On June 14, 2019 BerGenBio ASA (OSE:BGBIO) reported data showing significant efficacy in a Phase II clinical trial (BGBC003, NCT02488408) evaluating bemcentinib, a first-in-class selective oral AXL inhibitor, in combination with low-dose cytarabine (LDAC) as a potential new treatment regimen for AML patients unfit for intensive therapy (Press release, BerGenBio, JUN 14, 2019, View Source [SID1234537084]). The data will be presented by Professor Bjørn Tore Gjertsen MD PhD, Haukeland University Hospital and University of Bergen, at the 2019 annual congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA24), in Amsterdam, The Netherlands, Friday, June 14, 2019.

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In total, 16 patients were enrolled into the trial. Among the 14 patients evaluable for efficacy, 6 responses have been reported; 4 patients achieved complete remission / complete remission with incomplete hematologic recovery (CR/CRi) and 2 patients achieved partial remission (PR). Five of the six responses occurred among elderly AML patients (>75 years). Furthermore, two patients achieved durable stable disease for more than 3 months. The relapse-free survival rate for patients with CR/CRi is 7.9 months (range: 0.7 to 9.6 months) and continues to mature. The combination treatment of bemcentinib and LDAC was overall well-tolerated; the most common adverse events (>15% of patients) included anaemia, neutropenia and diarrhoea. Soluble protein (e.g. sAXL) and gene expression biomarker data is still maturing and will be reported in due course. A second biomarker poster from Prof. Gjertsen’s group, to be presented on June 15th, examined the effect of bemcentinib monotherapy from a phase 1b/2 clinical trial on patient AML cell signal transduction using mass cytometry. The high-dimensional single cell-level signalling analysis of AML blasts from 6 evaluable patients revealed significant effects already at 4 hours post-dosing of bemcentinib

Professor Bjørn Tore Gjertsen commented: "These early results are encouraging, especially among less fit AML patients with comparatively poor prognosis. Bemcentinib in combination with LDAC resulted in a substantially higher ORR than expected for single-agent cytarabine and clearly warrant further investigation of bemcentinib in an expansion cohort of AML patients unfit for intensive chemotherapy. Our signal cell-level biomarker analysis of AML blasts from patients indicates a substantial effect on cell signalling and represents a potential new biomarker strategy."

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "There are currently limited treatment options for AML patients unable to tolerate intensive chemotherapy, particularly those with relapsed and refractory disease. These promising preliminary data with bemcentinib in combination with low-dose cytarabine, reinforce data we recently at presented at ASCO (Free ASCO Whitepaper), and suggests that the addition of our selective AXL inhibitor can substantially improve AML patient outcomes. I am particularly encouraged by the high response rate observed in all patient groups studied, the extended duration of responses seen, which is still maturing, and how well the combination therapy was tolerated. We are still waiting on much of our biomarker data before we can report that and are very excited by cell signalling data presented by our collaborators at the University of Bergen. We will expand this study to include more patients and report more complete data in the coming months.¨

The posters presented at EHA (Free EHA Whitepaper) will be made available at www.bergenbio.com in the Investors / Presentations section to coincide with the following conference sessions:

Friday 14 June, 17:30 – 19:00 Central European Time
The Combination of bemcentinib, a novel, oral, selective AXL-Inhibitor and Low-Dose Cytarabine yields Durable Responses in AML patients Unfit for Intensive Chemotherapy

Sonja Loges et al.

Abstract: PF259

Location: Poster area

Saturday 15 June, 17:30 – 19:00 Central European Time
Single Cell Signaling Pharmacodynamics in a Phase 1b Clinical Trial of the AXL inhibitor bemcentinib in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Monica Hellesøy et al.

Abstract: PS999

Location: Poster area

– END –

About AML and the BGBC003 trial
Acute myeloid leukaemia (AML) is a rapidly progressing blood cancer. AML is the most common form of acute leukaemia in adults, where malignant AML blasts interfere with the normal functioning of the bone marrow leading to a multitude of complications like anaemia, infections and bleeding. AML is diagnosed in over 20,000 patients in the US annually and is rapidly lethal if left untreated. Successful treatment typically requires intensive therapy or bone marrow transplantation, and relapse and resistance are common. Consequently, there is an urgent need for effective novel therapies in relapsed/refractory patients, particularly those that are ineligible for intensive therapy or bone marrow transplant.

The BGBC003 trial is a phase Ib/II multi-centre open label study of bemcentinib in combination with cytarabine (part B2) and decitabine (part B3) in patients with AML who are unsuitable for intensive chemotherapy as a result of advanced age or existing-co-morbidities. Up to 28 patients will be enrolled at centres in the US, Norway, Germany and Italy.

For more information please access trial NCT02488408 at www.clinicaltrials.gov.

About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About Bemcentinib
Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

On June 14, 2019 Aura Biosciences, a leader in the development of novel targeted therapies in ocular oncology, reported that interim clinical data from its ongoing Phase 1b/2 clinical trial evaluating the safety and efficacy of light-activated AU-011, the Company’s lead product candidate for the treatment of primary choroidal melanoma, will be highlighted in an oral presentation at the European Society of Ophthalmology 2019 Congress being held June 13-16, 2019, in Nice, France (Press release, Aura Biosciences, JUN 14, 2019, View Source [SID1234537083]).

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"The data with additional follow up time continues to demonstrate a good tolerability and safety profile of light-activated AU-011 at single and multiple administrations. There is also consistent evidence of tumor control and visual acuity preservation, which are key benefits of this novel treatment," said Ivana K. Kim, M.D., Co-Director, Ocular Melanoma Center, Massachusetts Eye and Ear, Associate Professor of Ophthalmology, Harvard Medical School. "Interest in AU-011 as a potential first line treatment for early stage disease is very high as current treatments for primary choroidal melanoma typically result in severe vision loss and ocular morbidity."

Oral presentation details are as follows:

Title: Interim Results of a Phase 1b/2 Open-Label Clinical Trial of AU-011 for the Treatment of Small to Medium Choroidal Melanoma

Presenter: Ivana K. Kim, M.D., Co-Director, Ocular Melanoma Center, Massachusetts Eye and Ear and Associate Professor of Ophthalmology, Harvard Medical School

Session: Innovation in Retina

Date and time: Friday, June 14, 2019; 3:00-3:12pm CEST

Location: Gallieni 5, Acropolis Convention Centre

About Choroidal Melanoma

Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary intraocular tumor in adults and develops in the uveal tract of the eye. No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts and radiation retinopathy. The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor. The alternative is enucleation, or total surgical removal of the eye. Choroidal melanoma metastasizes in approximately 50 percent of cases with liver involvement in 80-90% of cases and, unfortunately, metastatic disease is universally fatal (source: OMF). There is a very high unmet need for a new vision sparing targeted therapy that could enable early treatment intervention for this life-threatening rare disease given the lack of approved therapies, and the comorbidities of radioactive treatment options.

About Light-Activated AU-011

AU-011 is a first-in-class targeted therapy in development for the treatment of primary choroidal melanoma. The therapy consists of proprietary viral-like particle bioconjugates (VPB) that are activated with an ophthalmic laser. The VPBs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute (NCI), recipient of the 2017 Lasker-DeBakey Award. Upon activation with an ophthalmic laser, the drug rapidly and specifically disrupts the cell membrane of tumor cells while sparing key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration and is currently in clinical development.

On June 14, 2019 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that new preclinical data for CG-806, its oral, first-in-class pan-FLT3/pan-BTK inhibitor, is being presented in a poster presentation today at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Amsterdam, the Netherlands (Press release, Aptose Biosciences, JUN 14, 2019, View Source [SID1234537082]).

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The poster, CG-806, preclinical in vivo efficacy and safety profile as a pan-FLT3 / pan-BTK inhibitor, highlights the in vivo anti-leukemic efficacy of CG-806 and its GLP toxicology and toxicokinetic profile. In a preclinical MV4-11 FLT3-ITD AML xenograft mouse model, CG-806 suppressed leukemia growth at all doses tested throughout the 28-day period of dosing. After dosing was halted, tumors treated with 10 mg/kg and 30 mg/kg resumed growth but responded again when CG-806 dosing was restarted. In the mice treated with 100 mg/kg, 5 of 11 (45%) were cured through day 120, and in the 300 mg/kg group, 10 of 11 (91%) of the mice were cured. Retreating the "uncured’ mice in these two dose groups for an additional 28 days beginning on day 88 led to rapid and robust antitumor response resulting in "cures" in all retreated mice through day 120. In the "re-treated" mice, no drug resistance and no toxicities were observed. GLP 28-day toxicology and TK studies mice and dogs showed no adverse CG-806-related effects on body weight, ophthalmic, respiratory or neurological examinations, clinical pathology (coagulation, clinical chemistry, or urinalysis), organ weight or macroscopic evaluations. No CG-806-related cardiovascular effects were noted in the 28-day GLP toxicology study or in a separate preclinical cardiovascular safety study.

The poster and abstract can be accessed here or at the publications and presentations section of Aptose’s website www.aptose.com.

"The wealth of preclinical data supporting CG-806 continues to grow and differentiate the molecule from other drugs on the market or in development," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We are pleased to have reached the clinic with this compound and are hopeful that clinical testing will prove it to be an effective therapy for hematologic malignancy patients greatly in need of new treatment options."

About CG-806
CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor in Phase 1 clinical development for hematologic malignancies. This small molecule, in-licensed from CrystalGenomics Inc. in Seoul, South Korea, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL/SLL, FL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B-cell cancers and AML.

On June 14, 2019 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a physician-led biopharmaceutical company focused on immuno-inflammatory and dermatological diseases, reported that management will present a company overview at the 2019 JMP Securities Life Sciences Conference on Thursday, June 20, 2019 at 11:30 AM ET at the St. Regis Hotel in New York, New York (Press release, Aclaris Therapeutics, JUN 14, 2019, View Source [SID1234537081]).

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A live audio webcast of the presentation may be accessed through the Company’s web site, www.aclaristx.com, on the ‘Events’ section. An archived version of the presentation will be available for 30 days.

On June 14, 2019 Xynomic Pharmaceuticals Holdings, Inc. ("Xynomic", Nasdaq: XYN), a clinical stage US-China oncology drug development company, reported that Xynomic has dosed the first patient in a Phase 1/2 trial that combines abexinostat with ibrutinib in patients with relapsed/refractory mantle cell lymphoma ("r/r MCL") or relapsed/refractory diffuse large B-cell lymphoma ("r/r DLBCL") at Memorial Sloan Kettering Cancer Center (MSK) (Press release, Xynomic Pharmaceuticals, JUN 14, 2019, View Source [SID1234537078]). This trial will enroll approximately 40 patients to assess the safety and efficacy of the combination in patients with r/r MCL or r/r DLBCL. This trial will also explore the biologic predictors of response and resistance to dual B-cell receptor (BCR) and histone deacetylase (HDAC) inhibition. Janssen Biotech, Inc. is providing ibrutinib as part of the study, with Xynomic providing abexinostat and funding support for the trial being conducted at MSK.

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Mantle cell lymphoma (MCL) has an annual incidence of approximately 6,500 in G7 countries, according to DR/Decision Resources, LLC. Ibrutinib has been approved by the United States Food and Drug Administration (FDA) for relapsed MCL and has response rates of 60-70% and median duration of response of 18 months. Abexinostat as a mono therapy has been shown to have response rate of 15.4% (7.7% complete response and 7.7% partial response) in r/r MCL patients. Researchers at MSK are testing whether abexinostat/ibrutinib combo could potentially improve response rates and duration of responses in r/r MCL patients, subject to the assessment upon the completion of the trial.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin’s lymphoma (NHL) subtype according to the Leukemia & Lymphoma Society (LLS). Researchers at MSK have shown preclinical data demonstrating that dual targeting of Bruton’s tyrosine kinase (BTK) in the BCR pathway with ibrutinib and inhibition of MyD88-driven NF-kB activation with a HDAC inhibitor lead to synergistic anti-lymphoma activity in MyD88 mutated, ABC-subtype DLBCL both in vitro and in vivo.

Abexinostat is a novel HDAC inhibitor in global pivotal trials against NHL and renal cell carcinoma. Ibrutinib is a first-in-class BTK inhibitor jointly developed and commercialized as IMBRUVICA by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company and has been approved for multiple hematological malignances and chronic graft-versus-host-disease (cGVHD).