SignalChem Lifesciences Corp

The article, titled “First-in-Human Phase I Clinical Trial of SLC-391, a Novel and Selective AXL Inhibitor, in Patients with Advanced Solid Tumours,” reports data from a multicentre, open-label Phase 1 dose-escalation study (NCT03990454) evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of SLC-391 in patients with heavily pretreated advanced solid tumours. Key findings from the study include: Favourable safety and tolerability profile: SLC-391 was generally well tolerated across evaluated once-daily (QD) and twice-daily (BID) dose levels. The maximum tolerated dose (MTD) was not reached. A total daily dose of 300 mg (150 mg BID) was identified as well tolerated, with no dose-limiting toxicities (DLTs) or serious adverse events (SAEs) observed at this dose. Manageable adverse events: The majority of treatment-emergent adverse events were Grade 1–2 and primarily gastrointestinal in nature, including nausea, fatigue, diarrhoea, and vomiting. Grade 3 treatment-related adverse events occurred in a limited number of patients and were manageable with dose modification or supportive care. Predictable pharmacokinetics supporting oral dosing: SLC-391 was rapidly absorbed, with a median time to maximum plasma concentration (Tmax) of approximately 2 hours. Plasma exposure increased in a generally dose-proportional manner, with steady-state concentrations achieved by Day 21. BID dosing reduced peak-to-trough variability and provided more consistent systemic exposure. Encouraging preliminary clinical activity: Twelve of 35 patients (34.3%) achieved stable disease with durations lasting up to 318 days on SLC-391 monotherapy. Clinical benefit was observed across multiple tumour types, including non-small cell lung cancer (NSCLC) and mesothelioma, in a heavily pretreated population. “These Phase 1 results demonstrate that SLC-391 has a promising safety profile and meaningful signs of clinical activity in patients with advanced solid tumours,” said Dr. Zaihui Zhang, corresponding author and CSO and VP R & D at SignalChem Lifesciences Corp. “The durability of stable disease observed in several patients supports the rationale for advancing SLC-391 into combination studies.” Based on these findings, SLC-391 has been evaluated in a Phase 1b/2a clinical trial in combination with pembrolizumab in patients with advanced or metastatic non-small cell lung cancer (NCT05860296). About SLC-391 SLC-391 is a next-generation, small-molecule, selective AXL kinase inhibitor designed to block AXL-mediated signalling pathways involved in tumour growth, metastasis, immune evasion, and resistance to anticancer therapies. About SignalChem Lifesciences Corp. SignalChem Lifesciences Corp. is a research-driven biotechnology company focused on the discovery and development of targeted kinase inhibitors for cancer and immune-mediated diseases. For more information, please visit https://www.signalchemlifesciences.com. Forward-Looking Statements and Information This release contains forward-looking statements that are not based on historical facts. These forward-looking statements involve risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from those expressed or implied. Readers are cautioned not to place undue reliance on such forward-looking statements. Contact Zaihui Zhang, PhD CSO, VP R & D SignalChem Lifesciences Corp. 778-717-5433 x:114 The Novel Discovery by The University of British Columbia and SignalChem Lifesciences Corporation Has Been Published by the Prestigious Journal “Blood” Key points： · AXL activity is upregulated in acute myeloid leukemia (AML) stem/progenitor cells. · A novel AXL inhibitor SLC-391 is developed with favorable pharmaceutical properties. · AXL inhibition sensitizes AML cells to venetoclax, with strong synergistic effects via AXL/BCL-2-mediated OXPHOS/signaling pathways. VANCOUVER, BRITISH COLUMBIA – March 31, 2021 – SignalChem Lifesciences Corporation (“SLC”) is pleased to announce that a paper entitled “Targeting AXL Kinase Uniquely Sensitizes Therapy-Insensitive Leukemic Stem and Progenitor Cells to Venetoclax Treatment in Acute Myeloid Leukemia” has been published as First Edition by the journal “Blood” today. The research work described in this paper is the collaboration between University of British Columbia and SLC and it was supported by MITACS Accelerate program. In this study, we demonstrated that a key GAS6/AXL axis is highly activated in AML patient cells, particularly in stem/progenitor cells. We developed a potent, selective AXL inhibitor that has favorable pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation (PDX) models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in PDX models. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition or in combination with venetoclax potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells, which shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. Inhibition of AXL or BCL-2 also differentially targets key signaling proteins to synergize in leukemic cell killing. These findings have direct translational impact on the treatment of AML and other cancers with high AXL activity. “This new study has uncovered that AXL, one of key cancer drivers, is abnormally activated in blood cancer cells from AML patients, a difficult disease to treat. In this study we found that both genetic inhibition of AXL and the use of a highly selective AXL inhibitor SLC-391, in combination with a BCL-2 inhibitor (venetoclax) preferentially eliminate AML blast cells from drug-insensitive patients both in vitro and in preclinical PDX models, while not being toxic to healthy bone marrow cells. This new combination treatment approach may lead to more effective disease eradication, especially in patients at high risk of drug resistance and disease progression. Encouragingly, SLC-391 is currently being evaluated in a Phase I clinical trial in solid tumors, which opens a promising avenue for combination cancer therapies,” commented by Professor Xiaoyan Jiang in the Department of Medical Genetics of the University of British Columbia and Distinguished Scientist at BC Cancer, the senior author and the principal investigator of this paper. “We are very pleased with the recognition of this discovery by Professor Jiang’s lab in collaboration with SLC. We are going to pursue the clinical research in combination therapy of SLC-391 with a putative BCL-2 inhibitor in this AML patient population and hope that it will provide another valuable therapy to fight against this terrible disease,” said Mr. Jun Yan, President of SLC, “We have been working very hard to develop new anti-tumour therapies which provide superior advantages over the existing treatments.” SLC-391 is clinical stage small molecule AXL inhibitor with good potency and selectivity with desirable pharmaceutical properties. It has good selectivity against other tyrosine kinases. The pharmacokinetic studies in rodents and dogs indicated that SLC-391 has high bioavailability with a simple suspension formulation (>50%). The in vivo studies demonstrated efficacy in different animal models including NSCLC, CML and AML models. Moreover, it has exhibited a strong synergistic effect in tumour growth inhibition in combination with erlotinib and paclitaxel in NSCLC xenograft models and demonstrated a strong synergistic effect in decreasing leukemia burden and enhancing survival of leukemic animals in a novel combination approach with BCL-2 inhibitor venetoclax in aggressive xenotransplant AML leukemic models and PDX models. In a CT-26 colon cancer syngeneic model, SLC-391 played a role in modulating both the innate and adaptive immune responses and demonstrated a synergistic effect in tumour growth inhibition and overall survival in combination with an anti-PD-1 antibody. In addition, SLC-391 promotes anti-tumour immunity through modulation of tumour-associated macrophage polarization. Currently, SLC-391 is under phase I safety clinical evaluations in multi-cancer centres in Canada and the dose expansion phase is anticipated to be complete by Q3/2021. About SignalChem SignalChem Lifesciences Corporation (“SLC”) is a multi-platform, clinical-stage, drug discovery and development company focusing on development of next generation of novel, small molecule kinase inhibitors as targeted therapy for the treatment of cancer. SLC has a strong small-molecule drug development pipeline. SLC is seeking strategic partners to aid in bringing our clinical-stage drug pipeline to the market. SignalChem Biotech Inc. (https://www.signalchem.com), a separate division from SignalChem Lifesciences, is a biotech company focused on the research, development and production of innovative and high-quality human recombinant cell signaling products. Throughout the years, SignalChem has capitalized on its core expertise in cellular signaling, molecular biology and protein biochemistry to generate more than 3,000 functional protein products. SignalChem strives to support scientists in academia, pharma and biotech companies around the world by creating effective research tools to advance the basic research in life sciences and to facilitate the efforts in drug discovery and development. For more information, please visit https://www.signalchemlifesciences.com. Forward-Looking Statements and Information This release contains forward-looking statements that are not based on historical facts. These forward-looking statements involve risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from those expressed or implied. Readers are cautioned not to place undue reliance on such forward-looking statements. Contact Zaihui Zhang, PhD CSO, VP R&D SignalChem Lifesciences Corp. + 604 232 4600 ext. 114

VANCOUVER, BRITISH COLUMBIA – March 23, 2021. SignalChem Lifesciences, a clinical-stage company developing novel targeted therapies for oncology, announces a collaboration with Merck, known as MSD outside of the United States and Canada, through a subsidiary, to evaluate the combination of SLC-391, a selective AXL inhibitor developed by SignalChem, with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with advanced non-small cell lung cancer (NSCLC). AXL, a member of the TAM family protein tyrosine kinases (Tyro3, AXL and Mer), plays a key role in cell survival, angiogenesis, metastasis and therapeutic resistance. SLC-391 is a clinical stage small molecule AXL inhibitor with high potency, selectivity and desirable pharmaceutical properties. SLC-391 disrupts cell division, inhibiting tumor growth and causing cancer cells to die. Based on emerging evidence, a clinical investigation has been initiated to evaluate SLC-391 in combination with KEYTRUDA in the treatment of patients with advanced NSCLC. SignalChem will conduct the study in multiple cancer centers in the US and Canada to evaluate the clinical outcome of combining SLC-391 and KEYTRUDA. The two companies plan to conduct the SKYLITE trial, a phase 2 study for patients with NSCLC. The SKYLITE trial is a multi-centre , single arm, open-label, Phase 2 Study of SLC-391 in combination with KEYTRUDA in subjects with NSCLC. Subjects will receive daily doses of SLC-391 orally for 21-day cycles in combination with the commercially approved dose and schedule of KEYTRUDA. The SKYLITE trial will evaluate the safety and efficacy of the combination therapy, and includes the exploration of biomarkers relating to AXL signaling that may correlate with anti-tumour activity. “We welcome the collaboration with Merck. We consider Merck’s clinical development expertise to be valuable and believe this relationship may contribute to the development of SLC-391 for the treatment of patients with advanced stage lung cancer. These patients experience aggressive tumors that are often difficult to treat. We hope this collaboration with Merck will lead to a new approach that addresses this important unmet need,” says Mr. Jun Yan, President, SignalChem Lifesciences. “We look forward to partnering with Merck as we aim to deliver new cancer treatments and advance SLC’s drug discovery platform. We at SLC are working hard to identify new anti-tumour, anti-metastatic, and anti-chemo-resistance therapies that provide meaningful alternatives to existing treatments.” About Lung Cancer Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than colon, breast and prostate cancers combined. NSCLC is the most common type of lung cancer, accounting for 84% of all lung cancer diagnoses. The overall 5-year survival rate for NSCLC is 24%, ranging from 61% for localized NSCLC to 6% for metastatic disease. About SLC-391 SLC-391 is a potent, selective and orally bioavailable small molecule AXL inhibitor. Currently, phase I clinical trial is ongoing in Canada to evaluate the safety and tolerability of SLC-391 in cancer patients with solid tumour. About SignalChem SignalChem Lifesciences Corporation (“SLC”), headquartered in British Columbia, Canada, is a clinical-stage company developing novel targeted therapies for oncology. SLC has a strong small-molecule drug development pipeline. Our novel targeted compounds are designed internally by a group of scientists with expertise and experience in kinase biology and drug discovery. SLC is seeking strategic partners to aid in bringing our clinical-stage drug pipeline to the market. SignalChem, a separate division from SignalChem Lifesciences, is a biotech company focused on the research, development and production of innovative and high-quality human recombinant cell signaling products. Throughout the years, SignalChem has capitalized on its core expertise in cellular signaling, molecular biology and protein biochemistry to generate more than 2,000 functional protein products. SignalChem strives to support scientists in academia, pharma and biotech companies around the world by creating effective research tools to advance the basic research in life sciences and to facilitate the efforts in drug discovery and development. For more information, please visit . Forward-Looking Statements and Information This release contains forward-looking statements that are not based on historical facts. These forward-looking statements involve risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from those expressed or implied. Readers are cautioned not to place undue reliance on such forward-looking statements. Contact: Zaihui Zhang, PhD CSO, VP R & D SignalChem Lifesciences Corp. + 604 232 4600 ext. 114