University of British Columbia

MONDAY, Dec. 29 2025 -- Population-level penetrance of inherited retinal degeneration (IRD)-associated genotypes is lower than traditionally assumed, while IRD genotypes are more prevalent than expected, according to a study published online Dec. 22 in the American Journal of Human Genetics . Kirill Zaslavsky, M.D., Ph.D., from the University of British Columbia in Vancouver, Canada, and colleagues used large biobanks with linked genomic and clinical data to quantify the population-level penetrance of IRD-associated variants. A cohort with definite IRD-compatible genotypes was curated by screening 317,964 All of Us (AoU) participants for loss-of-function or pathogenic IRD variants. To derive lower- and upper-bound penetrance estimates via disease annotation frequencies (DAFs), three nested International Classification of Diseases-9/10 code sets ("IRD," "retinopathy," and "screening") were defined. The researchers found that DAFs ranged from 9.4 to 28.1 percent for IRD and screening, respectively, within a cohort of 481 AoU participants with definite IRD-compatible genotypes; these were enriched relative to the prevalence of the code sets in AoU. Retinal imaging of U.K. Biobank participants who shared variants with the AoU cohort were examined for validation. Overall, 16.1 to 27.9 percent of participants with shared variants in the U.K. Biobank exhibited definite or possible IRD features, concordant with AoU estimates. Penetrance was not predicted by participant demographics, smoking, socioeconomic status, or comorbidities. The researchers note the findings suggest that IRD genotypes are more prevalent (0.7 to 2.1 percent) than expected. "The large number of individuals that do not develop an IRD despite having a compatible genotype provide an opportunity to design well-powered research studies to discover disease modifiers, which could spur development of novel therapies," Zaslavsky said in a statement. Abstract/Full Text

FRIDAY, Dec. 19, 2025 -- During the delta and omicron variant time periods, vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) prior to and during pregnancy was associated with a lower risk for severe maternal disease, according to a study published online Dec. 15 in the Journal of the American Medical Association . Elisabeth McClymont, Ph.D., from the University of British Columbia in Vancouver, Canada, and colleagues examined the impact of vaccination on maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy. Data were included for pregnant individuals infected with SARS-CoV-2 and their infants between April 5, 2021, and Dec. 31, 2022, during the delta and omicron variant time periods. The analysis included 19,899 cases, identified based on COVID-19 diagnoses in pregnancy. The researchers found that 72 and 28 percent of cases were vaccinated and unvaccinated, respectively, prior to their COVID-19 diagnosis. Among those vaccinated prior to diagnosis, 80 and 20 percent were vaccinated before and during pregnancy, respectively. Vaccination was associated with a lower risk for hospitalization (relative risks, 0.38 and 0.38 during delta and omicron, respectively), critical care unit admission (relative risks, 0.10 and 0.10 during delta and omicron, respectively), and preterm birth (relative risks, 0.80 and 0.64 during delta and omicron, respectively). After controlling for comorbid conditions, vaccination was associated with lower hospitalization risk in both variant time periods. Those unvaccinated had an adjusted relative risk for hospitalization of 2.43 and 3.82 in omicron and delta, respectively. "Vaccination against SARS-CoV-2 prior to and during pregnancy, before COVID-19 diagnosis, was associated with a lower risk of severe maternal disease and preterm birth regardless of variant time period," the authors write. Several authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text (subscription or payment may be required)

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