BAT8001 / Bio-Thera Solutions - LARVOL DELTA

Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (AACR 2023) - "Background: SHR-A1811 is an ADC comprised of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload. SHR-A1811 was well-tolerated and showed promising antitumor activity in heavily pretreated advanced solid tumors.Table 1. Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)≤381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35,..."

Clinical • Metastases • P1 data • PK/PD data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

Emerging new treatments in HER2 positive breast cancer (SG-BCC 2023) - P1 | "Trastuzumab deruxtecan (T-DXd) was approved in December 2022 by the FDA for patients with pretreated HER2- positive breast cancer based on the results of the phase III trial Destiny-Breast03 [3], showing an impressive improvement in progression-free survival with an hazard ratio of 0.33 (95% CI 0.26– 0.43, p-value<0.0001) compared to T-DM1, according to the last update presented at SABCS 2022 [4]...Besides T-DXd and SYD985, other ADCs have been or are under investigation, including, but not limited to, patritumab deruxtecan, disitamab vedotin, XMT-1522, MM-302, MEDI-4276, A166, ARX788, BAT8001 and PF-06804103...Several TKIs have been successfully developed, with tucatinib being the latest to enter clinical practice based on the results of the HER2CLIMB trial [7], with particular importance for patients with brain metastases. Other promising emerging treatments targeting HER2/3 receptors are the HER2- targeted bispecific antibodies (including, among others, KN026..."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Oncology • Solid Tumor • CDK4 • ER • HER-2 • KLRC1 • PD-L1 • PIK3CA

Messersmith Makes Sense of the Novel Approaches on the Rise in GI Malignancies (OncLive) - "The heterogeneity of tumors in GI cancers continues to pose a challenge, according to Messersmith. As such, understanding how circulating tumor DNA will play into the management of patients as RAS inhibitors emerge in the clinic will be an area of interest going forward, Messersmith added."

Media quote

226 million R&D costs have been lost, Biotech terminates an ADC project under development [Google translation] (Bioon.com) - "After the total investment 226 million yuan, Bio Integration announced the final stop ADC project BAT8001...for HER2-positive breast cancer in clinical trials...As for the reason for the termination of the project, Biotech issued an announcement to clarify that the phase III clinical study of BAT8001...after careful consideration of the subsequent development risks of BAT8001, it was decided to terminate the clinical trial of this project."

Discontinued • Breast Cancer • HER2 Positive Breast Cancer • Oncology

Bio-Thera‘s HER2 ADC fails to show efficacy in Phase III breast cancer study (GBI Health) - "Guangzhou-based biotech Bio-Thera Solutions (SHA.688177) announced the termination of a Phase III clinical breast cancer study for BAT8001, an anti-HER2 antibody drug conjugate (ADC) candidate...The domestic multicenter, randomized, open, positive control, superiority Phase III study was designed to assess the efficacy and safety of BAT8001 in later-line HER2 positive breast cancer patients with trastuzumab (or marketed biosimilars) and taxane each as a monotherapy or in combination. Study results showed that progression-free survival in the BAT8001 group, compared with the positive control lapatinib/capecitabine combo group, did not reach the pre-set superiority standard."

P3 data • Trial termination • Breast Cancer • HER2 Positive Breast Cancer • Oncology

Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study. (PubMed, Cancer Commun (Lond)) - "BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer."

Clinical • Journal • P1 data • PK/PD data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Thrombocytopenia • HER-2

The safety, tolerability, and pharmacokinetics of BAT8001 in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer: An open-label, dose-up, phase 1 study (SABCS 2019) - "Patients and methods In this open-label, phase 1 trial, we recruited 29 patients aged 18 years or older with HER2-positive advanced or recurrent breast cancer who had been previously treated with trastuzumab and/or lapatinib plus cytotoxic agents. Conclusions BAT8001 was safe, tolerable and the preliminary activity seems promising in patients with HER2-positive advanced or recurrent breast cancer. The results suggest that BAT8001 has the potential to provide a new therapeutic option in heavily pretreated patients with metastatic breast cancer."

Clinical • P1 data • PK/PD data • HER2

The Efficacy and Safety of BAT8001 Injection for the Treatment of HER2-positive Advanced Breast Cancer (clinicaltrials.gov) - P3; N=410; Active, not recruiting; Sponsor: Bio-Thera Solutions

Clinical • Head-to-Head • New P3 trial

A Clinical Trial of BAT8001 on Safety, Tolerability and Pharmacokinetics for Patients (clinicaltrials.gov) - P1; N=30; Active, not recruiting; Sponsor: Bio-Thera Solutions

Clinical • New P1 trial

A Phase I Clinical Trial of BAT1306 and BAT8001 Injection in Patients With Solid Tumor (clinicaltrials.gov) - P1/2; N=72; Enrolling by invitation; Sponsor: Bio-Thera Solutions

Clinical • New P1/2 trial

BAT8001, a potent anti-HER2 antibody drug conjugate with a novel uncleavable linker to reduce toxicity for patients with HER2-positive tumor (AACR 2019) - "The trial is designed to compare BAT8001 versus lapatinib combined with capecitabine which is 2nd-line standard of care for metastatic breast cancer patients in China. This Phase 3 trial plans to recruit approximately 410 patients and by Jan 2019 more than 130 patients have received the treatment of BAT8001. The BAT8001 benefit-risk profile continues to support further development and the clinical results will be revealed by early 2020."

Clinical

Bio-Thera solutions announces two poster presentations at the 2019 AACR Annual Meeting (Businesswire) - "The first poster...will highlight Phase I clinical data demonstrating the safety and efficacy of BAT8001 in HER2-positive cancer patients....The second poster...will present preclinical data that highlight advantages of BAT8003 as a potential treatment for gastric cancer patients. The IND for a Phase I clinical trial evaluating the safety and pharmacokinetics of BAT8003 was approved earlier this year by the China NMPA. Dosing of the first patient in this Phase I clinical trial is expected to occur during April 2019."

Enrollment status • Non-US regulatory • P1 data • Preclinical