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.

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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.

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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]).

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"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.

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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.

Actinium Pharmaceuticals Highlights 86% Response Rate and 71% MRD Negative Rate in Actimab-A CLAG-M Combination Trial in Patients with Relapsed or Refractory AML at ASH 2019 Annual Meeting

On December 9, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium")reported that highlighted new data from a Phase 1 trial studying Actimab-A in combination with the salvage chemotherapy regimen CLAG-M that was presented in a poster presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, DEC 9, 2019, View Source [SID1234552095]). The poster reported results from the ongoing Phase 1 combination trial that is being conducted at the Medical College of Wisconsin (MCW). Patients receiving Actimab-A at a dose of 0.50 uCi/kg in the second dose cohort in addition to CLAG-M had an 86% overall response rate (ORR), which is a 56% higher response rate and is substantially greater than what has been observed with CLAG-M and MEC and more than double that of CLAG in a similar patient population that was treated at MCW. Notably, 71% of patients (5/7) achieved negative minimal residual disease (MRD) status in the second dose cohort. In addition to response rates, the poster reported that three patients on the study proceeded to a bone marrow transplant after receiving Actimab-A and CLAG-M. The addition of Actimab-A to CLAG-M appears to have a clinically acceptable safety profile with no patient deaths reported. A table below compares the ORR of patients receiving Actimab-A and CLAG-M to that of the CLAG-M, MEC and CLAG salvage regimens. The full poster can be accessed HERE.

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(PRNewsfoto/Actinium Pharmaceuticals, Inc.)

Regimen

Overall Response Rate

Actimab-A + CLAG-M

86% (6/7)

CLAG-M

55% (41/74)

MEC

44% (25/57)

CLAG

40% (6/15)

Sameem Abedin, M.D., Assistant Professor of Medicine at the Medical College of Wisconsin and Principal Investigator of the study, stated, "CLAG-M has become our preferred salvage regimen for patients with relapsed or refractory AML, as it demonstrated a higher overall response rate than other salvage regimens such as CLAG and MEC. We are pleased by the significantly higher response rate of eighty-six percent that was observed when adding Actimab-A to CLAG-M compared to the fifty-five percent response rate we observed with CLAG-M in prior studies. This efficacy is highly encouraging particularly as the combination appears to have a clinically acceptable safety profile. We look forward to completing this Phase 1 trial and hope to advance to a Phase 2 trial that we believe can serve as a pivotal trial for this promising combination given the high unmet need of patients with relapsed or refractory AML."

Actimab-A is an Antibody Radiation-Conjugate (ARC) that delivers the potent alpha-emitting radioisotope Actinium-225 (Ac-225) via the antibody lintuzumab to cells that express CD33. CD33 is an antigen that is expressed on the vast majority of cancer cells in patients with acute myeloid leukemia (AML). CLAG-M is a salvage chemotherapy comprised of cytarabine, cladribine, G-CSF (granulocyte-colony stimulating factor) and mitoxantrone. The Phase 1 Actimab-A CLAG-M combination study is enrolling patients age 18 and older who have relapsed or refractory AML and are medically fit. The median age of patients enrolled in the trial to date is 62 and all patients had either intermediate risk or poor risk cytogenetics. Three patients had received three or more prior therapies and three patients had received a prior allogeneic bone marrow transplant. This patient population is similar to the study conducted at MCW that enrolled 146 patients, of which, 74 received CLAG-M, 57 received MEC and 15 received CLAG. MRD status was not reported in that study, however 71% of patients receiving 0.50 uCi/kg of Actimab-A and CLAG-M achieved MRD negative status1.

"These results further our excitement for the combination of Actimab-A and CLAG-M as well as other ARC combinations that we have ongoing like that with the Bcl-2 inhibitor venetoclax," commented Dr. Mark Berger, Actinium’s Chief Medical Officer. "The emergence of several recently approved agents, including targeted therapies, for patients with AML is exciting but their use can be limited to patients with a specific mutation and the lack of curative outcomes with these therapies points to a need for continued innovation. Our targeted Antibody Radiation-Conjugates can be a solution to the unmet need of many patients as radiation is a validated modality, hematologic cancers are sensitive and susceptible to radiation and patients with hematologic cancers are typically not exposed to external radiation given the diffuse nature of their disease. Because radiation is agnostic to genetic and cytogenetic abnormalities and there is no known resistance mechanism to alpha particles like actinium-225, we see great potential for additional combinations with other chemotherapy regimens like 7+3, targeted agents like FLT3 and IDH inhibitors and immunotherapies. Finally, these results increase our excitement for the Actimab-A venetoclax combination trial, and our Company looks forward to the clinical results next year that we believe can confirm the synergy we observed in our preclinical research."

The overall response rates observed with the Actimab-A CLAG-M combination compare favorably to response rates reported with recently approved therapies in patients with relapsed or refractory AML that are shown in the table below.

Agent or Regimen

Response Rate

Actimab-A + CLAG-M

83%

Gilteritinib (FLT3 inhibitor)2

68%

Venetoclax + HMA3

64%

Enasidenib (IDH2 inhibitor)4

40%

Venetoclax5

19%

Azacytidine (HMA)6

17%

The Actimab-A CLAG-M Phase 1 trial is expected to be completed in mid-2020. Actinium is also conducting a Phase 1 clinical trial studying Actimab-A in combination with the Bcl-2 inhibitor venetoclax in patients with relapsed or refractory AML to evaluate the safety of the combination and determine if the addition of Actimab-A to venetoclax can increase patient responses and outcomes. In preclinical studies, it was observed that Actimab-A can deplete Mcl-1, a protein that has been implicated in mediating resistance to Bcl-2 inhibitors like Venetoclax and provides a potentiating effect.

Sources:

1) MRD data from a subsequent analysis

2) Perl et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-1740.

3) Aldoss et al. Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia. Haematologica. 2018 Sep;103(9):e404-e407.

4) Stein et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Aug 10;130(6):722-731.

5) Konopleva et al. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia. Cancer Discov. 2016 Oct;6(10):1106-1117.

6) Itzykson et al. Azacitidine for the treatment of relapsed and refractory AML in older patients. Leuk Res. 2015 Feb;39(2):124-30.