • HER-2 • HRD • PIK3CA • TP53

COST-EFFECTIVENESS ANALYSIS OF BIREOCICLIB VERSUS ABEMACICLIB IN HR+/HER2- ADVANCED OR METASTATIC BREAST CANCER: COMPARING MATCHING-ADJUSTED INDIRECT COMPARISON AND SIMULATED TREATMENT COMPARISON APPROACHES (ISPOR 2026) - "Bireociclib was consistently estimated as a cost‑effective option compared with abemaciclib in this population. STC showed more positive survival outcomes than MAIC. However, considering the inherent methodological uncertainty in both MAIC and STC, the findings should be interpreted with consideration of these uncertainties, and further validation through head‑to‑head trials or real‑world studies is warranted."

Cost effectiveness • HEOR • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

BIREOCICLIB PLUS FULVESTRANT FOR HR+/HER2- ADVANCED OR METASTATIC BREAST CANCER: A COST-EFFECTIVENESS ANALYSIS (ISPOR 2026) - "Current evidence suggests that bireociclib combined with fulvestrant is a cost-effective alternative to abemaciclib plus fulvestrant. However, given the limited 8-month follow-up of BRIGHT-2 trial, these findings warrant further validation as mature long-term survival data becomes available"

Cost effectiveness • HEOR • Metastases • 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

Marketing approval for the third indication of Xuan Yue Ning of (bireociclib tablets) for the first-line treatment of HR+/HER2- advanced breast cancer granted by the NMPA (HKEXnews) - "The approval of this new indication is mainly based on the data results from the BRIGHT-3 study (NCT05257395)."

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

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

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

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