KEAP1

The largest review of papers for brain cancer that has spread from the lungs has found abnormalities in the brain cancer and for which licensed drugs could be clinically trialed to find out if they could treat the disease.  The research also found genetic differences between smokers and non-smokers. The largest review of papers for brain cancer that has spread from the lungs has found abnormalities in the brain cancer and for which licensed drugs could be clinically trialled to find out if they could treat the disease. The research led by the University of Bristol and published in Neuro-Oncology Advances also found genetic differences between smokers and non-smokers. Around 25,000 patients in the UK suffer from cancer that has spread to the brain -known as metastases -- most commonly from lung and breast cancer, and causes death in the majority of these patients. The genetic mutations in primary lung cancers have been widely studied, but less is known about the changes in the cancer once it has spread to the brain. The research team wanted to find out the genetic changes in brain metastasis from non-small cell lung cancer (NSCLC) and whether there are drugs already available that could potentially be offered to these patients. The researchers carried out a review from 72 papers of genetic mutations in brain metastasis of NSCLC from 2,346 patients' data on patient demographics, smoking status, genomic data, matched primary NSCLC, and PD-L1, which is a protein found on cancer cells. The study found the most commonly mutated genes were EGFR, TP53, KRAS, CDKN2A, and STK11. Common missense mutations -- mutations that lead to a single amino acid change in the protein coded by the gene -- included EGFR L858R and KRAS G12C In certain cases the genetic mutations were different in the brain metastasis from the primary lung cancer. There were also differences in the genetic mutations in smokers versus patients who had never smoked. Brain metastases of smokers versus non-smokers had different missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. The research team found from the top ten commonly mutated genes which had primary NSCLC data, 37% of the specific mutations assessed were different between primary NSCLC and brain metastases. The researchers suggest Medicines and Healthcare products Regulatory Agency-approved drugs already licensed could potentially be tested to treat the disease in clinical trials. The genetic landscape of the different subtypes of NSCLC is well known. TP53 and LRP1B mutations are common to all NSCLC subtypes, but certain subtypes also have specific alterations. Lung adenocarcinoma is the most common type of lung cancer and has higher frequencies of KRAS, EGFR, KEAP1, STK11, MET, and BRAF somatic mutations -- changes that have accumulated in the cancer genome. Some studies suggested the genomic landscape of NSCLC in smoker's vs non-smokers differ independent of subtype. One study found EGFR mutations, ROS1 and ALK fusions to be more prevalent in non-smokers, whereas KRAS, TP53, BRAF, JAK2, JAK3 and mismatch repair gene mutations were more commonly mutated in smokers. Kathreena Kurian, Professor of Neuropathology and Honorary Consultant at North Bristol NHS Trust, Head of the Brain Tumour Research Centre at the University of Bristol and co-author of the paper, said: "Our research recommends that all patients should have their brain metastasis examined for mutations in addition to their primary lung cancer because they may be different. "This evidence could form the backbone for new clinical trials for patients with brain metastasis in non-small cell lung cancer using drugs that are already available." The team suggest the next steps for the research would be to consider whole genome sequencing on brain metastasis to look for other types of mutations, such as, common insertions/deletions for which drugs are already available.

BERGEN, Norway, Nov. 14, 2023 /PRNewswire/ -- BerGenBio ASA (OSE: BGBIO), a clinical-stage bio-pharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, today announced financial results for the quarter ended September 30, 2023, and provided a business update. "We are pleased to report continued advancement of our focused strategy to study our lead compound bemcentinib, a highly selective AXL inhibitor, in first line (1L) Non-Small Cell Lung Cancer (NSCLC) patients harboring mutations in the STK11 gene (STK11m). The increasing recognition of STK11m as a poor prognostic factor for 1L NSCLC patients, as evidenced by real-world data presented at prestigious medical conferences, continues to substantiate high unmet medical needs and our clinical data continues to validate the potential role of bemcentinib in combination with standard of care therapies to improve the outcome for these patients. During the quarter, we activated additional clinical trial sites in the US and prepared for the addition of sites in Europe in anticipation of the expected initiation of the Ph2a portion of our study in 1L NSCLC STK11m patients in the first half of 2024. Our operating expenses in the quarter amounted to NOK 28.1 million compared to NOK 62.4 million in Q3 2022 reflecting the effects of our focused strategy and cost containment implemented in connection with the Rights Issue. At 30th September 2023 our cash position stood at NOK 169.3 million. We believe that our singular focus on advancing bemcentinib in 1L NSCLC STK11m combined with the potential funding from the exercise of outstanding warrants issued in the Rights Issue enable us to generate data that can position the significant potential of bemcentinib in NSCLC," said Martin Olin, Chief Executive Officer of BerGenBio. Clinical Development Bemcentinib BerGenBio's lead compound, bemcentinib, is a potentially first-in-class, oral, highly selective inhibitor of the receptor tyrosine kinase AXL, which is expressed and activated in response to oxidative stress, inflammation, hypoxia and drug treatment, resulting in several deleterious effects in cancer and severe respiratory infections. Bemcentinib selectively inhibits AXL activation to prevent the progression of serious diseases through the modulation of resistance mechanisms and the adaptive immune system. Bemcentinib is currently being developed in 1L STK11 mutated NSCLC and severe respiratory infections. Its novel mechanisms of action and primary accumulation in the lungs uniquely position it to address these severe lung diseases. Oncology: NSCLC 1L STK11m NSCLC (BGBC016) We continue to advance our focused strategy through the conduct of BGBC016, a global, open-label Phase 1b/2a trial designed to determine the safety, tolerability and efficacy of bemcentinib in combination with standard of care treatments in untreated advanced/metastatic non-squamous NSCLC patients with STK11m and no actionable mutations. Sites in the US have been activated and enrollment is ongoing while expansion into European sites is well underway, with regulatory approval to proceed received from regulatory authorities in the US and several European countries. The Phase 1b portion of the study is evaluating the safety and feasibility of three different doses of bemcentinib in combination with pembrolizumab and doublet chemotherapy in 1L advanced/metastatic non-squamous NSCLC patients, regardless of STK11 status. To date, no significant safety concerns have arisen in the Phase 1b study. The Phase 2a expansion will assess the safety and efficacy of up to two doses of bemcentinib in the same treatment combination in 1L advanced/metastatic non-squamous NSCLC patients with STK11m. A significant subgroup comprising of up to 20 % (> 30,000 patients in US and EU5) of 1L non-squamous NSCLC patients harbor STK11m, which are associated with immunosuppression and poor prognosis with standard 1L NSCLC treatment. Data suggests that STK11m NSCLC patients almost universally express AXL in tumors and/or on immune cells, resulting in the development of drug resistance, immune evasion, and metastases. Post-quarter, the Company announced that the final data from the BGBC008 study (2L+ NSCLC, bemcentinib in combination with pembrolizumab) presented on October 23rd at the European Society for Medical Oncology (ESMO) 2023 Annual Meeting held in Madrid. The Company believes that these data along with study BGBIL005 (2L+ NSCLC, bemcentinib in combination with docetaxel) provide clinical evidence of the anti-tumor effects of bemcentinib and its ability to modulate the tumor microenvironment to enhance the effects of immunotherapy and chemotherapy. We believe that the reversal of the effects of AXL with bemcentinib holds the promise of providing substantial survival benefits to NSCLC patients and specifically in patients harboring STK11m and potentially other hard-to treat mutations such as KRAS and KEAP1. We expect to report additional clinical data at upcoming major medical meetings during the remainder of 2023, including the Society for Immunotherapy of Cancer (SITC) Annual Meeting and the American Society of Hematology (ASH) Annual Meeting. Description of the 2L+ NSCLC Trial (BGBC008) The Ph2 BGBC008 trial enrolled 90 evaluable 2L+ NSCLC patients who had received at least one prior line of therapy: chemotherapy, immunotherapy or the combination. An analysis of AXL biomarker status indicates that the presence of AXL expression on either tumor cells and/or immune cells is predictive of improved survival in patients treated with bemcentinib + pembrolizumab. The vast majority (88%) of patients met the criteria for AXL presence (AXL positive patients) and obtained clinically meaningful benefits: Median overall survival was highly statistically significant at p=0.001 in AXL positive vs. AXL negative patients (14.1 mos. vs 6.5 mos). Median progression free survival was 6.0 mos. in AXL positive patients vs. 5.8 AXL negative patients. Analysis of available data for patients treated in subsequent therapies (3L+) following treatment with bemcentinib + pembrolizumab identified a higher than expected response rate, potentially pointing to long-lasting immune response benefits. Data from the BGBC008 study also indicate that patients with PD-L1 negative (TPS score <1%) benefit from the combination treatment of bemcentinib and pembrolizumab. Currently PD-L1 negative patients respond less well to immune checkpoint inhibition, potentially providing an opportunity to expand the patient population eligible for treatment with bemcentinib. The combination of bemcentinib and pembrolizumab appeared to benefit patients with mutations associated with poor outcome with available therapies, including STK11, KRAS, KEAP-1 and SMARCA4 mutations. These mutational patient populations may represent an incremental opportunity for bemcentinib and will be further assessed in our on-going BGBC016 study in 1L NSCLC patients. Severe Respiratory Infections (SRIs) The Company believes that bemcentinib blocks viral entry and replication, stimulates the innate immune system, and promotes lung tissue repair positioning it for the treatment of severe respiratory infections. On April 25, 2023, the Company decided to pause the bemcentinib arm of the Phase 2b EUSolidAct trial evaluating bemcentinib in hospitalized COVID-19 patients due to the limited number of hospitalizations observed across all European countries. The Company and the EU-SolidAct have agreed to maintain this study on pause until and unless such time both parties agree to resume the trial arm due to increased COVID hospitalizations or should a new pandemic arise. Bemcentinib is currently being evaluated in preclinical studies for SRIs causing Acute Respiratory Distress Syndrome (ARDS) and initial results are expected during 2023. Corporate Activities Rights Offering On June 13, 2023, the Company completed a rights issue raising gross proceeds of NOK 250m. The proceeds from this offering including any additional proceeds from the exercise of warrants will be dedicated to the conduct of BGBC016 in 1L STK11m NSCLC patients, preclinical studies in severe respiratory infections and for general corporate purposes. Warrants The outstanding warrants issued in the Rights Issue can be exercised in two defined windows; from 15 November 2023 09:00 am CET to 28 November 2023 4:30 pm CET, or 1 April 2024 to 14 April 2024 at an exercise price of the volume-weighted average price (VWAP) of the Company's shares on the Oslo Stock Exchange over the three last trading days prior to the exercise period less 30%, but in any event not less than NOK 0.10 and not higher than NOK 0.13. Additional information and instructions for exercise of warrants can be found on the Company's website. Our Chief Operating Officer James Barnes, decided to pursue new opportunities and will leave the company during December 2023. In connection with the implementation of the focused strategy, the role of Chief Operating Officer will not be replaced. Third Quarter 2023 Financial Highlights (Figures in brackets = same period 2022 unless otherwise stated) - Revenue was NOK 0 million (NOK 0 million) for the third quarter. - Total operating expenses for the third quarter were NOK 28.1 million (NOK 62.4 million) - The operating loss for the quarter came to NOK 28.1 million (NOK 62.4 million) - Cash and cash equivalents amounted to NOK 169.3 million by the end of September 2023 (NOK 226.0 million by end of June 2023). Presentation and Webcast Details The Q3 2023 presentation and Financial Report are available at the Company's website. BerGenBio's senior management team will provide a business update today at 10:00 am CET. The presentation will webcast live. To participate in the webcast please use the following link: A recording of the webcast will be available at in the Investors/Financial Reports section shortly afterwards. Contacts Martin Olin CEO, BerGenBio ASA [email protected] Rune Skeie, CFO, BerGenBio ASA [email protected] Media Relations Jan Lilleby [email protected] About BerGenBio ASA BerGenBio is a clinical-stage biopharmaceutical company focused on developing transformative drugs targeting AXL as a potential cornerstone of therapy for aggressive diseases, including cancer and severe respiratory infections. The Company is focused on its proprietary lead candidate, bemcentinib, a potentially first-in-class selective AXL inhibitor in development for STK11 mutated NSCLC and severe respiratory infections. BerGenBio is based in Bergen, Norway with a subsidiary in Oxford, UK. The company is listed on the Oslo Stock Exchange (ticker: BGBIO). For more information, visit About Bemcentinib Bemcentinib is a potentially first-in-class, potent and highly selective inhibitor of the tyrosine kinase AXL. Extensive studies confirm the ability to combine bemcentinib with immune checkpoint inhibitors, chemotherapies and targeted therapies with the goal of improving a patient's immune response and delaying the development of chemoresistance. Bemcentinib is currently being investigated in combination with immune checkpoint inhibition and chemotherapy in first line NSCLC patients harboring mutations in the STK11 gene, a known prognostic factor of poor response to existing therapies. Forward looking statements This announcement may contain forward-looking statements, which as such are not historical facts, but are based upon various assumptions, many of which are based, in turn, upon further assumptions. These assumptions are inherently subject to significant known and unknown risks, uncertainties, and other important factors. Such risks, uncertainties, contingencies and other important factors could cause actual events to differ materially from the expectations expressed or implied in this announcement by such forward-looking statements. This information is considered to be inside information pursuant to the EU Market Abuse Regulation and subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act. The following files are available for download: SOURCE BerGenBio ASA

Presented at 2023 SITC Meeting - A pre-planned biomarker analysis of patients treated with bemcentinib in combination with KEYTRUDA® (pembrolizumab) yields new understandings- BERGEN, Norway, Nov. 6, 2023 /PRNewswire/ -- BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, announced that a poster presentation detailing additional data from a Phase II trial of bemcentinib in combination with MSD's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) in second line Non-Small Cell Lung Cancer (NSCLC) patients was presented on November 4th at the 2023 Society of Immunotherapy of Cancer Annual Meeting. The pre-planned biomarker analysis of the BGBC008 study in 2L NSCLC patients adds to the clinical data recently announced at the 2023 ESMO meeting. The poster presentation entitled "Bemcentinib + Pembrolizumab show promising efficacy in metastatic NSCLC patients harboring mutations associated with poor prognosis: exploratory sub-analysis from the BGBC008 Trial", is now available on BerGenBio's website under the Scientific Publications section. Martin Olin, Chief Executive Officer of BerGenBio, commented "The findings add to the industry's understanding of the outcomes in 2L NSCLC patients and the potential for bemcentinib to benefit patients in combination with immune checkpoint inhibition. While the dataset in the analyses is relatively small, we believe bemcentinib in combination with pembrolizumab has the potential to improve outcomes in NSCLC patient sub-groups that have been associated with poor survival, including patients with negative/low PD-L1 levels, STK11 mutations, and KEAP1 mutations". KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Contacts Martin Olin CEO, BerGenBio ASA [email protected] Rune Skeie, CFO, BerGenBio ASA [email protected] Investor Relations / Media Relations Jan Lilleby [email protected] About Bemcentinib Bemcentinib is a potentially first-in-class, potent and highly selective inhibitor of the tyrosine kinase AXL. Extensive studies confirm the ability to combine bemcentinib with immune checkpoint inhibitors, chemotherapies and targeted therapies with the goal of improving a patient's immune response and delaying the development of chemoresistance. Bemcentinib is currently being investigated in combination with immune checkpoint inhibition and chemotherapy in first line NSCLC patients harboring mutations in the STK11 gene, a known prognostic factor of poor response to existing therapies. About BerGenBio ASA BerGenBio is a clinical-stage biopharmaceutical company focused on developing transformative drugs targeting AXL as a potential cornerstone of therapy for aggressive diseases, including cancer and severe respiratory infections. The Company is focused on its proprietary lead candidate, bemcentinib, a potentially first-in-class selective AXL inhibitor in development for STK11 mutated NSCLC and COVID-19. BerGenBio is based in Bergen, Norway with a subsidiary in Oxford, UK. The company is listed on the Oslo Stock Exchange (ticker: BGBIO). For more information, visit Forward looking statements This announcement may contain forward-looking statements, which as such are not historical facts, but are based upon various assumptions, many of which are based, in turn, upon further assumptions. These assumptions are inherently subject to significant known and unknown risks, uncertainties, and other important factors. Such risks, uncertainties, contingencies and other important factors could cause actual events to differ materially from the expectations expressed or implied in this announcement by such forward-looking statements. This information is subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act. The following files are available for download: