On December 5, 2023 SystImmune, Inc (SystImmune), a clinical-stage biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) authorized the company to proceed with the planned clinical study of the HER2-specific HIRE platform ADC, BL-M07D1, in the Investigational New Drug (IND) application on November 28, 2023 (Press release, SystImmune, DEC 5, 2023, View Source [SID1234638171]). This milestone paves the way for the multicenter Phase 1 study evaluating the safety, tolerability, pharmacokinetic profile, and initial efficacy of BL-M07D1 in subjects with metastatic or unresectable HER2 expressing cancers in the United States.

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Dr. Yi Zhu, Chief Executive Officer of SystImmune, remarked, "The FDA’s approval of our IND application for BL-M07D1 underscores our commitment to advancing innovative therapies in the field of oncology with our HIRE platform of ADCs. We look forward to collaborating with our clinical partners, trial treatment centers, and global regulatory agencies to contribute meaningfully to the ongoing evolution of cancer treatment."

The clearance of this IND application marks a significant milestone for SystImmune as the company continues to advance its pipeline of therapeutic candidates into global clinical development.

Updated Clinical Trial Results

New results from the ongoing study with the EGFRxHER3 bi-specific HIRE platform ADC, BL-B01D1, in patients with breast cancer treated in the trial registered as NCT05470348, are presented for the first time. Preliminary results demonstrated overall response rates of 44.7%, 31.4% and 39.1% and disease control rates of 91.4%, 94.7% and 87% in an analysis of 38, 35 and 23 pretreated patients with HER2-/HR+, TNBC and HER 2+ patients with breast cancer respectively. No interstitial lung disease (ILD) was observed in 127 patients treated with at least one dose. For more information visit poster: PS08-07 2023 San Antonio Breast Cancer conference.

Updated analysis from an ongoing phase 1 study of the HIRE platform HER2-specific ADC, BL-M07D1 in the trial registered as NCT05461768, continues to demonstrate impressive results in patients with breast cancer. Reported are response rate of 80%, confirmed responses over 60%, and disease control rate of 100% in 50 patients with HER2+ metastatic breast cancer. Prior treatment with HER2 ADCs did not prevent responses to BL-M07D1, as 18 subjects who had received prior ADC therapies showed similar overall response. Preliminary results from the same study demonstrated an overall response rate of 50%, confirmed responses in 28.9% and disease control rate of 86% in an analysis of 38 heavily pretreated patients with HER2 low-expressing metastatic breast cancer. Only 1 patient experienced ILD which was grade 2, in the 130 patients treated. For more information visit poster: PO2-04-03 2023 San Antonio Breast Cancer conference.

Dr. Martin S. Olivo, the Chief Medical Officer at SystImmune, reports the preliminary findings showcased in these two studies, underscoring their backing of the promising activity seen in the HIRE platform. Dr. Olivo emphasized the significance of the FDA clearance for the IND application of BL-M07D1, expressing optimism. "As the clinical development of BL-M07D1 and BL-B01D1 progress, we’re closer to assessing our potential to offer therapeutic pathways for patients diagnosed with breast cancer."

About BL-B01D1

BL-B01D1 is a first-in-class bispecific antibody-drug conjugate (ADC) developed by SystImmune, targeting both EGFR and HER3, proteins that are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 possesses two binding domains blocking each Growth Factor Receptor, which both drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 effectively blocks EGFR and HER3 signals to cancer cells, thereby reducing proliferation and survival signals. Upon antibody-mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

The two targets of BL-B01D1 are broadly expressed in epithelial tumors, including NSCLC, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal carcinoma, Gastrointestinal tumors, Gynecological tumors, and others. The therapeutic conjugated toxin of BL-B01D1 comprises SystImmune’s Ex-0115 linker-payload platform, a proprietary Topo1 inhibitor conjugated to the bi-specific antibody by a stable, cleavable linker. Each BL-B01D1 carries 7-8 units of SystImmune’s proprietary ED-04 toxin.

About BL-M07D1

BL-M07D1 is a HER2 specific antibody-drug conjugate (ADC) developed by SystImmune, targeting cancers that express HER2. The trastuzumab-based BL-M07D1 possesses two binding domains specific for the commonly overexpressed cancer growth factor receptor HER2, which drive cancer cell proliferation and survival. BL-M07D1 binding to HER2 leads to its internalization by cancer cells. Upon antibody-mediated internalization, BL-M07D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

The target of BL-M07D1, HER2, is highly expressed in solid tumors, including breast cancer, gastric cancer, endometrial cancer, cervical cancer, ovarian cancer, urothelial cancer, biliary tract cancer and others. The therapeutic conjugated toxin of BL-M07D1 comprises SystImmune’s Ex-0115 linker-payload platform, a proprietary Topo1 inhibitor conjugated to the antibody by a stable, cleavable linker. Each BL-M07D1 carries 7-8 units of SystImmune’s proprietary ED-04 toxin.

Clinical studies conducted thus far have demonstrated compelling results for BL-M07D1. In 107 subjects with HER2+ Breast cancer and other HER2+ cancer BL-M07D1 exhibited promising preliminary antitumor activity in patients with both breast cancer and non-small cell lung cancer. The maximum tolerated dose for BL-M07D1 was not reached. The observed toxicities were predominantly hematologic. These findings were recently presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in October 2023, and the abstract of the clinical study can be accessed at the following link: BL-M07D1 ESMO (Free ESMO Whitepaper) Abstract. These results indicate that further investigations and clinical trials are warranted to fully assess the efficacy and safety profile of BL-M07D1 in a larger and more diverse patient population.