Phase 1b/2a Safety and Tolerability Study of Bemcentinib With Pembrolizumab/Carboplatin/Pemetrexed in Subjects With Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/With a STK11 Mutation

The primary purpose of this study is to determine the safety and tolerability of the combination of bemcentinib with chemo-immunotherapy (CIT) to identify the recommended phase 2 dose (RP2D) when administered as first line (1L) treatment in participants with locally advanced (Stage IIIb/IIIC) or metastatic (Stage IV) non-squamous NSCLC with no actionable mutations and to determine the anti-tumor activity of the combination of bemcentinib with CIT when administered as 1L treatment in participants with locally advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with serine/threonine kinase 11 (STK11) mutation and no actionable mutations.

Start Date14 Dec 2022

Sponsor / Collaborator

BerGenBio ASA

NCT06469138 / CompletedPhase 1

A Phase 1, Open-label, Nonrandomized Study to Investigate the Mass Balance Recovery and Metabolic Profile of 14C-bemcentinib Following Single Oral Administration in Healthy Male Subjects

The aims of this Study are to determine:
How much of the Study Drug (bemcentinib) ends up in urine and faeces
How much of the Study Drug and its breakdown products get into the bloodstream
The breakdown products (metabolites) of the Study Drug
The safety of the Study Drug and any side effects that might be associated with it.

Start Date02 Aug 2022

Sponsor / Collaborator

BerGenBio ASA

ISRCTN14340698 / CompletedPhase 1

Phase I trial: Labcorp Drug Development Study: 8479217 [The full scientific title will be published within 30 months after the end of the trial]

Start Date02 Aug 2022

Sponsor / Collaborator

BerGenBio ASA

100 Clinical Results associated with BerGenBio ASA

0 Patents (Medical) associated with BerGenBio ASA

Literatures (Medical) associated with BerGenBio ASA

02 Nov 2023·Blood

Phase Ib/II Study (NCT02488408 / BGBC003) of Bemcentinib Monotherapy or in Combination with Cytarabine or Decitabine in Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS): FINAL Results

Author: Lemoli, Roberto Massimo ; Micklam, David ; Beumer, Niklas ; Kapp-Schwoerer, Silke ; McCracken, Nigel ; Loges, Sonja ; Ben Batalla, Isabel ; Sutamtewagul, Grerk ; Alvarado-Valero, Yesid ; Gorcea-Carson, Claudia ; Imbusch, Charles ; Waizenegger, Jonas ; Heuser, Michael ; Chromik, Jolanta ; Mattei, Daniele Giovanni ; Gjertsen, Bjorn T. ; Janning, Melanie ; Crugnola, Monica ; Oliva, Cristina ; Rieckmann, Lisa-Marie ; Fiedler, Walter ; Di Renzo, Nicola

Background: The standard of care (SOC) in newly-diagnosed (ND) AML patients (pts) unfit for intensive chemotherapy (IC) yields median overall survival (mOS) of 14.7 months. However, beyond 1 st line (1L), pts have limited treatment options and dismal mOS of 2.3 months (4.7 months in pre-venetoclax era), highlighting the need for more effective treatments in 2 nd line (2L) and beyond. Activation of AXL, a receptor tyrosine kinase, is associated with poor prognosis, resistance to chemotherapy and decreased antitumor immune response in AML. Bemcentinib (BEM) is a first-in-class, oral, highly selective AXL inhibitor.Aims: The BGBC003 PhIb/II trial studied the safety and efficacy of BEM as monotherapy in AML (cohort B1) and MDS (cohort B4) and in combination with decitabine (cohort B3) or low-dose cytarabine (LDAC) (cohorts B2 and B5) in ND and relapsed/refractory (R/R) AML pts unfit for IC. Pharmacokinetic/pharmacodynamic (PK/PD) analysis was conducted in pts treated with BEM monotherapy in the safety run-in phase (part A). Here, we present final efficacy and safety data, as well as PK/PD analysis from part A.Methods: In part A, 36 pts received BEM monotherapy in a dose escalation manner. In part B (cohorts B1-B5), pts received 3 loading doses at daily 400 mg BEM followed by 200 mg BEM daily. Study endpoints included OS, objective response rate (ORR), clinical benefit rate (CBR) (ORR+unchanged [UC]). Plasma and peripheral blood (PB) samples were used for PK and phospho-AXL (pAXL) analyses.Results: From Oct-14 to Jul-21, 86 pts were enrolled in part B (72 efficacy evaluable), with a median age of 76 years (range 50-86), 77% being R/R at study entry. BEM monotherapy and in combination was well tolerated, with a safety profile comparable to the known safety profile of the combination agents. The ORR was 18% (B1), 0% (B3), 25% (B2+B5), and 19% (B4). The CBR was 45% (B1), 31% (B3), 31% (B2+B5) and 56% (B4). The mOS (months) was 18 (B1), 6.4 (B3), 8.0 (B2+B5) and 9.2 (B4). BEM+LDAC (B2+B5) showed promising survival benefit in ND (mOS 16.5 months, n=5) and R/R pts (mOS 7.8 months, n=27). The PK/PD analysis showed inhibition of the biological target pAXL in PB following monotherapy. BEM showed dose-dependent inhibition of pAXL and downstream targets of pAXL (pAKT, pERK and pNFkB) with EC 50 values of 89-162 ng/mL.Summary/Conclusions: BEM demonstrated on-target effect by inhibition of pAXL and downstream signalling in a concentration-dependant manner. BEM monotherapy and in combination was well tolerated across all cohorts. The overall efficacy observed is comparable with historical data in 2L AML and MDS. Although the shift in 1L SOC in AML during the study limits adequate comparisons, a survival benefit was observed both in ND and R/R AML, warranting further investigation.Keywords: Acute myeloid leukemia, Clinical trial, Receptor tyrosine kinase

29 May 2021·Nephrology Dialysis Transplantation

MO074TILVESTAMAB, A FUNCTION-BLOCKING MONOCLONAL ANTIBODY INHIBITOR OF AXL RTK SIGNALLING, LIMITS THE ONSET OF RENAL FIBROTIC CHANGES IN HUMAN KIDNEYS EX VIVO

Author: Osman, Tarig Al-Hadi ; Marti, Hans-Peter ; Jackson, Akil ; Grøndal, Sturla Magnus ; Gausdal, Gro ; Micklem, David ; VanderHoeven, Barbara ; Boniecka, Anna ; Lorens, James B ; Nilsson, Linn Hodneland ; Landolt, Lea Zoe ; Blø, Magnus

AbstractBackground and AimsInterstitial fibrosis, characterised by the accumulation of extracellular matrix in the cortical interstitium, is directly correlated with progressive chronic kidney disease secondary to inflammatory, immunologic, obstructive or metabolic causes. An invariant histologic marker of this progression is the accumulation of fibroblasts, with the phenotypic appearance of activated myofibroblasts expressing alpha smooth muscle actin (αSMA) within intracellular contractile stress fibres. Once present, these myofibroblasts are prognostic indicators of expansion of fibrotic matrix and progressive tubular atrophy, leading towards end-stage disease.The Receptor Tyrosine Kinase AXL is involved in a range of kidney pathologies, with increased activity associated with Epithelial to Mesenchymal Transition (EMT) and tubular proliferation following podocyte loss. In mice treated with an angiotensin-converting enzyme (ACE) inhibitor, enhancement of AXL expression is localised to tubular segments within the medulla and there is evidence of parallel regulatory control of ACE and AXL. We have demonstrated enhanced expression of AXL and the mesenchymal marker, vimentin in diseased human kidney tissue secondary to diabetes or hypertension.Targeting AXL with a small-molecule inhibitor has previously been reported to attenuate fibrosis and reduce inflammation in the unilateral ureteric-outflow obstruction (UUO) model of kidney fibrosis in mice (Landolt et al., 2019). Tilvestamab is a novel function blocking humanized anti-AXL antibody. Tilvestamab blocks GAS6-mediated AXL receptor activation in fibroblasts and renal tubule epithelial cells and mediates AXL receptor internalization and degradation.In this study we aimed to further characterise AXL as a target in CKD and to investigate anti-fibrotic efficacy of tilvestamab.MethodEight weeks old male C57BL/6 mice underwent UUO operation. After 15 days, kidneys were dissociated and stained with a high dimensional single cell mass cytometry 33 markers antibody panel. Data were analysed using JMP Genomics (v.8.2).Precision Cut Kidney Slices (PCKSs) from explanted human kidney tissue were propagated in a bioreactor (Paish et al., 2019, FibroFind, UK). PCKS were incubated for 72hrs in the presence of investigational drugs. Secreted collagen1a1 were quantified by ELISA. RNA was reverse transcribed to cDNA and used in qPCRs to measure Col1a1 and αSMA. FFPE sections were stained for αSMA. High magnification images were taken of each slide and analysed for surface area covered by the stain.ResultsExpression pattern of AXL during development of kidney fibrosis in the UUO model was investigated using a mass cytometry antibody panel designed for identifying subpopulations of immune cells as well as cell populations of the fibrotic stroma. Two predominant cell populations were affected by ligation; the mesenchymal and the immune island. AXL was a marker characterising several of the key populations that expanded upon ligation supporting a role for AXL in kidney fibrosis pathogenesis.In an ex vivo model of human PCKS, tilvestamab dose-dependently reduced the levels of αSMA. When combined with the lower of two doses of the ACE inhibitor enalapril, the lowest dose of tilvestamab synergized to reduce αSMA levels further as well as reducing secreted Collagen 1a1.ConclusionAXL expression is induced in key cell populations during development of kidney fibrosis supporting AXL as a novel target in CKD. Tilvestamab represents a promising strategy for the pharmacologic intervention of kidney fibrosis, and the potential synergy with current reno-protective therapies warrants further exploration.

01 May 2021·The Journal of Immunology

Phosphatidylserine Receptor Enhancement of SARS-CoV-2 Entry: AXL as a Therapeutic Target for COVID-19

Author: Van Ert, Hanora ; Bohan, Dana ; Ruggio, Natalie ; Gao, Boning ; Minna, John ; Lorens, James ; Maury, Wendy ; Chávez, Roberth Anthony Rojas ; Micklem, David ; Haim, Hillel ; Stokowy, Tomasz ; Rogers, Kai

AbstractPhosphatidylserine (PS) receptors enhance infection of a wide range of enveloped RNA viruses through virion-associated PS binding that is termed apoptotic mimicry. Here we show that this broadly shared uptake mechanism is utilized by SARS-CoV-2. Under ACE2lo conditions, expression of members of the TIM and TAM families of PS receptors synergized with ACE2 to enhance SARS-CoV-2 infection; however, PS receptors alone did not mediate infection. PS receptors enhanced SARS-CoV-2 binding to the surface of cells. While PS receptors did not interact directly with purified SARS-CoV-2 spike, addition of PS liposomes reduced entry of VSV-SARS-CoV-2 spike pseudovirions, providing evidence that PS/PS receptor interactions are mediating the effect. AXL being abundant on airway cell lines, we evaluated small molecule inhibitors of AXL signaling such as bemcentinib for their ability to inhibit SARS-CoV-2 infection. Bemcentinib robustly inhibited virus infection of some lung cell lines that expressed AXL. This inhibition correlated well with inhibitors that block cathepsin activity, consistent with AXL-mediated uptake of SARS-CoV-2 into the endosomal compartment. RNAseq studies in Vero E6 and A549-hACE2 cells demonstrated that bemcentinib reduced SARS-CoV-2 transcripts dramatically. The ability of bemcentinib to decrease coronavirus infection in vivo was assessed using the betacoronavirus mouse hepatitis virus (MHV). Liver titers and virus load of MHV were significantly inhibited by bemcentinib at day 5 of infection. In total, our findings provide evidence that PS receptors facilitate infection of the pandemic coronavirus SARS-CoV-2 and that inhibition of signaling of the PS receptor AXL has therapeutic potential against SARS-CoV-2.

News (Medical) associated with BerGenBio ASA

07 Oct 2024

·www.prnewswire.com

BerGenBio Announces Safety Data from Dose Escalation Phase 1b in First Line NSCLC Patients

Ph1b data support safety, predictable PK and adequate plasma exposure BERGEN, Norway, Oct. 7, 2024 /PRNewswire/ -- BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, announced today preliminary safety data from the Phase 1b portion of the BGBC016 study in first-line (1L) Non-Small Cell Lung Cancer (NSCLC) patients. The Phase 1b part of the study evaluated three escalating doses of BerGenBio's selective AXL inhibitor bemcentinib in combination with standard chemo-immunotherapy (CIT), doublet chemotherapy and pembrolizumab, Keytruda®, for the 1L treatment of advanced/metastatic NSCLC patients. The primary endpoint was the assessment of the safety profile of the combination in NSCLC patients regardless of their STK11 mutational status. Key conclusions include: All three selected doses demonstrated that the triplet combination is well tolerated with no new safety signals identified, supporting the further clinical development of bemcentinib and CIT in 1L NSCLC patients. No dose-related impact on electrocardiographic changes (QTc), a known class effect of tyrosine kinase inhibitors, was reported for bemcentinib during the observation period. Pharmacokinetic analyses confirmed adequate plasma exposure of bemcentinib, achieving levels consistent with that previously observed in responders in BerGenBio's BGBC008 study of bemcentinib and pembrolizumab in second-line NSCLC patients. Martin Olin, Chief Executive Officer of BerGenBio, commented: "The data show that bemcentinib has a manageable safety profile and gives us increased confidence in continuing the BGBC016 clinical trial. The global trial is currently enrolling patients in Phase 2a targeting patients with a mutation in the STK11 gene, and we look forward to sharing the first preliminary data as they mature." Contacts Martin Olin CEO, BerGenBio ASA [email protected] Rune Skeie, CFO, BerGenBio ASA [email protected] Investor Relations / Media Relations Jan Lilleby [email protected] About STK11m NSCLC Patients with STK11m NSCLC have a significantly poorer response to current therapies, including immune checkpoint inhibitors, when compared with patients with wild-type (non-mutated) STK11. AXL plays a significant role in the survival and spread of cancer and STK11m NSCLC patients have a high expression of AXL suggesting that AXL is an important target to prevent disease progression and resistance to existing therapies. Bemcentinib's selective inhibition of AXL has been shown to improve the response to immune checkpoint inhibition in STK11m patient-derived preclinical models and in early clinical studies. There are currently no targeted therapies available for the STK11m NSCLC patient population, which represents up to 20% of 1L NSCLC patients. 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 This information is subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act. This information was brought to you by Cision SOURCE BerGenBio ASA WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ImmunotherapyPhase 1Phase 2Clinical Result

21 Aug 2024

·www.prnewswire.com

BerGenBio Second Quarter Results 2024: Solid clinical and financial progress

BERGEN, Norway, Aug. 21, 2024 /PRNewswire/ -- BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, today announced financial results for the quarter and half year ended June 30, 2024, and provided a business update. Highlights, including post period: BGBC016 1L NSCLC STK11m study continues to progress as planned. Enrollment in the Ph1b part completed. Data Safety Monitoring Board review of data from the final Ph1b dose cohort supports safety and tolerability of the combination of bemcentinib with standard of care chemo/immunotherapy allowing initiation of the 2 nd dose in the Ph2a part. All Ph2a sites have now been activated. Innovative approach established with leading genomic AI provider to accelerate development of bemcentinib. Established data and regulatory collaboration with technology company Tempus AI (Nasdaq: TEM) to provide prospective comparative clinical data from 1L STK11m NSCLC patients to aid in the evaluation of BGBC016 results. Strengthened financial position. Secured gross funding of NOK 138.9 million from warrant exercise in June 2024 securing funding into H2 2025. Financial position of NOK 200.1 million end of Q2 2024. Stable cash use. Continued decreased and stabilized operating expenses at NOK 90.5 million for first half 2024 compared to NOK 120.2 million in first half 2023. Operating expenses NOK 50.8 million in Q2 2024 compared to NOK 47.8 million in Q2 2023. Martin Olin, Chief Executive Officer of BerGenBio stated: "The BGBC016 clinical trial continued to progress well during the quarter. An independent review of the final cohort in the Ph1b part showed acceptable safety allowing initiation of the 2nd dose in the Ph2a part, and we completed the activation of the Ph2a sites. We now look forward to sharing preliminary efficacy data from the Ph2a portion of the study as they mature. During the quarter we strengthened our financial position which will, combined with our continuing cost discipline, fund our planned activities into the second half of 2025. The BGBC016 clinical trial is our highest priority, and we remain dedicated to unlocking the significant value potential in bemcentinib." Presentation and Financial Report The Q2 2024 Financial report is attached to this stock exchange announcement and the report and the Q2 2024 presentation are available at the Company's website . Webcast details BerGenBio's senior management team will provide a business update today at 9:45 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 clinical development for STK11 mutated NSCLC and preclinical development for 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 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. This information was brought to you by Cision The following files are available for download:

Financial StatementClinical Study

20 Aug 2024

·www.prnewswire.com

BerGenBio Collaborates with Tempus to Potentially Accelerate Development in STK11m Non-Small Cell Lung Cancer

BERGEN, Norway, Aug. 20, 2024 /PRNewswire/ -- BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, announced today a collaboration with Tempus, a technology company leading the adoption of AI to advance precision medicine and patient care, to advance the clinical development of BerGenBio's selective AXL inhibitor bemcentinib in first line (1L) Non-Small Cell Lung Cancer (NSCLC) patients with STK11 mutations (STK11m). BerGenBio's on-going BGBC016 Phase 1b/2a trial is designed to assess the benefit of adding bemcentinib to the current standard of care treatment (immunotherapy + doublet chemotherapy) in 1L STK11m patients, a population with poor outcomes and no specific therapies today. The collaboration will provide BerGenBio with access to a tailored cohort of Tempus' real-world clinical and molecular data that is intended to establish a synthetic control to provide a contextual benchmark for BerGenBio's innovative study, which aims to address the urgent medical need for effective treatments in STK11m NSCLC patients. Tempus' comprehensive, AI-enabled platform will enable BerGenBio to receive customized analyses of Tempus data and gain deeper insights into the genomic landscape and therapeutic responses of NSCLC patients with STK11m. Upon conclusion of the BGBC016 study, the parties intend to present insights derived from the resulting data to appropriate regulatory agencies as a next step in the further development of bemcentinib. Martin Olin, CEO of BerGenBio, expressed enthusiasm about the collaboration, stating, "We are excited to partner with Tempus to harness the power of their advanced technology in our mission to improve outcomes for NSCLC patients with STK11 mutations. By integrating Tempus' platform into our study, we aim to enhance our understanding of the disease biology and treatment outcomes, ultimately driving our ability to accelerate further development of bemcentinib". "We are excited to collaborate with BerGenBio to accelerate the development of precision therapies for STK11m NSCLC patients," said Kate Sasser, Chief Scientific Officer at Tempus. "Together, we aim to unlock new insights that will ultimately improve patient outcomes and redefine the standard of care in this challenging disease setting." For further information, please contact: Martin Olin CEO, BerGenBio ASA [email protected] Rune Skeie, CFO, BerGenBio ASA [email protected] Investor Relations / 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 This information is subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act. This information was brought to you by Cision

ImmunotherapyClinical Study

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Pipeline Snapshot as of 26 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Drug(Targets)	Indications	Global Highest Phase

Bemcentinib ( AXL )	Advanced Lung Adenocarcinoma More	Phase 2
BGB-101 ( AXL )	Pancreatic Cancer More	Preclinical
BGB-002 ( AXL )	Neoplasms More	Discovery
BGB-149 ( AXL )	Recurrent Platinum-Resistant Ovarian Carcinoma More	Discontinued
BGB-003 ( AXL )	Neoplasms More	Discontinued

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