On December 3, 2018 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company focused on developing a pipeline of first-in-class AXL kinase inhibitors to treat multiple cancer indications, reported that it presented a comprehensive analysis of monotherapy data from its BGBC003 clinical trial (NCT02488408) with selective AXL inhibitor bemcentinib in patients with relapsed/refractory Acute Myeloid Leukaemia (AML) or high-risk Myelodysplastic Syndrome (MDS) (Press release, BerGenBio, DEC 3, 2018, View Source [SID1234531807]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In a poster presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) in San Diego entitled: "Comprehensive Analysis of the Dose Escalation, Expansion and Correlates in the Ph I/II Trial BGBC003 with the Selective Oral AXL Inhibitor Bemcentinib (BGB324) in Relapsed/Refractory AML and MDS", Professor Sonja Loges, attending physician at the University Hospital in Hamburg-Eppendorf and lead investigator of the BGBC003 trial, detailed the following:

14 of 26 (54%) of patients found to be AXL positive (denoted by low serum AXL, sAXL, levels at start of treatment).
Response rate of 43% CR/Cri/CRp to bemcentinib monotherapy in AXL positive patients and 22% overall.
Mild and manageable side effect profile with a low incidence of Grade 3/4 events and low incidence of haematological toxicity.
Furthermore, the Company announces that enrolment is complete into the phase II combination cohort of bemcentinib and decitabine in first line AML. Analysis of the activity of the combination will be submitted for presentation at a future medical congress.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "I am very encouraged by the data presented today, we are consistently seeing AXL positive patients report a superior response to bemcentinib therapy alone or in combination with standard of care therapy. The value of our biomarkers to identify patients most likely to benefit from bemcentinib is tremendous. Based on our clinical data, more than 50% of AML/MDS patients are AXL positive, of which 43% reported complete response within the first few weeks of starting bemcentinib monotherapy treatment. Bemcentinib is very well tolerated by patients as a single agent and in combination with other drugs, which is an important feature supporting bemcentinib’s broad utility. We are making excellent progress recruiting the chemotherapy combination arms of this study and look forward to reporting the data from these patients in the coming months".

END

About AML
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.

About the BGBC003 trial
The BGBC003 trial is a phase Ib/II multi-centre open label study of bemcentinib as a single agent in patients with AML or high risk MDS or in a combination with cytarabine and decitabine in AML patients. Up to 75 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 the 60th ASH (Free ASH Whitepaper) Annual Meeting in San Diego, California
The 60th American Society of Haematologist Annual Meeting and Exposition is the most comprehensive haematology conference worldwide and attracts more than 25,000 haematology professionals from every subspecialty.

On December 2, 2018 Aprea Therapeutics, a clinical-stage biotechnology company developing novel anticancer therapies targeting the p53 tumor suppressor protein, reported the closing of a EUR 50 million Series C financing round led by the Redmile Group, with participation by new investor Rock Springs Capital and existing investors 5AM Ventures, Versant Ventures, HealthCap, Sectoral Asset Management and Karolinska Development AB (Nasdaq Stockholm: KDEV) (Press release, Aprea, DEC 3, 2018, View Source [SID1234531806]). A representative from Redmile Group will also be appointed as Director to the Aprea Therapeutics Board of Directors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are thrilled to close this financing, initiate a Phase III clinical study in myelodysplastic syndromes (MDS) with our lead compound, APR-246, and drive the company toward its next value inflection point," said Christian S. Schade, President and Chief Executive Officer of Aprea. "The addition of Redmile and Rock Springs to our investor group broadens the US investor base and we believe positions the company for future strategic opportunities. We are committed to bringing this important new therapy to cancer patients with limited therapeutic options."

Proceeds from the financing will be used to advance the clinical development of APR-246, a first-in-class anticancer agent that reactivates mutated p53 tumor suppressor protein. Aprea is planning to begin a Phase 3 clinical study in myelodysplastic syndromes (MDS) and is nearing completion of a Phase Ib/II clinical trial in p53 mutated high-risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML) with APR-246 and azacitidine. The Phase II part of the study is ongoing, with updated data to be presented at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to contribute to disease progression. Mutations in p53 are found in up to 20% of MDS and AML patients and are associated with poor overall prognosis.

About p53 and APR-246

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 has been shown to reactivate mutant and inactivated p53 protein – by restoring wild-type p53 conformation and function – and thereby induce programmed cell death in human cancer cells. APR-246 has demonstrated pre-clinical anti-tumor activity in a wide variety of solid and hematological (blood) tumors, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase I/II clinical program with APR-246 has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.

On December 3, 2018 Significant developments in breast cancer research reported that it will be presented by NantHealth (NASDAQ: NH) at the San Antonio Breast Cancer Symposium this week (Press release, NantHealth, DEC 3, 2018, View Source;p=RssLanding&cat=news&id=2378988 [SID1234531804]). NantHealth, a leader in breakthrough cancer research and solutions to improve patient care and lower healthcare costs, will discuss the findings of three investigations, which examine the theme of providing oncologists with insights that enable cancer treatment tailored to the individual characteristics of each patient.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Symposium, which will be held at the Henry B. Gonzalez Convention Center in San Antonio from Dec. 4-8, is designed to provide state-of-the-art information on the experimental biology, etiology, prevention, diagnosis and therapy of breast cancer and premalignant breast disease, to an international audience of academic and private physicians and researchers.

"About 1 in 8 U.S. women or about 12.4% will develop invasive breast cancer over the course of her lifetime. Such staggering statistics make breast cancer research and progress critical," said Sandeep "Bobby" Reddy MD, Chief Medical Officer, NantHealth. "We are honored to have an integral role at the San Antonio Breast Cancer Symposium, which provides a dynamic forum for interaction, communication, and education for a broad spectrum of researchers, health professionals, and those with a special interest in breast cancer."

Title: "Germline potentially pathogenic variants in breast cancer intrinsic molecular subtypes are not associated with somatic TMB"
Presenting Author: Elias Obeid, MD, MPH
Senior Author: Christopher Szeto, PhD
Contributors: Sandeep "Bobby" Reddy MD; Lori J. Goldstein, MD; Mary B. Daly, MD, PhD; Stephen C. Benz, PhD; and Michael J. Hall, MD, MS
Description: Comprehensive DNA and RNA profiling of 270 patients revealed intrinsic molecular subtypes of breast cancer have significantly distinct profiles of pathogenic germline variants. However, despite some breast cancer subtypes having higher frequency of germline pathogenic variants within DNA-damage repair genes, there is little evidence that these patients have subsequently higher mutational burden within their somatic genomes.
Key Takeaway: Pathogenic germline variants in key DNA damage repair genes such as BRCA1/2 are likely not adequate biomarkers for immune checkpoint therapy response, but are potentially biomarkers of differential tumorigenesis pathways.

Title: "Time-course DNA and RNA profiling of tumors from intra-patient cross-over trial of sequential use of aromatase inhibitors"
Presenting Author: Charles Vaske
Senior Authors: Vessela Kristensen and Jürgen Geisler
Contributors: Rahul Parulkar, Nazli Bahrami, Torill Sauer, Marie Loeng, Berit Gravdehaug, Belal Aljabri, Vahid Bemanian, Jonas Lindstrøm and Torben Lüders
Description: Early analysis from the ongoing NEOLETEXE trial examines a time-series of biopsies taken while transitioning patients from steroidal to non-steroidal aromatase inhibitors (AI) and vice versa. Acquired markers of AI-therapy resistance, and potential markers of sequential therapy sensitization, were explored. Two months after initial therapy, mutational burden decreased and clonality increased, yet by 4mo post-initialization mutations particularly in PIK3CA had repopulated.
Key Takeaway: Switching AI therapies sequentially in a clinical study is a model system to study differences in anti-tumor-effects of AIs. This ongoing trial may lead to a novel strategy to resensitize tumors to hormonal treatment and to elucidate the differences between steroidal and non-steroidal AIs.

Title: "Identification of a neoantigen targeted by tumor-infiltrating lymphocytes in a patient with Her2+ breast cancer"
Presenting Author: Hannah Kranich
Senior Authors: Peter A. Fasching and Anita N. Kremer
Contributors: Andrew Nguyen, Hanna Hübner, Erber Ramona, Judith Bausenwein, Edith D. van der Meijden, Michael P. Lux, Sebastian Jud, Claudia Rauh, John Zachary Sanborn, Stephen C. Benz, Shahrooz Rabizadeh, Matthias W. Beckmann, Andreas Mackensen and Matthias Rübner
Description: In our study, we identify tumor infiltrating T-cells (TILS) that recognize tumor specific mutations (Neoepitopes) found by next-generation sequencing of breast cancer tumors. These identified TILS are further immortalized and characterized to bind the patient’s specific HLA alleles.
Key Takeaway: Identification of TILS recognizing patient specific neoepitopes allow development of personalized medicine in a pre-clinical setting.

Since 1977, the San Antonio Breast Cancer Symposium mission has been to provide state-of-the-art information on breast cancer research. From a one-day regional conference, the Symposium has grown to a five-day program attended by a broad international audience of academic and private researchers and physicians from over 90 countries. For more information visit: View Source

On December 3, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported longer-term data from the phase Ib/II GO29365 study showing that polatuzumab vedotin, an investigational anti-CD79b antibody drug conjugate (ADC), in combination with MabThera/Rituxan (rituximab) plus bendamustine (BR), demonstrated a median overall survival (OS) of over one year compared to the BR arm (12.4 vs. 4.7 months, HR 0.42; 95% CI 0.24, 0.75), in people with R/R DLBCL not eligible for a haematopoietic stem cell transplant. OS was an exploratory endpoint (Press release, Hoffmann-La Roche, DEC 3, 2018, View Source [SID1234531799]). Adverse events (AEs) were consistent with those seen in previous studies of polatuzumab vedotin, and of BR, with no new safety signals observed. These data were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Saturday 1 December 2018, at 18:15-20:15 PT (Sunday 2 December 2018, 03:15-05:15 CET; abstract #1683).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Treatment with polatuzumab vedotin plus BR resulted in a 66% reduction in risk of disease progression or death (as measured by investigator-assessed progression free survival; PFS; HR=0.34; 95% CI 0.2-0.570; p<0.0001), with 40% achieving a complete response (CR) compared to 18% in the BR arm (primary endpoint, as measured by positron emission tomography (PET); CR rates assessed by independent review committee; p=0.026). Furthermore, patients treated with polatuzumab vedotin plus BR achieved higher CR rates and longer PFS and OS compared with BR in all subgroups tested, including patients from cell-of-origin groups, germinal centre B-cell-like and activated B-cell-like, which are associated with a worse prognosis in DLBCL.

"There is a significant need for new and more effective treatment options for the approximately 40% of people with diffuse large B-cell lymphoma whose disease either does not respond to initial treatment or returns – a situation that is associated with a very poor prognosis that worsens after each relapse," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are delighted that polatuzumab vedotin has demonstrated sustained clinical benefits and has the potential to hopefully improve survival rates in this population. We are working with health authorities to make this novel regimen available to patients worldwide."

The phase Ib/II GO29365 study is the first and only randomised study to suggest a survival benefit for R/R DLBCL patients who are ineligible for haematopoietic stem cell transplant. Results were presented at the 60th ASH (Free ASH Whitepaper), and the data for the polatuzumab vedotin plus BR arm of the GO29365 study in R/R DLBCL will be submitted to health authorities around the world for approval consideration.

Polatuzumab vedotin is a first-of-its-kind anti-CD79b ADC currently being investigated for the treatment of several types of non-Hodgkin lymphoma. It is the only ADC targeted to CD79b, a protein that is highly specific, expressed in the majority of types of B-cell malignancies. Polatuzumab vedotin in combination with BR has been granted Breakthrough Therapy Designation and orphan drug designation by the US Food and Drug Administration, as well as PRIority MEdicines designation and orphan drug designation by the European Medicines Agency, for the treatment of adult patients with R/R DLBCL who are not candidates for haematopoietic stem cell transplantation.

About the GO29365 study
GO29365 is a global, phase Ib/II study evaluating the safety, tolerability and activity of polatuzumab vedotin in combination with MabThera/Rituxan (rituximab) or Gazyva/Gazyvaro (obinutuzumab) plus bendamustine in relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma. The phase II stage randomised 80 patients with previously treated R/R DLBCL to receive either bendamustine plus MabThera/Rituxan (BR), or BR in combination with polatuzumab vedotin. Patients enrolled had received a median of two prior therapies (a range of 1-7 prior therapies in the polatuzumab vedotin arm and a range of 1-5 prior therapies in the BR alone arm). The primary endpoint was complete response (CR) at the end of treatment, as measured by positron emission tomography (PET) and assessed by an independent review committee (IRC). Other key endpoints included objective response (OR; CR and partial response, PR) by investigator and IRC assessment, best objective response at the end of treatment by investigator assessment, duration of response (DOR), progression-free survival (PFS), event-free survival (EFS) and overall survival (OS).

About polatuzumab vedotin
Polatuzumab vedotin is a first-of-its-kind anti-CD79b antibody drug conjugate (ADC) currently being investigated for the treatment of several subtypes of non-Hodgkin lymphoma (NHL). The CD79b protein is highly specific and expressed in the majority of types of B-cell NHL, making it a promising target for the development of new therapies.[1;2] Polatuzumab vedotin is thought to bind to CD79b, triggering internalisation of the drug into the cells. This targets the chemotherapy (which is attached to the monoclonal antibody) to these B-cells. This process is thought to maximise tumour cell death while potentially minimising the effects on normal healthy cells.[3;4] Polatuzumab vedotin is being developed by Roche utilising Seattle Genetics ADC technology.

About diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.[5] DLBCL is an aggressive (fast-growing) type of NHL, which is generally responsive to treatment in the frontline.[6] However, as many as 40% of patients will relapse, at which time salvage therapy options are limited and survival is short.[1,4] Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.[7]

On December 2, 2018 Nordic Nanovector ASA (OSE: NANO) reported that updated results from its LYMRIT 37-01 Phase 1/2 clinical study of Betalutin (177Lu-lilotomab-satetraxetan) in patients with relapsed/refractory indolent non-Hodgkin’s lymphoma (R/R iNHL) have been presented in a poster at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (1-4 December 2018 in San Diego, CA, USA) (Press release, Nordic Nanovector, DEC 2, 2018, View Source [SID1234553486]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The published dataset (as of 2 November 2018) includes 74 evaluable patients; all patients received Betalutin as a single administration and have six or more months of follow-up.

Lisa Rojkjaer, MD, Chief Medical Officer of Nordic Nanovector, commented: "We are very pleased with the clinical data, which continue to support our decision to compare two promising dose regimens in the pivotal Phase 2b PARADIGME trial. The efficacy and safety profile of Betalutin, the duration of response and the convenience of a single administration underscore the potential of Betalutin for the treatment of patients with advanced-stage follicular lymphoma."

The conclusions from the updated study results are that a single administration of Betalutin is well-tolerated and continues to demonstrate encouraging anti-tumour activity in recurrent iNHL, especially in follicular lymphoma (FL) patients, the primary NHL population for which Betalutin is being developed. Key results are:

Patients Number of patients (n) Overall Response Rate (ORR) Complete Responses (CR)
All iNHL patients 74 61 % 28 %
FL patients 57 65 % 28 %
3L FL patients (≥2 prior therapies) 37 70 % 32 %
FL patients in Arm 1
(40 mg lilotomab followed by 15 MBq/kg Betalutin) 25 64 % 32 %
FL patients in Arm 4
(100 mg/m2 lilotomab followed by 20 MBq/kg Betalutin) 16 69 % 25 %
RTX refractory FL, ≥2 prior therapies 21 62 % 19 %
The median follow-up time for all patients was 18.4 months (range 3.2-61.6 months). The median duration of response (mDoR) was 9.0 months for all patients and 20.7 months for those with a CR. Twenty-five patients (34%) have remained free of disease progression for 12 months or more. Follow-up for duration of response is on-going.

Betalutin therapy was well tolerated with no unexpected safety findings and most common adverse events were predictable and manageable.

Two recommended Phase 2 doses were identified from this study and are now being compared in the pivotal, randomised Phase 2b PARADIGME trial in relapsed, anti-CD20 refractory FL patients who have received two or more prior therapies.

Poster details

Abstract 2879

Abstract title: LYMRIT 37-01: A phase I/II study of 177Lu-lilotomab satetraxetan (Betalutin) antibody-radionuclide-conjugate (ARC) for the treatment of relapsed non-Hodgkin’s lymphoma (NHL) – Analysis with 6-month follow-up

Authors: A. Kolstad, A et al.

The abstract is available at View Source the poster has been published on the Nordic Nanovector website in the section: /what-we-do/scientific-publications/scientific-posters.

Conference call/audio cast details:

Nordic Nanovector will host a conference call, 3 December 2018, at 08:00 CET. A question and answering session will follow the presentation. The conference call presentation will be available at: View Source

To participate in the call either:

Press crtl+click on the link https://bit.ly/2AzfKlS or paste it into your browser

Please note that the link will become active 15 minutes prior to the event. You will be asked to type in your phone number and registration details. The Event Conferencing system will automatically call you back on the phone number you provide and place you into the event.

Or

Use the manual dial-in numbers and participant passcode: 332692 (note that this connection might take more time):

Norway Dial-in Tollfree/Freephone 800 51025

Norway, Oslo Dial-in Local +47 2100 2613

About ASH (Free ASH Whitepaper)

The ASH (Free ASH Whitepaper) annual meeting is the premier event for scientific exchange in the field of haematology, attracting more than 20,000 attendees from all over the world. Typically, more than 5,000 scientific abstracts are submitted each year, and more than 3,000 abstracts are accepted for oral and poster presentations through an extensive peer review process.

About Betalutin

Betalutin is a tumour-seeking anti-CD37 antibody (lilotomab) conjugated to a low-intensity radionuclide (lutetium-177). It has shown promising efficacy and safety in the first part of the Phase 1/2 LYMRIT 37-01 clinical study in relapsed/refractory follicular lymphoma (R/R FL). A global, randomised Phase 2b trial, PARADIGME, in third line (3L) FL patients who are refractory to anti-CD20 immunotherapy (including rituximab, RTX) is currently on-going.

Betalutin is also being investigated in the Phase 1b Archer-1 study in combination with RTX in second-line FL patients, and in the Phase 1 LYMRIT 37-05 study in patients with R/R diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin’s lymphoma (NHL).

Betalutin has been granted Fast Track designation in the US and Promising Innovative Medicine (PIM) Designation in the UK for the treatment of patients with R/R FL. Betalutin also received Orphan Drug designations for FL in both the USA and Europe in 2014.

Betalutin is selective for CD37, which is highly expressed on the surface of B-cell non-Hodgkin’s lymphoma (NHL) cells. When bound to CD37 on tumour cells, Betalutin is internalised, causing DNA damage and cell death.

About LYMRIT 37-01

LYMRIT 37-01 is a Phase 1/2 dose-escalation study to determine the safety, pharmacokinetics and preliminary efficacy of a single dose of Betalutin in patients with relapsed iNHL, and to establish a recommended Phase 2 dose for the global, randomised Phase 2b PARADIGME trial.

LYMRIT 37-01 recruited 74 pts [57 follicular (FL), 7 mantle cell (MCL), 9 marginal zone (MZL), 1 small lymphocytic (SLL)] at 13 sites between December 2012 and February 2018. Median age was 68 years (range 38-87; 69% ≥ 65); the median number of prior therapies was 3 (range 1-9); 48 pts (65%) received 2 or more prior therapies.