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ArQule Announces Final Phase 1 Clinical Data for Its Reversible BTK Inhibitor, ARQ 531, at the American Society of Hematology 2019 Annual Meeting

On December 9, 2019 ArQule, Inc. (Nasdaq: ARQL) reported final results from the phase 1 study for ARQ 531, an orally bioavailable, potent and reversible dual inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) in patients with relapsed or refractory hematologic malignancies at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting & Exposition in Orlando, Florida (Press release, ArQule, DEC 9, 2019, View Source [SID1234552104]).

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"The final phase 1 data set confirms the potential utility of ARQ 531 for the treatment of these heavily pretreated CLL patients. We were excited to observe such deep and durable responses at a well-tolerated dose in this highly refractory population," commented Dr. Brian Schwartz, Chief Medical Officer of ArQule. "In addition, the three responses we observed in Richter’s Transformation patients were a welcome outcome and allowed several patients to transition to potentially curative therapies."

"ARQ 531 was selected and extensively tested preclinically to address the emerging therapeutic needs of patients who have become resistant to covalent BTK inhibitors in a broad set of hematologic malignancies," commented Dr. Jennifer Woyach, Associate Professor of Medicine at The Ohio State University and the Principal Investigator of the study. "It is tremendously gratifying to witness the emergence of a potential therapeutic for patients with such a high degree of unmet need, such as C481S-mutant CLL and Richter’s Transformation, and beyond. The data presented in this poster provide compelling proof-of-concept for this novel class of reversible BTK inhibitors."

The reported data are from the phase 1, open label, single arm dose escalation study and include patients (n=47) initially dosed at levels of 5, 10, 15, 20, 30, 45, 65 and 75 mg once a day with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), Richter’s Transformation, Waldenström macroglobulinemia and other B-cell Non-Hodgkin lymphomas.

Key Findings:

65 mg QD was selected as the Recommended Phase 2 Dose (RP2D) for further studies
Across all disease subsets, ARQ 531 showed a low incidence of associated toxicities, including one grade three DLT and no atrial fibrillation or bleeding observed
At 65 mg QD, ARQ 531 has a steady state mean Cmin above 1 µM and long plasma half-life of 56 hours resulting in complete pBTK inhibition
Clinical Anti-Tumor Activity:
In CLL, an Overall Response Rate (ORR) of 89% (8/9 responses in evaluable patients) was achieved in heavily pretreated R/R CLL patients (7/8 harboring BTK-C481S mutation) dosed at ≥65 mg QD. Eleven of 19 patients treated at 65 mg QD remain on study
In Richter’s Transformation, an ORR of 50% (3/6 responses in evaluable patients) was achieved at 65 mg QD
Two additional PRs were observed including one patient with Follicular Lymphoma (FL) and 1 patient with Diffuse Large B-cell Lymphoma (DLBCL)
Durability:
100% (5/5) evaluable CLL patients that received a third scan (cycle 9) are durable confirmed PRs and remain on therapy
67% (2/3) of Richter’s patients that achieved PRs came off study after becoming eligible for CAR-T therapy
The Follicular Lymphoma patient that achieved a PR has been on study for 120 weeks and remains a PR and on therapy
The poster at ASH (Free ASH Whitepaper) presenting these data entitled, "Final Results of Phase 1, Dose Escalation Study Evaluating ARQ 531 in Patients with Relapsed or Refractory B-Cell Lymphoid Malignancies," is available on the company’s website at www.arqule.com/publications-presentations/.

In addition, earlier today Merck and ArQule announced that the companies have entered into a definitive agreement under which Merck, through a subsidiary, will acquire ArQule. A copy of the joint press release is available on ArQule’s website, www.arqule.com.

ArQule will host a conference call and webcast for investors on Monday, December 9, 2019 at 8:15 a.m. EST to discuss the ARQ 531 clinical data. The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events & Presentations" or by visiting click here. You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. and providing conference ID 4573858. A replay will be available two hours after the completion of the call and can be accessed in the "Investors & Media" section of our website, www.arqule.com, under "Events and Presentations."

ArQule management will host an Investor Event to answer questions and discuss these data in Orlando tonight, Monday, December 9, 2019 from 8:00–10:00 p.m. EST. Investors, sell side analysts, and industry representatives are welcome to attend. For event details and to RSVP, please email [email protected].

About BTK and ARQ 531

Bruton’s tyrosine kinase, BTK, is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers. ARQ 531 is an orally bioavailable, potent and reversible dual inhibitor of both wild type and C481S-mutant BTK. The C481S-mutation is a known resistance mechanism for first generation irreversible BTK inhibitors. ARQ 531 has demonstrated a manageable safety profile, predictable PK, convincing pharmacodynamic effects and signs of clinical activity.

Aptose Presents Highlights From Corporate Event At ASH

On December 9, 2019 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS) reported that highlights from a corporate event and clinical update held at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, FL (Press release, Aptose Biosciences, DEC 9, 2019, View Source [SID1234552103]). The event was hosted by the Aptose management team and included Stephen B. Howell, MD, Acting Chief Medical Officer, Distinguished Professor of Medicine, Moores Cancer Center, University of California, San Diego (UCSD); with analysis by Rafael Bejar, MD, PhD, Aptose’s incoming Senior Vice President and Chief Medical Officer and currently the Director, MDS Center of Excellence, Moores Cancer Center, UCSD; and participation remotely by Brian J. Druker, MD, Chair of the Aptose Scientific Advisory Board, Professor of Medicine, Division of Hematology/Medical Oncology, Director, Knight Cancer Institute, Oregon Health & Science University.

The slides are available and the recording of the presentation will be archived on Aptose’s website here shortly after the conclusion of the event.

As the first clinical data from CG-806 in patients with chronic lymphocytic leukemia (CLL) have begun to emerge, Drs. Howell, Bejar, and Druker highlighted the consistency between the drug’s robust preclinical profile and the early clinical observations on safety, tolerability, pharmacokinetics, and activity. William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose also provided a corporate update on the clinical activities of CG-806, Aptose’s highly potent pan-FLT3/pan-BTK inhibitor.

CG-806, an oral, first-in-class mutation-agnostic FLT3/BTK kinase inhibitor, is in a Phase 1 trial in patients with B cell malignancies, including CLL and non-Hodgkin lymphomas (NHL), who have failed or are intolerant to standard therapies. The first two dose levels, which required only one patient at each level, are complete. The first two patients, both of whom were CLL patients that had previously failed a host of other agents, completed multiple dose cycles at 150 mg BID and 300 mg BID, respectively. Screening is ongoing for the third dose level, which is planned to enroll three patients.

Key findings from dose levels 1 and 2 of CG-806 in heavily pretreated R/R CLL patients:

CG-806’s safety profile remains clean; no unexpected toxicities have been observed to date
Notably, no myelosuppression, no drug-related adverse events or dose-limiting toxicity

Early evidence of clinical response has already been observed in a R/R CLL patient at dose level 2
Robust increase in peripheral blood lymphocytes (lymphocytosis)

Evidence of Bruton’s tyrosine kinase (BTK) target engagement
Lymphocytosis, which is known as an indicator of BTK inhibition
Inhibition of Phospho-BTK, Phospho-SYK and Phospho-ERK have been observed with a plasma inhibitory assay (PIA) using plasma from the CLL patient on dose level 2

Meaningful oral absorption and predictable pharmacokinetic (PK) profile

Exposures are likely therapeutic for acute myeloid leukemia (AML) patients
A separate trial with CG-806 in relapsed/refractory AML patients is in the planning stage
APTO-253, the only clinical stage agent that directly targets the MYC oncogene, is demonstrating safety and MYC target engagement in a Phase 1b clinical trial for the treatment of patients with relapsed or refractory AML or high-risk myelodysplastic syndrome (MDS).

Key highlights:

Aptose has completed dosing of the first three cohorts (up to a dose of 66 mg/m2) of the Phase 1b trial with MYC inhibitor APTO-253 in patients with AML and MDS.

In the patients on the first three dose cohorts, no drug-related adverse events have been observed, including no myelosuppression, and dosing is planned to continue to ascend until a maximum tolerated dose is reached. The next expected dosing level is 100 mg/m2.

MYC biomarker data from AML and MDS patients in the first three cohorts continue to demonstrate reductions of MYC gene expression in their peripheral blood cells. The dose escalation portion of the study is designed to transition, as appropriate, to single-agent expansion cohorts in AML and MDS, followed by combination studies.
The Company continues to escalate dosing with both assets, as all current dose cohorts to date have exhibited favorable safety profiles and evidence of target engagement.

Amarantus to Present at 12th Annual LD Micro Main Event

On December 9, 2019 Amarantus Bioscience Holdings, Inc. (OTC Pink: AMBS) (the "Company," or AMBS), a US-based JLABS-alumnus biotechnology holding company, developing first-in-class orphan neurologic, regenerative medicine and ophthalmic therapies, and diagnostics through its subsidiaries, reported that its President & CEO Gerald Commissiong will be presenting a corporate overview at the 12th Annual LD Micro Main Event on December 10th, 2019 at 4:00 p.m. PST (Press release, Amarantus Biosciences, DEC 9, 2019, View Source [SID1234552102]). Management will be available to meet with interested parties 1 on 1 throughout both events.

Presentation Details

Event: 12th Annual LD Micro Invitation

Date: December 10, 2019

Time: 4:00 p.m. Pacific Time / 7:00 p.m. Eastern Time

Location: Luxe Sunset Hotel, 11461 Sunset Blvd, Los Angeles, CA 90049

Website: View Source

AbbVie and Scripps Research announce collaboration to develop a broad range of new therapeutics

On December 9, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company and Scripps Research, an international leader in non-profit biomedical research and drug discovery, reported a collaboration to develop new therapies for a range of diseases, including in the therapeutic areas of oncology, immunology, neurology and fibrosis (Press release, AbbVie, DEC 9, 2019, View Source [SID1234552101]).

"Based on our strong switchable CAR-T alliance launched in 2018, we feel the expanded relationship with AbbVie represents a robust path forward for some of our programs, complementing a diverse ecosystem of innovation we’ve created over the past several years at Scripps to advance life-changing therapies," says Peter Schultz, Ph.D., chief executive officer, Scripps Research and Calibr, its drug discovery division.

In addition to programs initially named in the collaboration from preclinical to IND stages of development, Scripps Research will present to AbbVie a certain number of preclinical programs of mutual interest per year for consideration to be included in the collaboration. Scripps and AbbVie will also work together in parallel to advance CD3 bispecifics against oncology targets nominated by AbbVie.

Under the terms of the license agreement, Scripps Research will continue to conduct pre-clinical research and development activities and, in some cases, Phase 1 clinical trials with AbbVie having an exclusive option to further develop and commercialize.

Upon AbbVie’s decision to exercise its option to a given program, Scripps Research is eligible to receive additional payments from AbbVie, including option exercise fees, success-based development and commercial milestone payments, as well as tiered royalties. AbbVie will make an undisclosed upfront payment, as well as a near-term milestone payment upon achievement of certain success criteria.

"The best way to develop transformational medicines is through collaborations that bring together the brightest minds," says Mohit Trikha, Ph.D., vice president and head of oncology early development, AbbVie. "This partnership with Scripps Research will collaboratively advance next generation programs, build stronger relationships with proven and emerging scientific leaders, and most importantly help us advance novel medicines for patients. We are eager to partner with Scripps on these assets as they enter the clinic over the next few years as Scripps has one of the strongest track records of any academic institution when it comes to advancing novel medicines for patients."

Oncolytics Biotech(R) Announces Positive Multiple Myeloma Data Presented at the 61st Annual Meeting & Exposition of the American Society of Hematology

On December 9, 2019 Oncolytics Biotech Inc. (NASDAQ:ONCY)(TSX:ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that a poster presentation was given over the weekend highlighting pre-clinical and clinical results of combining pelareorep with the proteasome inhibitor carfilzomib in the treatment of multiple myeloma (Press release, Oncolytics Biotech, DEC 9, 2019, View Source [SID1234552096]). The presentation was given on Saturday, December 7 as part of the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exhibition.

The poster, titled, "Carfilzomib Impairs the Innate Antiviral Immune Response and promotes cytotoxic T-cell Expansion in Oncolytic Virus Treated Multiple Myeloma Patients" describes synergies between proteasome inhibitors and pelareorep concerning immune cell changes and response in myeloma patients.

"These findings demonstrate that pelareorep, in combination with carfilzomib, infects multiple myeloma cells, thereby providing a strong scientific rationale regarding immune cell changes," said Dr. Rita Laeufle, Chief Medical Officer at Oncolytics Biotech. "The combination of carfilzomib and pelareorep promotes expansion of killer T cells in patients on an ongoing phase 1b study and how it may lead to tumor response when pelareorep is combined with proteasome inhibitors. We are confident that pelareorep could add significant clinical value to the treatment of multiple myeloma patients with the combination of these agents. Our first data in patients from an ongoing study has been very encouraging and further data will be presented at subsequent clinical conferences."

Key data and conclusions:

Demonstrated that pelareorep treatment selectively infected multiple myeloma cells and not normal bone marrow cells
Carfilzomib enhances reovirus entry, infection, and killing of multiple myeloma cells
Reovirus significantly increases the frequency and activation of certain killer T cells, and increases the anti-tumor activity of immune cells in multiple myeloma
Data supports that the combination of pelareorep, and carfilzomib potentiates the expansion of CD8+ killer T cells
The poster presentation was authored by Dr. Flavia Pichiorri, Associate Professor in the Judy and Bernard Briskin Center for Multiple Myeloma Research within the Hematologic Malignancies and Stem Cell Transplantation Institute at the City of Hope, et al. The poster can be found on the Posters & Publications page of Oncolytics’ website, View Source

Title: Carfilzomib Impairs the Innate Antiviral Immune Response and promotes cytotoxic T-cell Expansion in Oncolytic Virus Treated Multiple Myeloma Patients

Number: 1816
Presenter: Dr. Flavia Pichiorri
Program: Oral and Poster Abstracts
Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster I

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.