1stOncology™: Cancer Intelligence Service – Page 12633 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

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.

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 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.

(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.

Aurinia Announces Public Offering of Common Shares

On December 9, 2019 Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH) (TSX:AUP) ("Aurinia" or the "Company"), a late-stage clinical biopharmaceutical company focused on advancing voclosporin in multiple indications, reported that it has commenced a registered underwritten public offering of US$150,000,000 of its common shares (the "Offering") (Press release, Aurinia Pharmaceuticals, DEC 9, 2019, View Source [SID1234552094]).

Jefferies LLC and SVB Leerink LLC are acting as joint book-running managers for the Offering. H.C. Wainwright & Co. LLC, Oppenheimer & Co. Inc., and Bloom Burton Securities Inc. are acting as co-managers for the Offering.

The Company will grant the underwriters an option exercisable, in whole or in part, in the sole discretion of the underwriters, to purchase up to an aggregate of US$22,500,000 of additional shares, for a period of up to 30 days. The Offering is subject to market conditions, and there can be no assurance as to whether or when the Offering may be completed, or as to the actual size or terms of the Offering.

The Company intends to use the net proceeds of the Offering for pre-commercialization and launch activities, as well as working capital and general corporate purposes.

The Offering is subject to customary closing conditions, including NASDAQ and TSX approvals. For the purposes of the TSX approval, the Company intends to rely on the exemption set forth in Section 602.1 of the TSX Company Manual, which provides that the TSX will not apply its standards to certain transactions involving eligible interlisted issuers on a recognized exchange, such as NASDAQ.

The Offering is being made pursuant to a U.S. registration statement on Form F-10, declared effective by the United States Securities and Exchange Commission (the "SEC") on March 29, 2018 (the "Registration Statement"), and the Company’s existing Canadian short form base shelf prospectus (the "Base Shelf Prospectus") dated March 26, 2018. The prospectus supplements relating to the Offering (together with the Base Shelf Prospectus and the Registration Statement, the "Offering Documents") will be filed with the securities commissions in the provinces of British Columbia, Alberta and Ontario in Canada, and with the SEC in the United States. The Offering Documents will contain important detailed information about the securities being offered. Before you invest, you should read the Offering Documents and the other documents the Company has filed for more complete information about the Company and the Offering. Copies of the Offering Documents will be available for free by visiting the Company’s profiles on the SEDAR website maintained by the Canadian Securities Administrators at www.sedar.com or the SEC’s website at www.sec.gov, as applicable. Alternatively, copies of the prospectus supplement will be available upon request by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022; by phone at (877) 821-7388; or by e-mail at [email protected]; or SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525, ext. 6132, or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, nor will there be any sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

Actinium Pharmaceuticals Announces Phase 3 SIERRA Trial Dosimetry Results Support Low Dose Iomab-B for Targeted Lymphodepletion Prior to Adoptive Cell Therapy

On December 9, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") presented new findings from its pivotal Phase 3 SIERRA trial for Iomab-B (Iodine-131 apamistamab) at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting on Sunday, December 8, 2019 in a poster presentation (Press release, Actinium Pharmaceuticals, DEC 9, 2019, View Source [SID1234552093]). Actinium is advancing the development of low dose Iodine-131 apamistamab, a CD45 targeting antibody radiation-conjugate (ARC), as an alternative to today’s standard practice of chemotherapy-based lymphodepletion regimens like fludarabine/cyclophosphamide (Flu/Cy), which have been implicated in CAR-T toxicities including cytokine release syndrome (CRS) and neurotoxicity.

The analysis of dosimetric results with Iomab-B in the pivotal Phase 3 SIERRA trial was conducted to model a non-myeloablative dose level to be used for lymphodepletion prior to CAR-T, as well as the time frame in which an adoptive cell therapy such as CAR-T could be administered. Based on the results from 56 evaluable patients that received a dosimetric dose of Iodine-131 apamistamab, including patients initially randomized to receive Iomab-B and those that received Iomab-B upon crossover from the control arm, it was determined that a single 75 mCi dosage of Iodine-131 apamistamab would deliver approximately 200 cGy to the bone marrow, the threshold that is considered non-myeloablative. At this dose level, it expected that an adoptive cell therapy could be administered approximately six days following Iomab-ACT lymphodepletion. Actinium intends to advance its Iomab-ACT program into human proof-of-concept clinical trials in conjunction with an adoptive cell therapy. The poster can be accessed on Actinium’s investor relations page of its website HERE.

Key findings presented in the poster include:

At fractional dose levels of Iodine-131 apamistamab (median 10mCi) used for dosimetry analysis in the SIERRA trial, approximately 1/10 of the targeted lymphodepletion dose, a significant but transient reduction in lymphocytes and white blood cells was observed compared to pre-dosimetry infusion levels
85% reduction in lymphocytes was observed at the post-dosimetry infusion time point, a 67% decrease at day 1 post-dosimetric infusion, and a 43% decrease one week later just prior to the Iomab-B therapeutic infusion, demonstrating potent yet reversible lymphodepletion at this dose level
35% reduction in peripheral leukemic blasts was observed at the post-dosimetry infusion time point, suggesting a rapid anti-leukemic effect with single-agent Iodine-131 apamistamab consistent with findings from SIERRA presented at ASCO (Free ASCO Whitepaper) 2019
The levels of platelets, red blood cells, and neutrophils did not significantly change between pre-infusion and post-dosimetry infusion
Based on the analysis of the 56 treated patients, a non-myeloablative dosage of 75 mCi has been proposed as a starting dose for human clinical testing in combination with a CAR-T
Analysis of the dosimetry data establishes that the proposed 75 mCi dosage of Iodine-131 apamistamab would be sufficiently cleared in approximately 147 hours (6.1 days) to allow for CAR-T administration
Dale Ludwig, Ph.D., Actinium’s Chief Scientific Officer, said, "CAR-T, adoptive cell therapy, and gene therapy are revolutionary medical advances with great promise. However, despite the innovation in these technologies, they continue to rely on generic chemotherapies for the necessary pre-conditioning prior to their administration, which are non-targeted and toxic. We believe this restricts the true potential of these therapies by hindering their efficacy and durability while increasing toxicities such as cytokine release syndrome and neurotoxicity. With a starting clinical dose and time to clearance defined and supported by clinical results from the SIERRA trial, we look forward to our next step of advancing this program into human clinical testing with a cell therapy while continuing to introduce the Iomab-ACT program to cell and gene therapy developers."

About the Iomab-ACT program

Iomab-ACT is a lower dose of Actinium’s lead program Iomab-B, which has been studied in over 300 patients and is currently being investigated in a pivotal Phase 3 trial for targeted conditioning prior to a Bone Marrow Transplant (BMT). Iomab-ACT targets CD45, an antigen expressed on many of the cells that are relevant to CAR-T including lymphocytes, macrophages and regulatory T-cells and that have been associated with CAR-T challenges such as durability of response, cytokine release syndrome (CRS) and neurotoxicity. Actinium has generated preclinical data that targeted lymphodepletion via Iomab-ACT has the potential to improve tumor control, selectively deplete necessary cells, and be highly differentiated in terms of tolerability compared to chemotherapy-based lymphodepletion regimens, namely fludarabine/cyclophosphamide (Flu/Cy). The Iomab-ACT program may enable lymphodepletion through a single-dose outpatient administration versus Flu/Cy or other chemo-based lymphodepletion regimens that require multiple infusions in an inpatient setting over several days.

BERGENBIO PRESENTS PRELIMINARY CLINICAL DATA FROM PHASE II COMBINATION TRIAL OF BEMCENTINIB AND LDAC IN ELDERLY AML PATIENTS AT ASH 2019

On December 9, 2019 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported that it will provide an update from the Company’s phase II study of bemcentinib (BGB324), a first-in-class highly selective oral AXL inhibitor, in combination with low-dose cytarabine (LDAC) in elderly AML patients in a poster presentation at the 61st Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting, being held from 7-10 December in Orlando, Florida (Press release, BerGenBio, DEC 9, 2019, View Source [SID1234552092]).

The bemcentinib-LDAC combination was safe and well tolerated in elderly AML patients and showed promising efficacy among both newly diagnosed and relapsed/refractory AML patients. The overall response rate and duration surpass historical benchmarks and compare favorably to other LDAC combinations. Pretreatment sAXL holds as a predictive biomarker in AML patients treated with the combination, and a new novel blood based predictive biomarker is identified and associated with clinical benefit in AML and Lung cancer patients receiving bemcentinib.

Professor Sonja Loges, attending physician and principal investigator, University Medical Centre Hamburg Eppendorf, Germany commented: "I am very encouraged by these early results. The duration of response and successful treatment beyond progression are consistent with the previously reported immunomodulatory activity of bemcentinib. I look forward to conducting a deeper analysis of AXL signalling in tumor and immune cells from patient biopsy samples to further elucidate this unique mechanism-of-action."

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "This combination trial of bemcentinib with low-dose cytarabine continues to show promising results in AML patients who are unable to tolerate intensive chemotherapy and have limited treatment options. The current data further highlight the novel tumor-immune effects of bemcentinib observed in previous cohorts and in other cancer types. Although these are early findings, we are encouraged by the response rate and duration, and we are focused on advancing our late stage development programme."

Details of the presentation are below.

Title: Durable responses observed in elderly AML patients unfit for intensive chemotherapy with first-in class selective AXL inhibitor bemcentinib (BGB324) in combination with LDAC: Phase II open-label study

Date: Monday 9th December 2019

Session Name: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III

Time, Location: 6:00 PM – 8:00 PM, Orange County Convention Center, Hall B

The poster will be available at www.bergenbio.com in the section: Investors/Presentations from 14.00 CET Monday 9th December 2019.

– 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.