On April 1, 2019 Resolution Bioscience, Inc. reported that scientists from Dana-Farber Cancer Institute are presenting the results of a retrospective liquid biopsy comparison study between Resolution’s ctDx-Lung assay and Guardant Health’s Guardant360 test this morning at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Resolution Bioscience, APR 1, 2019, View Source [SID1234534857]).

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Liquid biopsy assays have the potential to expand access to personalized care for those whose tissue biopsies are inadequate or unavailable and may present an opportunity for enhanced cancer monitoring and detection of minimal residual disease. The study was conducted to explore the technical differences and test the reliability of cell-free DNA next-generation sequencing (NGS) assays, which are not completely characterized at this time.

The comparison study highlights detection challenges of complex mutations such as gene fusions, as well as the need for platform cross-comparisons to realize the potential of liquid biopsy and increase access to personalized cancer care. A cohort of 169 non-small cell lung cancer (NSCLC) patients with Guardant360 results were screened for gene fusions. The team of scientists at Dana-Farber used a soon-to-be-released ctDx-Lung kit to analyze 16 cases that had a rearrangement in their tumor, along with additional banked plasma. All personnel involved in sample analysis were blinded to tumor genotype and Guardant360 results. The team found that the Resolution ctDx-Lung assay identified more actionable gene fusion mutations with higher allele frequencies than the Guardant360 test. The results further demonstrate the potential of the ctDx-Lung kit for patients with advanced NSCLC.

The ctDx-lung kit detected 13 out 16 fusions (allele frequency range 80-0.3%), while Guardant360 detected only seven (allele frequency range 10-0.3%). Of the 13 cases where an oncogenic fusion was detected in plasma, 89% of patients with productive fusions and 75% of patients with ‘non-productive’ fusions responded to tyrosine kinase inhibitor (TKI) therapies. Additional unblinding is ongoing to better understand false negative cases.

"This study is another strong validation of our targeted NGS-based liquid biopsy platform and its ability to outperform other assays, such as the Guardant360 test," said Mark Li, CEO of Resolution Bioscience. "These results prove our kits can be run at the leading cancer centers around the world, enabling more scientists to detect more of these actionable mutations, which will soon transform the way we diagnose, treat and monitor devastating diseases like NSCLC."

Attendees interested in the presentation, "Building an effective concordance study: Plasma Next Generation Sequencing (NGS) for oncogenic fusion detection in non-small cell lung carcinoma (NSCLC)," by Cloud Paweletz, PhD, of the Belfer Center at Dana-Farber Cancer Institute can reference abstract 1374/13. The study is being presented today between 8 AM-12 PM in Section 19 of the Georgia World Congress Center Exhibit Hall.

The funding for the study was provided by the Expect Miracles Foundation, the Robert and Renee Belfer Foundation, the Damon Runyon Cancer Research Foundation, and the Harold and Gail Kirstein Lung Cancer Research Fund.

To view the scientific poster, please visit www.resolutionbio.com/publications/AACR2019_DFCI_Fusions.pdf.

About Resolution ctDx-Lung

ctDx-Lung is built on Resolution’s patented cell-free DNA NGS analysis platform. The liquid biopsy assay captures and analyzes circulating tumor DNA (ctDNA) for driver mutations in 20 genes associated with NSCLC using Resolution’s proprietary targeted capture NGS chemistry and cloud-based bioinformatics.

On April 1, 2019 Exicure, Inc. (OTCQB: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported that its CEO, Dr. David Giljohann, will give a company presentation on Monday, April 8, 2019 at 11:50 am GMT at the H.C. Wainwright Global Life Sciences Conference (Press release, Exicure, APR 1, 2019, View Source;p=RssLanding&cat=news&id=2392908 [SID1234534807]). The presentation will be made in the Stratton Suite of the Grosvenor House in London.

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A live audio webcast will be available on the Investors section of Exicure’s website: www.exicuretx.com. The webcast will be archived for approximately 30 days following the event.

On April 1, 2019 BerGenBio ASA (OSE:BGBIO) reported that on a top-line, preliminary basis, the first efficacy endpoint has been met 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 acute myeloid leukaemia (AML) patients unable to tolerate intensive therapy (Press release, BerGenBio, APR 1, 2019, View Source [SID1234534826]). A second cohort evaluating bemcentinib in combination with decitabine is also ongoing and data is further maturing.

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The pre-specified efficacy endpoint in this trial requires at least three patients out of the first 14 patients (21%) to achieve clinical responses* when treated with the novel drug combination.

The cohort evaluating bemcentinib in combination with LDAC, summarised below, has met its primary endpoint; data is further maturing:

In total, 15 patients were enrolled of which 10 are evaluable for response to date. Among these, 4 were newly diagnosed and 6 relapsed or refractory (R/R).
In newly-diagnosed patients, one complete remission (CR) and one CR with incomplete haematologic recovery(CRi) were observed (2 out of 4) and one CR among R/R patients (1 out of 6), yielding a CR/CRi rate of 30% (3 out of 10).
All responders were above the age of 75, at least one had secondary disease, and two had unfavourable cytogenetic profiles. Responses had an early onset (after 1 to 2 cycles), were durable and deepened over time and the combination of bemcentinib with LDAC was well tolerated causing no overlapping or new toxicities compared to each agent given alone.
An extensive translational programme continues to explore potential biomarkers for bemcentinib combination therapy. Further details will be presented at upcoming medical conferences.

Furthermore, the Company is proceeding with preparations for a late-stage bemcentinib monotherapy trial in AML. The study, expected to start in the second half of 2019, will aim to confirm previously reported monotherapy efficacy of bemcentinib in AML patients whose disease has progressed on standard of care therapy. Correlation with relevant biomarkers will be explored with the ambition to pursue an accelerated development path in a selected patient population.

Professor Dr Dr Sonja Loges, attending physician at the University Hospital Hamburg-Eppendorf and lead investigator of the BGBC003 trial, commented: "Data gathered by our group and others have established AXL as a negative prognostic factor in patients with AML and other malignancies. AXL acts both as a driver of leukaemic cell proliferation and as negative regulator of anti-tumour immunity and therefore represents a novel and promising target in AML. Bemcentinib, an oral tablet, targets AXL selectively and I am pleased to see activity in my patients receiving bemcentinib alone or in combination with standard low-intensity therapies while side effects thus far have proven to be limited and manageable. These early results warrant further investigation of bemcentinib in a larger trial addressing AML patients unfit for intensive chemotherapy."

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Clearing the efficacy threshold for bemcentinib in combination with LDAC is very encouraging, particularly as we have seen responses in a less fit AML patient population who are considered to have unfavourable prognosis after the failure of first-line therapies, or those with high risk cytogenetics. AML patients represent a challenging patient population for clinical trials, but we are keen to pursue AML monotherapy as our first indication based on the high unmet need, strength of clinical proof-of-concept with biomarker correlation, excellent safety and potential for a fast and first route to registration. We look forward to providing more details on the trial design upon initiation and reporting further data with bemcentinib combinations in this indication as it matures." *defined as objective response (OR), as measured by the revised recommendations of the International Working Group (IWG) in AML

END

About AML and the BGBC003 trial
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.

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.

On April 1, 2019 Peloton Therapeutics, Inc., a clinical-stage biopharmaceutical company advancing first-in-class oral medicines for cancer and other serious conditions, reported the presentation of data from the Phase 2 portion of the company’s Phase 1/2 clinical trial of its lead drug candidate, PT2977, at the Fourteenth European International Kidney Cancer Symposium in Dubrovnik, Croatia (Press release, Peloton Therapeutics, APR 1, 2019, View Source [SID1234534842]). In the Phase 2 portion of the trial, highlighted in an oral presentation and poster session at the symposium, PT2977 showed encouraging anti-tumor activity with a favorable safety profile in patients with previously-treated advanced renal cell carcinoma (RCC).

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The presentation titled, "A First-in-Human Phase 1/2 Trial of the Oral HIF-2α Inhibitor PT2977 in Patients with Advanced RCC," was delivered by lead author Toni K. Choueiri, M.D., Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School.

PT2977 is an oral, small molecule inhibitor of hypoxia-inducible factor (HIF)-2α, a transcription factor that is the key oncogenic driver in RCC. Inhibiting HIF-2α can impact multiple pathways that contribute to RCC progression.

The Phase 1/2 study evaluated the safety and efficacy of PT2977. The Phase 1 portion included a once daily administration schedule dose escalation cohort of 37 patients with advanced solid tumors. Based on the results of this cohort, 120 mg once daily was selected as the recommended Phase 2 dose (RP2D). In the Phase 2 portion, 52 patients with advanced clear-cell RCC who had received at least one prior therapy received PT2977 at the RP2D. The data presented included all 52 patients from the Phase 2 portion and three RCC patients from the Phase 1 portion treated at the RP2D, for a total of 55 patients. The data cut-off date for the presentation was January 1, 2019.

Among the 55 patients who were treated at the RP2D, 12 patients (22%) had a confirmed partial response. Median progression free survival (PFS) was not yet reached in the study with a median follow-up of 9 months, and 36% of patients remained on study at the time of the data cut-off.

PT2977 was well tolerated. The most common adverse event was anemia, which was anticipated given regulation of erythropoietin (EPO) by HIF-2α. Two patients discontinued treatment for drug-related adverse events and three other patients required dose reductions for drug-related adverse events.

"The data from this trial indicate that HIF-2α inhibition has the potential to become a promising new treatment option for patients with renal cancer," said Dr. Choueiri. "The data show that PT2977 can provide clinically meaningful responses in heavily pre-treated patients with a favorable safety and tolerability profile."

"We are delighted with these results," said John A. Josey, Ph.D., Peloton’s Chief Executive Officer. "The data presented today pave the way for a planned monotherapy Phase 3 trial that will further explore this exciting new mechanism of action in patients with advanced kidney cancer."

Further information on the clinical trial of PT2977 can be found on clinicaltrials.gov (Study identifier: NCT02974738). The poster and presentation slides are available online at: View Source

About PT2977

PT2977 is a once-daily, oral inhibitor of hypoxia-inducible factor-2α (HIF-2α). PT2977 has demonstrated anti-tumor activity with a favorable safety profile in an early-stage clinical study in patients with solid tumors. Peloton is also currently evaluating PT2977 in an international Phase 2 trial in von Hippel-Lindau (VHL) disease-associated RCC.

On April 1, 2019 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported that management will host a conference call on Tuesday, April 2nd at 8:00 a.m. Eastern Time to provide a clinical development update (Press release, Sangamo Therapeutics, APR 1, 2019, View Source [SID1234534858]).

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The conference call will be webcast live and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 6063108. For those unable to listen in at the designated time, a conference call replay will be available for one week following the call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 6063108.